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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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