Familial hyperaldosteronism

Familial hyperaldosteronism (FH) is a group of inherited disorders characterized by excessive production of the hormone aldosterone by the adrenal glands. Aldosterone is a key regulator of blood pressure and electrolyte balance, and its overproduction leads to primary aldosteronism (also known as Conn syndrome when sporadic). The condition primarily affects the cardiovascular and renal systems, causing early-onset and often severe hypertension (high blood pressure), low potassium levels (hypokalemia), and metabolic alkalosis. Over time, uncontrolled hyperaldosteronism can lead to serious complications including left ventricular hypertrophy, stroke, kidney damage, and increased cardiovascular morbidity. Familial hyperaldosteronism encompasses several subtypes. FH type I (also called glucocorticoid-remediable aldosteronism, or GRA) is caused by a chimeric CYP11B1/CYP11B2 gene and is uniquely responsive to suppression with exogenous glucocorticoids such as dexamethasone. FH type II is linked to mutations in the CLCN2 gene encoding a chloride channel. FH type III is caused by gain-of-function mutations in the KCNJ5 gene, which encodes a potassium channel, and can present with massive adrenal hyperplasia and severe hypertension in childhood. FH type IV is associated with mutations in the CACNA1H gene encoding a calcium channel. Diagnosis involves measurement of the aldosterone-to-renin ratio, confirmatory testing, genetic analysis, and adrenal imaging. Treatment varies by subtype: FH type I responds to low-dose glucocorticoids (dexamethasone) and/or mineralocorticoid receptor antagonists such as spironolactone or eplerenone. Other subtypes are managed primarily with mineralocorticoid receptor antagonists and antihypertensive medications. In severe cases, particularly FH type III with bilateral adrenal hyperplasia refractory to medical therapy, bilateral adrenalectomy may be considered. Early diagnosis and treatment are essential to prevent long-term cardiovascular and renal complications.

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