IN FAMILIAL HYPERALDOSTERONISM TYPE-I, HYBRID GENE-INDUCED ALDOSTERONE PRODUCTION DOMINATES THAT INDUCED BY WILD-TYPE GENES

We compared the aldosterone-producing potency of the angiotensin II-se nsitive wild-type aldosterone synthase genes and the ACTH-sensitive hy brid 11 beta-hydroxylase/aldosterone synthase gene by examining aldost erone, PRA, and cortisol day-curves (2-hourly levels over 24 h) in pat ients with familial hyperaldosteronism type I, before and during long- term (0.8-13.5 yr) glucocorticoid treatment. In 8 untreated patients, PRA levels were usually suppressed, and aldosterone correlated strongl y with cortisol (r = 0.69-0.99). Fourteen studies were performed on 10 patients receiving glucocorticoid treatment that corrected hypertensi on, hypokalemia, and PRA suppression in all. ACTH was markedly and con tinuously suppressed in 6 studies, 3 of which demonstrated strong corr elations between aldosterone and PRA (r = 0.77-0.92), ACTH was only pa rtially suppressed in the remaining 8 studies; aldosterone correlated strongly: 1) with cortisol alone in 5 (r = 0.71-0.98); 2) with cortiso l (r = 0.90) and PRA (r = 0.74) in one; 3) with PRA only in one (r = 0 .80); and 4) with neither PRA nor cortisol in one. Unless ACTH is mark edly and continuously suppressed, aldosterone is more responsive to AC TH than to renin/angiotensin II, despite the latter being unsuppressed . This is consistent with the hybrid gene being more powerfully expres sed than the wild-type aldosterone synthase genes in familial hyperald osteronism type I.