From the Guidelines
Familial hyperaldosteronism should be treated with aldosterone antagonists, such as spironolactone or eplerenone, to reduce morbidity and mortality associated with excessive aldosterone production. The most recent and highest quality study, published in 2024 1, recommends the use of mineralocorticoid receptor antagonists (MRAs) as the primary treatment for primary aldosteronism, including familial hyperaldosteronism.
Treatment Options
- Spironolactone, starting at 25-100 mg daily, is a commonly used MRA for treating familial hyperaldosteronism.
- Eplerenone, starting at 25-50 mg daily, is an alternative MRA that can be used, especially in patients who experience side effects with spironolactone.
- For type I familial hyperaldosteronism (glucocorticoid-remediable aldosteronism), low-dose glucocorticoids like dexamethasone (0.125-0.25 mg nightly) or prednisone (2.5-5 mg daily) can suppress aldosterone production.
Diagnosis and Screening
- The aldosterone:renin activity ratio is the most accurate and reliable means of screening for primary aldosteronism, including familial hyperaldosteronism 1.
- Genetic testing is recommended for family members of affected individuals to identify those at risk of developing familial hyperaldosteronism.
Management and Monitoring
- Blood pressure management often requires additional antihypertensive medications, such as calcium channel blockers or ACE inhibitors.
- Potassium supplementation may be necessary to correct hypokalemia.
- Regular monitoring of blood pressure, serum electrolytes, and plasma renin activity is essential for treatment adjustment.
- The condition results from genetic mutations affecting aldosterone synthesis, with type I caused by a chimeric gene fusing regulatory elements of 11β-hydroxylase to aldosterone synthase, causing ACTH-regulated aldosterone production instead of the normal renin-angiotensin system regulation.
The use of MRAs, such as spironolactone or eplerenone, has been shown to improve outcomes in patients with primary aldosteronism, including reduced morbidity and mortality 1. Therefore, treatment with MRAs should be initiated as soon as possible to reduce the risk of cardiovascular complications associated with familial hyperaldosteronism.
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).
The question about Familial hyperaldosteronism is not directly addressed in the provided drug labels 2 and 2. The labels discuss Primary Hyperaldosteronism but do not specifically mention Familial hyperaldosteronism. Therefore, no conclusion can be drawn about the use of spironolactone for Familial hyperaldosteronism based on the provided information.
From the Research
Definition and Forms of Familial Hyperaldosteronism
- Familial hyperaldosteronism is a rare genetic disorder characterized by the overproduction of aldosterone, leading to hypertension and hypokalaemia 3.
- There are three known variants of familial hyperaldosteronism: type I, type II, and type III, each with distinct genetic and clinical characteristics 4.
Genetic Causes and Inheritance
- Familial hyperaldosteronism type I is caused by a hybrid gene mutation formed by a crossover of genetic material between the 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, leading to ACTH-regulated aldosterone secretion 3, 5.
- Familial hyperaldosteronism type II is characterized by autosomal dominant inheritance of autonomous aldosterone hypersecretion, but the precise genetic cause remains to be elucidated 3, 5.
- The genetic causes of familial hyperaldosteronism type III are still being researched 4.
Clinical Characteristics and Diagnosis
- Patients with familial hyperaldosteronism often present with early-onset hypertension and severe target organ damage 4.
- Diagnosis is based on a combination of clinical evaluation, laboratory tests, and genetic analysis, including the plasma aldosterone:plasma renin activity ratio and genetic testing for hybrid gene mutations 6, 5.
- A sound family history is essential to discover the Mendelian pattern of inheritance and identify affected family members 4.
Treatment and Management
- Treatment of familial hyperaldosteronism type I involves glucocorticoid therapy, which can suppress aldosterone production and correct hypertension, but only partial suppression of ACTH is required to achieve this effect 7.
- The treatment approach for familial hyperaldosteronism types II and III is still being researched, but early identification and treatment can potentially cure or specifically treat the condition 4.