Dominguez A, Muppidi V, Gupta S. Hyperaldosteronism. StatPearls. 2020 Jan. [Medline]. [Full Text].
Cobb A, Aeddula NR. Primary Hyperaldosteronism. StatPearls. 2020 Jan. [Medline]. [Full Text].
Kasifoglu T, Akalin A, Cansu DU, Korkmaz C. Hypokalemic paralysis due to primary hyperaldosteronism simulating Gitelman's syndrome. Saudi J Kidney Dis Transpl. 2009 Mar. 20(2):285-7. [Medline].
Korzynska W, Jodkowska A, Gosławska K, Bogunia-Kubik K, Mazur G. Genetic aspects of primary hyperaldosteronism. Adv Clin Exp Med. 2018 Aug. 27 (8):1149-1158. [Medline]. [Full Text].
Aronova A, Iii TJ, Zarnegar R. Management of hypertension in primary aldosteronism. World J Cardiol. 2014 May 26. 6(5):227-33. [Medline]. [Full Text].
Weisbrod AB, Webb RC, Mathur A, Barak S, Abraham SB, Nilubol N, et al. Adrenal histologic findings show no difference in clinical presentation and outcome in primary hyperaldosteronism. Ann Surg Oncol. 2013 Mar. 20(3):753-8. [Medline]. [Full Text].
Funder JW. The genetic basis of primary aldosteronism. Curr Hypertens Rep. 2012 Apr. 14(2):120-4. [Medline].
Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature. 1992 Jan 16. 355(6357):262-5. [Medline].
Torpy DJ, Gordon RD, Lin JP, Huggard PR, Taymans SE, Stowasser M, et al. Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. J Clin Endocrinol Metab. 1998 Sep. 83(9):3214-8. [Medline].
Lafferty AR, Torpy DJ, Stowasser M, Taymans SE, Lin JP, Huggard P, et al. A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22). J Med Genet. 2000 Nov. 37(11):831-5. [Medline]. [Full Text].
Choi M, Scholl UI, Yue P, Björklund P, Zhao B, Nelson-Williams C, et al. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science. 2011 Feb 11. 331(6018):768-72. [Medline]. [Full Text].
Scholl UI, Nelson-Williams C, Yue P, Grekin R, Wyatt RJ, Dillon MJ, et al. Hypertension with or without adrenal hyperplasia due to different inherited mutations in the potassium channel KCNJ5. Proc Natl Acad Sci U S A. 2012 Feb 14. 109(7):2533-8. [Medline]. [Full Text].
Charmandari E, Sertedaki A, Kino T, Merakou C, Hoffman DA, Hatch MM, et al. A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension. J Clin Endocrinol Metab. 2012 Aug. 97(8):E1532-9. [Medline]. [Full Text].
Boulkroun S, Beuschlein F, Rossi GP, Golib-Dzib JF, Fischer E, Amar L, et al. Prevalence, clinical, and molecular correlates of KCNJ5 mutations in primary aldosteronism. Hypertension. 2012 Mar. 59(3):592-8. [Medline].
Taguchi R, Yamada M, Nakajima Y, Satoh T, Hashimoto K, Shibusawa N, et al. Expression and mutations of KCNJ5 mRNA in Japanese patients with aldosterone-producing adenomas. J Clin Endocrinol Metab. 2012 Apr. 97(4):1311-9. [Medline].
Monticone S, Hattangady NG, Nishimoto K, Mantero F, Rubin B, Cicala MV, et al. Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas and adrenocortical cells. J Clin Endocrinol Metab. 2012 Aug. 97(8):E1567-72. [Medline]. [Full Text].
Azizan EA, Lam BY, Newhouse SJ, Zhou J, Kuc RE, Clarke J, et al. Microarray, qPCR, and KCNJ5 sequencing of aldosterone-producing adenomas reveal differences in genotype and phenotype between zona glomerulosa- and zona fasciculata-like tumors. J Clin Endocrinol Metab. 2012 May. 97(5):E819-29. [Medline].
Al-Salameh A, Cohen R, Desailloud R. Overview of the genetic determinants of primary aldosteronism. Appl Clin Genet. 2014. 7:67-79. [Medline]. [Full Text].
Escher G. Hyperaldosteronism in pregnancy. Ther Adv Cardiovasc Dis. 2009 Apr. 3(2):123-32. [Medline].
Fuller PJ. Adrenal Diagnostics: An Endocrinologist's Perspective focused on Hyperaldosteronism. Clin Biochem Rev. 2013 Nov. 34(3):111-6. [Medline]. [Full Text].
Prejbisz A, Warchol-Celinska E, Lenders JW, Januszewicz A. Cardiovascular Risk in Primary Hyperaldosteronism. Horm Metab Res. 2015 Dec. 47 (13):973-80. [Medline].
Holland OB, Brown H, Kuhnert L, Fairchild C, Risk M, Gomez-Sanchez CE. Further evaluation of saline infusion for the diagnosis of primary aldosteronism. Hypertension. 1984 Sep-Oct. 6(5):717-23. [Medline].
Ignatowska-Switalska H, Chodakowska J, Januszewicz W, Feltynowski T, Adamczyk M, Lewandowski J. Evaluation of plasma aldosterone to plasma renin activity ratio in patients with primary aldosteronism. J Hum Hypertens. 1997 Jun. 11(6):373-8. [Medline].
Galati SJ, Hopkins SM, Cheesman KC, Zhuk RA, Levine AC. Primary aldosteronism: emerging trends. Trends Endocrinol Metab. 2013 Sep. 24(9):421-30. [Medline].
Guichard JL, Clark D 3rd, Calhoun DA, Ahmed MI. Aldosterone receptor antagonists: current perspectives and therapies. Vasc Health Risk Manag. 2013. 9:321-31. [Medline]. [Full Text].
Weiner ID. Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism. Semin Nephrol. 2013 May. 33(3):265-76. [Medline]. [Full Text].
Harvey AM. Hyperaldosteronism: diagnosis, lateralization, and treatment. Surg Clin North Am. 2014 Jun. 94(3):643-56. [Medline].
Lai S, Petramala L, Mastroluca D, et al. Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease. Medicine (Baltimore). 2016 Jul. 95 (29):e4175. [Medline].
Rossi GP, Cesari M, Cuspidi C, Maiolino G, Cicala MV, Bisogni V, et al. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension. 2013 Jul. 62(1):62-9. [Medline].
Fourkiotis V, Vonend O, Diederich S, Fischer E, Lang K, Endres S, et al. Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism. Eur J Endocrinol. 2013 Jan. 168(1):75-81. [Medline].
Rossi GP, Maiolino G, Flego A, et al. Adrenalectomy Lowers Incident Atrial Fibrillation in Primary Aldosteronism Patients at Long Term. Hypertension. 2018 Apr. 71 (4):585-591. [Medline]. [Full Text].
Künzel HE. Psychopathological symptoms in patients with primary hyperaldosteronism--possible pathways. Horm Metab Res. 2012 Mar. 44(3):202-7. [Medline].
Schmiemann G, Gebhardt K, Hummers-Pradier E, Egidi G. Prevalence of hyperaldosteronism in primary care patients with resistant hypertension. J Am Board Fam Med. 2012 Jan-Feb. 25(1):98-103. [Medline].
Kumar B, Swee M. Aldosterone-renin ratio in the assessment of primary aldosteronism. JAMA. 2014 Jul. 312(2):184-5. [Medline].
Gouli A, Kaltsas G, Tzonou A, Markou A, Androulakis II, Ragkou D, et al. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Invest. 2011 Nov. 41(11):1227-36. [Medline].
Lucatello B, Benso A, Tabaro I, Capello E, Caprino MP, Marafetti L, et al. Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion. Eur J Endocrinol. 2013 Apr. 168(4):525-32. [Medline].
Wu CH, Yang YW, Hu YH, Tsai YC, Kuo KL, Lin YH, et al. Comparison of 24-h urinary aldosterone level and random urinary aldosterone-to-creatinine ratio in the diagnosis of primary aldosteronism. PLoS One. 2013. 8(6):e67417. [Medline]. [Full Text].
Piaditis GP, Kaltsas GA, Androulakis II, Gouli A, Makras P, Papadogias D, et al. High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clin Endocrinol (Oxf). 2009 Dec. 71(6):772-8. [Medline].
Gordon RD. Primary aldosteronism. J Endocrinol Invest. 1995 Jul-Aug. 18(7):495-511. [Medline].
Gordon RD, Stowasser M, Klemm SA, Tunny TJ. Primary aldosteronism--some genetic, morphological, and biochemical aspects of subtypes. Steroids. 1995 Jan. 60(1):35-41. [Medline].
Markou A, Pappa T, Kaltsas G, Gouli A, Mitsakis K, Tsounas P, et al. Evidence of primary aldosteronism in a predominantly female cohort of normotensive individuals: a very high odds ratio for progression into arterial hypertension. J Clin Endocrinol Metab. 2013 Apr. 98(4):1409-16. [Medline].
Papanastasiou L, Markou A, Pappa T, Gouli A, Tsounas P, Fountoulakis S, et al. Primary aldosteronism in hypertensive patients: clinical implications and target therapy. Eur J Clin Invest. 2014 Aug. 44(8):697-706. [Medline].
Mussa A, Camilla R, Monticone S, Porta F, Tessaris D, Verna F, et al. Polyuric-polydipsic syndrome in a pediatric case of non-glucocorticoid remediable familial hyperaldosteronism. Endocr J. 2012 Jun 30. 59(6):497-502. [Medline].
Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014 Jan. 63(1):151-60. [Medline].
Rossitto G, Regolisti G, Rossi E, Negro A, Nicoli D, Casali B, et al. Elevation of angiotensin-II type-1-receptor autoantibodies titer in primary aldosteronism as a result of aldosterone-producing adenoma. Hypertension. 2013 Feb. 61(2):526-33. [Medline].
Di Martino M, Garcia Sanz I, Munoz de Nova JL, Marin Campos C, Martinez Martin M, Dominguez Gadea L. NP-59 test for preoperative localization of primary hyperaldosteronism. Langenbecks Arch Surg. 2017 Mar. 402 (2):303-8. [Medline].
Spyridonidis TJ, Apostolopoulos DJ. Is there a role for Nuclear Medicine in diagnosis and management of patients with primary aldosteronism?. Hell J Nucl Med. 2013 May-Aug. 16(2):134-9. [Medline].
Chen Cardenas SM, Santhanam P. ¹¹C-metomidate PET in the diagnosis of adrenal masses and primary aldosteronism: a review of the literature. Endocrine. 2020 Sep 4. [Medline].
Feldman RD. Aldosterone and blood pressure regulation: recent milestones on the long and winding road from electrocortin to KCNJ5, GPER, and beyond. Hypertension. 2014 Jan. 63(1):19-21. [Medline].
Scholl UI, Goh G, Stölting G, de Oliveira RC, Choi M, Overton JD, et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet. 2013 Sep. 45(9):1050-4. [Medline]. [Full Text].
Cerny MA. Progress towards clinically useful aldosterone synthase inhibitors. Curr Top Med Chem. 2013. 13(12):1385-401. [Medline].
Sacks BA, Sacks AC, Faintuch S. Radiofrequency ablation treatment for aldosterone-producing adenomas. Curr Opin Endocrinol Diabetes Obes. 2017 Feb 28. [Medline].
Uppot RN, Gervais DA. Imaging-guided adrenal tumor ablation. AJR Am J Roentgenol. 2013 Jun. 200(6):1226-33. [Medline].
Spence JD. Diagnosis of primary aldosteronism: for medical management, not just surgery. J Hypertens. 2009 Jan. 27(1):204-5; author reply 205. [Medline].
Hu YH, Wu CH, Er LK, Lin CD, Liu YB, Chueh SC, et al. Laparoendoscopic single-site adrenalectomy in patients with primary hyperaldosteronism: A prospective study with long-term follow up. Asian J Surg. 2015 Nov 25. [Medline].
Korah HE, Scholl UI. An Update on Familial Hyperaldosteronism. Horm Metab Res. 2015 Oct 7. [Medline].

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Physiologic regulation of the renin-angiotensin-aldosterone axis.

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Table 1. Factors affecting interpretation of ARR results

False Negative Results
Factor	Aldosterone	Renin	ARR
Medications
K-sparing diuretics	↑	↑↑	↓
K-wasting diuretics (Non-K-sparing diuretics, such as thiazides, induce renal potassium losses and reduce plasma potassium concentrations, leading to decreased aldosterone secretion.)	→↑	↑↑	↓
ACE inhibitors	↓	↑↑	↓
Angiotensin receptor blockers	↓	↑↑	↓
DHPs (It is a shared opinion that dihydropyridinic calcium channel blockers do not significantly affect aldosterone secretion, mainly causing an increase in PRA, which rarely gives false negatives.)	→↓	↑	↓
Other conditions
Hypokalemia	↓	→↑	↓
Sodium-restricted diet	↑	↑↑	↓
Pregnancy	↑	↑↑	↓
Renovascular hypertension	↑	↑↑	↓
Malignant hypertension	↑	↑↑	↓
False Positive Results
Beta-adrenergic blockers	↓	↓↓	↑
Central alpha-2 agonists (eg, clonidine, alpha-methyldopa)	↓	↓↓	↑
NSAIDS	↑	↓↓	↑
Other conditions
Potassium loading	↑	→↓	↑
Sodium-loaded diet	↓	↓↓	↑
Advancing age	↓	↓↓	↑
Renal dysfunction	→↑	↓	↑
PHA-2	→	↓	↑
Luteal phase of menstrual cycle	↑	PRA: Unchanged	↑
Antihypertensive Medications With Minimal Effect on the ARR
Prazosin, doxazosin, terazosin			←→
Verapamil, hydralazine			←→
Other medications
Renin inhibitors (Renin inhibitors raise the ARR if renin is measured as PRA [false positive] and lower it if measured as DAR concentration [false negative.])	↓	↑↓	↑↓
SSRIs	↑	↑	↓
OCPs (OCPs have little effect on ARR when renin is measured as PRA. Use of immunometric measurements of DAR rather than PRA may give false positive results. Subdermal etonogestrel has no effect on ARR.)	↑	↓DAR	↑
Liddle syndrome	↓	↓	Normal
ARR, aldosterone-renin ratio; NSAIDs, non-steroidal anti-inflammatory drugs; K, potassium; ACE, angiotensin converting enzyme; ARBs, angiotensin II type 1 receptor blockers; DHPs, dihydropyridines; PHA-2, pseudohypoaldosteronism type 2; PRA, plasma renin activity; DAR, direct active renin; OCPs, oral contraceptive agents; SSRIs, selective serotonin reuptake inhibitors

Table 2. Drugs Used in the Management of Idiopathic Hyperaldosteronism in Children

Drug	Class	Pediatric Dose
Spironolactone	Aldosterone antagonist	0-10 kg: 6.25 mg/dose PO q12h 11-20 kg: 12.5 mg/dose PO q12h 21-40 kg: 25 mg/dose PO q12h >40 kg: 25 mg PO q8h
Potassium canrenoate	Aldosterone antagonist	3-8 mg/kg IV qd; not to exceed 400 mg
Amiloride	Potassium-sparing diuretic	0.2 mg/kg q12h
Triamterene	Potassium-sparing diuretic	2 mg/kg/dose q8-24h
Nifedipine	Dihydropyridine calcium channel antagonist	0.25-0.5 mg/kg PO q6-8h
Amlodipine	Calcium channel antagonist	0.05-0.2 mg/ day PO
Doxazosin	Alpha₁ -specific adrenergic antagonist	0.02-0.1 mg/day; not to exceed 4 mg
Prazosin	Alpha₁ -specific adrenergic antagonist	0.005 mg/kg test dose, then 0.025-0.1 mg/kg/dose q6h; not to exceed 0.5 mg/dose

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Author

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, American College of Endocrinology

Disclosure: Nothing to disclose.

Coauthor(s)

Amalia Sertedaki, PhD Research Associate, Molecular Endocrinology Laboratory, Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Aghia Sophia Children's Hospital, University of Athens Medical School, Greece

Disclosure: Nothing to disclose.

Eleni Magdalini Kyritsi, MD, PhD Clinical Resident in Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens Medical School, Greece

Disclosure: Nothing to disclose.

Chief Editor

Robert P Hoffman, MD Professor and Program Director, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Division of Pediatric, Endocrinology, Diabetes, and Metabolism, Nationwide Children's Hospital

Robert P Hoffman, MD is a member of the following medical societies: American College of Pediatricians, American Diabetes Association, American Pediatric Society, Christian Medical and Dental Associations, Endocrine Society, Midwest Society for Pediatric Research, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Antony Lafferty, MB ChB, FRACP Senior Lecturer of Pediatric Endocrinology, Monash University Department of Pediatrics, National Institutes of Health, Bethesda, MD, and Princess Margaret Hospital for Children, Perth, Western Australia

Antony Lafferty, MB ChB, FRACP is a member of the following medical societies: Endocrine Society

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI; NovoNordisk Consulting fee Consulting; Onyx Heart Valve Consulting fee Consulting

Thomas A Wilson, MD Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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