How to work up hyperaldosteronism (Hyperaldosteronism)?

From the Guidelines

To work up hyperaldosteronism, start with screening by measuring plasma aldosterone concentration (PAC) and plasma renin activity (PRA) or direct renin concentration in the morning from a seated patient, calculating the aldosterone-to-renin ratio (ARR) with a cutoff value of >30 ng/dL per ng/mL/h, as recommended by the most recent guidelines 1. The diagnosis of primary aldosteronism requires a stepwise approach, beginning with screening, followed by confirmatory testing, and ultimately, localization of the source of aldosterone excess.

• Before testing, it is essential to discontinue interfering medications, such as spironolactone, eplerenone, and amiloride for 4-6 weeks; ACE inhibitors, ARBs, and diuretics for 2 weeks; and beta-blockers, central alpha-2 agonists, and NSAIDs for 1-2 weeks, to ensure accurate results 1.
• The aldosterone-to-renin ratio (ARR) is the most accurate and reliable means of screening for primary aldosteronism, with a ratio >30 ng/dL per ng/mL/h suggesting primary hyperaldosteronism, as long as the plasma aldosterone concentration is at least 10 ng/dL 1.
• If the ARR is elevated, confirmation with a suppression test, such as oral sodium loading, saline infusion, fludrocortisone suppression, or captopril challenge, is necessary to establish the diagnosis of primary aldosteronism 1.
• Once confirmed, adrenal imaging with CT or MRI can help identify adrenal adenomas, and for patients considering surgery, adrenal vein sampling is recommended to determine if aldosterone production is unilateral (suggesting an adenoma) or bilateral (suggesting hyperplasia) 1. The management of primary aldosteronism depends on its subtype, with unilateral forms being amenable to surgical treatment and bilateral forms requiring lifelong medical treatment with mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone 1.
• The effective dose of spironolactone can be titrated up to 300–400 mg once daily, if necessary, while eplerenone is also used, despite being less potent and requiring twice-daily administration, with the advantage of causing less gynaecomastia and erectile dysfunction in men 1.
• Newer agents, such as finerenone and exarenone, and the aldosterone synthase inhibitor baxdrostat, are being tested for treating primary aldosteronism, offering potential alternative treatment options in the future 1.

From the FDA Drug Label

2.5 Treatment of Primary Hyperaldosteronism Administer spironolactone tablets in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone tablets can be used as long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

The workup for Primary Hyperaldosteronism involves administering spironolactone in doses of 100 mg to 400 mg daily. This can be used for:

• Preparation for surgery
• Long-term maintenance therapy for patients who are not candidates for surgery, at the lowest effective dosage determined for the individual patient 2.

Key points to consider:

• Diagnosis and treatment of primary hyperaldosteronism may involve spironolactone therapy.
• Dosing should be individualized based on patient response and tolerance.
• Monitoring for potential side effects, such as hyperkalemia, is essential when using spironolactone 2.

From the Research

Diagnostic Approach

To work up hyperaldosteronism, it is essential to understand the underlying causes and the appropriate treatment options.

Treatment Options

• For aldosterone-producing adenoma and unilateral adrenal hyperplasia, endoscopic adrenalectomy is the treatment of choice 3, 4.
• For bilateral adrenal hyperplasia, mineralocorticoid receptor antagonists such as spironolactone (starting dose 12.5-25mg/day with titration up to 100mg/day) or eplerenone (50-100mg/day) are the primary treatment options 3, 4, 5.
• If blood pressure is not normalized by first-line treatment, additional treatment with potassium-sparing diuretics (such as amiloride or triamterene), calcium channel antagonists, or ACE inhibitors may be necessary 3, 4, 6.
• However, the use of ACE inhibitors in primary aldosteronism is debated, and some studies suggest that they may not be effective in lowering blood pressure in patients with low renin levels 7.

Monitoring and Follow-up

• The start of medication should be closely monitored by serum electrolyte and creatinine controls 3, 4.
• Regular follow-up is necessary to adjust the treatment regimen and to monitor for potential side effects of medication.