back to the search page

Query Topic: Hyperaldosteronism

Query Date:

bartter syndrome(221)

Diagnosis and management of Bartter syndrome: executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders.
Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure. The primary pathogenic mechanism is defective salt reabsorption predominantly in the thick ascending limb of the loop of Henle. There is significant variability in the clinical expression of the disease, which is genetically heterogenous with 5 different genes described to date. Despite considerable phenotypic overlap, correlations of specific clinical characteristics with the underlying molecular defects have been demonstrated, generating gene-specific phenotypes. As with many other rare disease conditions, there is a paucity of clinical studies that could guide diagnosis and therapeutic interventions. In this expert consensus document, the authors have summarized the currently available knowledge and propose clinical indicators to assess and improve quality of care.
Publication Date: 2021-01-30 00:00:00
Journal: Kidney international

case report(117)

Spindle Cell Hemangioma and Atypically Localized Juxtaglomerular Cell Tumor in a Patient with Hereditary BRIP1 Mutation: A Case Report.
Spindle cell hemangioma is a benign vascular tumor typically occurring in the dermis or subcutis of distal extremities as red-brown lesions that can grow in both size and number over time. They can be very painful and potentially disabling. A family history of cancer or previous history may be relevant and must be taken into consideration. Juxtaglomerular cell tumor (reninoma) is an extremely rare cause of secondary hypertension diagnosed mostly among adolescents and young adults. Excessive renin secretion results in secondary hyperaldosteronism. Subsequent hypokalemia and metabolic alkalosis, together with high blood pressure, are clues for clinical diagnosis. Histological examination of the excised tumor leads to a definitive diagnosis. Reninoma is found in subcapsular localization, in most cases as a solitary mass, in imaging studies of kidneys. Exceptionally, it can be located in another part of a kidney. Both spindle cell hemangioma and reninoma are extremely rare tumors in children and adolescents. Herein, the authors present a case report of a patient with hereditary BRCA1 interacting protein C-terminal helicase 1 (BRIP1) mutation, spindle cell hemangioma, and secondary hypertension caused by atypically localized reninoma.
Publication Date: 2021-02-07 00:00:00
Journal: Genes

adrenal vein sampling(115)

Adrenal Vein Sampling Without Discontinuation of Mineralocorticoid Receptor Antagonist Therapy.
Guidelines recommend withdrawing mineralocorticoid-receptor antagonists (MRAs) for 4 weeks prior to adrenal vein sampling (AVS), but this is not always feasible because of hypertension and hypokalemia. This retrospective study of primary aldosteronism (PA) patients who underwent AVS between 2008 and 2018 assessed the effect of continuing MRA on the AVS procedure. Clinical data including antihypertensive regimen defined by the World Health Organization Daily Defined Dose (DDD) system were collected for 19 patients with adequate cannulation and lateralization during AVS. Results were compared between 5 patients who continued and 14 patients who discontinued MRA therapy (MRA and non-MRA groups). At diagnosis, plasma renin activity, plasma aldosterone concentration (PAC), potassium (K) doses, and DDD were not significantly different between groups. Aldosterone-renin ratio was significantly higher in the MRA group (median, 375.0; interquartile range [IQR], 224.8 to 544.3 vs. 148.7, 118.4 to 192.1; P = .034). No difference was found in lateralization index (median 48.3; IQR, 23.6 to 52.1 vs. 8.7; 4.9 to 20.2; P = .10). Contralateral suppression, defined as aldosterone-cortisol ratio of unaffected adrenal to periphery, trended lower in the MRA group (median, 0.17; IQR, 0.03 to 0.39 vs. 0.51; 0.27 to 1.1; P = .056). All five MRA patients underwent successful adrenalectomy with at least 50% reduction in DDD and PAC and normal K postoperatively. One MRA patient did not lateralize, which was confirmed on repeat AVS, after MRA withdrawal. Continuation of MRA may not interfere with AVS lateralization or affect contralateral adrenal suppression. Continuation of MRA in preparation for AVS may be considered, especially in patients with severe PA, to avoid uncontrolled hypertension and severe hypokalemia.
Publication Date: 2021-01-21 00:00:00
Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

adrenal venous sampling(112)

Association of Adrenal Venous Sampling With Outcomes in Primary Aldosteronism for Unilateral Adenomas.
Adrenal venous sampling is recommended prior to adrenalectomy for all patients with hyperaldosteronism; however, cross-sectional imaging resolution continues to improve, while the procedure remains invasive and technically difficult. Therefore, certain patients may benefit from advancing straight to surgery. To determine whether clinical and biochemical resolution varied for patients with primary aldosteronism with unilateral adenomas who underwent adrenal venous sampling vs those who proceeded to surgery based on imaging alone. Retrospective, international cohort study of patients treated at 3 tertiary medical centers from 2004 to 2019, with a median follow-up of approximately 6 months. A total of 217 patients were consecutively enrolled. Exclusion criteria consisted of unknown postoperative serum aldosterone level and imaging inconsistent with unilateral adenoma with a normal contralateral gland. A total of 125 patients were included in the analysis. Data were analyzed between October 2019 and July 2020. Adrenal venous sampling performed preoperatively. The primary outcome measurements were the clinical and biochemical success rates of surgery for the cure of hyperaldosteronism secondary to aldosterone-producing adenoma. A total of 125 patients were included (45 cross-sectional imaging with adrenal venous sampling and 80 imaging only). The mean (SD) age of the study participants was 50.2 (10.6) years and the cohort was 42.4% female (n = 53). Of those patients for whom race or ethnicity were reported (n = 80), most were White (72.5%). Adrenal venous sampling failure rate was 16.7%, and the imaging concordance rate was 100%. Relevant preoperative variables were similar between groups, except ambulatory systolic blood pressure, which was higher in the imaging-only group (150 mm Hg; interquartile range [IQR], 140-172 mm Hg vs 143 mm Hg, IQR, 130-158 mm Hg; P = .03). Resolution of autonomous aldosterone secretion was attained in 98.8% of imaging-only patients and 95.6% of adrenal venous sampling patients (P = .26). There was no difference in complete clinical success (43.6% [n = 34] vs 42.2% [n = 19]) or partial clinical success (47.4% [n = 37] vs 51.1% [n = 23]; P = .87) between groups. Complete biochemical resolution was similar as well (75.9% [n = 41] vs 84.4% [n = 27]; P = .35). There was no difference in clinical or biochemical cure rates when stratified by age, although complete clinical success rates downtrended in the older cohorts, and sample sizes were small. Given the improved sensitivity of cross-sectional imaging in detection of adrenal tumors, adrenal venous sampling may be selectively performed in appropriate patients with clearly visualized unilateral adenomas without affecting outcomes. This may facilitate increased access to surgical cure for aldosterone-producing adenomas and will decrease the incidence of morbidities associated with the procedure.
Publication Date: 2020-11-05 00:00:00
Journal: JAMA surgery

laparoscopic adrenalectomy(95)

Predicting factors related with uncured hypertension after retroperitoneal laparoscopic adrenalectomy for unilateral primary aldosteronism.
Although unilateral primary aldosteronism (PA) is the most common surgically correctable cause of hypertension, the cure rate varies widely. The predicting factors related to uncured hypertension are not completely established. This study was designed to determine predicting factors associated with resolution of hypertension after adrenalectomy for PA.The records of unilateral PA patients who had undergone retroperitoneal laparoscopic adrenalectomy were retrospectively reviewed from January 2010 to December 2017 in a single center. Patient demographics and preoperative factors were analyzed, including age, sex, smoking history, family history of hypertension, the presence of diabetes, body mass index (BMI), systolic blood pressure, diastolic blood pressure, biochemical results and tumor characteristics. Univariate and multivariate Logistic regression analysis were used for statistical assessment.126 patients with unilateral PA were enrolled, and the mean age at the time of surgery was 54.2 years. Of these patients, 74 (58.7%) were women, and the mean BMI and duration of hypertension were 26 kg/m and 61 months, respectively. Hypertension was cured in 46% patients, of the patients with uncured hypertension, 91% had improved control of hypertension. In univariate analysis, age (P = .03), BMI (P = .01), duration of hypertension >5 years (P = .03), preoperative antihypertensive agents>2 (P = .02), contralateral abnormalities (P = .03) were the main factors related to uncured hypertension after adrenalectomy. In multivariate regression analysis, uncured hypertension was independently associated with obesity (25.00-29.99: odds ratio [OR], 2.97, P < .02; ≥30: OR, 6.42, P < .01), duration of hypertension >5 years (OR, 6.25, P < .01), preoperative antihypertensive agents >2 (OR, 5.30, P < .001), and contralateral adrenal abnormalities (OR, 8.38, P < .01).The hypertension cure rate of unilateral adrenalectomy in PA is not high. Obesity, duration of hypertension >5 years, preoperative antihypertensive agents >2 and contralateral adrenal abnormalities were independently associated with uncured hypertension.
Publication Date: 2019-07-28 00:00:00
Journal: Medicine


Aldosterone- and cortisol-cosecreting adrenal adenoma, ovarian hyperthecosis and breast cancer.
We describe a 56-year-old postmenopausal woman with hypertension, hypokalemia and severe alopecia who was found to have a 4.5-cm lipid-poor left adrenal mass on CT scan performed to evaluate her chronic right-sided abdominal pain. Hormonal studies revealed unequivocal evidence of primary aldosteronism and subclinical hypercortisolemia of adrenal origin. Although a laparoscopic left adrenalectomy rendered her normotensive, normokalemic and adrenal insufficient for 2.5 years, her alopecia did not improve and she later presented with facial hyperpigmentation acne, worsening hirsutism, clitoromegaly, and an estrogen receptor-positive breast cancer. Further testing demonstrated markedly elevated serum androstenedione and total and free testosterone and persistently undetectable DHEAS levels. As biochemical and radiologic studies ruled out primary adrenal malignancy and obvious ovarian neoplasms, a bilateral salpingo-oophorectomy was undertaken, which revealed bilateral ovarian hyperthecosis. This case highlights how the clinical manifestations associated with hyperaldosteronism and hypercortisolemia masqueraded the hyperandrogenic findings. It was only when her severe alopecia failed to improve after the resolution of hypercortisolism, hyperandrogenic manifestations worsened despite adrenal insufficiency and an estrogen receptor-positive breast cancer was found, did it becomes apparent that her symptoms were due to ovarian hyperthecosis. As cortisol cosecretion appears to be highly prevalent in patients with primary aldosteronism, the term 'Connshing' syndrome has been suggested. The associated subclinical hypercortisolemia could be the driver for the increased metabolic alterations seen in patients with Conn syndrome. The identification of these dual secretors before adrenal venous sampling could alert the clinician about possible equivocal test results. The identification of these dual secretors before unilateral adrenalectomy could avoid unexpected postoperative adrenal crises. Hyperfunctioning adrenal and ovarian lesions can coexist, and the clinical manifestations associated with hypercortisolemia can masquerade the hyperandrogenic findings.
Publication Date: 2021-01-13 00:00:00
Journal: Endocrinology, diabetes & metabolism case reports

resistant hypertension(84)

Resistant Hypertension: A Clinical Perspective.
Resistant hypertension is a common clinical entity, defined as suboptimal blood pressure response to multiple therapies after excluding medication nonadherence and secondary forms of hypertension. Patients with resistant hypertension generally share several comorbidities. Resistant hypertension is more common in individuals of African descent. Blood pressure should be optimized using multiple strategies, including lifestyle changes and single-pill combination therapies, with the aim of reducing cardiovascular events while reducing side effects from using antihypertensive therapy. A renin/aldosterone-based diagnostic and treatment approach will help tailor therapy. The use of mineralocorticoid receptor antagonists or amiloride as appropriate is favored.
Publication Date: 2019-10-28 00:00:00
Journal: Endocrinology and metabolism clinics of North America


Familial hyperaldosteronism type 1 and pregnancy: successful treatment with low dose dexamethasone.
Familial hyperaldosteronism type 1 (FH-1) is an autosomal dominant form of primary aldosteronism (PA), featuring a marked phenotypic heterogeneity, ranging from mild forms of PA and arterial hypertension (HT) to severe forms complicated by stroke at a young age. Affected patients usually reach the fertile age; hence, transmission of the disease to offspring is common. Notwithstanding this, only anecdotal reports of FH-1 in pregnancy exist and recommendations for treatment remain vague. We herein report on a novel FH-1 pedigree featuring very severe HT, fatal aortic dissection, and high rate of early stroke, where a young FH-1 woman was successfully managed throughout pregnancy with low-dose dexamethasone. Based on this experience and on available information on pathophysiology of FH-1 in pregnancy, the pros and cons of dexamethasone administration in the treatment of FH-1 in pregnancy are also discussed.
Publication Date: 2021-01-05 00:00:00
Journal: Blood pressure

adrenal vein(140)

Approach to the Patient with Primary Aldosteronism: Utility and Limitations of Adrenal Vein Sampling.
Several studies over the past 3 decades document a higher prevalence of primary aldosteronism (PA) among hypertensive patients than generally presumed. PA exists as a spectrum from mild to severe aldosterone excess. Although a variety of PA subtypes exist, the two most common are aldosterone-producing adenomas (APAs) and bilateral hyperaldosteronism (BHA). The distinction is important, because APA - and other subtypes with aldosterone production mostly from one adrenal - can be cured surgically, and BHA should be treated medically with mineralocorticoid-receptor antagonists (MRAs). The major shortcomings in the tailored management of patients with possible PA are the low rates of screening for case identification and the expensive and technically challenging imaging and interventional procedures required to distinguish APA from BHA, especially adrenal vein sampling (AVS). When AVS identifies an APA and allows the patient to be cured surgically, the procedure is of great value. In contrast, the patient with BHA is treated with MRA whether AVS is performed or not. Consequently, it is prudent to gauge how likely it is to benefit from imaging and AVS in each case prior to embarking on these studies. The explosion of information about PA in the last decade, including predictors of APA and of surgical benefit, are useful in limiting the evaluation for some patients with a positive PA screening test. This article will review our suggestions for approaching these patients in a pragmatic style, recognizing the limitations to even the best resources and facilities.
Publication Date: 2021-01-01 00:00:00
Journal: The Journal of clinical endocrinology and metabolism


Late-Onset Bartter Syndrome Type II Due to a Homozygous Mutation in KCNJ1 Gene: A Case Report and Literature Review.
BACKGROUND Bartter syndrome is a rare genetic disease characterized by hypokalemia, metabolic alkalosis, and hyperreninemic hyperaldosteronism. Five different subtypes have been described based on the genetic defect identified. Bartter syndrome type II is caused by homozygous or compound heterozygous loss-of-function mutations in the KCNJ1 gene encoding ROMK. This subtype is typically described as a severe antenatal form of the disease, often presenting with polyhydramnios before childbirth. CASE REPORT Here, we describe the case of a 26-year-old man who presented with generalized body weakness and hypokalemia and was ultimately diagnosed with Bartter syndrome type II based on his clinical features coupled with the identification of a homozygous missense mutation in KCNJ1. CONCLUSIONS To the best of our knowledge, this is the fifth case of late-onset Bartter syndrome type II. Interestingly, the mutation identified in our patient has been previously described in patients with antenatal Bartter's Syndrome. The late presentation in our patient suggests a surprising degree of phenotypic variability, even in patients carrying the identical disease-causing mutation.
Publication Date: 2020-10-01 00:00:00
Journal: The American journal of case reports

aldosterone-producing adenoma(92)

131I-6β-iodomethyl-19-norcholesterol adrenal scintigraphy as an alternative to adrenal venous sampling in differentiating aldosterone-producing adenoma from bilateral idiopathic hyperaldosteronism.
To assess the correlation value between adrenal venous sampling (AVS) and I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy in differentiating aldosterone-producing adenoma (APA) from bilateral idiopathic hyperaldosteronism (BHA), and the use of NP-59 scintigraphy as an alternative to AVS. Overall, 29 patients with APA or BHA who underwent AVS and dexamethasone-suppression NP-59 scintigraphy were included between 2010 and 2017. The correlation value between AVS and dexamethasone-suppression NP-59 scintigraphy was assessed using each lateralisation index (LIAVS and LI1NP-59). Tumour presence and size were evaluated using computed tomography. The sensitivity and specificity of dexamethasone-suppression NP-59 scintigraphy for APA according to each lateralisation index threshold were calculated. Of 29 patients, 12 presented with APA and 17 with BHA according to AVS. The correlation value between LIAVS and LI1NP-59 was 0.63 (P < 0.001). If the cut-off points were 2.55 and 1.80 in all cases, the sensitivity and specificity were 0.33 and 1.00 as well as 0.58 and 0.94, respectively. In adrenal microtumours (maximum diameter ≤10 mm), no cases revealed a cut-off point of >1.8. However, in adrenal macrotumours (maximum diameter >10 mm), the cut-off point of 2.55 represented the best compromise (sensitivity: 0.44; specificity: 1.00). NP-59 scintigraphy can be used as an alternative to AVS if there is a strong lateralisation on NP-59 scintigraphy and adrenal macrotumours observed on the computed tomography when AVS is technically challenging, particularly in the right adrenal vein cannulation, and if contraindications, such as allergy to contrast materials and renal failure, are observed.
Publication Date: 2020-09-22 00:00:00
Journal: Nuclear medicine communications


Diverse pathological lesions of primary aldosteronism and their clinical significance.
Primary aldosteronism (PA) is mainly clinical y classified as unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism. Immunohistochemistry for aldosterone synthase reveals a diverse PA pathology, including pathological APA and aldosterone-producing cell clusters. The relationship between PA pathology and adrenalectomy outcomes was examined herein. Data from 219 unilaterally adrenalectomized PA cases were analyzed. Pathological analyses revealed diverse putative aldosterone-producing lesions. Postoperative biochemical outcomes in 114 cases (test cohort) were classified as complete success (n = 85), partial success (n = 19), and absent success (n = 10). Outcomes in the large and small PA lesion groups, rather than between PA lesion types, were compared at five threshold values for PA lesion sizes (2-6 mm with 1-mm increments) to streamline the results. The proportion of complete success was significantly higher in the large PA lesion group than in the small PA lesion group at the 5-mm threshold only. The proportion of absent success was significantly higher in the small PA lesion group than in the large PA lesion group at all thresholds. Univariate and multivariate analyses of the test cohort identified serum K as an independent predictive factor for the small PA lesion group, which was confirmed in the 105-case validation cohort. Chi-squared automatic interaction detector analysis revealed that the best threshold of serum K for predicting large PA lesions was 2.82 mEq/L. These results will be beneficial for treating PA in clinical settings because patients with low serum K levels and apparent adrenal masses on CT may be subjected to adrenalectomy even if the adrenal venous sampling test is unavailable.
Publication Date: 2021-01-14 00:00:00
Journal: Hypertension research : official journal of the Japanese Society of Hypertension

secondary hypertension(71)

[Diagnostics in Secondary Hypertension: What is to Consider?]
The prevalence of arterial hypertension with its cardiovascular diseases like myocardial infarction, stroke, chronic kidney disease and peripheral artery disease is increasing in our aging population. Despite numerous efficient and well-tolerated antihypertensive drugs more than eight million people die worldwide from the consequences of insufficiently controlled hypertension every year. One third of the german adult population suffers from high blood pressure. The fact that in only 50 % of hypertonic patients the blood pressure is on a string is even more disturbing. Several factors can counteract sufficient blood pressure control. This article should help to identify patients with possible secondary hypertension It is certainly not decisive to request a broad screening for all hypertensive patients. A certain pre-selection of potential patients is mandatory. The most common types of secondary hypertension are discussed and the diagnostic and therapeutic pathways are specified.
Publication Date: 2020-01-21 00:00:00
Journal: Deutsche medizinische Wochenschrift (1946)

blood pressure(96)

Diurnal blood pressure pattern and cardiac damage in hypertensive patients with primary aldosteronism.
The aim of our study was to evaluate the relationship between the 24-h blood pressure (BP) profile, plasma NT-proBNP levels and left ventricular hypertrophy (LVH) in subjects with primary aldosteronism (PA) compared to patients with essential hypertension (EH). A total of 385 consecutive patients with PA [187 with aldosterone producing adenoma (APA) and 198 with idiopathic hyperaldosteronism (IHA)] and 385 patients with EH were matched based on age, sex, body mass index (BMI), BP values and duration of hypertension. Twenty-four-hour ambulatory BP monitoring (ABPM), plasma levels of NT-proBNP, left ventricular mass index (LVMI), and other clinical medical data were assessed in all patients. No differences in age, sex, BMI, clinical BP, 24-h mean BP, daytime BP, or duration of hypertension were found between groups. Nighttime systolic BP (130 ± 16 vs. 127 ± 17 mmHg, p < 0.05) and diastolic BP (82 ± 10 vs. 79 ± 11 mmHg, p < 0.01) were higher in PA patients than in EH patients. In addition, nocturnal BP decline was reduced, while median NT-proBNP (53.7 vs. 33.2 pg/ml, P < 0.001) and LVMI (113 ± 25 vs. 102 ± 26 g/m Patients with PA show higher nighttime BP and NT-proBNP levels and lower nocturnal BP decline than those with EH. In addition, higher nocturnal systolic BP has been shown to be strongly associated with cardiac damage in PA patients.
Publication Date: 2021-01-22 00:00:00
Journal: Endocrine


Finerenone - Halting Relative Hyperaldosteronism in Chronic Kidney Disease.
Publication Date: 2020-10-24 00:00:00
Journal: The New England journal of medicine

adrenal venous(118)

Adrenal venous sampling guided adrenalectomy rates in primary aldosteronism: results of an international cohort (AVSTAT).
Adrenal venous sampling (AVS) is the current criterion standard lateralization technique in primary aldosteronism (PA). Japanese registry data found that 30% of patients with unilateral PA did not undergo adrenalectomy, but the reasons for this and whether the same pattern is seen internationally are unknown. To assess the rate of AVS-guided adrenalectomy across an international cohort and identify factors that resulted in adrenalectomy not being performed in otherwise eligible patients. Retrospective, multinational, multicenter questionnaire-based survey of management of PA patients from 16 centers between 2006 and 2018. Rates of AVS implementation, AVS success rate, diagnosis of unilateral PA, adrenalectomy rate, and reasons why adrenalectomy was not undertaken in patients with unilateral PA. Rates of AVS implementation, successful AVS and unilateral disease were 66.3%, 89.3% and 36.9% respectively in 4818 patients with PA. Unilateral PA and adrenalectomy rate in unilateral PA were lower in Japanese than in European centers (24.0% vs 47.6% and 78.2% vs 91.4% respectively). The clinical reasoning for not performing adrenalectomy in unilateral PA were more likely to be physician-derived in Japan and patient-derived in Europe. Physician-derived factors included non-AVS factors e.g. good blood pressure control, normokalemia, and the absence of adrenal lesions on imaging, which were present before AVS. Considering the various unfavorable aspects of AVS, stricter implementation and consideration of surgical candidacy prior to AVS will increase its diagnostic efficiency and utility.
Publication Date: 2020-10-09 00:00:00
Journal: The Journal of clinical endocrinology and metabolism


Primary Hyperaldosteronism in End-Stage Renal Disease: Diagnostic Challenges and Treatment Considerations.
An ad renal incidentaloma is defined as an ad renal mass measuring at least 1 cm that is discovered surreptitiously in an imaging study done for reasons other than the evaluation of ad renal disease. The increase in the prevalence of ad renal incidentalomas has paralleled the increase in diagnostic imaging done for evaluation of other abdominal pathologies. However, most of these ad renal incidentalomas are benign non-hyperfunctioning adenomas. When an ad renal incidentaloma is discovered, the simultaneous presence of hypokalemia, metabolic alkalosis, mild hypernatremia, and mild to severe drug-resistant hypertension may alert a clinician to underlying primary hyperaldosteronism. We present a case of ad renal incidentaloma noted in a patient with end-stage renal disease on hemodialysis which presented a diagnostic challenge due to the correction of metabolic parameters with hemodialysis. The patient was found to have an aldosterone-producing adenoma based on an elevated aldosterone-to-renin ratio and was started on a mineralocorticoid antagonist.
Publication Date: 2020-09-15 00:00:00
Journal: Cureus

aldosterone-producing adenomas(62)

Presence of Subclinical Hypercortisolism in Clinical Aldosterone-Producing Adenomas Predicts Lower Clinical Success.
The clinical characteristics and outcomes in patients with clinical aldosterone-producing adenomas harboring
Publication Date: 2020-09-15 00:00:00
Journal: Hypertension (Dallas, Tex. : 1979)

essential hypertension(54)

Atherosclerotic Burden and Arterial Stiffness are Not Increased in Patients with Milder Forms of Primary Aldosteronism Compared to Patients with Essential Hypertension.
Patients with primary aldosteronism (PA) are at increased cardiovascular risk, compared to patients with essential hypertension (EH). Cardiovascular damage could depend on PA phenotype, potentially being lower in milder forms of PA. Our aim was to assess atherosclerotic burden and arterial stiffness in 88 prospectively recruited patients, including 44 patients with mild PA and EH respectively. All patients underwent a structured study program, including measurements of ankle-brachial index, oscillometric measurement of central pulse wave velocity (cPWV) and vascular ultrasound examination of the supraaortic arteries, the abdominal aorta, and the femoropopliteal arteries. A plaque score was calculated to estimate atherosclerotic burden for each patient. This is a prospective case-control study set at a tertiary care hospital. Patients with PA and EH matched well for age, gender, blood pressure, BMI, and cardiovascular risk factors such as diabetes mellitus and smoking status. Common carotid intima-media thickness (0.77 vs. 0.75 mm; p=0.997) and cPWV (7.2 vs. 7.1 m/s; p=0.372) were comparable between patients with PA and EH. The atherosclerotic burden, as expressed by the plaque score, did not differ between the two groups (p=0.159). However, after initiation of treatment cPWV was significantly decreased in patients with PA (p=0.017). This study shows that subclinical atherosclerotic burden and arterial stiffness in patients with milder forms of PA is comparable to patients with EH. Nevertheless, specific treatment for PA significantly improved cPWV, which argues for a more liberal use of mineralocorticoid receptor antagonists in patients with arterial hypertension.
Publication Date: 2021-01-14 00:00:00
Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

arterial hypertension(53)

Atrial fibrillation, arterial hypertension, and primary aldosteronism: a dangerous and unexpected trio.
Publication Date: 2020-01-09 00:00:00
Journal: Journal of hypertension


[A delicate balance: Gitelman syndrome and gestational diabetes. A case report].
Gitelman s syndrome (GS) is a rare autosomal recessive disorder characterized by hypokalemia, hypomagnesaemia, metabolic alkalosis, hypocalciuria and secondary hyperaldosteronism. The impact of GS on pregnant patients is still not clear, despite the many clinical cases described in literature. In particular, there is no data on the development of gestational diabetes. Altered glucose metabolism and insulin sensitivity have recently been described in patients with GS. We describe here the clinical case of a young woman suffering from GS who started pregnancy and developed gestational diabetes. Our experience, while confirming the need of assiduous ionic monitoring especially in the first trimester of pregnancy, seems to help scaling down the maternal-fetal risk in patients suffering from GS. We also suggest the introduction of a low-glucose diet to prevent the onset of gestational diabetes, a condition burdened with severe complications. Finally, a reminder that drugs active on ionic balance must be of proven maternal and fetal safety.
Publication Date: 2020-08-19 00:00:00
Journal: Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia


The first cases of genetically confirmed congenital diarrhea with chloride loss in Slovakia.
Chloride ions are involved in regulating cell volume, secreting body fluids and maintaining acid-base balance. Hypo/hyperchloraemia in neonates and infants is an emergent situation requiring careful differential diagnosis to detect a cause of the condition. The rare causes of severe hypochloremia include congenital chloridorhea (CLD), characterized by profound bulky diarrhea, high chloride concentration in stool, and severe metabolic alkalosis. CLD is a rare autosomal recessive disease caused by the mutation of the SLC26A3 gene located on chromosome 7q31, which encodes the transmembrane protein in intestinal cells. Genetic defect causes a disorder of intestinal chloride absorption and bicarbonate secretion. Profound diarrhea induces significant losses of water and electrolytes, leading to volume depletion, hyperreninemia, hyperaldosteronism, renal loss of potassium and occasionally to the development of chronic nephropathy. The authors present rare cases of two brothers with genetically confirmed CLD. Both children were born with lower birth weight and shortly after birth required administration to ICU because of notable distended abdomen and diarrhea with severe dehydration and electrolyte imbalance. Significant hypochloraemia (76 mmol/l or 78 mmol/l) and extreme metabolic alkalosis (pH 7.63; HCO3 46 mmol/l and pH 7.73; HCO3 40 mmol/l resp.) were dominant laboratory features. Renal chloride losses and cystic fibrosis were excluded; the chloride concentration test in stool was not available. After intravenous suplementation of electrolytes, the biochemical abnormalities were partially normalized and watery stools persist. In further development, the frequent episodes of dehydratation reguiring the parenteral treatment were present. Renal functions are at age 6 or 2 years resp. normal, but USG signs of nephrocalcinosis in the older boy have been observed. By molecular genetic testing the same genotype in both siblings was identified the previously not described variant c.629_63Ildel (p.Ile210del) and the pathogenic variant in the heterozygous state of the SLC26A3 gene. In persistent watery diarrhea, hypochloraemia, hypokalaemia and metabolic alkalosis, a congenital chloridorhea should be consider. The diagnosis is based on a typical clinical picture of watery diarrhea from neonatal age, evidence of a high chloride concentration in stool > 90 mmol/l and molecular-genetic examination. CLD patients require regular nephrologic monitoring for the risk of chronic nephropathy or functional tubular damage.
Publication Date: 2020-09-26 00:00:00
Journal: Vnitrni lekarstvi


Quadriplegia and rhabdomyolysis as a presenting feature of Conn's syndrome.
Conn s syndrome is an important endocrine cause for secondary hypertension. Hypokalaemia paralysis and rhabdomyolysis with accelerated hypertension may be the presenting symptoms of Conn s syndrome. Here, we present one such case of a 38-year-old woman presenting with accelerated hypertension and acute onset quadriplegia. On biochemical evaluation, she was found to have severe hypokalaemia, metabolic alkalosis and elevated creatinine phosphokinase. Further evaluation revealed an elevated aldosterone renin ratio suggestive of primary hyperaldosteronism which was localised to left adrenal adenoma on contrast-enhanced CT. Patient's blood pressure and serum potassium levels normalised after resection of the adrenal adenoma.
Publication Date: 2021-01-27 00:00:00
Journal: BMJ case reports

hypertensive patients(53)

Confounders of the aldosterone-to-renin ratio when used as a screening test in hypertensive patients: A critical analysis of the literature.
The aldosterone-to-renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, there are many factors which could confound the ARR test result and reduce the accuracy of this test. The present review's objective is to identify these factors and to describe to what extent they affect the ARR. Our analysis revealed that sex, age, posture, and sodium-intake influence the ARR, whereas assay techniques do not. Race and body mass index have an uncertain effect on the ARR. We conclude that several factors can affect the ARR. Not taking these factors into account could lead to misinterpretation of the ARR.
Publication Date: 2020-12-29 00:00:00
Journal: Journal of clinical hypertension (Greenwich, Conn.)

adrenal gland(48)

Glucose metabolism disorders in patients with adrenal gland disorders: pathophysiology and management.
The aim of this review is to explore and discuss disorders of glucose metabolism that can arise in individuals with adrenal gland disorders, as well as to enumerate the available therapeutic treatments for these while considering their benefits and drawbacks. Hyperfunctioning adrenal gland , as in hypercortisolism, hyperaldosteronism, and malignancy, or hypofunctioning of adrenal gland , as in adrenal insufficiency, can lead to carbohydrate metabolism dysregulation with subsequent glucometabolic repercussions, either hyperglycemia or hypoglycemia. Glycemic disorders further affect patients' quality of life and represent a therapeutic dilemma for physicians. Current management strategies for glycemic dysregulation in individuals with adrenal gland disorders are fighting the underlying causes, as well as utilizing antidiabetic therapies that aid in maintaining euglycemia. Further research focused on discovering drug preparations of greater accuracy and effectiveness tailored to patients with adrenal problems as well as studies investigating optimal lifestyle management models for these individuals will assist towards achieving optimal regulation of glucose metabolism.
Publication Date: 2019-11-14 00:00:00
Journal: Hormones (Athens, Greece)


Are the Clinical Presentations (Phenotypes) of Gitelman's and Bartter's Syndromes Gene Mutations Driven by Their Effects on Intracellular pH, Their "pH" Enotype?
Gitelman's syndrome (GS) and Bartter's syndrome (BS) are rare inherited salt-losing tubulopathies whose variations in genotype do not correlate well with either clinical course or electrolyte requirements. Using GS/BS patients as nature's experiments, we found them to be a human model of endogenous Ang II antagonism with activated Renin-Angiotensin System (RAS), resulting in high Ang II levels with blunted cardiovascular effects. These patients are also characterized by increased and directly correlated levels of both Angiotensin Converting Enzyme 2 (ACE2) and Ang 1-7. Understanding the myriad of distinctive and frequently overlapping clinical presentations of GS/BS arises remains challenging. Efforts to find a treatment for COVID-19 has fueled a recent surge in interest in chloroquine/hydroxychloroquine and its effects. Of specific interest are chloroquine/hydroxychloroquine's ability to inhibit SARS-CoV infection by impairing ACE2, the SARS-CoV2 entry point, through terminal glycosylation via effects on TGN/post-Golgi pH homeostasis. Several different studies with a GS or a BS phenotype, along with a nonsyndromic form of X-linked intellectual disability linked to a mutated SLC9A7, provide additional evidence that specific gene defects can act via misregulation of TGN/post-Golgi pH homeostasis, which leads to a common mechanistic basis resulting in overlapping phenotypes. We suggest that linkage between the specific gene defects identified in GS and BS and the myriad of distinctive and frequently overlapping clinical findings may be the result of aberrant glycosylation of ACE2 driven by altered TGN/endosome system acidification caused by the metabolic alkalosis brought about by these salt-losing tubulopathies in addition to their altered intracellular calcium signaling due to a blunted second messenger induced intracellular calcium release that is, in turn, amplified by the RAS system.
Publication Date: 2020-08-14 00:00:00
Journal: International journal of molecular sciences


[Application of aldosterone/direct renin ratio before drug washout in the screening of primary aldosteronism].
Publication Date: 2020-11-10 00:00:00
Journal: Zhonghua yi xue za zhi

familial hyperaldosteronism(57)

Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation.
Gain-of-function mutations in the chloride channel ClC-2 were recently described as a cause of familial hyperaldosteronism type II (FH-II). Here, we report the generation of a mouse model carrying a missense mutation homologous to the most common FH-II-associated CLCN2 mutation. In these Clcn2
Publication Date: 2019-11-16 00:00:00
Journal: Nature communications


The effect of medication on the aldosterone-to-renin ratio. A critical review of the literature.
The aldosterone-to-renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, patients often use medications that could confound the ARR and, thereby, reduce the interpretability of the test. Since it is not always feasible to stop such medication, several drugs that are supposedly neutral with respect to the ARR have been recommended as alternative treatment. The objective of the present review is to explore whether sufficient evidence exists to justify the recommendations. To this end, we performed a systematic PubMed and Cochrane literature search regarding medications that may influence the ARR. Our review revealed that many commonly prescribed antihypertensives seem to have significant effects on renin, aldosterone, and resulting ARR values. However, the magnitude of these effects is poorly quantifiable with the present level of research. We conclude that several medications can affect the ARR. Not taking this into account could lead to misinterpretation of the ARR. Therefore, standardization of the medications used during ARR measurement is advisable for a reliable and accurate interpretation. Further research is needed to ascertain how to best optimize these medications.
Publication Date: 2021-01-19 00:00:00
Journal: Journal of clinical hypertension (Greenwich, Conn.)


Impact of primary aldosteronism on renal function in patients with type 2 diabetes.
Renal dysfunction might quickly progress in patients with type 2 diabetes mellitus, when accompanied by hypertension. However, whether primary aldosteronism (PA), which autonomously over-secretes aldosterone, causes additional renal damage in patients with type 2 diabetes mellitus is unclear. We evaluated the impact of PA on renal function in patients with type 2 diabetes mellitus. A retrospective review of all patients with type 2 diabetes mellitus who visited Yokohama Rosai Hospital's (Yokohama Japan) outpatient department between April 2017 and March 2018 was carried out. Records of patients with PA who underwent PA treatment by adrenalectomy or mineralocorticoid receptor antagonists (PA group) and those without PA (non-PA group) were extracted, and renal function was compared between the two groups. Untreated PA patients were excluded, as their renal function might be overestimated as a result of glomerular hyperfiltration. There were 83 patients in the PA group and 1,580 patients in the non-PA group. The PA group had significantly lower estimated glomerular filtration rates than the non-PA group (66.3 [52.4-78.2] vs 70.5 [56.0-85.6] mL/min/1.73 m Our results show that in patients with type 2 diabetes mellitus, PA is an independent risk factor for renal dysfunction. To prevent the progression of renal failure, PA should not be overlooked.
Publication Date: 2020-06-26 00:00:00
Journal: Journal of diabetes investigation

adrenal incidentalomas(32)

Malignancy Risk and Hormonal Activity of Adrenal Incidentalomas in a Large Cohort of Patients from a Single Tertiary Reference Center.
A rise in adrenal incidentalomas (AIs) detection has been observed recently. Even though AIs are detected in asymptomatic patients, thorough assessment may reveal hormonal and metabolic abnormalities or malignant character. Medical records of 2005 patients (1301 women, 704 men) with 2498 tumors aged 61 ± 11.3 (18-93) years, who had been hospitalized due to AI diagnosis, were reviewed. Patients underwent clinical examination, adrenal CT and hormonal assessment. In patients subjected to adrenalectomy, histopathological character of AI was confirmed. AIs most frequently occurred in patients in their 7th decade of life. Hypertension was present in 76.6%, glucose metabolism disorders in 41.3%, and hypercholesterolemia in 60.1% of patients. Lipid-rich adenomas (83.2%) and hormonally inactive tumors (83.1%) predominated. Autonomous cortisol secretion was present or suspected in 6.6%, pheochromocytoma in 4.7%, hyperandrogenism in 3.1%, and primary hyperaldosteronism in 2.4% of patients. The risk of malignancy increased in patients with tumors >6 cm was 37.7%. The logistic regression analysis revealed that the strongest predictor of hormonal activity of AIs was lipid-poor picture on CT scan (OR 7.072; CI 5.118-9.771), while the most important factor increasing the risk of malignancy was lipid-poor adenoma or non-adenoma on CT scan (OR 4.843; CI 1.697-13.819). Final histopathology was available for 214 tumors; 106 adrenocortical adenomas, 46 pheochromocytomas, and 18 adrenocortical carcinomas were diagnosed. Most AIs are hormonally inactive adenomas. The most frequent hormonal manifestation of AI is subclinical hypercortisolemia. Presence of AI is often accompanied by features of metabolic syndrome. The tumor density on CT scan picture may be predictive of both hormonal activity and the risk of malignancy. Tumors of all sizes may exhibit hormonal activity, while the risk of malignancy significantly increases with the size above 6 cm.
Publication Date: 2019-05-30 00:00:00
Journal: International journal of environmental research and public health


Identification of Somatic Mutations in
Somatic mutations driving aldosterone production have been identified in approximately 90% of aldosterone-producing adenomas (APAs) using an aldosterone synthase (CYP11B2) immunohistochemistry (IHC)-guided DNA sequencing approach. In the present study, using CYP11B2-guided whole-exome sequencing (WES) and targeted amplicon sequencing, we detected 2 somatic variants in
Publication Date: 2020-10-10 00:00:00
Journal: Journal of the Endocrine Society


[The Value of Serum Potassium and Ratio of Sodium to Potassium after Saline Infusion Test in Differential Diagnosis of Primary Hyperaldosteronism].
To explore the electrolyte characteristics between different types of primary aldosteronism (PA), especially the value of serum potassium and the ratio of sodium to potassium after saline infusion test (SIT) in differential diagnosis of PA. The clinical data was collected from 135 patients who received screening for the causes of hypertension from Jan. 2009 to Dec. 2018 in West China Hospital. The patients were divided into two groups: essential hypertension group (EH group, 34 patients) and primary aldosteronism group (PA group, 101 patients). PA patients were divided into aldosterone-producing adenoma group (APA group, 60 patients) and idiopathic hyperaldosteronism group (IHA group, 41 patients). To analyze the value of serum potassium and the ratio of sodium to potassium after SIT in the differential diagnosis of PA with receiver operating characteristic (ROC) curve. Compared with EH group, the serum potassium level of APA group was lower either before or after SIT ( The serum potassium and the ratio of sodium to potassium after SIT has limited diagnostic value for its low sensitivity in differential diagnosis of PA.
Publication Date: 2020-06-17 00:00:00
Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition


Minimally invasive partial versus total adrenalectomy for unilateral primary hyperaldosteronism-a retrospective, multicenter matched-pair analysis using the new international consensus on outcome measures.
Primary hyperaldosteronism is a recognized risk factor for myocardial infarction, stroke, and atrial fibrillation. Minimally invasive adrenalectomy is the first-line treatment for localized primary hyperaldosteronism. Whether minimally invasive adrenalectomy should be performed using a cortex-sparing technique (partial minimally invasive adrenalectomy) or not (total minimally invasive adrenalectomy) remains a subject of debate. The aim of our study was to evaluate the clinical and biochemical efficacy of both procedures and to examine the morbidity associated with partial minimally invasive adrenalectomy versus total minimally invasive adrenalectomy in a multicenter study. Using a retrospective study design, we determined the efficacy, morbidity, and mortality of partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy. The Primary Aldosteronism Surgical Outcome Study classification was used to explore clinical and biochemical success. Matched-pair analysis was used in order to address possible bias. We evaluated 234 matched patients with unilateral primary hyperaldosteronism: 78 (33.3%) underwent partial minimally invasive adrenalectomy, and 156 (66.7%) were treated with total minimally invasive adrenalectomy. Complete clinical success was achieved in 40.6%, and partial clinical success in an additional 52.6% of patients in the entire cohort. Complete biochemical success was seen in 94.0% of patients. Success rates and the incidence of perioperative complications were comparable between groups. Both postoperative hypocortisolism (11.5% vs 25.0% after partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy, respectively; P < .001) and postoperative hypoglycemia (2.6% vs 7.1% after partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy; P = .039) occurred more frequently after total minimally invasive adrenalectomy. Our study provides evidence that patients with unilateral primary hyperaldosteronism are good surgical candidates for partial minimally invasive adrenalectomy. Not only is the surgical outcome comparable to that of total minimally invasive adrenalectomy, but also postsurgical morbidity, particularly in terms of hypocortisolism and hypoglycemia, may be reduced.
Publication Date: 2020-10-21 00:00:00
Journal: Surgery

heart failure(38)

Disturbed ventricular-arterial coupling and increased left atrial stiffness in a patient with heart failure with preserved ejection fraction and hyperaldosteronism: a case report.
Aldosterone is involved in almost all parts of the cardiovascular system. Hyperaldosteronism causes arterial hypertension and might predispose to stroke, atrial fibrillation, and heart failure A 60-year-old obese woman with long-standing hypertension, hypokalaemia, and shortness of breath was admitted to our hospital. Hypertension was caused by primary hyperaldosteronism due to an adenoma of the adrenal gland. Detailed transthoracic echocardiography revealed diastolic dysfunction, disturbed ventricular-arterial interaction, and atrial compliance resulting in heart failure with preserved ejection fraction (HFPEF). Three months of aldosterone antagonist treatment improved ventricular-arterial coupling, while left ventricular diastolic and atrial dysfunction remained unchanged. Presumably, hyperaldosteronism is the reason for HFPEF in this case. Standard criteria to diagnose HFPEF include clinical symptoms of heart failure and an ejection fraction (EF) >50% as well as echocardiographically or invasively assessed elevated filling pressures. Single beat pressure-volume analysis gives insights on the pathophysiology of increased filling pressures, showing in our case diastolic dysfunction as well as disturbed ventricular-arterial interaction. Three months of aldosterone antagonist treatment reduced blood pressure with concomitant improvement of ventricular-arterial interaction, thereby reducing stroke work while stroke volume remained nearly unchanged. Diastolic dysfunction and increased atrial stiffness were unaltered.
Publication Date: 2020-01-09 00:00:00
Journal: European heart journal. Case reports

unilateral primary aldosteronism(23)

Preoperative non-stimulated adrenal venous sampling index for predicting outcomes of adrenalectomy for unilateral primary aldosteronism.
The aim of this study was to predict outcomes of adrenalectomy for unilateral primary aldosteronism (PA) using non-stimulated adrenal venous sampling (AVS) indices and the standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Patients with unilateral PA who underwent adrenalectomy based on non-stimulated AVS and had follow-up data regarding surgical outcomes between 2011 and 2016 were enrolled. Demographic data and non-stimulated AVS indices, including lateralization index (LI) and contralateral suppression, were collected for analysis. This study included 54 patients who underwent adrenalectomy. Clinical and biochemical outcomes were evaluated in all patients and in 52 (96.3%) patients, respectively. Complete clinical and biochemical success was achieved in 31 (57.4%) of 54 patients and 42 (80.8%) of 52 patients, respectively. An LI > 4 was significantly associated with complete clinical and biochemical success (OR = 4.30, 95% CI 1.18-15.68, p = 0.03, and OR = 7.55, 95% CI 1.28-44.47, p = 0.03, respectively). Contralateral suppression was an independent predictor of complete biochemical success (OR = 17.27, 95% CI 1.95-153.21, p = 0.01). Non-stimulated AVS indices including LI and contralateral suppression are reliable preoperative determinants for predicting the outcomes of adrenalectomy in patients with unilateral PA. Our findings provide more evidence and confidence to clinicians when applying non-stimulated AVS to determine PA treatment.
Publication Date: 2020-05-11 00:00:00
Journal: Journal of the Formosan Medical Association = Taiwan yi zhi


Adrenocortical hyperplasia: A multifaceted disease.
Adrenocortical hyperplasia may develop in different contexts. Primary adrenal hyperplasia may be secondary to primary bilateral macronodular adrenocortical hyperplasia (PBMAH) or micronodular bilateral adrenal hyperplasia (MiBAH) which may be divided in primary pigmented nodular adrenocortical disease (PPNAD) and isolated micronodular adrenocortical disease (i-MAD). Both lead to oversecretion of cortisol and potentially to Cushing's syndrome. Moreover, adrenocortical hyperplasia may be secondary to longstanding ACTH stimulation in ACTH oversecretion as in Cushing's disease, ectopic ACTH secretion or glucocorticoid resistance syndrome and congenital adrenal hyperplasia secondary to various enzymatic defects within the cortex. Finally, idiopathic bilateral adrenal hyperplasia is the most common cause of primary aldosteronism. We will discuss recent findings on the multifaceted forms of adrenocortical hyperplasia.
Publication Date: 2020-03-03 00:00:00
Journal: Best practice & research. Clinical endocrinology & metabolism

endocrine hypertension(25)

Diagnosis and Management of Endocrine Hypertension in Children and Adolescents.
Hypertension in childhood and adolescence has increased in prevalence. Interest in the disease was raised after the 2017 clinical practice guidelines of the American Academy of Paediatrics on the definition and classification of paediatric hypertension. Among the secondary causes of paediatric hypertension, endocrine causes are relatively rare but important due to their unique treatment options. Excess of catecholamine, glucocorticoids and mineralocorticoids, congenital adrenal hyperplasia, hyperaldosteronism, hyperthyroidism and other rare syndromes with specific genetic defects are endocrine disorders leading to paediatric and adolescent hypertension. Adipose tissue is currently considered the major endocrine gland. Obesity-related hypertension constitutes a distinct clinical entity leading to an endocrine disorder. The dramatic increase in the rates of obesity during childhood has resulted in a rise in obesity-related hypertension among children, leading to increased cardiovascular risk and associated increased morbidity and mortality. This review presents an overview of pathophysiology and diagnosis of hypertension resulting from hormonal excess, as well as obesity-related hypertension during childhood and adolescence, with a special focus on management.
Publication Date: 2020-11-14 00:00:00
Journal: Current pharmaceutical design

adrenal tumors(31)

Current role of open surgery in adrenal tumors.
The aim of this retrospective evaluation is to assess the current role of open adrenalectomy, in particular in cases of adrenocortical carcinoma (ACC). From January 2009 to May 2019, 26 open out of 233 adrenalectomies were performed in our Academic Department. Open adrenalectomy was performed by the anterior approach. A midline abdominal incision or a subcostal surgical incision was used to reach the peritoneal cavity. The resection was defined R0 if the margins of the sample were negative for malignancy. Open adrenalectomy was performed in 26 patients: 10 men and 16 women with a mean age of 61±25.3 years and a mean BMI of 28.4±2.9. The right adrenal gland was removed in 15 cases Romaand the left in 11 cases.We reported 18 diagnosis of malignant pathology. The other diagnosis concerned 5 cases of pheochromocytoma, 1 case of Cushing's disease and 2 cases of hyperaldosteronism. Mean tumor size was 7.7±5.5. Mean operative time was 160 min (range=110-205 minutes). Mean postoperative stay was 7±2 days. Only 3 (10%) patient showed postoperative grade II complications, according to Clavien-Dindo classification. Midline abdominal incision was used in 18 patients, subcostalsurgical incision in 5 patients and bilateral subcostal surgical incision in 3 patients. 3 right nephrectomy was necessary to remove the entire tumor mass. An en bloc R0 tumor resection was accomplished in all cases.There was no intra and perioperative mortality. All patients recovered well from surgery. The mean follow-up period was 15 (range=6-48) months. In conclusion, our retrospective study points out the role of open adrenalectomy as the treatment of choice in selected cases with known or suspected malignant adrenal tumors and with size greater than 12 cm.
Publication Date: 2020-02-11 00:00:00
Journal: Il Giornale di chirurgia

familial hyperaldosteronism type(39)

Response to Letter to the Editor: "Adrenalectomy Completely Cured Hypertension in Familial Hyperaldosteronism Type I Patients with Somatic KCNJ5 Mutation".
Publication Date: 2019-10-22 00:00:00
Journal: The Journal of clinical endocrinology and metabolism


Effect of spironolactone on cardiovascular morbidity and mortality in patients with hypertension and glucose metabolism disorders (ESCAM): a study protocol for a pragmatic randomised controlled trial.
Hypertension combined with diabetes and hypokalemia is more likely to develop hyperaldosteronism and is at higher risk of cardiovascular events. There is evidence that activation of aldosterone and mineralocorticoid receptors may play a significant role in the occurrence of cardiovascular events in patients with hypertension and diabetes. Clinical studies have demonstrated that spironolactone can reduce the incidence of cardiovascular events in patients with chronic kidney diseases or severe heart failure. However, the effect of spironolactone on cardiovascular risk in patients with hypertension and glucose metabolism disorders (GMD) and low potassium has been scarcely studied. Therefore, this study aims to evaluate whether add-on spironolactone (conventional antihypertensive drugs alone vs conventional antihypertensive drugs+spironolactone) can reduce the morbidity and mortality of cardiovascular events in this population. In this multicentre, randomised, parallel-controlled study, a total of 7140 hypertensive patients aged 45-75 years with GMD and low potassium will be randomised in a 1:1 manner to the control or the spironolactone group (20 mg/day or with a maximum dose of 40 mg). The primary objective is to estimate the difference in the HR of composite cardiovascular events between the two groups. We will also assess the effects of spironolactone on individual cardiovascular events and the progression of diabetes and renal dysfunction. This protocol was approved by the Independent Ethics Committee of People's Hospital of Xinjiang Uygur Autonomous Region (no. 2020020618). The results will be disseminated in peer-reviewed journals and at scientific conferences. ChiCTR2000028909.
Publication Date: 2021-01-15 00:00:00
Journal: BMJ open

adrenal hyperplasia(38)

Co-Existence of Congenital Adrenal Hyperplasia and Bartter Syndrome due to Maternal Uniparental Isodisomy of HSD3B2 and CLCNKB Mutations.
We present a patient with co-existence of 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency and Bartter syndrome, a unique dual combination of opposing pathologies that has not been reported previously in the literature. A female infant (46,XX) born at 34/40 weeks' gestation, weighing 2.67 kg (-1.54 standard deviation score) to non-consanguineous parents presented on day 4 of life with significant weight loss. Subsequent investigations revealed hyponatraemia, hypochloraemia, metabolic alkalosis, elevated 17-hydroxyprogesterone, ACTH, and renin. Urine steroid profile suggested HSD3B2 deficiency, which was confirmed by the identification of a homozygous HSD3B2 mutation. Due to the persistence of the hypochlo-raemic and hypokalemic alkalosis, an underlying renal tubulopathy was suspected. Sequence analysis of a targeted tubulopathy gene panel revealed a homozygous deletion in CLCNKB, consistent with Bartter syndrome type 3. The mother was found to be heterozygous for both mutations in -HSD3B2 and CLCNKB, and the father was negative for both. Single-nucleotide polymorphism microarray analysis confirmed 2 segments of homozygosity on chromosome 1 of maternal ancestry, encompassing both HSD3B2 and CLCKNB. Identification of a homozygous rare mutation in an offspring of non-consanguineous parents should raise suspicion of uniparental disomy, especially if the phenotype is unusual, potentially encompassing more than one disorder. The persistence of hypokalemic alkalosis, the biochemical fingerprint of hyperaldosteronism in a child with a form of CAH in which aldosterone production is severely impaired, challenges our current understanding of mineralocorticoid-mediated effects in the collecting duct.
Publication Date: 2020-06-09 00:00:00
Journal: Hormone research in paediatrics


Mineralocorticoid Receptor Antagonists Decrease the Rates of Positive Screening for Primary Aldosteronism.
Mineralocorticoid receptor antagonists (MRAs) are effective in patients with resistant hypertension and/or primary aldosteronism (PA). Screening for PA should ideally be conducted after stopping medications that might interfere with the renin-angiotensin-aldosterone system, but this is challenging in patients with recalcitrant hypertension or hypokalemia. Herein, we aimed to evaluate the impact of MRAs on PA screening in clinical practice. We conducted a retrospective cohort study of patients with hypertension who had plasma aldosterone and renin measurements before and after MRA use in a tertiary referral center, over 19 years. A total of 146 patients, 91 with PA, were included and followed for up to 18 months. Overall, both plasma renin and aldosterone increased after MRA initiation (from median, interquartile range: 0.5 [0.1, 0.8] to 1.2 [0.6, 4.8] ng/mL/hour and from 19.1 [12.9, 27.7] to 26.4 [17.1, 42.3] ng/dL, respectively; P<.0001 for both), while the aldosterone/renin ratio (ARR) decreased from 40.3 (18.5, 102.7) to 23.1 (8.6, 58.7) ng/dL per ng/mL/hour (P<.0001). Similar changes occurred irrespective of the MRA treatment duration and other antihypertensives used. Positive PA screening abrogation after MRA initiation was found in 45/94 (48%) patients. Conversely, 17% of patients had positive PA screening only after MRA treatment, mostly due to correction of hypokalemia. An initially positive screening test was more likely altered by high MRA doses and more likely persistent in patients with confirmed PA or taking beta-blockers. MRAs commonly reduce ARR and the proportion of positive PA screening results. When PA is suspected, screening should be repeated off MRAs. ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARR = aldosterone/renin ratio; DRC = direct renin concentration; MRA = mineralocorticoid receptor antagonist; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; RAAS = renin-angiotensin-aldosterone system.
Publication Date: 2021-01-21 00:00:00
Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

adrenal adenoma(40)

High aldosterone, hypertension and adrenal adenoma in a 36-year-old pregnant patient: Is this primary aldosteronism?
A 36-year-old woman presented at 16 weeks' gestation with severe hypertension. In comparison to the non-pregnant reference normal ranges, potassium was 3.1-3.9 mmol/L, aldosterone 2570-3000 pmol/L (N 250-2885) renin was unsuppressed (24-76.4 ng/L (N1.7-23.9)), with aldosterone to renin ratios in the reference range. An adrenal MRI scan demonstrated a 1.8 × 1.4 cm left adrenal adenoma Primary aldosteronism was strongly suspected and surgery considered. However, she was managed conservatively with labetalol and modified-release nifedipine with no obstetric complications. Post-partum blood pressures remained elevated with normal aldosterone (539 pmol/L), unsuppressed renin (5.2 ng/L) and normal aldosterone-to-renin ratio (104 (N < 144)). Suspected primary hyperaldosteronism is challenging to investigate and manage in pregnancy. The accepted screening and confirmatory tests are either contraindicated or not validated in pregnancy. Pregnancy has significant effects on the renin-angiotensin-aldosterone pathway leading to physiologic elevations in both aldosterone and renin. While primary hyperaldosteronism has been associated with poor pregnancy outcomes, optimal management in pregnancy is not clearly established.
Publication Date: 2020-07-28 00:00:00
Journal: Obstetric medicine


A long-term study of the effects of SLC12A1 homozygous mutation (g.62382825G>A, p.Pro372Leu) in Japanese Black cattle.
Recessive missense mutation in the solute carrier family 12, member 1 (SLC12A1) gene (g.62382825G>A) is associated with hydrallantois, which is the accumulation of fluid in the allantoic cavity of a pregnant animal, and usually causes fetal death in Japanese Black cattle. However, the symptoms of a homozygote with this mutation that do not result in fetal death have not previously been tracked and evaluated. In the present study, we observed a homozygote with the SLC12A1 risk allele over a long-term period. The calf did not show any obvious clinical symptoms, although it did exhibit a slight growth retardation that accompanied mild calciuria. At 28 months of age, the homozygote showed renal dysfunction, which in turn resulted in hydronephrosis. The time course of the symptoms was consistent with the phenotype of Bartter syndrome in humans. Additionally, the risk heterozygous genotype did not any effects on carcass traits, which indicates that eliminating the risk allele would not have any unfavorable effects. Therefore, we emphasize that both the fetal- and late-stage symptoms associated with the SLC12A1 risk allele compromise animal welfare, and consequently may result in severe economic losses for individual farmers if the SLC12A1 risk allele is not eliminated from the population.
Publication Date: 2020-07-17 00:00:00
Journal: Animal science journal = Nihon chikusan Gakkaiho

angiotensin ii(44)

Measurement of Equilibrium Angiotensin II in the Diagnosis of Primary Aldosteronism.
Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/ angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system. Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST). Peripheral levels of eqAngII, plasma renin activity (PRA) and direct renin concentration (DRC) were measured. EqAngII showed good consistency with DRC and PRA independent of PA diagnosis, posture, and fludrocortisone administration. EqAngII showed close (P < 0.01) correlations with DRC (r = 0.691) and PRA (r = 0.754) during FST. DRC and PRA were below their assays' functional sensitivity in 43.9% and 15.1%, respectively, of the total 312 samples compared with only 7.4% for eqAngII (P < 0.01). Bland-Altman analysis revealed an overestimation of PRA and DRC compared with eqAngII in a subset of samples with low renin levels. The AA2R showed not only consistent changes with the ARR but also close (P < 0.01) correlations with the ARR, whether renin was measured by DRC (r = 0.878) or PRA (r = 0.880). Dynamic changes of eqAngII and the AA2R show good consistency and close correlations with renin and the ARR. The eqAngII assay shows better sensitivity than DRC and PRA assays, especially at low concentrations. Whether the AA2R can reduce the impact of some factors that influence the diagnostic power of the ARR warrants further study.
Publication Date: 2020-02-19 00:00:00
Journal: Clinical chemistry


Targeted metabolomics as a tool in discriminating endocrine from primary hypertension.
Identification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL] and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and endocrine conditions associated with hypertension. Use TM to identify distinct metabolic patterns between primary hypertension (PHT) and EHT and test its discriminating ability. Retrospective analyses of PHT and EHT patients from a European multicentre study (ENSAT-HT). TM was performed on stored blood samples using liquid chromatography mass spectrometry. To identify discriminating metabolites a "classical approach" (CA) (performing a series of univariate and multivariate analyses) and a "machine learning approach" (MLA) (using Random Forest) were used. The study included 282 adult patients (52% female; mean age 49 years) with proven PHT (n=59) and EHT (n=223 with 40 CS, 107 PA and 76 PPGL), respectively. From 155 metabolites eligible for statistical analyses, 31 were identified discriminating between PHT and EHT using the CA and 27 using the MLA, of which 15 metabolites (C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC16:0, lysoPCaC20:4, lysoPCaC24:0, PCaeC42:0, SM C18:1, SM C20:2) were found by both approaches. The ROC curve built on the top 15 metabolites from the CA provided an area under the curve (AUC) of 0.86, which was similar to the performance of the 15 metabolites from MLA (AUC 0.83). TM identifies distinct metabolic pattern between PHT and EHT providing promising discriminating performance.
Publication Date: 2021-01-01 00:00:00
Journal: The Journal of clinical endocrinology and metabolism


Despite increasing aldosterone, elevated potassium is not necessary for activating aldosterone-sensitive HSD2 neurons or sodium appetite.
Restricting dietary sodium promotes sodium appetite in rats. Prolonged sodium restriction increases plasma potassium (pK), and elevated pK is largely responsible for a concurrent increase in aldosterone, which helps promote sodium appetite. In addition to increasing aldosterone, we hypothesized that elevated potassium directly influences the brain to promote sodium appetite. To test this, we restricted dietary potassium in sodium-deprived rats. Potassium restriction reduced pK and blunted the increase in aldosterone caused by sodium deprivation, but did not prevent sodium appetite or the activation of aldosterone-sensitive HSD2 neurons. Conversely, supplementing potassium in sodium-deprived rats increased pK and aldosterone, but did not increase sodium appetite or the activation of HSD2 neurons relative to potassium restriction. Supplementing potassium without sodium deprivation did not significantly increase aldosterone and HSD2 neuronal activation and only modestly increased saline intake. Overall, restricting dietary sodium activated the HSD2 neurons and promoted sodium appetite across a wide range of pK and aldosterone, and saline consumption inactivated the HSD2 neurons despite persistent hyperaldosteronism. In conclusion, elevated potassium is important for increasing aldosterone, but it is neither necessary nor sufficient for activating HSD2 neurons and increasing sodium appetite.
Publication Date: 2021-01-20 00:00:00
Journal: Physiological reports


Primary hyperaldosteronism: a rare cause of acute aortic dissection.
Publication Date: 2020-09-19 00:00:00
Journal: The Korean journal of internal medicine


Two novel mutations in the
Classic Bartter syndrome is a rare condition caused by mutations in the
Publication Date: 2020-07-07 00:00:00
Journal: BMJ case reports

plasma renin activity(25)

Elevated Plasma Renin Activity Caused by Accelerated-malignant Hypertension in a Patient with Aldosterone-producing Adenoma Complicated with Renal Insufficiency.
During the malignant phase of hypertension in patients with primary aldosteronism complicated with severe renal failure, the plasma renin activity may markedly increase with a false negative screening result for primary aldosteronism, thus potentially leading to a missed diagnosis of primary aldosteronism. We herein report the case of 37-year-old man who presented with accelerated-malignant hypertension complicated with severe renal insufficiency. The plasma renin activity was markedly increased in the malignant phase of hypertension, which were atypical results for primary aldosteronism. However, a plain abdominal computed tomography scan revealed a left adrenal nodule, which was diagnosed as aldosterone-producing adenoma by adrenal venous sampling.
Publication Date: 2019-07-12 00:00:00
Journal: Internal medicine (Tokyo, Japan)


An unmet medical need vs. regulatory recommendations: how should we treat patients with hyperaldosteronism and advanced chronic kidney disease when surgery is not feasible?
Publication Date: 2019-10-31 00:00:00
Journal: European journal of clinical pharmacology


Baseline Plasma Aldosterone Level and Renin Activity Allowing Omission of Confirmatory Testing in Primary Aldosteronism.
Previous studies have proposed cutoff value of baseline plasma aldosterone concentration (bPAC) under renin suppression that could diagnose primary aldosteronism (PA) without confirmatory testing. However, those studies are limited by selection bias due to a small number of patients and a single-center study design. This study aimed to determine cutoff value of bPAC and baseline plasma renin activity (bPRA) for predicting positive results in confirmatory tests for PA. The multi-institutional, retrospective, cohort study was conducted using the PA registry in Japan (JPAS/JRAS). We compared bPAC in patients with PA who showed positive and negative captopril challenge test (CCT) or saline infusion test (SIT) results. Patients with PA who underwent CCT (n = 2256) and/or SIT (n = 1184) were studied. The main outcomes were cutoff value of bPAC (ng/dL) and bPRA (ng/mL/h) for predicting positive CCT and/or SIT results. In patients with renin suppression (bPRA ≤ 0.3), the cutoff value of bPAC that would give 100% specificity for predicting a positive SIT result was lower than that for predicting a positive CCT result (30.85 vs 56.35, respectively). Specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results remained high (100.0% and 97.0%, respectively) in patients with bPRA ≤ 0.6. However, the specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results decreased when patients with bPRA > 0.6 were included. Confirmatory testing could be omitted in patients with bPAC ≥ 30.85 in the presence of bPRA ≤ 0.6.
Publication Date: 2020-03-12 00:00:00
Journal: The Journal of clinical endocrinology and metabolism

unilateral adrenal hyperplasia(20)

[Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution].
Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution.
Publication Date: 2016-10-25 00:00:00
Journal: Hipertension y riesgo vascular


Changes in Glucose Metabolism after Adrenalectomy or Treatment with a Mineralocorticoid Receptor Antagonist for Primary Aldosteronism.
Data on the effects of excess aldosterone on glucose metabolism are inconsistent. This study compared the changes in glucose metabolism in patients with primary aldosteronism (PA) after adrenalectomy or treatment with a mineralocorticoid receptor antagonist (MRA). Overall, 241 patients were enrolled; 153 underwent adrenalectomy and 88 received an MRA. Fasting glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and homeostatic model assessment of β-cell function (HOMA-β) were compared between the treatment groups after 1 year. Plasma aldosterone concentration (PAC) and factors determining HOMA-IR and PAC were evaluated. No baseline differences were observed between the groups. Fasting insulin, HOMA-IR, and HOMA-β increased in both groups and there were no significant differences in fasting glucose following treatment. Multiple regression analysis showed associations between PAC and HOMA-IR (β=0.172, P=0.017) after treatment. Treatment with spironolactone was the only risk factor associated with PAC >30 ng/dL (odds ratio, 5.2; 95% confidence interval [CI], 2.7 to 10; P<0.001) and conferred a 2.48-fold risk of insulin resistance after 1 year compared with surgery (95% CI, 1.3 to 4.8; P=0.007). Spironolactone treatment might increase insulin resistance in patients with PA. This strengthened the current recommendation that adrenalectomy is the preferred strategy for patient with positive lateralization test. Achieving a post-treatment PAC of <30 ng/dL for improved insulin sensitivity may be appropriate.
Publication Date: 2020-12-03 00:00:00
Journal: Endocrinology and metabolism (Seoul, Korea)


L- and T-type calcium channels control aldosterone production from human adrenals.
Aldosterone, which plays a key role in the regulation of blood pressure, is produced by zona glomerulosa (ZG) cells of the adrenal cortex. Exaggerated overproduction of aldosterone from ZG cells causes primary hyperaldosteronism. In ZG cells, calcium entry through voltage-gated calcium channels plays a central role in the regulation of aldosterone secretion. Previous studies in animal adrenals and human adrenal adrenocortical cell lines suggest that the T-type but not the L-type calcium channel activity drives aldosterone production. However, recent clinical studies show that somatic mutations in L-type calcium channels are the second most prevalent cause of aldosterone-producing adenoma. Our objective was to define the roles of T and L-type calcium channels in regulating aldosterone secretion from human adrenals. We find that human adrenal ZG cells mainly express T-type CaV3.2/3.3 and L-type CaV1.2/1.3 calcium channels TTA-P2, a specific inhibitor of T-type calcium channel subtypes, reduced basal aldosterone secretion from acutely prepared slices of human adrenals. Surprisingly, nifedipine, the prototypic inhibitor of L-type calcium channels also decreased basal aldosterone secretion, suggesting that L-type calcium channels are active under basal conditions. In addition, TTA-P2 or nifedipine also inhibited aldosterone secretion stimulated by angiotensin II- or elevations in extracellular K+. Remarkably, blockade of either L- or T-type calcium channels inhibits basal and stimulated aldosterone production to a similar extent. Low concentrations of TTA-P2 and nifedipine showed additive inhibitory effect on aldosterone secretion. We conclude that T- and L-type calcium channels play equally important roles in controlling aldosterone production from human adrenals.
Publication Date: 2019-10-28 00:00:00
Journal: The Journal of endocrinology

adrenal incidentaloma(23)

Clinical Characteristics and Follow-Up Results of Adrenal Incidentaloma.
It is recommended that adrenal incidentaloma patients should be monitored for radiological changes, increase in size and new functionality that may occur in the future, even if they are benign and nonfunctional at the initial evaluation. Our aim is to evaluate the key clinical characteristics of adrenal incidentaloma patients focusing on changes during follow-up and associated clinical outcomes. A total of 755 patients (median age: 56 years), with an adrenal incidentaloma > 1 cm and underwent functionality tests, were included in the study. Clinical characteristics, functionality status and follow-up durations were recorded. During the course of follow-up, any changes in size and development of new functionality, and clinical consequences thereof were evaluated. In 71.8% of patients, incidentalomas were non-functional. Most frequent functionality (15.8%, n=119) was subclinical hypercortisolemia (SH) [10.9% (n=82) possible autonomous cortisol secretion (PACS) and 4.9% (n=37) autonomous cortisol secretion (ACS)] of all incidentalomas. Frequencies of Cushing's syndrome (CS), pheochromacytoma and primary hyperaldosteronism were 4.9% (n=37), 3.8% (n=29) and 3.7% (n=28), respectively. Adrenocortical carcinoma frequency was 1.5% (n=11). Of 755 patients, 43% (n=325) were followed up regularly more than 6 months. Median follow-up duration was 24 months (6-120). A total of 17 (5.2%) patients, which had non-functional incidentalomas at baseline had developed new functionality during follow-up, of which 15 (4.6%) were SH [13 patients (4%) PACS and 2 patients (0.6%) ACS] and 2 (0.6%) were CS. During follow-up, 24% (n=78) of the patients had an increase in mass size between 5-9 mm, while 11.7% (n=38) of the patients had an increase of ≥10 mm. During follow-up, 4% (n=13) of the patients developed a new lesion with a diameter ≥10 mm on the opposite side. In patients with a follow-up duration of more than 2 years, frequencies of size increase and new lesion emerging at the opposite adrenal gland were higher. 14 patients (4.3% of the patients with regular follow-up) underwent surgery due to increase in size or development of new functionality during follow-up. Our study demonstrated that a necessity for surgery may arise due to increase in size and development of functionality during follow-up period in adrenal incidentaloma patients, and thus continuing patient follow-up, even with wider intervals, will be appropriate.
Publication Date: 2020-01-21 00:00:00
Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association


Vitamin D supplementation: a novel therapy for aldosteronism?
Publication Date: 2020-04-15 00:00:00
Journal: Nature reviews. Endocrinology

unilateral adrenalectomy(33)

[Hyperpothemasia and functional hypoaldosteronism after unilateral adrenalectomy for primary hyperaldosteronism in monorrene patient with chronic renal insufficiency].
Publication Date: 2020-03-23 00:00:00
Journal: Hipertension y riesgo vascular


[The Diagnostic Value of Captopril Challenge Test for Primary Aldosteronism].
To investigate the diagnostic value of different captopril challenge test (CCT) diagnostic criteria for diagnosing primary aldosteronism (PA). We collected the clinical data of 184 patients with hypertension retrospectively in West China Hospital of Sichuan University. Receiver operating characteristic (ROC) curves were used to analyze the post-CCT efficacy of aldosterone renin activity ratio (ARR), plasma aldosterone concentration (PAC), plasma renin activity (PRA) and PAC suppression rate for PA diagnosis. This study included 125 cases of primary aldehyde (PA group) and 59 cases of essential hypertension (EH group), and there were 38 normal renin primary hypertension (NREH group) and 21 low renin primary hypertension (LREH group) in EH group. The post-CCT PAC suppression rate (median (P Both ARR and PAC have higher diagnostic value than the post-CCT PAC suppression rate, post-CCT PAC is especially suitable as a confirmatory test ng criterion of PA.
Publication Date: 2021-01-22 00:00:00
Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition


Ion Channel Function and Electrical Excitability in the Zona Glomerulosa: A Network Perspective on Aldosterone Regulation.
Aldosterone excess is a pathogenic factor in many hypertensive disorders. The discovery of numerous somatic and germline mutations in ion channel in primary hyperaldosteronism underscores the importance of plasma membrane conductances in determining the activation state of zona glomerulosa (zG) cells. Electrophysiological recordings describe an electrically quiescent behavior for dispersed zG cells. Yet, emerging data indicate that in native rosette structures in situ, zG cells are electrically excitable, generating slow periodic voltage spikes and coordinated bursts of Ca
Publication Date: 2020-11-13 00:00:00
Journal: Annual review of physiology

computed tomography(32)

Improved Visualization and Identification of the Right Adrenal Vein in 70-kVp Contrast-Enhanced Computed Tomography.
The aim of this study was to assess the utility of 70-kilovoltage-peak (kVp) contrast-enhanced computed tomography (CECT) for visualization and identification of the right adrenal vein (RAV) in comparison with that of conventional 120-kVp CECT. This retrospective study included patients who underwent adrenal venous sampling with concurrent biphasic 120-kVp (120-kVp group, n = 43) or 70-kVp (70-kVp group, n = 47) CECT. Signal-to-noise ratios, contrast-to-noise ratios, longitudinal lengths, conspicuity scores, RAV detection rates, and size-specific dose estimates were compared between the 2 groups. In comparison with the 120-kVp group, the 70-kVp group had significantly higher signal-to-noise and contrast-to-noise ratios (P < 0.001-P = 0.033), greater longitudinal lengths (P < 0.001-P = 0.002), superior conspicuity scores for the RAV (P < 0.001), higher RAV detection rates (P = 0.015-P = 0.033), and lower size-specific dose estimates (P < 0.001). Seventy-kilovoltage-peak CECT has advantages over conventional 120-kVp CECT and is potentially useful for noninvasive assessment of the precise anatomy of the RAV.
Publication Date: 2020-01-16 00:00:00
Journal: Journal of computer assisted tomography


MANAGEMENT OF ENDOCRINE DISEASE: The role of surgical adrenalectomy in primary aldosteronism.
Primary aldosteronism is common and contributes to adverse cardiovascular, kidney, and metabolic outcomes. When instituted early and effectively, targeted therapies can mitigate these adverse outcomes. Surgical adrenalectomy is among the most effective treatments because it has the potential to cure, or attenuate the severity of, pathologic aldosterone excess, resulting in a host of biochemical and clinical changes that improve health outcomes. Herein, we review the role of surgical adrenalectomy in primary aldosteronism while emphasizing the physiologic ramifications of surgical intervention, and compare these to other targeted medical therapies for primary aldosteronism. We specifically review the role of curative adrenalectomy for unilateral primary aldosteronism, the role of non-curative adrenalectomy for bilateral primary aldosteronism, and how these interventions influence biochemical and clinical outcomes in relation to medical therapies for primary aldosteronism.
Publication Date: 2020-10-21 00:00:00
Journal: European journal of endocrinology


Mass spectrometry reveals misdiagnosis of primary aldosteronism with scheduling for adrenalectomy due to immunoassay interference.
Diagnosis of primary aldosteronism (PA) involves a multistep process reliant on the accuracy of aldosterone measurements at each step. We report on immunoassay interference leading to a wrongful diagnosis and indication for surgical intervention. A 38-year old hypertensive male with a 1.4 cm left adrenal mass was diagnosed with PA based on an elevated aldosterone:renin ratio and a positive saline infusion test. Adrenal venous sampling (AVS) indicated left-sided aldosterone hypersecretion, supporting a decision to remove the left adrenal. The patient was also enrolled in a study to evaluate mass spectrometry-based steroid profiling, which indicated plasma aldosterone concentrations measured in five different peripheral samples averaging only 11% those of the immunoassay. Mass spectrometric measurements did not support left-sided adrenal aldosterone hypersecretion. Two independent laboratories confirmed differences in measurements by immunoassay and mass spectrometry. Lowered concentrations measured by the immunoassay that matched those by mass spectrometry were achieved after sample purification to remove macromolecules, confirming immunoassay interference. Although our patient may represent an isolated case of immunoassay interference leading to misdiagnosis of PA, unnecessary AVS and potentially wrongful removal of an adrenal, it is also possible that such inaccuracies may impact the diagnostic process and treatment for other patients.
Publication Date: 2020-04-22 00:00:00
Journal: Clinica chimica acta; international journal of clinical chemistry

differential diagnosis(30)

Mimicry and well known genetic friends: molecular diagnosis in an Iranian cohort of suspected Bartter syndrome and proposition of an algorithm for clinical differential diagnosis.
Bartter Syndrome is a rare, genetically heterogeneous, mainly autosomal recessively inherited condition characterized by hypochloremic hypokalemic metabolic alkalosis. Mutations in several genes encoding for ion channels localizing to the renal tubules including SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, MAGED2 and CASR have been identified as underlying molecular cause. No genetically defined cases have been described in the Iranian population to date. Like for other rare genetic disorders, implementation of Next Generation Sequencing (NGS) technologies has greatly facilitated genetic diagnostics and counseling over the last years. In this study, we describe the clinical, biochemical and genetic characteristics of patients from 15 Iranian families with a clinical diagnosis of Bartter Syndrome. Age range of patients included in this study was 3 months to 6 years and all patients showed hypokalemic metabolic alkalosis. 3 patients additionally displayed hypercalciuria, with evidence of nephrocalcinosis in one case. Screening by Whole Exome Sequencing (WES) and long range PCR revealed that 12/17 patients (70%) had a deletion of the entire CLCNKB gene that was previously identified as the most common cause of Bartter Syndrome in other populations. 4/17 individuals (approximately 25% of cases) were found to suffer in fact from pseudo-Bartter syndrome resulting from congenital chloride diarrhea due to a novel homozygous mutation in the SLC26A3 gene, Pendred syndrome due to a known homozygous mutation in SLC26A4, Cystic Fibrosis (CF) due to a novel mutation in CFTR and apparent mineralocorticoid excess syndrome due to a novel homozygous loss of function mutation in HSD11B2 gene. 1 case (5%) remained unsolved. Our findings demonstrate deletion of CLCNKB is the most common cause of Bartter syndrome in Iranian patients and we show that age of onset of clinical symptoms as well as clinical features amongst those patients are variable. Further, using WES we were able to prove that nearly 1/4 patients in fact suffered from Pseudo-Bartter Syndrome, reversing the initial clinical diagnosis with important impact on the subsequent treatment and clinical follow up pathway. Finally, we propose an algorithm for clinical differential diagnosis of Bartter Syndrome.
Publication Date: 2019-02-15 00:00:00
Journal: Orphanet journal of rare diseases

left ventricular(41)

Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism.
Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m
Publication Date: 2020-04-07 00:00:00
Journal: Hypertension (Dallas, Tex. : 1979)

mineralocorticoid receptor(36)

Aldosterone and Mineralocorticoid Receptor Antagonists on Pulmonary Hypertension and Right Ventricular Failure: A Review.
There is an increasing number of therapeutic agents being developed for the treatment of pulmonary artery hypertension (PAH) which is a condition characterized by raised pulmonary artery pressure and right heart failure. Despite our better understanding of the pathophysiology of PAH, the treatment outcomes are still suboptimal. There is growing evidence suggesting the role of increases in the levels of aldosterone, which is a mineralocorticoid hormone, in the pathophysiology of PAH; however, the extent to which hyperaldosteronism is associated with PAH in patients is unclear. There are also a few studies assessing the effects of mineralocorticoid receptor antagonists (MRA) in PAH. MRAs are a recognized treatment for heart failure and hypertension. In this review, we focus on the relationship between aldosterone level in patients with PAH and right ventricular failure and the effect of MRAs on the PAH severity.
Publication Date: 2020-05-24 00:00:00
Journal: Current pharmaceutical design

kidney disease(26)

Pathophysiological mechanisms of mineralocorticoid receptor-dependent cardiovascular and chronic kidney disease.
Accumulating evidence has indicated the potential contributions of aldosterone and mineralocorticoid receptor (MR) to the pathophysiology of cardiovascular disease (CVD) and chronic kidney disease (CKD). Patients with primary aldosteronism have a higher risk of CVD and CKD than those with essential hypertension. MR is strongly expressed in endothelial cells, vascular smooth muscle cells, cardiomyocytes, fibroblasts, macrophages, glomerular mesangial cells, podocytes, and proximal tubular cells. In these cardiovascular and renal cells, aldosterone-induced cell injury is prevented by MR blockade. Interestingly, MR antagonists elicit beneficial effects on CVD and CKD in subjects with low or normal plasma aldosterone levels. Recent studies have shown that during development of CVD and CKD, cardiovascular and renal MR is activated by glucocorticoid and ligand-independent mechanisms, such as Rac1 signaling pathways. These data indicate that inappropriate activation of local MR contributes to cardiovascular and renal tissue injury through aldosterone-dependent and -independent mechanisms. In this review, recent findings on the specific role of cardiovascular and renal MR in the pathogenesis of CVD and CKD are summarized.
Publication Date: 2018-12-14 00:00:00
Journal: Hypertension research : official journal of the Japanese Society of Hypertension


Significance of Discordant Results Between Confirmatory Tests in Diagnosis of Primary Aldosteronism.
Current clinical guidelines recommend confirmation of a positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results The aim of the present study was to explore the role of 2 confirmatory tests in subtype diagnosis of PA. A retrospective cross-sectional study was conducted at two referral centers. We identified 360 hypertensive patients who underwent both a captopril challenge test (CCT) and a saline infusion test (SIT) and exhibited at least one positive result. Among them, we studied 193 patients with PA whose data were available for subtype diagnosis based on adrenal vein sampling (AVS). The prevalence of bilateral subtype on AVS according to the results of the confirmatory tests was measured. Of patients studied, 127 were positive for both CCT and SIT (double-positive), whereas 66 were positive for either CCT or SIT (single-positive) (n = 34 and n = 32, respectively). Altogether, 135 were diagnosed with bilateral subtype on AVS. The single-positive patients had milder clinical features of PA than the double-positive patients. The prevalence of bilateral subtype on AVS was significantly higher in the single-positive patients than in the double-positive patients. (63/66 [95.5%] vs 72/127 [56.7%], P < .01). Several clinical parameters were different between CCT single-positive and SIT single-positive patients. Patients with discordant results between CCT and SIT have a high probability of bilateral subtype of PA on AVS.
Publication Date: 2020-11-10 00:00:00
Journal: The Journal of clinical endocrinology and metabolism


Hypertension Accompanied by Hyperaldosteronism, Hyperkalemia, and Hyperchloremic Acidosis: A Case Report and Literature Review.
This study reported on a 24-year-old woman who complained of a paroxysmal headache for six months and elevated blood pressure for four months. Laboratory examination revealed increased serum potassium and chloride levels, metabolic acidosis, suppressed renin activity, and increased plasma aldosterone concentration. Whole-exome sequencing revealed a heterozygous mutation in exon 11 of the KLHL3 gene: c.1298G > A. After treatment with low-dose hydrochlorothiazide, her clinical problems were controlled. This patient is the first case of Gordon syndrome (GS) within the Chinese population caused by a heterozygous KLHL3 mutation. A systematic review of the published literature identified 27 patients with GS caused by a KLHL3 mutation. These patients had a mean age of 28.2 ± 22.0 years; 74.1% presented with hypertension, 76.9% with hyperkalemia, and 59.1% with metabolic acidosis. The patients also had varying levels of plasma renin activity and plasma aldosterone concentrations.
Publication Date: 2020-08-11 00:00:00
Journal: Case reports in endocrinology


Evaluation of Adrenal Vein Sampling Use and Outcomes in Patients With Primary Aldosteronism.
Primary aldosteronism (PA) occurs in 10%-20% of patients with resistant hypertension. Guidelines recommend adrenal vein sampling (AVS) to identify patients for surgical management. We evaluate the use of AVS in managing PA to better understand the selection and outcomes of medical versus surgical treatment. A retrospective review was performed, and patients were divided into those who did (AVS) and did not have AVS (non-AVS). Demographics, aldosterone and renin levels, blood pressure, comorbidities, and antihypertensive medications were recorded. Reasons to defer AVS and medical versus surgical decision-making were examined and groups were compared. We included 113 patients; 39.8% (45/113) had AVS, whereas 60.2% (68/113) did not. Groups were similar in age, body mass index, and initial systolic blood pressure (SBP). In patients who underwent AVS, 31 of 45 (68.9%) had unilateral secretion and were referred for surgery, whereas 13 of 45 (28.9%) had bilateral secretion. Of the 31 referred for surgery, 26 underwent laparoscopic adrenalectomy, all cured; four refused surgery; and one counseled toward medical management by their physician. In 68 non-AVS patients, 6 (8.8%) underwent adrenalectomy without sampling and 2 with no clinical improvement. The remaining deferrals were because of normal or bilateral adrenal nodules on imaging (8/68, 11.8%); medical management due to poor surgical candidacy (12/68, 17.6%); patient refusal of intervention (13/68, 19.1%); or reasons not stated (28/68, 41.1%). At the follow-up, patients who underwent AVS had lower median SBP (135.4 mmHg versus 144.7 mmHg, P = 0.0241) and shorter follow-up (17.7 mo versus 54.0 mo, P < 0.0001). Surgically managed patients had biochemical resolution of PA with normalization of potassium levels (3.6 to 4.7mEq/L, P < 0.00001). AVS correctly selects patients for surgical management avoiding unnecessary surgery. However, despite guidelines, AVS is not always pursued as part of PA treatment, potentially excluding surgical candidates.
Publication Date: 2020-08-23 00:00:00
Journal: The Journal of surgical research


Different pathogenesis of glucose intolerance in two subtypes of primary aldosteronism: Aldosterone-producing adenoma and idiopathic hyperaldosteronism.
An increased risk of diabetes mellitus has been reported in primary aldosteronism, but the pathogenesis of glucose intolerance between the primary aldosteronism subtypes remains unclear. This study aimed to evaluate glucose metabolism in oral glucose tolerance test between aldosterone-producing adenoma and idiopathic hyperaldosteronism, and characterize patients with improved glucose intolerance after primary aldosteronism treatment. Oral glucose tolerance test was carried out in 116 patients who were diagnosed with primary aldosteronism and received adrenal venous sampling for subtyping. Oral glucose tolerance test was re-evaluated after starting the treatment of primary aldosteronism for those who had glucose intolerance before the treatment. A total of 46.4% and 52.3% of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism, respectively, were diagnosed with impaired glucose tolerance or diabetes. The insulinogenic index was significantly lower in aldosterone-producing adenoma than in idiopathic hyperaldosteronism (P = 0.045), whereas the Matsuda insulin sensitivity index was significantly higher in aldosterone-producing adenoma than in idiopathic hyperaldosteronism (P = 0.022). After the treatment of primary aldosteronism, glucose intolerance was improved in 66.6% and 45.8% of aldosterone-producing adenoma and idiopathic hyperaldosteronism, respectively. The presence of obesity and central obesity were significantly lower in patients who improved glucose intolerance after the treatment of primary aldosteronism as compared with those not improved (P = 0.013 and P = 0.033, respectively). Insulin secretion impairment and insulin resistance play pathogenic roles for glucose intolerance in aldosterone-producing adenoma and idiopathic hyperaldosteronism, respectively. In addition, primary aldosteronism treatments can ameliorate glucose intolerance more effectively in patients without obesity and/or central obesity.
Publication Date: 2020-05-30 00:00:00
Journal: Journal of diabetes investigation

metabolic alkalosis(27)

Classic Bartter Syndrome: A Cause of Severe Hypokalemic Metabolic Alkalosis.
Publication Date: 2019-06-25 00:00:00
Journal: Clinical pediatrics

pseudo-bartter syndrome(24)

Clinical features and accompanying findings of Pseudo-Bartter Syndrome in cystic fibrosis.
Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population. The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS. Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF.
Publication Date: 2020-05-05 00:00:00
Journal: Pediatric pulmonology


Characterization and Management of Juxtaglomerular Cell Tumor: Analysis of 9 Cases and Literature Review
Juxtaglomerular cell tumor is a rare kidney tumor This study aimed to report the clinic features of juxtaglomerular cell tumor and our treatment experience. The medical records of 9 juxtaglomerular cell tumor patients treated in our hospital from 1997 to 2017 were retrospectively reviewed. Clinical characteristics, immunohistochemical findings, treatments and outcomes were collected. The mean age of 9 patients was 24±8.1 years (range: 18-37). All cases had symptoms of hypertension, hyperaldosteronism, high plasma renin, high plasma angiotensin II. Four cases had hypokalemia. The renal masses were found by enhanced contrast tomography in all patients. One case received ultrasound-guided ablation and was clinically diagnosed with juxtaglomerular cell tumor Among the remaining 8 cases, 2 cases received nephrectomy while 6 underwent partial nephrectomy. The 8 cases were pathologically diagnosed with juxtaglomerular cell tumor Immunohistochemical findings showed that juxtaglomerular cell tumor was positive for vimentin, CD34, and actin but negative for chromogranin A. After treatment, all the patients had normal levels of blood pressure, serum renin activity, potassium, and aldosterone. No patients had tumor progress or metastasis within a median follow-up period of 94 (range: 33-241) months. Hypertension combined with hyperaldosteronism and hypokalemia secondary to high plasma renin activity are the typical symptoms of juxtaglomerular cell tumor Partial nephrectomy is an optimal treatment for juxtaglomerular cell tumor
Publication Date: 2020-05-23 00:00:00
Journal: Balkan medical journal

aldosterone production(26)

GRK2-Mediated Crosstalk Between β-Adrenergic and Angiotensin II Receptors Enhances Adrenocortical Aldosterone Production In Vitro and In Vivo.
Aldosterone is produced by adrenocortical zona glomerulosa (AZG) cells in response to angiotensin II (AngII) acting through its type I receptors (AT
Publication Date: 2020-01-23 00:00:00
Journal: International journal of molecular sciences

diabetes mellitus(22)

Clinical characteristics of primary aldosteronism in newly diagnosed diabetes mellitus with hypertensive patients.
To investigate the prevalence of primary aldosteronism (PA) in newly diagnosed diabetic patients with hypertension and to compare clinical differences between newly diagnosed diabetes mellitus with essential hypertension (EH) and PA, and to explore the relationship between plasm aldosterone concentration (PAC) and clinical biochemical variables. A total of 270 newly diagnosed diabetic patients with hypertension were prospectively enrolled in this study. All patients were screened for PA. The positive patients in the screening test were further confirmed by captopril challenge test (CCT) to determine the prevalence of PA. Clinical biochemical indexes were detected. The prevalence of PA in 270 newly diagnosed diabetic patients with hypertension was 18.5%. Compared with patients in the EH group, patients in the PA group had higher systolic blood pressure (SBP), PAC, aldosterone to renin ratio (ARR), and carbondioxide binding force, but lower plasma renin activity (PRA) and serum potassium. Correlation analysis showed that the PAC was positively correlated with homeostasis model assessment-insulin resistance (HOMA-IR) in the EH group ( The prevalence of PA is relatively high in newly diagnosed diabetic patients with hypertension. Patients with hypertension above grade 2 should be actively screened for aldosterone. Newly diagnosed diabetic patients with hypertension combined with PA has a higher hypertension compared with the patients without PA.In newly diagnosed diabetic patients with hypertension, PAC may be related to insulin resistance.
Publication Date: 2020-10-15 00:00:00
Journal: Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences

aldosterone secretion(29)

ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion.
Microarray comparison of the transcriptomes of human adrenal zona glomerulosa (ZG) and zona fasciculata found several ZG-specific genes that negatively regulate aldosterone secretion The third and most significantly upregulated ZG-gene (19.9-fold compared with zona fasciculata,
Publication Date: 2019-10-01 00:00:00
Journal: Hypertension (Dallas, Tex. : 1979)


Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism.
First described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is well established as a relevant cause of secondary hypertension and accounts for about 5-10 % of hypertensives. The importance of considering PA is based on its deleterious target organ damage far beyond the effect of elevated blood pressure and on PA being a potentially curable form of hypertension. Aside the established contributory role of high dietary salt intake to arterial hypertension and cardiovascular disease, high salt intake is mandatory for aldosterone-mediated deleterious effects on target-organ damage in patients with primary aldosteronism. Consequently, counselling patients on the need to reduce salt intake represents a major component in the treatment of PA to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is high and far beyond the target values of 5 g per day, recommended by the World Health Organization. Insufficient patient motivation for lifestyle interventions can be further complicated by enhancing effects of aldosterone on salt appetite, via central and gustatory pathways. In this context, treatment for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake and might therefore provide further reduction of cardiovascular risk in PA than specific medical treatment alone. Furthermore, there is evidence from clinical studies that even after sufficient treatment of PA dietary salt intake remains a relevant prognostic factor for cardiovascular risk. This review will focus on the synergistic benefits derived from both blockade of aldosterone-mediated effects and reduction in dietary salt intake on cardiovascular risk.
Publication Date: 2020-04-07 00:00:00
Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme


Adrenal Vein Sampling to Distinguish Between Unilateral and Bilateral Primary Hyperaldosteronism: To ACTH Stimulate or Not?
The aim of this study is to determine the accuracy of adrenal vein sampling (AVS) with and without adrenocorticotropic hormone (ACTH) stimulation to distinguish between unilateral and bilateral primary hyperaldosteronism (PA). Retrospective analysis of a prospective database from a referral center between 1984 and 2009, 76 patients had simultaneous cannulation of bilateral adrenal veins and AVS with and without ACTH stimulation. All patients had adrenalectomies. The selectivity index (SI, cut-off value ≥2) was used for confirmation of successful cannulation of the adrenal vein. The lateralization index (LI, cut-off value >2 and >4) was used for distinguishing between unilateral and bilateral PA. The SI ratio was higher with ACTH stimulation compared to without for the right adrenal vein (p = 0.027). The LI >2 ratio was higher with ACTH stimulation compared to without (p = 0.007). For the LI >4 ratio, there was no difference between with and without ACTH stimulation (p = 0.239). However, for a LI >4, 7 patients (9.2%) were not lateralized with ACTH stimulation, but they did lateralize without ACTH stimulation. AVS with ACTH stimulation is associated with a higher SI ratio compared to AVS without ACTH stimulation. However, when using LI >4 for AVS, samples without ACTH stimulation should also be included to detect a subset of patients with unilateral disease that are not detected with ACTH stimulation.
Publication Date: 2020-05-18 00:00:00
Journal: Journal of clinical medicine

idiopathic hyperaldosteronism(20)

[Clinical Characteristics of Aldosterone Producing Adenoma and Idiopathic Hyperaldosteronism with Obstructive Sleep Apnea Hypopnea Syndrome].
To investigate the clinical characteristics of aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) complicated with obstructive sleep apnea hypopnea syndrome (OSAHS) and the effect of OSAHS on renin-angiotensin-aldosterone system (RAAS) in APA and IHA patients. The clinical data of 127 patients with primary aldosteronism (PA) diagnosed from May 2010 to Aug. 2019 were retrospectively analyzed. There were 70 cases of APA, 53 cases of IHA. Another 4 cases were primary adrenal hyperplasia (PAH), so not included into further analysis. According to the results of polysomnography, the 123 patients of APA or IHA were divided into OSAHS group (96 cases) and non-OSAHS group (27 cases ). The patients with OSAHS were divided into mild, moderate and severe subgroups based on apnea hypopnea index (AHI).The clinical characteristics, biochemical parameters, plasma renin activity, aldosterone levels, and the ratio of aldosterone to renin activity (ARR) in the patients of APA and IHA complicated with OSAHS were compared with those of the patients without OSAHS. There were 49 OSAHS cases (49/70, 70.0%) in APA patients. and 47 OSAHS cases (47/53, 88.7%) in IHA patients. The age, male ratio, body mass index (BMI), waist circumference, triglyceride, blood uric acid, and blood creatinine in APA patients with OSAHS were higher than those in APA patients without OSAHS ( The prevalence of OSAHS is significantly higher in the patients with PA than normal population, and OSAHS may aggravate glycose, lipid and uric acid metabolism in PA patients. Moderate/severe OSAHS can increase renin levels and decrease ARR values in APA patients, but has no significant effect on RAAS in IHA patients.
Publication Date: 2020-06-17 00:00:00
Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition


Effect of Dietary Sodium Modulation on Pig Adrenal Steroidogenesis and Transcriptome Profiles.
Primary aldosteronism is a frequent form of endocrine hypertension caused by aldosterone overproduction from the adrenal cortex. Regulation of aldosterone biosynthesis has been studied in rodents despite differences in adrenal physiology with humans. We, therefore, investigated pig adrenal steroidogenesis, morphology, and transcriptome profiles of the zona glomerulosa (zG) and zona fasciculata in response to activation of the renin-angiotensin-aldosterone system by dietary sodium restriction. Six-week-old pigs were fed a low- or high- sodium diet for 14 days (3 pigs per group, 0.4 g sodium kg feed versus 6.8 g sodium kg). Plasma aldosterone concentrations displayed a 43-fold increase (
Publication Date: 2020-10-20 00:00:00
Journal: Hypertension (Dallas, Tex. : 1979)


Normotensive hypokalemic primary hyperaldosteronism mimicking clinical features of anorexia nervosa in a young patient: A case report.
The typical clinical presentations of patients with primary aldosteronism (PA) include generalized weakness, fatigue, high blood pressure, and potassium deficiency. However, normotensive PA is rare. Therefore, an atypical presentation of normal blood pressure is a challenge for the diagnosis and treatment of PA. A 43-year-old, thin, and tall woman (body mass index, 18.6 kg/m) with generalized weakness for 1 day presented to our emergency department, where hypokalemia was a significant finding. The initial diagnosis was anorexia nervosa with the evidence of renal potassium wasting with low urinary sodium and chloride levels, metabolic alkalosis, normal blood pressure, and low body mass index. However, neither vomiting features nor other specific induced vomiting features were noted. The laboratory examination revealed high plasma aldosterone level, low plasma renin activity, and extremely high aldosterone-to-renin ratio indicating the diagnosis of PA, confirmed via adrenal computed tomography. Surgical adrenalectomy was performed. Pathological diagnosis was a benign cortical adenoma. Patient's serum potassium level and hormonal status became normalized after surgical removal of adrenal adenoma. She fully recovered without any further sequelae. It is too early to rule out PA based on the presence of normal blood pressure in a patient with metabolic alkalosis and renal wasting hypokalemia. Moreover, PA should be considered in a normotensive patient with an unknown hypokalemic etiology to avoid delayed diagnosis and treatment.
Publication Date: 2020-07-25 00:00:00
Journal: Medicine

obstructive sleep apnea(17)

[Prevalence and clinical characteristics of obstructive sleep apnea in patients with primary hyperaldosteronism].
Publication Date: 2020-10-30 00:00:00
Journal: Zhonghua nei ke za zhi

chronic kidney disease(16)

[Mineralocorticoid receptor antagonists in chronic kidney disease - pros and cons].
Aldosterone takes part in the regulation of body fluid volume, blood pressure and kalemia. In a number of pathological conditions, including chronic kidney disease (CKD), secondary hyperaldosteronism occurs, leading to development of edema, hypervolemia and hypertension. Aldosterone has also a proinflammatory action, leading to heart and blood vessels damage, and is an independent risk factor of death. Some of the research conducted to confirm the expected benefits of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) therapy in CKD patients did not yield positive results, probably due to "aldosterone escape". Mineralocorticoid receptor antagonists (MRA) are being introduced also in the treatment of CKD patients, although the risk of developing hyperkalemia exists. A number of papers suggest a positive influence of MRA on slowing down the progression of renal failure, reduction of cardiovascular risk, and decreasing mortality, with relative safety of treatment, however the data are based on small and heterogenous groups of patients, therefore conclusive information is expected from large trials which are currently being conducted (BARACK D, ALCHEMIST).
Publication Date: 2017-01-01 00:00:00
Journal: Wiadomosci lekarskie (Warsaw, Poland : 1960)

type ii(25)

Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.
The application of advanced genetic techniques has recently begun to unravel the genetic basis for familial primary aldosteronism type 2 (FH-II). Whole-exome sequencing in a large family with FH-II revealed a shared rare damaging heterozygous variant in CLCN2 (chr.3: g.184075850C>T, p.Arg172Gln) in three severely affected members. The gene encodes a chloride channel, ClC-2. A cohort of 80 unrelated individuals diagnosed with early-onset primary aldosteronism was also examined for CLCN2 mutations finding three further occurrences of p.Arg172Gln mutations and four single cases of other potentially damaging heterozygous mutations for an overall prevalence of 9.9%. A concurrent report also found a different CLCN2 mutation (p.Gly24Asp) in a single severely affected patient from a cohort of 12 with early-onset PA for a prevalence of 8.3%. Cases of primary aldosteronism associated with CLCN2 mutations appear to be bilateral and respond well to medical treatment. In the adrenal, ClC-2 has been demonstrated to localize predominantly to the zona glomerulosa (ZG), and functional analysis suggests that mutations in ClC-2 predispose ZG cells to depolarization, thus leading to calcium influx via activation of voltage-gated calcium channels and increased aldosterone production. Germline CLCN2 mutations appear to account for a substantial proportion of early-onset primary aldosteronism cases, and genetic testing for mutations in this gene should be considered in appropriate cases.
Publication Date: 2019-04-06 00:00:00
Journal: Current hypertension reports


Diabetes Mellitus Itself Increases Cardio-Cerebrovascular Risk and Renal Complications in Primary Aldosteronism.
The prevalence of diabetes mellitus (DM) in patients with primary aldosteronism (PA) is higher than in those with essential hypertension and the general population. Although DM is a common major risk factor for cardio-cerebrovascular (CCV) diseases and renal complications, details of its effects in PA have not been demonstrated. The aim of this study was to determine the effects of coexistent DM on the risk of CCV events and progression of renal complications in PA patients. A multi-institutional, cross-sectional study was conducted. PA patients experienced between January 2006 and October 2016 and with available data of CCV events and DM were enrolled from the Japan PA registry of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Diseases Study (n = 2524). CCV events and renal complications were compared between a DM group and a non-DM group by logistic and liner-regression analysis. DM significantly increased the odds ratio (OR) of CCV events (OR 1.59, 95% CI: 1.05-2.41) and that of proteinuria (OR 2.25, 95% CI: 1.59-3.16). DM correlated significantly with declines in estimated glomerular filtration rate (β = .05, P = .02). This the first report to demonstrate the presence of DM as an independent risk factor for CCV events and renal complications, even in PA patients. Management of DM should be considered in addition to the specific treatment of PA.
Publication Date: 2020-04-11 00:00:00
Journal: The Journal of clinical endocrinology and metabolism


Mutations of the Twik-Related Acid-Sensitive K+ Channel 2 Promoter in Human Primary Aldosteronism.
Because blunted expression of the twi k related acid-sensitive K channel 2 (TAS K 2) is a common feature of aldosterone-producing adenoma (APA) causing primary aldosteronism (PA), we sequenced the promoter region of the TAS K 2 gene ( K N K ) in APAs (n = 76), primary hypertensive patients (n = 98), and 20-year-old healthy volunteers (n = 71), searching for variants that could affect expression of this channel. We found TAS K 2 promoter mutations in 25% of the APAs: C999T in 6.6%, G595A in 5.3%, G36A in 5.3%, and C562T, Gins468, G265C, C1247T, G1140T, and C1399T in 1.3% each. The C999T mutation was found in only one of the 98 primary hypertensive patients, but mutations were detected also in 12% of volunteers: 4 carried the C999T, 3 G1288C, 1 the G1140T mutation, and 1 the 468ins mutation. After a 16-year follow-up, none of these patients developed hypertension or PA. The effect of C999T mutation was investigated in H295R cells using reporter vectors with the mutated or the wild-type (WT) TAS K 2 promoters. TAS K 2 gene expression was decreased by 31% ± 18% (P = 0.01) in mutated compared with WT APA. Li k wise, in transfected H295R cells, the C999T mutation decreased TAS K 2 transcriptional activity by 35% (normalized luciferase signal fold change: 0.65 ± 0.25, P < 0.001). Thus, mutations in the promoter region of the TAS K 2 gene can account for the low expression in ∼25% of APAs. As they did not result in hypertension or PA during long-term follow-up in healthy participants, these mutations do not seem to be a factor in causing PA by themselves.
Publication Date: 2018-01-03 00:00:00
Journal: Endocrinology

cystic fibrosis(23)

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis.
Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.
Publication Date: 2018-03-10 00:00:00
Journal: Frontiers of medicine


Aldosterone-Secreting Adrenocortical Carcinoma Presenting With Cardiac Arrest.
Adrenocortical carcinoma (ACC) is a rare malignancy that usually is detected as a result of symptoms of hormone excess or mass effect. We describe a rare presentation of ACC with primary aldosterone production leading to profound hypokalemia and cardiac arrest. The patient was previously asymptomatic with low-grade, untreated hypertension and no documented electrolyte abnormalities. She had sudden cardiac arrest, and potassium levels were undetectable. After successful resuscitation, imaging showed a 6-cm left adrenal mass highly suspicious for malignancy. Biochemical workup revealed aldosterone excess as well as cortisol excess, despite the absence of Cushingoid symptoms. Histopathological examination after surgical resection demonstrated high-grade ACC. This case illustrates that the workup of cardiac arrest as a result of electrolyte abnormalities should include evaluation for adrenal pathology.
Publication Date: 2019-08-24 00:00:00
Journal: Journal of the Endocrine Society

primary aldosteronism patients(14)

Higher Blood Urea Nitrogen and Urinary Calcium: New Risk Factors for Diabetes Mellitus in Primary Aldosteronism Patients.
Publication Date: 2020-03-03 00:00:00
Journal: Frontiers in endocrinology

aldosterone producing adenoma(13)

[Efficacy of Screening and Confirmatory Tests of Primary Aldosteronism in Diagnosing Aldosterone Producing Adenoma].
To assess the efficacy of screening and confirmatory tests of primary aldosteronism (PA) in diagnosing aldosterone producing adenoma (APA). Clinical data of 167 hypertensive patients were retrospectively reviewed,including 93 patients with APA and 74 patients with essential hypertension (EH). The area under curves ( APA patients had higher supine PAC,higher percentage of third degree hypertension,and lower serum potassium level than EH patients ( Screening tests using supine ARR>30 plus supine PAC>17.83 ng/dL are preferred with high sensitivity and specificity. The absolute values of PAC post SIT and CCT are recommended for confirming APA.
Publication Date: 2018-07-18 00:00:00
Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition

mineralocorticoid receptor antagonists(16)

Mineralocorticoid Receptor Antagonists in ESKD.
Publication Date: 2020-04-10 00:00:00
Journal: Clinical journal of the American Society of Nephrology : CJASN

aldosterone excess(24)

Five Reasons for the Failure to Diagnose Aldosterone Excess in Hypertension.
Primary hyperaldosteronism (PA) is a well-known cause of hypertension although its exact prevalence amongst patients with apparent essential hypertension has been a matter of debate. A number of recent studies have suggested that mild forms of PA may be relatively common taking into consideration factors that were previously either overestimated or ignored when developing diagnostic tests of PA and when applying these tests into normotensive individuals. The performance characteristics and diagnostic accuracy of such tests are substantially increased when the adrenocorticotrophin effect, inappropriate potassium levels and their application in carefully selected normotensive individuals are considered. In the present review, we critically analyze these issues and provide evidence that several, particularly mild, forms of PA can be effectively identified exhibiting potentially important clinical implications.
Publication Date: 2020-09-04 00:00:00
Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme


Mass Spectrometry Imaging Establishes 2 Distinct Metabolic Phenotypes of Aldosterone-Producing Cell Clusters in Primary Aldosteronism.
Aldosterone-producing adenomas (APAs) are one of the main causes of primary aldosteronism and the most prevalent surgically correctable form of hypertension. Aldosterone-producing cell clusters (APCCs) comprise tight nests of zona glomerulosa cells, strongly positive for CYP11B2 (aldosterone synthase) in immunohistochemistry. APCCs have been suggested as possible precursors of APAs because they frequently carry driver mutations for constitutive aldosterone production, and a few adrenal lesions with histopathologic features of both APCCs and APAs have been identified. Our objective was to investigate the metabolic phenotypes of APCCs (n=27) compared with APAs (n=6) using in situ matrix-assisted laser desorption/ionization mass spectrometry imaging of formalin-fixed paraffin-embedded adrenals from patients with unilateral primary aldosteronism. Specific distribution patterns of metabolites were associated with APCCs and classified 2 separate APCC subgroups (subgroups 1 and 2) indistinguishable by CYP11B2 immunohistochemistry. Metabolic profiles of APCCs in subgroup 1 were tightly clustered and distinct from subgroup 2 and APAs. Multiple APCCs from the same adrenal displayed metabolic profiles of the same subgroup. Metabolites of APCC subgroup 2 were highly similar to the APA group and indicated enhanced metabolic pathways favoring cell proliferation compared with APCC subgroup 1. In conclusion, we demonstrate specific subgroups of APCCs with strikingly divergent distribution patterns of metabolites. One subgroup displays a metabolic phenotype convergent with APAs and may represent the progression of APCCs to APAs.
Publication Date: 2020-01-21 00:00:00
Journal: Hypertension (Dallas, Tex. : 1979)


No evidence for brain renin-angiotensin system activation during DOCA-salt hypertension.
Brain renin-angiotensin system (RAS) activation is thought to mediate deoxycorticosterone acetate (DOCA)-salt hypertension, an animal model for human primary hyperaldosteronism. Here, we determined whether brainstem angiotensin II is generated from locally synthesized angiotensinogen and mediates DOCA-salt hypertension. To this end, chronic DOCA-salt-hypertensive rats were treated with liver-directed siRNA targeted to angiotensinogen, the angiotensin II type 1 receptor antagonist valsartan, or the mineralocorticoid receptor antagonist spironolactone (n = 6-8/group). We quantified circulating angiotensinogen and renin by enzyme-kinetic assay, tissue angiotensinogen by Western blotting, and angiotensin metabolites by LC-MS/MS. In rats without DOCA-salt, circulating angiotensin II was detected in all rats, whereas brainstem angiotensin II was detected in 5 out of 7 rats. DOCA-salt increased mean arterial pressure by 19 ± 1 mmHg and suppressed circulating renin and angiotensin II by >90%, while brainstem angiotensin II became undetectable in 5 out of 7 rats (<6 fmol/g). Gene silencing of liver angiotensinogen using siRNA lowered circulating angiotensinogen by 97 ± 0.3%, and made brainstem angiotensin II undetectable in all rats (P<0.05 vs. non-DOCA-salt), although brainstem angiotensinogen remained intact. As expected for this model, neither siRNA nor valsartan attenuated the hypertensive response to DOCA-salt, whereas spironolactone normalized blood pressure and restored brain angiotensin II together with circulating renin and angiotensin II. In conclusion, despite local synthesis of angiotensinogen in the brain, brain angiotensin II depended on circulating angiotensinogen. That DOCA-salt suppressed circulating and brain angiotensin II in parallel, while spironolactone simultaneously increased brain angiotensin II and lowered blood pressure, indicates that DOCA-salt hypertension is not mediated by brain RAS activation.
Publication Date: 2021-01-07 00:00:00
Journal: Clinical science (London, England : 1979)

hyperaldosteronism type ii(12)

CLCN2 chloride channel mutations in familial hyperaldosteronism type II.
Primary aldosteronism, a common cause of severe hypertension
Publication Date: 2018-02-07 00:00:00
Journal: Nature genetics


Effect of cosyntropin during adrenal venous sampling on subtype of primary aldosteronism: analysis of surgical outcome.
We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA). Multicenter retrospective study by Japan PA study. We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcome among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Compared with U to U group, U to B group had poor clinical and biochemical outcome and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcome via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Although PA patients in U to B group had worse surgical outcome than did those in U to U group, basal LI could discriminate among patients with better surgical outcome in U to B group.
Publication Date: 2020-02-11 00:00:00
Journal: European journal of endocrinology

surgical treatment(24)

Persistent severe hyperkalemia following surgical treatment of aldosterone-producing adenoma.
Primary aldosteronism is one of the most common causes of secondary hypertension. This condition is characterized by autonomous hypersecretion of aldosterone which produces sodium retention and potassium excretion, resulting in high blood pressure and potential hypokalemia. Transient postoperative hyporeninemic hypoaldosteronism with an increased risk of hyperkalemia may occur in some patients. We report the case of a 63-year-old patient with persistent hypokalemia, periodic paralysis, and refractory hypertension who was diagnosed with primary hyperaldosteronism due to elevated aldosterone, undetectable plasmatic renin concentration, and the presence of a left adrenal mass. One month after the surgery, the patient was admitted with signs of severe hyperkalemia (8 mmol/L) and worsened renal function, thus requiring hemodialysis. Fluid resuscitation, loop diuretic, and sodium bicarbonate treatment decreased his potassium. Zona glomerulosa insufficiency was confirmed by hormonal tests which exposed low aldosterone-renin axis. The fludrocortisone treatment was initiated and maintained, with consequent potassium and creatinine stabilization. Old age, long duration of hypertension, impaired renal function, severe hypokalemia before surgery, and large size of the aldosterone-producing adenoma are important risk factors for serious potassium imbalance after removal of the adenoma. We have to consider monitoring the patients after surgery for primary hyperaldosteronism in order to prevent severe hyperkalemia; therefore, postoperative immediate follow-up (arterial pressure, potassium, and renal function) is mandatory.
Publication Date: 2020-03-17 00:00:00
Journal: Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences

liddle syndrome(9)

High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana.
Liddle syndrome (LS) is an autosomal dominant disorder due to a gain-of-function mutation in the epithelial Na(+) channel and is perceived to be a rare condition. A cross-sectional study of 149 hypertensive patients with hypokalemia (<4 mmol/dL) or elevated serum bicarbonate (>25 mmol/dL) was conducted at a Veterans' Administration Medical Center Hypertension Clinic in Shreveport, LA. Data on demographics, blood pressure, and select blood tests were collected and expressed as percentages for categoric variables and as mean ± standard deviation (SD) for continuous variables. Patients were diagnosed with likely LS when the plasma renin activity (PRA) was <0.35 μU/mL/h and the aldosterone was <15 ng/dL and likely primary hyperaldosteronism (PHA) with PRA <0.35 μU/mL/h and aldosterone level >15 ng/dL. The cohort included predominantly elderly (67.1±13.4 years), male (96%), and Caucasian (57%) patients. The average blood pressure was 143.8/79.8 mm Hg±27.11/15.20 with 3.03±1.63 antihypertensive drugs. Based on the above criteria, 9 patients (6%) satisfied the criteria for likely LS and 10 patients (6.7%) were diagnosed with likely PHA. In this hypothesis-generating study, the authors detected an unusually high prevalence of biochemical abnormalities compatible with likely LS syndrome from Northwestern Louisiana, approaching that of likely PHA.
Publication Date: 2010-11-09 00:00:00
Journal: Journal of clinical hypertension (Greenwich, Conn.)

metabolic syndrome(19)

Role of Mineralocorticoid Receptors in Obstructive Sleep Apnea and Metabolic Syndrome.
This review will summarize recent developments in the research on the mineralocorticoid receptor and its impact on obstructive sleep apnea and metabolic syndrome Aldosterone excess plays an important role in the association between resistant hypertension and obstructive sleep apnea. The prevalence of obesity is increasing rapidly worldwide and is especially common among patients with obstructive sleep apnea, resistant hypertension, and metabolic syndrome suggesting probable mechanistic links between these three conditions. Mineralocorticoid receptor expression is increased in obese individuals, which may contribute to the common association between obesity and hyperaldosteronism. Mineralocorticoid receptor blockers reduce the severity of obstructive sleep apnea among resistant hypertension patients. A large body of literature demonstrates a strong association between obesity, hyperaldosteronism, resistant hypertension, and sleep apnea, including specific benefit of treatment with mineralocorticoid receptor blockers for these separate disorders.
Publication Date: 2018-03-21 00:00:00
Journal: Current hypertension reports

renin ratio(22)

The aldosterone to renin ratio in the diagnosis of primary aldosteronism: Promises and challenges.
The complexity of evaluating patients for secondary treatable causes of hypertension is underappreciated. Primary aldosteronism (PA) is the most prevalent cause of secondary hypertension (3%-32% of hypertensive patients). The recent endocrine society clinical practice guideline (ESCPG), "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment", differs from the previous version in the explicit recognition of PA as a major public health issue. Despite this, PA is underdiagnosed. The guidelines call on physicians to substantially ramp up the screening of hypertensive patients at risk of PA. Further, it recommends the plasma aldosterone to renin ratio (ARR), as the test of choice for screening for PA. However, the ARR is a highly variable test with reported diagnostic sensitivities and specificities ranging from 66% to 100% and 61% to 100%, respectively. Variability of the ARR can be attributed to the high degree of within-subject variation, differences in sampling protocols, laboratory assays, reporting units, the effect of medications and the population characteristics used to establish the decision thresholds. These factors render the possibility of false positive and false negative results-which have the potential to adversely impact patients. The limitations and caveats to the use of the ARR necessitate an effective clinic-laboratory interface, with specialist physician and clinical scientist collaboration for ARR result interpretation. Improvement in the diagnostic sensitivity and specificity of the ARR is predicated on harmonisation of pretesting patient preparation criteria, knowledge of the analytical methods used to derive the ratio and the method-specific threshold for PA.
Publication Date: 2019-04-23 00:00:00
Journal: International journal of clinical practice


Serum steroid profiling by mass spectrometry in adrenocortical tumors: diagnostic implications.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS), allowing the reliable measurement of large panels of steroids, opened a new era in the characterization of adrenal diseases. This review summarizes the most recent findings on serum steroid profile in benign adrenocortical tumors and provides a focus on the most promising analytical developments. Recently developed LC-MS/MS assays included challenging compounds, providing new knowledge on adrenal steroid secretion. Pioneering studies highlighted the potential of incoming technologies in increasing measurement selectivity and implementing the steroidomic approach. In primary aldosteronism, several studies highlighted the signature of aldosterone-producing adenomas, mainly characterized by secretion of hybrid steroids. The combination of steroid panel and radiological data reached an agreement with adrenal vein sampling-based classification in more than 80% of the cases. The serum steroid profiling in patients with Cushing's syndrome, mainly characterized by reduced androgens and increased 11-dexoycorticosterone in adrenal hypercortisolism, showed a good discriminant power for patients' subtyping (90% correct classification rate). Finally, a selected panel of steroids, including 11-deoxycortisol as the main discriminant compound, was able to achieve a good separation of patients with and without adrenocortical carcinomas. The constantly evolving serum steroid profiling by MS may improve the diagnosis of different types of adrenocortical tumors.
Publication Date: 2019-03-21 00:00:00
Journal: Current opinion in endocrinology, diabetes, and obesity

saline infusion test(16)

Confirmatory testing of primary aldosteronism with saline infusion test and LC-MS/MS.
Saline infusion test ng (SIT) for confirmation of primary aldosteronism (PA) is based on impaired aldosterone suppression in PA compared to essential hypertension (EH). In the past, aldosterone was quantified using immunoassays (IA). Liquid chromatography tandem mass spectrometry (LC-MS/MS) is increasingly used in clinical routine. We aimed at a method-specific aldosterone threshold for the diagnosis of PA during SIT and explored the diagnostic utility of steroid panel analysis. Retrospective cohort study of 187 paired SIT samples (2009-2018). Diagnosis of PA (n = 103) and EH (n = 84) was established based on clinical routine workup without using LC-MS/MS values. Tertiary care center. LC-MS/MS using a commercial steroid panel. Receiver operator characteristics analysis was used to determine method-specific cut-offs using a positive predictive value (PPV) of 90% as criterion. Aldosterone measured by IA was on average 31 ng/L higher than with LC-MS/MS. The cut-offs for PA confirmation were 54 ng/L for IA (sensitivity: 95%, 95% CI: 89.0-98.4; specificity: 87%, 95% CI: 77.8-93.3; area under the curve (AUC): 0.955, 95% CI: 0.924-0.986; PPV: 90%, 95% CI: 83.7-93.9) and 69 ng/L for LC-MS/MS (79%, 95% CI: 69.5-86.1; 89%, 95% CI: 80.6-95.0; 0.902, 95% CI: 0.857-0.947; 90%, 95% CI: 82.8-94.4). Other steroids did not improve SIT. Aldosterone quantification with LC-MS/MS and IA yields comparable SIT-cut-offs. Lower AUC for LC-MS/MS is likely due to the spectrum of disease in PA and previous decision making based on IA results. Until data of a prospective trial with clinical endpoints are available, the suggested cut-off can be used in clinical routine.
Publication Date: 2020-10-29 00:00:00
Journal: European journal of endocrinology

oxidative stress(17)

Response to 'Oxidative stress in patients affected by primary aldosteronism'.
Publication Date: 2015-04-29 00:00:00
Journal: Journal of hypertension

renal disease(15)

Primary aldosteronism diagnosed in a patient with severe renal disease.
Although initially considered a rarity, primary aldosteronism now is one of the more common causes of secondary hypertension. Based on older data, it was originally estimated that primary aldosteronism accounted for less than 1% of all patients with hypertension. Subsequent data, however, indicated that it may actually occur in as many as 5-15% of patients with hypertension. Here we present a 66-year-old patient with a history of hypertension who was diagnosed with primary hyperaldosteronism at the time he had developed a severe renal failure secondary to a vascular nephropathy. This case report illustrates the difficulties in diagnosis of primary hyperaldosteronism, and highlights the effects of the delay of diagnosis on renal survival and on patient quality of life.
Publication Date: 2018-11-16 00:00:00
Journal: La Tunisie medicale

aldosterone synthase(22)

Immunohistochemistry for aldosterone synthase CYP11B2 and matrix-assisted laser desorption ionization imaging mass spectrometry for in-situ aldosterone detection.
Immunohistochemistry for aldosterone synthase (CYP11B2) has markedly provided a comprehensive picture of the adrenocortical diseases, particularly primary aldosteronism. The findings from CYP11B2-immunohistochemistry are consistent with the clinical courses of most patients with primary aldosteronism. We herein review the updated pathophysiology and usefulness of the method for understanding individual patients with different subtypes of primary aldosteronism. After our discovery of aldosterone-producing cell clusters (APCCs) using the immunohistochemistry for CYP11B2, we found possible APCC-to-APA transitional lesions (pAATLs) in a few cases that had been hitherto classified as unilateral hyperplasia or multiple nodules. On the basis of morphological and functional features of pAATLs as well as distributions of somatic mutations within the lesions, we have made a hypothesis that APCC grows to APA via pAATL for one of developmental courses of APA. Recently, we successfully performed in-situ detection of aldosterone on adrenal tissue sections using a state-of-the-art technique, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-imaging). This method revealed in-situ synthesis of aldosterone in APCCs and APAs in addition to several other steroids. CYP11B2 immunohistochemistry revealed the pathophysiology of aldosterone production in the past decade, especially formation of APCC in normal adrenals and pAATL that is a possible lesion developing from APCC to APA. The term 'idiopathic hyperaldosteronism' may soon become obsolete.
Publication Date: 2019-01-05 00:00:00
Journal: Current opinion in nephrology and hypertension

bilateral adrenal(27)

Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism.
Primary aldosteronism (PA) is the most common cause of secondary hypertension with a high prevalence among patients with resistant hypertension. Despite the recent discovery of somatic variants in aldosterone-producing adenoma (APA)-associated PA, causes for PA due to bilateral aldosterone production (bilateral hyperaldosteronism; BHA) remain unknown. Herein, we identified rare gene variants in ATP2B4, in a cohort of patients with BHA. ATP2B4 belongs to the same family of Ca-ATPases as ATP2B3, which is involved in the pathogenesis of APA. Endogenous ATP2B4 expression was characterized in adrenal tissue, and the gene variants were functionally analyzed for effects on aldosterone synthase (CYP11B2) expression, steroid production in basal and agonist-stimulated conditions, and for changes in biophysical properties of channel properties. Knockdown of ATP2B4 in HAC15 exhibited reduced angiotensin II stimulation in one of four shRNA clones. Stable HAC15 cell lines with doxycycline (dox) - inducible wild-type and variant forms of ATP2B4 - were generated, and dox-induced upregulation of ATP2B4 mRNA and protein was confirmed. However, ATP2B4 variants did not alter basal or agonist-stimulated CYP11B2 expression. Whole-cell recordings in HAC15 cells indicated robust endogenous ATP2B4 conductance in native cells but reduced conductance with overexpressed WT and variant ATP2B4. The previously defined PA-causing ATP2B3 variant served as a positive control and exhibited elevated CYP11B2 mRNA. In conclusion, while this study did not confirm a pathogenic role for ATP2B4 variants in BHA, we describe the sequencing analysis for familial and sporadic BHA and outline a template for the thorough in vitro characterization of gene variants.
Publication Date: 2020-02-01 00:00:00
Journal: Hormones & cancer

adrenocortical adenoma(18)

Unique Sex Steroid Profiles in Estrogen-Producing Adrenocortical Adenoma Associated With Bilateral Hyperaldosteronism.
Because of its rarity, our understanding of steroidogenesis in estrogen-producing adrenocortical adenoma including the response to adrenocorticotropic hormone (ACTH) stimulation, remains limited. A 65-year-old man was referred to us because of primary aldosteronism and a right adrenal tumor. Endocrinological evaluations revealed secondary hypogonadism due to hyperestrogenemia. Adrenal venous sampling (AVS) and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated bilateral hyperaldosteronism and a right estrogen-producing adrenocortical tumor. He subsequently underwent right unilateral adrenalectomy, which resulted in clinical remission of hypogonadism. Subsequent histopathological analysis identified a right estrogen-producing adrenocortical adenoma and multiple, concomitant adrenocortical micronodules. Sequential evaluation of steroid profiles using LC-MS/MS revealed unique hormone production, including adrenal androgens, and less responsiveness to ACTH in the right estrogen-producing adrenocortical adenoma as compared to the nonneoplastic adrenal cortex. This case study revealed unique profiles of steroid production in estrogen-producing adrenocortical adenoma associated with concomitant primary aldosteronism. Sequential steroid profiling analysis using LC-MS/MS in combination with AVS can contribute to the diagnosis of various adrenal disorders.
Publication Date: 2020-02-27 00:00:00
Journal: Journal of the Endocrine Society

clinical practice(14)

[Primary aldosteronism - why is it still underdiagnosed in clinical practice?]
Primary aldosteronism (PA) represents the leading cause of endocrine hypertension, accounting for 4-13 % of all cases. Simultaneously, it is the most common endocrine form of hypertension that can be cured by surgery. Estimates suggest that 2.5 million people in Germany are affected, yet only 8 % of hypertensive patients undergo the proper diagnostic screening for PA. The diagnosis of PA is evidently not taken into account sufficiently when it comes to the everyday management of hypertension. Since PA patients carry an increased risk of cardio- and cerebrovascular events as well as metabolic comorbidities, early screening and diagnosis is crucial.This manuscript highlights the current guidelines of screening and diagnosing PA and addresses some currently published findings regarding this area. The aim is to raise awareness when it comes to diagnosing and screening for PA in the everyday management of hypertensive patients. DEFINITION, KLASSIFIZIERUNG UND PRäVALENZ:  Der primäre Hyperaldosteronismus (PA) ist die häufigste chirurgisch therapierbare Form der sekundären Hypertonie. Hauptursachen des PA sind ein 1-seitiges Aldosteron-produzierendes Nebennierenadenom oder eine bilaterale idiopathische Nebennierenrindenhyperplasie (Bilateral Adrenal Hyperplasia, BAH). In den letzten Jahren ist das Phänomen der autonomen Kortisol-Co-Sekretion (ACS) im Rahmen des Conn-Syndroms in den Fokus gerückt. Während der Mineralokortikoidexzess für die Hypertonie verantwortlich ist, scheint die ACS vor allem zu metabolischen Komorbiditäten wie erhöhtem BMI, gestörter Glukosetoleranz und Diabetes mellitus Typ 2 zu führen. Das sogenannte „Connshing“-Syndrom (zusammengezogen von Conn- und Cushing-Syndrom) wird als neuer metabolischer Subtyp angesehen. DIAGNOSE:  Folgende Hypertoniegruppen sollen unter anderem gescreent werden (etwa 50 % aller Hypertoniker): Patienten mit therapierefraktärer Hypertonie, mit arterieller Hypertonie und Hypokaliämien, mit arterieller Hypertonie und obstruktivem Schlafapnoe-Syndrom (OSAS), mit arterieller Hypertonie und adrenalem Nebennierenzufallstumor, mit Hypertonie und Blutdruck > 150/90 mmHg sowie jüngere Patienten mit Hypertonie. Das Screening erfolgt mittels des Aldosteron-Renin-Quotienten. Der nächste Schritt ist häufig die Bestätigung der Diagnose PA mittels Kochsalzbelastungs- und/oder Captopril-Test. Neu ist, dass bei sehr ausgeprägtem biochemischem Phänotyp, z. B. bei Patienten mit spontaner Hypokaliämie sowie maximal supprimierten Renin- und Aldosteron-Werten > 550 pmol/l, ohne weiteren Bestätigungstest direkt eine Subtypdifferenzierung erfolgen kann. Die Subtypdifferenzierung erfolgt mittels CT-Bildgebung der Nebennieren und (als Goldstandard) Nebennierenvenenkatheterisierung. Bei technisch nicht erfolgreichen Katheterisierungen werden nuklearmedizinische Verfahren (z. B. CXCR4-PET/CT) in Einzelfällen eingesetzt. THERAPIE:  Bei gesichertem unilateralem PA ist eine Adrenalektomie indiziert. Entsprechend der Primary-Aldosteronism-Surgical-Outcome-Study-Kriterien profitieren Frauen, jüngere Patienten (< 50 Jahre), Patienten mit geringerer Laufzeit der Hypertonie (< 5 Jahre) und Patienten mit geringerer Anzahl (< 2) von Antihypertensiva am meisten von einer Adrenalektomie. Im Fall einer BAH sollte eine Therapie mittels Spironolacton (initial 25–50 mg/d) eingeleitet werden, mit entsprechender Steigerungsoption zum Anheben des Renin als Ziel.
Publication Date: 2020-06-04 00:00:00
Journal: Deutsche medizinische Wochenschrift (1946)

left ventricular hypertrophy(14)

Cortisol Excess in Patients With Primary Aldosteronism Impacts Left Ventricular Hypertrophy.
Primary aldosteronism (PA) represents the most frequent form of endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce excessive left ventricular hypertrophy (LVH) compared with matched essential hypertensives. In recent studies frequent cosecretion of cortisol and aldosterone has been reported in patients with PA. Our aim was to investigate the impact of cortisol cosecretion on LVH in patients with PA. We determined 24-hour excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass spectrometry and assessed cardiac remodeling using echocardiography initially and 1 year after initiation of treatment of PA. We included 73 patients from the Munich center of the German Conn's registry: 45 with unilateral aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. At the time of diagnosis, 85% of patients with PA showed LVH according to left ventricular mass index [(LVMI); median 62.4 g/m2.7]. LVMI correlated positively with total glucocorticoid excretion (r2 = 0.076, P = 0.018) as well as with tetrahydroaldosterone excretion (r2 = 0.070, P = 0.024). Adrenalectomy led to significantly reduced LVMI in aldosterone-producing adenoma (P < 0.001) whereas mineralocorticoid receptor antagonist therapy in bilateral adrenal patients with hyperplasia reduced LVMI to a lesser degree (P = 0.024). In multivariate analysis, the decrease in LVMI was positively correlated with total glucocorticoid excretion and systolic 24-hour blood pressure, but not with tetrahydroaldosterone excretion. Cortisol excess appears to have an additional impact on cardiac remodeling in patients with PA. Treatment of PA by either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This effect was most pronounced in patients with high total glucocorticoid excretion.
Publication Date: 2018-08-17 00:00:00
Journal: The Journal of clinical endocrinology and metabolism

mineralocorticoid hypertension(13)

Inherited forms of mineralocorticoid hypertension.
Aldosterone plays an essential role in the maintenance of fluid and electrolyte homeostasis in the distal nephron. Monogenic forms of mineralocorticoid hypertension result from genetic defects leading to excessive production of aldosterone (or other mineralocorticoids) from the adrenal cortex or to illegitimate mineralocorticoid effects in the kidney. They are characterized in the majority of cases by early onset, severe or resistant hypertension and associated with suppressed renin levels. Depending on their causes, these diseases are distinguished at the clinical and biochemical level and differently affect aldosterone levels and kalemia. The diagnosis is confirmed by genetic testing, which allows in many cases targeted treatment to prevent severe cardiovascular consequences of high blood pressure or aldosterone excess. In this review we describe the different forms of inherited mineralocorticoid hypertension providing an overview of their clinical and biochemical features, their underlying genetic defects and specific therapeutic options.
Publication Date: 2015-08-26 00:00:00
Journal: Best practice & research. Clinical endocrinology & metabolism


Aldosterone-Mediated Sodium Retention Is Reflected by the Serum Sodium to Urinary Sodium to (Serum Potassium)
The serum sodium to urinary sodium ratio divided by the (serum potassium)
Publication Date: 2020-08-06 00:00:00
Journal: Diagnostics (Basel, Switzerland)

systematic review(21)

Primary hyperaldosteronism presenting as persistent postpartum hypertension: Illustrative case and systematic review.
We present a case of persistent postpartum hypertension found to be secondary to primary hyperaldosteronism in a woman with a history of recurrent hypertensive disorders of pregnancy and associated fetal complications. Our systematic review revealed only 18 cases of primary aldosteronism diagnosed in women with postpartum hypertension, suggesting that this disorder is under-studied in the postpartum period. A review of these cases suggests that women with primary hyperaldosteronism commonly present with hypertensive disorders of pregnancy, but may only be identified de novo postpartum. However, a high index of suspicion is needed to diagnose primary hyperaldosteronism in the postpartum period, guided by a woman's obstetric history.
Publication Date: 2019-12-20 00:00:00
Journal: Obstetric medicine


Familial periodic paralysis associated with a rare KCNJ5 variant that supposed to have incomplete penetrance.
The periodic paralyses are a group of skeletal muscle channelopathies caused by variants in several ion channel genes. Potassium Inwardly Rectifying Channel Subfamily J Member 5 ( KCNJ5 encodes the G-protein-activated inwardly rectifying potassium channel 4 (Kir3.4) and the heterozygous KCNJ5 variants cause familial hyperaldosteronism and long QT syndrome (LQTS). Recent studies suggested that variants in KCNJ5 are also causative for Andersen-Tawil syndrome, which showed periodic paralysis and characteristic electrocardiogram features. We found a heterozygous KCNJ5 variant c.1159G > C, p.(Gly387Arg) in an individual with familial periodic paralysis using exome sequencing. Sanger sequencing revealed that this variant was inherited from his affected mother. The same variant had been previously found in two cases of familial LQTS or Andersen-Tawil syndrome, and functional analysis suggested that this variant might have loss of function effect on channel activity. However, the allele frequency of c.1159G > C variant in an East Asian population of public databases ranged from 0.21% to 0.25%, indicating possible incomplete penetrance. Our two patients expand the phenotypic spectrum associated with the c.1159G > C KCNJ5 variant, though the variant has very low penetrance.
Publication Date: 2020-11-18 00:00:00
Journal: Brain & development


High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan.
To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is high r than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or χ Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.
Publication Date: 2019-04-24 00:00:00
Journal: Diabetes care

atrial fibrillation(15)

Clinical efficacy of potassium canreonate-canrenone in sinus rhythm restoration among patients with atrial fibrillation - a protocol of a pilot, randomized, double -blind, placebo-controlled study (CANREN-AF trial).
Atrial fibrillation (AF) is the most frequent cardiac arrhythmia which increases the risk of thromboembolic complications and impairs quality of life. An important part of a therapeutic approach for AF is sinus rhythm restoration. Antiarrhythmic agents used in pharmacological cardioversion have limited efficacy and potential risk of proarrhythmia. Simultaneously, underlying conditions of AF should be treated (e.g. electrolyte imbalance, increased blood pressure, neurohormonal disturbances, atrial volume overload). There is still the need for an effective and safe approach to increase AF cardioversion efficacy. This randomized, double-blind, placebo-controlled, superiority clinical study is performed in patients with AF in order to evaluate the clinical efficacy of intravenous canrenone in sinus rhythm restoration. Eighty eligible patients with an episode of AF lasting less than 48 h are randomized in a 1:1 ratio to receive canrenone or placebo. Patients randomized to a treatment intervention are receiving canrenone intravenously at a dose of 200 mg within 2-3 min. Subjects assigned to a control group obtain the same volume of 0.9% saline within the same time. The primary endpoint includes return of sinus rhythm documented in the electrocardiogram within 2 h after drug or placebo administration. Other endpoints and safety outcomes analyses, due to expected lack of statistical power, are exploratory. Current evidence supports renin-angiotensin-aldosterone system (RAAS) inhibition as an upstream therapy in AF management. Excess aldosterone secretion results in proarrhythmic effects. Among the RAAS inhibitors, only canrenone is administered intravenously. Canrenone additionally increases the plasma level of potassium, lowers blood pressure and reduces preload. It has been already used in primary and secondary hyperaldosteronism in the course of chronic liver dysfunction and in heart failure., NCT03536806. Registered on 25 May 2018.
Publication Date: 2020-05-14 00:00:00
Journal: Trials


Exploration Of The Seated Saline Suppression Test For The Diagnosis Of Primary Aldosteronism In The Chinese Population.
We prospectively investigated the accuracy of the seated saline suppression test (SSST) in 113 patients with hypertension (including 93 primary aldosteronism [PA] and 20 essential hypertension patients) in the Department of Endocrinology and Metabolism. Each patient underwent a recumbent saline suppression test (RSST) and SSST. The accuracy of the SSST for a confirmative PA diagnosis and subtype classification was evaluated and compared with the RSST. The area under the receiver operating characteristic (ROC) curve of plasma aldosterone concentration (PAC) for the SSST was significantly greater than that for the RSST (0.945±0.0199 vs. 0.828 ± 0.0404; P<.05). The ROC analysis showed that the optimal PAC cut-off values were 12.94 ng/dL for the SSST (sensitivity 86.02%, specificity 95%; Youden index [YI] 0.810) and 12.04 ng/dL for the RSST (sensitivity 83.15%, specificity 57%; YI 0.401). The optimal PAC cut-off value for classifying aldosterone-producing adenoma and idiopathic hyperaldosteronism was 18.12 ng/dL for the SSST (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSST. The SSST is safe and convenient for PA diagnosis. The accuracy of the SSST for a confirmatory diagnosis of PA was better than that of the RSST. The SSST is a reliable alternative for PA confirmation in Chinese individuals. APA = aldosterone-producing adenoma; ARR = aldosterone to renin ratio; AVS = adrenal vein sampling; CT = computed tomography; EH = essential hypertension; IHA = idiopathic hyperaldosteronism; MRI = magnetic resonance imaging; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; ROC = receiver operating characteristic; RSST = recumbent saline suppression test; SSST = seated saline suppression test; YI = Youden index.
Publication Date: 2021-01-21 00:00:00
Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists


Functional imaging of adrenal cortex.
The rising number of high-resolution imaging scans has increased the adrenal lesions detection, which require a differential diagnosis. Currently, the most commonly used scans are CT and MRI, but these are sometimes not very specific. In these cases, nuclear medicine scans with
Publication Date: 2020-11-24 00:00:00
Journal: Revista espanola de medicina nuclear e imagen molecular


Can unilateral forms of primary aldosteronism be excluded with confidence preoperatively by methods other than adrenal venous sampling? The search continues.
Publication Date: 2020-06-06 00:00:00
Journal: Journal of hypertension