What is the workup for primary hyperaldosteronism (Conn's syndrome)?

From the Guidelines

The workup for hyperaldosteronism begins with screening tests in patients with suspected primary aldosteronism, including those with resistant hypertension, hypokalemia, adrenal incidentaloma, or early-onset hypertension, and initial screening involves measuring the aldosterone-to-renin ratio (ARR) while the patient is on a normal salt diet, with an ARR greater than 30 ng/dL per ng/mL/hr considered positive, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Initial Screening

Initial screening for hyperaldosteronism involves measuring the aldosterone-to-renin ratio (ARR) while the patient is on a normal salt diet.

• An ARR greater than 30 ng/dL per ng/mL/hr is considered positive.
• Certain medications can affect results, so ideally, patients should discontinue interfering medications like spironolactone, eplerenone, and amiloride for 4-6 weeks, and beta-blockers, ACE inhibitors, and ARBs for 2 weeks before testing.
• If medication discontinuation isn't feasible, results should be interpreted cautiously.

Confirmation Testing

Confirmation testing follows a positive screen, with options including:

• Oral sodium loading
• Saline infusion
• Captopril challenge
• Fludrocortisone suppression tests

Subtype Differentiation

Once primary aldosteronism is confirmed, subtype differentiation is necessary through:

• Adrenal CT imaging
• Adrenal vein sampling to distinguish between unilateral (typically aldosterone-producing adenoma) and bilateral (idiopathic hyperaldosteronism) disease. This distinction is crucial as unilateral disease may be cured surgically while bilateral disease requires medical management with mineralocorticoid receptor antagonists like spironolactone (starting at 25-50 mg daily) or eplerenone (starting at 25 mg twice daily) 1.

Medical Management

Medical treatment is currently based on MRAs, with spironolactone being the most widely available, and the effective dose can be titrated up to 300–400 mg once daily, if necessary 1. Eplerenone is also used and, despite being less potent than spironolactone and requiring twice-daily administration, it has the advantage of causing less gynaecomastia and erectile dysfunction in men. Newer agents, such as the non-steroidal MRAs finerenone and exarenone, and the aldosterone synthase inhibitor baxdrostat, which lower BP in resistant hypertension, are also being tested for treating primary aldosteronism 1.

From the FDA Drug Label

1. 4 Primary Hyperaldosteronism Spironolactone tablets are indicated in the following settings: Short-term preoperative treatment of patients with primary hyperaldosteronism. Long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).

The workup for primary hyperaldosteronism may involve the use of spironolactone for:

• Short-term preoperative treatment
• Long-term maintenance therapy for patients who are not candidates for surgery or have bilateral micro or macronodular adrenal hyperplasia 2. Key considerations in the workup and treatment of primary hyperaldosteronism include:
• Aldosterone antagonist activity: Spironolactone competes with aldosterone for receptor sites, providing effective therapy for edema and ascites in conditions involving secondary aldosteronism 2.
• Dosage and administration: Spironolactone can be administered in doses of 100 mg to 400 mg daily for short-term preoperative treatment, and at the lowest effective dosage for long-term maintenance therapy 2.

From the Research

Hyperaldosteronism Workup

The workup for hyperaldosteronism typically involves several steps, including screening and diagnostic tests.

• The initial screening test is the aldosterone-to-renin ratio (ARR) 3, 4, 5, 6, 7.
• If the ARR is elevated, confirmatory testing is performed to establish a biochemical diagnosis 3, 4, 5, 6, 7.
• Confirmatory tests may include:
  • Oral salt loading 3
  • Saline infusion 3, 4, 5
  • Captopril challenge 3
  • Fludrocortisone suppression test 3, 4, 5
• Adrenal imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI), may be performed to define the disease subtype 4, 6, 7.
• Adrenal venous sampling (AVS) may be necessary to determine lateralization in patients who are surgical candidates 5, 6, 7.

Diagnosis and Management

The diagnosis of primary aldosteronism (PA) is important, as it can have significant implications for treatment and management.

• PA is a common cause of secondary hypertension, and its diagnosis can lead to targeted treatment and improved outcomes 3, 4, 5, 6, 7.
• The treatment of PA depends on the subtype, with unilateral disease potentially being cured by adrenalectomy, and bilateral disease being treated with mineralocorticoid receptor antagonists 4, 5, 6, 7.
• Medical therapy using optimal doses of mineralocorticoid receptor antagonists can control symptoms and normalize plasma renin activity 7.