Familial hyperaldosteronism

Aldosterone, the major circulating mineralocorticoid, participates in blood volume and serum potassium homeostasis, Primary aldosteronism is a disorde r characterised by hypertension and hypokalaemia due to autonomous aldoster one secretion from the adrenocortical zona glomerulosa. Improved screening techniques, particularly application of the plasma aldosterone:plasma renin activity ratio, have led to a suggestion that primary aldosteronism may be more common than previously appreciated among adults with hypertension. Gl ucocorticoid-remediable aldosteronism (GRA) was the first described familia l form of hyperaldosteronism. The disorder is characterised by aldosterone secretory function regulated chronically by ACTH. Hence, aldosterone hypers ecretion can be suppressed, on a sustained basis, by exogenous glucocortico ids such as dexamethasone in physiologic range doses. This autosomal domina nt disorder has been shown to be caused by a hybrid gene mutation formed by a crossover of genetic material between the ACTH-responsive regulatory por tion of the 11 beta -hydroxylase (CYP11B1) gene and the coding region of th e aldosterone synthase (CYP11B2) gene. Familial hyperaldosteronism type II (FH-II), so named to distinguish the disorder from GRA or familial hyperald osteronism type I(FH-I), is characterised by autosomal dominant inheritance of autonomous aldosterone hypersecretion which is not suppressible by dexa methasone. Linkage analysis in a single large kindred, and direct mutation screening, has shown that this disorder is unrelated to mutations in the ge nes for aldosterone synthase or the angiotensin II receptor. The precise ge netic cause of FH-U remains to be elucidated.