Syndrome of Apparent Mineralocorticoid Excess (SAME)

Syndrome of Apparent Mineralocorticoid Excess (SAME) is a rare genetic condition that affects the body's ability to regulate salt and water balance. It primarily involves the kidneys, which normally control blood pressure by managing sodium and potassium levels. In this syndrome, the body mistakenly acts as if there is too much of a hormone called aldosterone, leading to high blood pressure, low potassium levels, and excessive salt retention. This happens because the enzyme that normally protects the body from excess aldosterone is not working properly. The condition can cause symptoms like muscle weakness, fatigue, and headaches due to these imbalances. Early diagnosis is important to manage the effects on the heart and kidneys.

Syndrome of Apparent Mineralocorticoid Excess (SAME) is an autosomal recessive disorder caused by mutations in the HSD11B2 gene, which encodes the enzyme 11β-hydroxysteroid dehydrogenase type 2. This enzyme normally converts active cortisol to inactive cortisone in the renal tubules, preventing cortisol from inappropriately activating the mineralocorticoid receptor. Loss of enzyme function leads to cortisol-mediated mineralocorticoid receptor activation, mimicking hyperaldosteronism despite low aldosterone levels. Clinically, SAME presents with hypertension, hypokalemia, metabolic alkalosis, and low plasma renin and aldosterone levels. The disorder is significant because it causes severe, early-onset hypertension and can lead to end-organ damage if untreated. It is distinguished from other mineralocorticoid excess states by its unique enzymatic defect and biochemical profile.