• Clinical science

Primary hyperaldosteronism (Conn syndrome)

Summary

Primary hyperaldosteronism, sometimes referred to as Conn syndrome, is an excess of aldosterone caused by autonomous overproduction, usually at the adrenal cortex. It is typically due to adrenal hyperplasia or adrenal adenoma. Primary hyperaldosteronism is one of the common causes of secondary hypertension. High systemic aldosterone levels result in increased sodium reabsorption and potassium secretion in the collecting ducts of the kidney, which leads to the retention of water along with sodium, as well as hypokalemia. Patients are often asymptomatic and found to have hypertension at routine health checks. It will often emerge that the patient's hypertension is resistant to pharmaceutical therapy, and they may have other signs suggestive of secondary hypertension, such as an age of onset below 30 years or above 55 years. If symptoms are present, they typically include headache, muscle weakness, and polyuria. Initial labs in primary hyperaldosteronism classically show a hypertensive patient with hypokalemia, metabolic alkalosis, high plasma aldosterone concentration (PAC) and low plasma renin activity (PRA). Following biochemical confirmation of primary hyperaldosteronism with oral or intravenous sodium loading tests, imaging modalities such as CT and adrenal venous sampling are used to locate the source of autonomous aldosterone secretion. Treatment of primary hyperaldosteronism consists of surgical resection of adrenal adenoma or pharmaceutical therapy with aldosterone antagonists (e.g., spironolactone, eplerenone) in cases of bilateral adrenal hyperplasia.

Epidemiology

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathophysiology

Autonomous aldosterone secretion and hypertension

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

Hypokalemia and metabolic alkalosis

Clinical features

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

Diagnostics

Approach [5]

Screening tests

Plasma aldosterone concentration to plasma renin activity (PAC/PRA ratio)

The PAC/PRA ratio is used to detect primary hyperaldosteronism.

Confirmatory tests

Oral sodium loading test

  • Procedure
    • High-sodium diet (5000 mg) or oral sodium chloride tablets (2 g taken three times daily) for 3 days
    • Followed by 24-hour urine measurements of aldosterone, sodium (to confirm appropriate sodium loading), and creatinine (to assess adequate urine collection)
  • Healthy individuals: RAAS is physiologically suppressed → inhibition of aldosterone secretion
  • Primary hyperaldosteronism: failure to suppress aldosterone secretion (high urine aldosterone > 12 mcg/day and urine sodium > 200 mEq)

Saline infusion test

  • Procedure: infusion of 2 L of normal saline over 4 hours
  • Healthy individuals: RAAS is physiologically suppressed → inhibition of aldosterone secretion to plasma concentration < 5 ng/dL (139 pmol/L)
  • Primary hyperaldosteronism: failure to suppress aldosterone secretion (PAC > 10 ng/dL, or 277 pmol/L)

Fludrocortisone suppression test

  • Procedure: administration of fludrocortisone (0.1 mg every 6 h) for a duration of 4 days (with simultaneous replacement of sodium chloride and potassium)
  • Healthy individuals: RAAS is physiologically suppressed → substantial decrease of aldosterone < 50 ng/mL or ≤ 6 ng/dL (measured in upright position at 10am on day 4)
  • Primary hyperaldosteronism: Failure to suppress the aldosterone secretion (serum levels > 50–60 ng/mL or > 6 ng/dL)

Captopril suppression test [6]

  • Procedure: PRA and PAC are measured at baseline and 2 hours after administration of a single dose of captopril (25–50 mg).
  • Healthy individuals: RAAS is physiologically suppressed → inhibition of aldosterone secretion (more than 30% suppression from baseline)
  • Primary hyperaldosteronism: failure to suppress the aldosterone secretion (less than 30% suppression from baseline)

Imaging

Adrenal CT

  • Initial test to identify the cause of biochemically confirmed primary hyperaldosteronism
  • Allows exclusion or detection of carcinoma and differentiation of bilateral adrenal hyperplasia from unilateral adrenal adenoma

Adrenal venous sampling

  • Overview
    • Standard for differentiating between unilateral adenoma and bilateral hyperplasia
    • Administered if surgical treatment of primary hyperaldosteronism is desired
  • Procedure: PAC measured via catheter in blood from right adrenal vein, left adrenal vein, and inferior vena cava
    • Four-fold increase in PAC compared with the contralateral side is suggestive of unilateral disease
    • Small or no difference in PAC between the two sides (i.e. PAC is bilaterally elevated) is suggestive of bilateral hyperplasia

Differential diagnoses

Secondary hyperaldosteronism

Pseudohyperaldosteronism

The differential diagnoses listed here are not exhaustive.

Treatment

Bilateral adrenal hyperplasia

Unilateral autonomous aldosterone secretion (e.g., adenoma, unilateral hyperplasia, carcinoma)

  • 1. Fagugli RM, Taglioni C. Changes in the Perceived Epidemiology of Primary Hyperaldosteronism. International Journal of Hypertension. 2011; 2011: pp. 1–7. doi: 10.4061/2011/162804.
  • 2. Woo K, Waisman J, Melamed J, Lepor H. Primary aldosteronism caused by unilateral adrenal hyperplasia. Rev Urol. 2000; 2(2): pp. 100–4. pmid: 16985748.
  • 3. Funder JW. Primary Aldosteronism. Hypertension. 2019; 74(3): pp. 458–466. doi: 10.1161/hypertensionaha.119.12935.
  • 4. 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): pp. 215–222. doi: 10.1172/jci10366.
  • 5. 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): pp. 1889–1916. doi: 10.1210/jc.2015-4061.
  • 6. Ergin AB, Hamrahian AH, Kennedy AL, Gupta MK. Captopril Challenge Test. Springer International Publishing; 2015: pp. 67–70.
last updated 11/11/2020
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