Production of 18-oxo-cortisol in subtypes of primary aldosteronism.
1. In familial hyperaldosteronism type I (FH-I), expression of an adrenocorticotropic hormone (ACTH)-dependent hybrid 11 beta-hydroxylase/aldosterone synthase gene causes excessive 'hybrid steroid' (18-hydroxy- and 18-oxo-cortisol) production. In order to study the mechanism of elevated 'hybrid steroid' levels in angiotensin-unresponsive (AII-U) aldosterone-producing adenoma (APA), we compared responses of 24 h urinary 18-oxo-cortisol, aldosterone and cortisol to dexamethasone (0.5 mg q6h for 4 days) in 11 FH-I patients, 11 patients with AII-U APA, 11 patients with AII-responsive (AII-R) APA and 10 patients with bilateral adrenal hyperplasia (BAH). 2. Consistent, marked suppression (by at least 60%) of 18-oxo-cortisol levels by dexamethasone was seen in all groups except AII-U APA. Aldosterone levels were consistently suppressed to undetectable levels only in FH-I. Cortisol levels were suppressed to undetectable levels in all patients except two with AII-U APA. 3. Production of both 18-oxo-cortisol and aldosterone (and occasionally cortisol) in AII-U APA appears relatively ACTH-independent, consistent with a common mechanism involved in the formation of these two steroids from their respective precursors, which differs from that in FH-I. 4. In AII-R APA and BAH, 18-oxo-cortisol production appears markedly ACTH-dependent, but aldosterone production is not.
Stowasser
M
M
Hypertension Unit, Greenslopes Hospital, Brisbane, Queensland, Australia.
Bachmann
A W
AW
Tunny
T J
TJ
Gordon
R D
RD
D000236:Adenoma / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000378:metabolism; D000450:Aldosterone / Q000652:urine; D003907:Dexamethasone; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000652:urine; D006929:Hyperaldosteronism / Q000378:metabolism* / Q000652:urine; D012083:Renin / Q000097:blood
D005938:Glucocorticoids; C038135:18-oxocortisol; D000450:Aldosterone; D003907:Dexamethasone; D012083:Renin; D006854:Hydrocortisone