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Primary hyperaldosteronism

Last updated: August 27, 2021

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Primary hyperaldosteronism, sometimes referred to as Conn syndrome, is an excess of aldosterone caused by autonomous overproduction. It is typically due to adrenal hyperplasia (most commonly bilateral) or adrenal adenoma (typically unilateral). Primary hyperaldosteronism is a common cause of secondary hypertension, occurring in > 5–12% of hypertensive patients. High systemic aldosterone levels result in increased renal sodium reabsorption and potassium secretion, which lead to water retention and hypokalemia. Patients are often asymptomatic and found to have hypertension at routine health checks. Hypertension due to primary hyperaldosteronism is often resistant to pharmacotherapy, and patients may have other signs suggestive of secondary hypertension, such as onset before the age of 30 or after the age of 55. If symptoms are present, these are usually manifestations of hypokalemia (e.g., headache, muscle weakness, and polyuria). Initial laboratory values in primary hyperaldosteronism classically show hypokalemia, metabolic alkalosis, high plasma aldosterone concentration (PAC), and low plasma renin activity (PRA). The plasma aldosterone-to-renin ratio is the initial screening test, followed by confirmatory testing. Further subtyping with imaging and/or adrenal venous sampling can determine whether aldosterone hypersecretion is unilateral or bilateral, which guides management. Treatment of unilateral disease consists of surgical resection, whereas bilateral disease is managed medically with aldosterone antagonists (e.g., spironolactone, eplerenone).

Epidemiological data refers to the US, unless otherwise specified.

Autonomous aldosterone secretion and hypertension

In edematous disorders the aldosterone escape mechanism is impaired, resulting in worsening edema.

Hypokalemia and metabolic alkalosis

Primary hyperaldosteronism is characterized by hypokalemia and drug-resistant hypertension.

Approach [3]

Agents known to affect renin levels include aldosterone receptor antagonists, ACE inhibitors, and potassium-wasting diuretics. Alternatives include alpha blockers and hydralazine.

Screening: aldosterone-to-renin ratio (ARR) [3][12][13]

The aldosterone-to-renin ratio (ARR) is used to screen for primary hyperaldosteronism and differentiate it from other causes of elevated aldosterone (e.g., secondary hyperaldosteronism). [14]

  • Considerations
  • Interpretation
    • ↑ ARR: positive screening result (cutoffs vary) [3][15]
    • PAC: verifies elevated aldosterone and decreases false positive results compared to using ARR alone
    • Example: ARR > 20 (preferably with PAC > 15 ng/dL) suggests elevated aldosterone and suppressed renin.

Patients with primary hyperaldosteronism have elevated aldosterone levels (PAC) that cause decreased renin activity (PRA), resulting in an elevated ARR. [(PAC/PRA) = ↑↑ ARR] [3].

Confirmatory studies [3][5][12][13]

A specialist will order confirmatory testing to verify that aldosterone production is nonsuppressible (i.e., not regulated by the RAAS).

Determining the subtype

Once hyperaldosteronism is confirmed, imaging helps determine the underlying cause and select treatment.

Adrenal CT [3]

Adrenal CT excludes large tumors and helps differentiate possible surgical candidates (e.g., unilateral adenoma) from nonsurgical candidates (e.g., bilateral adrenal hyperplasia). [3]

Adrenal venous sampling (AVS) [3][5]

AVS is the gold standard for biochemically differentiating unilateral aldosterone overproduction from bilateral aldosterone overproduction. [3]

Additional testing for rare causes of primary hyperaldosteronism

When the underlying cause of primary hyperaldosteronism remains unclear or if specific criteria are met, a specialist may order further testing to evaluate for rare causes, e.g., familial hyperaldosteronism or ectopic aldosterone production (see “Etiology”).

Secondary hyperaldosteronism

Pseudohyperaldosteronism

The differential diagnoses listed here are not exhaustive.

Primary hyperaldosteronism can be treated surgically and/or medically with the objective of reducing blood pressure and limiting end-organ damage. In general, unilateral disease is treated surgically and bilateral disease is treated medically. [3]

Surgical treatment [3][5]

  • Indications: confirmed unilateral adrenal hyperaldosteronism in patients with no contraindications to surgery
  • Procedure: laparoscopic unilateral adrenalectomy
  • Additional considerations
    • Correct hypokalemia prior to surgery.
    • Monitor for hyperkalemia immediately following the surgery. [3]
    • Following discharge, a specialist will monitor blood pressure and the ARR to determine whether additional medical management is necessary. [3][5]

Medical management [3]

  1. Fagugli RM, Taglioni C. Changes in the Perceived Epidemiology of Primary Hyperaldosteronism. International Journal of Hypertension. 2011; 2011 : p.1-7. doi: 10.4061/2011/162804 . | Open in Read by QxMD
  2. Dick SM, Queiroz M, Bernardi BL, Dall’Agnol A, Brondani LA, Silveiro SP. Update in diagnosis and management of primary aldosteronism. Clinical Chemistry and Laboratory Medicine (CCLM). 2018; 56 (3): p.360-372. doi: 10.1515/cclm-2017-0217 . | Open in Read by QxMD
  3. Funder JW, Carey RM, Mantero F et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016; 101 (5): p.1889-1916. doi: 10.1210/jc.2015-4061 . | Open in Read by QxMD
  4. Lenzini L, Prisco S, Caroccia B, Rossi GP. Saga of Familial Hyperaldosteronism. Hypertension. 2018; 71 (6): p.1010-1014. doi: 10.1161/hypertensionaha.118.11150 . | Open in Read by QxMD
  5. Williams TA, Reincke M. MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of primary aldosteronism: the Endocrine Society guideline 2016 revisited. Eur J Endocrinol. 2018; 179 (1): p.R19-R29. doi: 10.1530/eje-17-0990 . | Open in Read by QxMD
  6. Abdelhamid S, Müller-Lobeck H, Pahl S, et al. Prevalence of adrenal and extra-adrenal Conn syndrome in hypertensive patients. Arch Intern Med. 1996; 156 (11): p.1190-5.
  7. Cui Y, Zhang Y, Ding J, et al. A Rare Aldosterone-Producing Adenoma Detected by 68Ga-pentixafor PET-CT: A Case Report and Literature Review. Front Endocrinol. 2019; 10 . doi: 10.3389/fendo.2019.00810 . | Open in Read by QxMD
  8. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines.. Hypertension (Dallas, Tex. : 1979). 2020; 75 (6): p.1334-1357. doi: 10.1161/HYPERTENSIONAHA.120.15026 . | Open in Read by QxMD
  9. Vaidya A, Mulatero P, Baudrand R, Adler GK. The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment. Endocr Rev. 2018; 39 (6): p.1057-1088. doi: 10.1210/er.2018-00139 . | Open in Read by QxMD
  10. Stowasser M, Taylor PJ, Pimenta E, Ahmed AH, Gordon RD. Laboratory investigation of primary aldosteronism. Clin Biochem Rev. 2010; 31 (2): p.39-56.
  11. Morera J, Reznik Y. MANAGEMENT OF ENDOCRINE DISEASE: The role of confirmatory tests in the diagnosis of primary aldosteronism. European Journal of Endocrinology. 2019; 180 (2): p.R45-R58. doi: 10.1530/eje-18-0704 . | Open in Read by QxMD
  12. Igaz P. Practical Clinical Endocrinology. Springer Nature ; 2021
  13. Maiolino G, Rossitto G, Bisogni V, et al. Quantitative Value of Aldosterone‐Renin Ratio for Detection of Aldosterone‐Producing Adenoma: The Aldosterone‐Renin Ratio for Primary Aldosteronism (AQUARR) Study. J Am Heart Assoc. 2017; 6 (5). doi: 10.1161/jaha.117.005574 . | Open in Read by QxMD
  14. Funder JW. Primary Aldosteronism. Hypertension. 2019; 74 (3): p.458-466. doi: 10.1161/hypertensionaha.119.12935 . | Open in Read by QxMD
  15. Wang X-Y, Masilamani S, Nielsen J, et al. The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon. J Clin Invest. 2001; 108 (2): p.215-222. doi: 10.1172/jci10366 . | Open in Read by QxMD