Abnormality of Aldosterone and Cortisol Late Pathways in Glucocorticoid-Remediable Aldosteronism.

Patients with glucocorticoid-remediable aldosteronism (GRA) possess
a chimeric gene resulting from fusion of the genes encoding steroid
aldosterone synthase and 11 beta-hydroxylase. In the adrenal zona
fasciculata, this may lead to ectopic expression under ACTH control
of aldosterone synthase activity and increased formation of
cortisol C18 oxidation products. We assessed mineralocorticoid and
glucocorticoid pathways in three patients with GRA. Baseline plasma
progesterone, 17 alpha-hydroxyprogesterone, corticosterone, and
cortisol were normal in all patients, whereas
11-deoxycorticosterone, aldosterone, and 11-deoxycortisol were
above normal. The ratios of both
corticosterone/11-deoxycorticosterone and cortisol/11-deoxycortisol
were abnormally low, and decreased further 60 min after
administration of ACTH-(1-24) (250 micrograms) as an i.v. bolus. A
low corticosterone/11-deoxycorticosterone ratio is consistent with
an increased aldosterone synthase activity forming aldosterone by
corticosterone. Similarly, a decreased cortisol/11-deoxycortisol
ratio could reflect enhanced cortisol C18 oxidation. Our findings
are in agreement with a hyperfunction of the 11
beta-hydroxylase/aldosterone synthase complex in the adrenal zona
fasciculata of GRA induced by the new chimeric gene.