What is the best management approach for primary aldosteronism?

From the Guidelines

The best management approach for primary aldosteronism is to first determine the subtype, with surgical removal (adrenalectomy) recommended for unilateral disease and medical therapy for bilateral disease, as stated in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Key Considerations

• For patients with unilateral aldosterone-producing adenoma, laparoscopic adrenalectomy is the treatment of choice as it can cure or significantly improve hypertension and normalize potassium levels in most patients.
• For bilateral adrenal hyperplasia, medical therapy with mineralocorticoid receptor antagonists is recommended, typically starting with spironolactone at 12.5-25 mg daily and titrating up to 100-400 mg daily as needed based on blood pressure response and potassium levels.
• Eplerenone (50-100 mg twice daily) is an alternative with fewer anti-androgenic side effects but less potency, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Diagnosis and Screening

• The aldosterone:renin activity ratio is currently the most accurate and reliable means of screening for primary aldosteronism, with a cutoff value of 30 when plasma aldosterone concentration is reported in nanograms per deciliter (ng/dL) and plasma renin activity in nanograms per milliliter per hour (ng/mL/h) 1.
• Patients should have unrestricted salt intake, serum potassium in the normal range, and mineralocorticoid receptor antagonists (e.g., spironolactone or eplerenone) withdrawn for at least 4 weeks before testing 1.

Treatment Monitoring

• Treatment should be monitored with regular blood pressure measurements, serum potassium levels, and renal function tests.
• Dietary sodium restriction enhances the effectiveness of both surgical and medical approaches.
• Patients should also be evaluated for target organ damage such as left ventricular hypertrophy and albuminuria, as primary aldosteronism causes cardiovascular and renal damage beyond what would be expected from hypertension alone, as highlighted in the guideline-driven management of hypertension: an evidence-based update 1.

From the FDA Drug Label

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). 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 best management approach for primary aldosteronism includes:

• Short-term preoperative treatment with spironolactone tablets in doses of 100 mg to 400 mg daily
• Long-term maintenance therapy with spironolactone tablets at the lowest effective dosage for patients who are not candidates for surgery, including those with:
  • Discrete aldosterone-producing adrenal adenomas
  • Bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism) 2 2

From the Research

Diagnosis and Treatment of Primary Aldosteronism

The management of primary aldosteronism involves a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management 3. The goals of treatment are to normalize both blood pressure and excessive aldosterone production, and the primary aims are to reduce associated comorbidities, improve quality of life, and reduce mortality.

Treatment Approaches

• For unilateral disease, surgery offers the possibility of cure, with total laparoscopic unilateral adrenalectomy being the treatment of choice 3, 4.
• Bilateral forms are treated mainly with mineralocorticoid receptor antagonists 3, 5, 4.
• Mineralocorticoid receptor antagonists (MRAs) are currently recommended for PA patients with bilateral adrenal disease, but these agents effectively decrease blood pressure also in patients with unilateral disease 5.
• New therapeutic approaches include routine screening on first presentation for hypertension, harmonisation of cut-offs for renin and aldosterone, and adoption of a dexamethasone enhanced seated saline suppression test for confirmation exclusion 6.

Management Considerations

• Adrenal venous sampling is key for reliable subtype identification, but can be bypassed in patients with specific characteristics 3, 7.
• Genetic testing for inherited forms in suspected cases of familial hyperaldosteronism avoids the burdensome diagnostic investigation in positive patients 3.
• The start of medication should be closely monitored by serum electrolyte and creatinine controls 4.
• Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism 7.