PRODUCTION OF 18-OXO-CORTISOL IN SUBTYPES OF PRIMARY ALDOSTERONISM

1. In familial hyperaldosteronism type I(FH-I), expression of an adren ocorticotropic hormone (ACTH)-dependent hybrid 11 beta-hydroxylase/ald osterone synthase gene causes excessive 'hybrid steroid' (18-hydroxy- and Il-oxo-cortisol) production, In order to study the mechanism of el evated 'hybrid steroid' levels in angiotensin-unresponsive (AII-U) ald osterone-producing adenoma (APA), we compared responses of 24 h urinar y Ig-oxo-cortisol, aldosterone and cortisol to dexamethasone (0.5 mg q 6h for 4 days) in 11 FH-I patients, If patients with AII-U APA, II pat ients with AII-responsive (AII-R) APA and 10 patients with bilateral a drenal hyperplasia (BAH), 2. Consistent, marked suppression (by at lea st 60%) of 18-oxo-cortisol levels by dexamethasone was seen in all gro ups except AII-U APA, Aldosterone levels were consistently suppressed to undetectable levels only in FH-1, Cortisol levels were suppressed t o undetectable levers in all patients except two with AII-U APA, 3. Pr oduction of both 18-oxo-cortisol and aldosterone (and occasionally cor tisol) in AII-U APA appears relatively ACTH-independent, consistent wi th 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.