What is the treatment for Primary Aldosteronism (Hyperaldosteronism)?

From the Guidelines

Treatment for primary hyperaldosteronism should be guided by the subtype, with surgical removal of the offending adrenal gland considered for unilateral forms, and mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone as the mainstay of therapy for bilateral forms or when surgery is not possible. The management of primary aldosteronism depends on its subtype, particularly on adrenal lesions being unilateral or bilateral, because the unilateral forms are amenable to surgical treatment while the latter require lifelong medical treatment 1.

Key Considerations

• For unilateral primary aldosteronism, surgical removal of the offending adrenal gland is typically considered, unless the patient is older or has co-morbidities of concern 1.
• Medical treatment is currently based on MRAs, with spironolactone being the most widely available, and its effective dose usually ranging from 50–100 mg once daily, titrated up to 300–400 mg once daily if necessary 1.
• Eplerenone is also used, despite being less potent than spironolactone and requiring twice-daily administration, it has the advantage of causing less gynaecomastia and erectile dysfunction in men 1.
• Newer agents, such as the non-steroidal MRAs finerenone and exarenone, and the aldosterone synthase inhibitor baxdrostat, are also being tested for treating primary aldosteronism 1.

Diagnostic Approach

• The diagnosis of primary aldosteronism generally requires a confirmatory test, such as an intravenous saline suppression test or oral salt-loading test 2.
• Adrenal venous sampling is used to determine whether the increased aldosterone production is unilateral or bilateral in origin 2.
• 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) 2.

Treatment Outcomes

• Unilateral laparoscopic adrenalectomy improves BP in virtually 100% of patients and results in a complete cure of hypertension in about 50% 2.
• Medical therapy with MRAs is effective in lowering BP and reversing left ventricular hypertrophy (LVH) 2.
• Patients should also follow a low-sodium diet and have regular monitoring of blood pressure, serum potassium, and renal function during treatment.

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

• Short-term preoperative treatment
• Long-term maintenance therapy for patients who are not candidates for surgery, including those with: + Discrete aldosterone-producing adrenal adenomas + Bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism) [3] [4].

From the Research

Treatment Options for Hyperaldosteronism

• Adrenalectomy is considered a treatment option for patients with unilateral adrenal disease, such as aldosterone-producing adenoma and unilateral adrenal hyperplasia 5, 6, 7.
• Mineralocorticoid receptor antagonists (MRAs) are recommended as the first-line treatment for patients with bilateral primary aldosteronism, and can also be effective in patients with unilateral disease 5, 8, 7, 9.
• MRAs, such as spironolactone and eplerenone, can improve blood pressure control, reverse left ventricular hypertrophy, albuminuria, and carotid intima-media thickness, and reduce the risk of cardiovascular events and renal disease progression 8, 7, 9.

Medical Treatment

• The starting dose of spironolactone is 12.5-25mg/day, with titration up to 100mg/day, and eplerenone can be started at 50-100mg/day 5.
• Additional treatment with potassium-sparing diuretics, such as amiloride or triamterene, or calcium channel antagonists may be necessary if blood pressure is not normalized by MRAs 5.
• MRAs can be used as a first-line or add-on agent in patients with MR-associated hypertension, which includes primary aldosteronism and other types of hypertension with high aldosterone levels 8.

Special Considerations

• Adrenalectomy may not be the best option for patients with primary aldosteronism during pregnancy, in patients of advanced age, or in hereditary forms of primary aldosteronism, where medical treatment is considered especially indicated as the first line therapy 6.
• The use of MRAs in patients with primary aldosteronism can have significant benefits, but also carries a risk of atrial fibrillation, and requires close monitoring of serum electrolyte and creatinine levels 5, 9.