Familial hyperaldosteronism

Primary aldosteronism (PAL) may be as much as ten times more common than ha s been traditionally thought, with most patients normokalemic. The study of familial varieties has facilitated a fuller appreciation of the nature and diversity of its clinical, biochemical, morphological and molecular aspect s. In familial hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 g ene. Genetic testing has greatly facilitated diagnosis. Hypertension severi ty varies widely, demonstrating relationships with gender, affected parent' s gender, urinary kallikrein level, degree of biochemical disturbance and h ybrid gene crossover point position. Analyses of aldosterone/PRA/cortisol ' day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertens ion in FH-I requires only partial suppression of ACTH, and much smaller glu cocorticoid doses than those previously recommended. Familial hyperaldoster onism type II is not glucocorticoid-remediable, and is clinically, biochemi cally and morphologically indistinguishable from apparently sporadic PAL. I n one informative family available for linkage analysis, FH-II does not seg regate with either the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlie r detection of PAL and other curable or specifically treatable forms of hyp ertension. (C) 2001 Elsevier Science Ltd. All rights reserved.