Aldosteronism

Primary Author: Meikle, A. Wayne, MD.

  • Key Points
  • Diagnosis
  • Algorithms
  • Screening
  • Background
  • Lab Tests
  • References
  • Related Topics

Confirmation Testing for Primary Aldosteronism (PA)

The Endocrine Society suggests a three-tiered approach that includes screening, confirmation of diagnosis, and determination of the specific subtype of PA (Endocrine Society Clinical Practice Guidelines, 2008).

Confirmation of Clinical Suspicion/Screening

  • Initial testing − ARR (plasma aldosterone-renin ratio); positive or equivocal results requires confirmation
    • Negative result – good evidence for absence of primary aldosteronism (PA)

Subtype Differentiation

Indications for Testing

  • Refer to Screening tab

Laboratory Testing

  • Refer to Key Points tab

Imaging Studies

Differential Diagnosis

  • Essential hypertension
  • Cushing syndrome
  • Obstructive sleep apnea
  • Pheochromocytoma
  • Liddle syndrome
  • Excessive licorice ingestion
  • Renal artery stenosis
  • Aortic coarctation
  • Endocrine Society Clinical Practice Guidelines (2008)
    • Stage 2 or 3 hypertension (BP >160/100)
    • Drug-resistant hypertension
    • Hypertension with diuretic-induced or spontaneous hypokalemia
    • Hypertension with adrenal incidentaloma
    • Hypertension with family history of early onset hypertension or cerebrovascular accident <40 years
    • Hypertension with primary aldosteronism in first-degree relative
  • Initial screen – aldosterone-renin ratio (ARR) most reliable
    • Renin testing alone not recommended as screen
    • Remove any drugs that can interfere with test results 4 weeks before test
      • α1-antagonists used in hypertension do not affect ARR
      • Secondary agent can be used – nondihydropyridine calcium channel blocker (eg, verapamil) or α1-antagonist (eg, prazosin)
    • ARR increase is not diagnostic – proceed with confirmatory testing

Aldosteronism is a syndrome caused by excessive and inappropriate aldosterone production and is the most common form of endocrine hypertension.

Epidemiology

  • Prevalence – >10% of random hypertensive patients (Endocrine Society, 2008)
  • Age – 30s-40s
  • Sex – M<F, 1:2

Etiologies

  • Unilateral or bilateral cortical nodular hyperplasia
  • Aldosterone-producing adenoma (Conn syndrome)
  • Aldosterone-producing adrenocortical carcinoma (rare)
  • Familial syndromes (see Genetics section)
  • Ectopic aldosterone-producing adenoma or carcinoma

Genetics

  • Three forms of familial hyperaldosteronism (FH)
    • FHI (AD)
      • Unequal recombination between CYP11B1 and CYP11B2
      • Glucocorticoid-remediable aldosteronism (GRA)
    • FHII (AD)
      • Linkage chromosome 7p22 mutation
      • Familial occurrence of adenoma or hyperplasia
      • Not glucocorticoid-remediable
    • FHIII
      • KCNJ5 mutation
      • Severe hypertension and massive adrenal hyperplasia
  • Mutations in nonfamilial disease (Stowasser, 2015)
    • KCNJ5
      • Tends to be female and younger
      • Higher in Japanese
      • More severe PA
    • Others
      • ATP1A1
      • ATP2B3
      • CACNA1D
      • These mutations tend to be more common in males, small adenomas

Pathophysiology

  • Hypersecretion of aldosterone increases the reabsorption of sodium for potassium and hydrogen by the renal distal tubule
    • Excess sodium reabsorption leads to hypertension
    • Progressive depletion of potassium and hydrogen leads to hypokalemia and metabolic alkalosis
  • Classification
    • Primary – excessive aldosterone secretion by the adrenal glands
    • Secondary – renin-mediated secretion

Clinical Presentation

  • Constitutional – weakness, fatigue
  • Renal – polyuria, proteinuria, renal failure
  • Cardiac – hypertension, cardiac hypertrophy
  • Edema – rarely exists
  • Electrolyte abnormalities – hypokalemia not the usual presenting abnormality

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Aldosterone/Renin Activity Ratio 0070073
Method: Quantitative Chemiluminescent Immunoassay

Follow Up

Positive/equivocal results require confirmation

Aldosterone and Renin, Direct with Ratio 2002582
Method: Quantitative Chemiluminescent Immunoassay/Quantitative Immunoradiometry

Follow Up

Positive/equivocal results require confirmation

Aldosterone 60 Minute 0070017
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Hypokalemia should be corrected before testing

Related Tests

Guidelines

Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young WF, Montori VM, Endocrine Society. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008; 93(9): 3266-81. PubMed

General References

Chao C, Wu V, Kuo C, Lin Y, Chang C, Chueh J, Wu K, Pimenta E, Stowasser M. Diagnosis and management of primary aldosteronism: an updated review. Ann Med. 2013; 45(4): 375-83. PubMed

Gates LJ, Benjamin N, Haites NE, MacConnachie AA, McLay JS. Is random screening of value in detecting glucocorticoid-remediable aldosteronism within a hypertensive population? J Hum Hypertens. 2001; 15(3): 173-6. PubMed

Kempers MJ E, Lenders JW M, van Outheusden L, van der Wilt GJan, Kool LJ Schultze, Hermus AR M M, Deinum J. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2009; 151(5): 329-37. PubMed

Monticone S, Viola A, Tizzani D, Crudo V, Burrello J, Galmozzi M, Veglio F, Mulatero P. Primary aldosteronism: who should be screened? Horm Metab Res. 2012; 44(3): 163-9. PubMed

Nanba K, Tamanaha T, Nakao K, Kawashima S, Usui T, Tagami T, Okuno H, Shimatsu A, Suzuki T, Naruse M. Confirmatory testing in primary aldosteronism. J Clin Endocrinol Metab. 2012; 97(5): 1688-94. PubMed

Nishikawa T, Saito J, Omura M. Prevalence of primary aldosteronism: should we screen for primary aldosteronism before treating hypertensive patients with medication? Endocr J. 2007; 54(4): 487-95. PubMed

Stowasser M. Update in primary aldosteronism. J Clin Endocrinol Metab. 2015; 100(1): 1-10. PubMed

Sukor N. Primary aldosteronism: from bench to bedside. Endocrine. 2012; 41(1): 31-9. PubMed

Tomaschitz A, Pilz S. Aldosterone to renin ratio--a reliable screening tool for primary aldosteronism? Horm Metab Res. 2010; 42(6): 382-91. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Malabanan A, Meikle A, Swenson L, Bope E, Blackwell E. Suspected Hyperaldosteronism. In Choose the Right Tests: Endocrine Disorders, Columbus, Ohio: Anadem Publishing, 2004.

Ray JA, Kushnir MM, Palmer J, Sadjadi S, Rockwood AL, Meikle W. Enhancement of specificity of aldosterone measurement in human serum and plasma using 2D-LC-MS/MS and comparison with commercial immunoassays. J Chromatogr B Analyt Technol Biomed Life Sci. 2014; 970: 102-7. PubMed

Medical Reviewers

Last Update: May 2016