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Aldosterone signaling defect in young infants: single-center report and review.
Wijaya, M, Ma, H, Zhang, J, Du, M, Li, Y, Chen, Q, Guo, S
BMC endocrine disorders. 2021;(1):149
Abstract
BACKGROUND Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. METHODS A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. RESULTS A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240-1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. CONCLUSION Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency.
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2.
Obesity and the diagnostic accuracy for primary aldosteronism.
Tirosh, A, Hannah-Shmouni, F, Lyssikatos, C, Belyavskaya, E, Zilbermint, M, Abraham, SB, Lodish, MB, Stratakis, CA
Journal of clinical hypertension (Greenwich, Conn.). 2017;(8):790-797
Abstract
The effects of body mass index on the diagnostic accuracy of primary aldosteronism (PA) are inconsistent and yet important considering the high prevalence and frequent co-occurrence of obesity and hypertension. The current study included 59 adult patients who underwent a stepwise evaluation for PA, using aldosterone to renin ratio for case detection and plasma aldosterone concentration after saline suppression test and/or 24-hour urinary aldosterone after oral sodium loading for case confirmation. Body mass index had a quadratic (U-shaped) correlation with plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, and plasma aldosterone concentration after saline suppression test. Among patients with a body mass index ≥30 kg/m2 , the aldosterone to renin ratio yielded lower case detection accuracy of PA. We conclude that obesity results in a nonlinear correlation with plasma aldosterone concentration, plasma renin activity, and aldosterone to renin ratio, which affects the accuracy of case detection for PA. Patients with a body mass index ≥30 kg/m2 are less accurately identified as having PA when saline suppression and/or oral salt loading tests are used for case confirmation.
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3.
Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.
Weir, MR, Bakris, GL, Gross, C, Mayo, MR, Garza, D, Stasiv, Y, Yuan, J, Berman, L, Williams, GH
Kidney international. 2016;(3):696-704
Abstract
Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.
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4.
Prevalence and clinical correlates of somatic mutation in aldosterone producing adenoma-Taiwanese population.
Wu, VC, Huang, KH, Peng, KY, Tsai, YC, Wu, CH, Wang, SM, Yang, SY, Lin, LY, Chang, CC, Lin, YH, et al
Scientific reports. 2015;:11396
Abstract
Primary aldosteronism (PA) is a common form of secondary hypertension and has significant cardiovascular consequences. Mutated channelopathy due to the activation of calcium channels has been recently described in aldosterone-producing adenoma (APA). The study involved 148 consecutive PA patients, (66 males; aged 56.3 ± 12.3years) who received adrenalectomy, and were collected from the Taiwan PA investigator (TAIPAI) group. A high rate of somatic mutation in APA was found (n=91, 61.5%); including mutations in KCNJ5 (n=88, 59.5%), ATP1A1 (n=2, 1.4%), and ATP2B3 (n=1, 0.7%); however, no mutations in CACNA1D were identified. Mutation-carriers were younger (<0.001), had lower Cyst C (p=0.042), pulse wave velocity (p=0.027), C-reactive protein (p=0.042) and a lower rate of proteinuria (p=0.031) than non-carriers. After multivariate adjustment, mutation carriers had lower serum CRP levels than non-carriers (p=0.031. Patients with mutation also had a greater chance of recovery from hypertension after operation (p=0.005). A high incidence of somatic mutations in APA was identified in the Taiwanese population. Mutation-carriers had lower CRP levels and a higher rate of cure of hypertension after adrenalectomy. This raises the possibility of using mutation screening as a tool in predicting long-term outcome after adrenalectomy.