Corticosteroids are major contributors to normal blood pressure control and to hypertension. The diagnosis of 'primary aldosteronism' based on raised aldosterone: renin ratios is now common although demonstration of an adrenocortical tumour remains rare. Moreover, the relationship between aldosterone and renin or angiotensin II in essential hypertension is often disturbed, suggestive of altered control of aldosterone biosynthesis. Aldosterone is synthesised from 11-deoxycorticosterone via a multistage pathway in which corticosterone and 18-hydroxycorticosterone are putative intermediates. In addition, in certain types of mineralocorticoid excess, levels of 18-hydroxycortisol (18-OHF) and 18-oxoF are raised. Variability in the efficiencies of these stages of synthesis is most conveniently evaluated in human subjects using the excretion rates of unique metabolites. To this end, a convenient method of profiling based on GCMS of their trimethyl silyl- methoxy-derivatives has been developed. In 31 normal volunteers (20 males, 11 females; ages 11-65 years), the following excretion rates (nmol/24h, mean±SEM) were obtained: aldosterone: 27±2; tetrahydro(TH)aldosterone: 116±14; THcorticosterone (THB): 414±74; alloTHB: 765±66; 18-OHB: 29±2.7; 18-OH-TH-11-dehydroB: 203±29; 18OHF: 108±13; 18-oxoF: 17±2. The simultaneous evaluation of these compounds will facilitate assessment of aldosterone metabolism in large population samples and will allow comparison with genetic variations in aldosterone synthase.
08 - 11 Apr 2002
British Endocrine Societies