Adrenal cortex, tumor, and peripheral production of deoxycorticosterone

A method is reported for the measurement of the urine excretion rates of tetrahydro-11-deoxycorticosterone (3 alpha,5 beta-THDOC), an important metabolite of 11-deoxycorticosterone (DOC). Quantification using gas chromatography/mass spectrometry (GC/MS) was achieved by comparing the ion fragment response for the molecular ion (m/z 507) of the analyte (as methyloxime trimethylsilyl ether derivative) to that of a fixed amount of an isomer of THDOC added to urine as internal standard. To improve the specificity of measuring THDOC in clinical samples, an additional Sephadex LH-20 chromatography step was introduced to separate 11-deoxycortisol and some progesterone metabolites. In the luteal phase of the menstrual cycle, THDOC excretion was higher than in the follicular phase; it was also higher than in women taking oral contraceptives. The correlation of THDOC with progesterone production, independent of a constant cortisol output, supports an ovarian or peripheral conversion of progesterone to DOC. The assay proved useful (1) in monitoring for the recurrence of a mineralocorticoid-secreting tumor and (2) when adrenal production of DOC was not fully suppressed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Under the latter circumstances, the renin-angiotensin system seemed to be an important regulator of DOC production.