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-sensitive wild-type aldosterone synthase genes and the ACTH-sensitive hybrid 11 beta-hydroxylase/aldosterone synthase gene by examining aldosterone, PRA, and cortisol day-curves (2-hourly levels over 24 h) in patients 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 strongly with cortisol (r = 0.69-0.99). Fourteen studies were performed on 10 patients receiving glucocorticoid treatment that corrected hypertension, hypokalemia, and PRA suppression in all. ACTH was markedly and continuously suppressed in 6 studies, 3 of which demonstrated strong correlations between aldosterone and PRA (r = 0.77-0.92). ACTH was only partially suppressed in the remaining 8 studies; aldosterone correlated strongly: 1) with cortisol alone in 5 (r = 0.71-0.98); 2) with cortisol (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 markedly and continuously suppressed, aldosterone is more responsive to ACTH than to renin/angiotensin II, despite the latter being unsuppressed. This is consistent with the hybrid gene being more powerfully expressed than the wild-type aldosterone synthase genes in familial hyperaldosteronism type I.
Stowasser
M
M
University Department of Medicine, Greenslopes Hospital, Brisbane, Australia.
Gartside
M G
MG
Taylor
W L
WL
Tunny
T J
TJ
Gordon
R D
RD
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology*; D002648:Child; D002940:Circadian Rhythm; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011187:Posture; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*
D005938:Glucocorticoids; D000804:Angiotensin II; C038135:18-oxocortisol; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D012083:Renin; D011188:Potassium; D006854:Hydrocortisone