19-nordeoxycorticosterone and Adrenal-Hyperplasia--Congenital

17 alpha-hydroxylase deficiency syndrome (17-OHDS) is associated with hypogonadism, hypertension, and hypokalemia. Aldosterone production, however, is not elevated, and therefore, other known or unknown mineralocorticoids must account for the excess in mineralocorticoid activity. This study sought to determine whether 19-nor-deoxycorticosterone (19-nor-DOC), a potent hypertensinogenic mineralocorticoid, was elevated in this syndrome. Plasma and urine from a young woman with 17-OHDS were examined from various corticosteroids before and after ACTH, dexamethasone, and cortisol administration. In the basal state, urinary and plasma 17-hydroxycorticosteroids were decreased, but 17-deoxycorticosteroids were extremely elevated, including corticosterone (B), 18-hydroxy-B (18-OH-B), tetrahydro-B (TH-B), TH-DOC, and 18-OH-TH-DOC. Basal urinary (UF) 19-nor-DOC measured by both high pressure liquid chromatography (4255 ng/day) and RIA [3800 ng/day; normal, 102 +/- 27 (+/- SD), was markedly elevated. UF 19-nor-DOC did not increase further after ACTH administration (4255 ng/day), but it decreased after both dexamethasone (less than 100 ng/day) and cortisol therapy (612 and 218 ng/day). Basal plasma 19-nor-DOC was elevated and increased after ACTH stimulation (366 pg/ml) and decreased during dexamethasone suppression (6 pg/ml). A plasma 19-nor-DOC precursor that converted to nor-DOC upon acidification (perhaps 19-oic-DOC) also was detectable (172 pg/ml). This study, therefore, demonstrates a marked elevation in UF 19-nor-DOC in 17-OHDS, which could account for some of the excess mineralocorticoid activity in this syndrome.

Topics: Adolescent; Adrenal Hyperplasia, Congenital; Chromatography, High Pressure Liquid; Desoxycorticosterone; Female; Humans; Hypogonadism; Radioimmunoassay; Steroid Hydroxylases

The fraction of urine containing free steroids was analyzed in a specimen obtained from a patient with 17 alpha-hydroxylase deficiency and contained deoxycorticosterone (DOC) (approximately 0.9 micrograms/24 h), 19 nor-DOC (approximately 1.1 micrograms/24 h) and tetrahydro-DOC (approximately 15.2 micrograms/24 h). These steroids were identified by combined gas chromatography/mass spectrometry. If present, tetrahydro-19-nor-DOC was at a concentration below the limits of detection, but it was the major metabolite found in urine of a normal person after ingestion of the steroid. This strongly suggests that little 19-nor-DOC passes through the liver after synthesis and is therefore further evidence that the final stage of its synthesis occurs in the kidney in close proximity to the site of excretion.

Topics: Adrenal Hyperplasia, Congenital; Chromatography, Gas; Desoxycorticosterone; Gas Chromatography-Mass Spectrometry; Humans; Kidney

Tetrahydro-19-nor-deoxycorticosterone (3 alpha, 21-dihydroxy-19-nor-5 beta-pregnan-20-one, a presumed metabolite of 19-nor-DOC was sought in the conjugated steroid fractions of urine from patients with 17 alpha-hydroxylase deficiency syndrome. The reference material was prepared by microbial reduction (Clostridium paraputrificum) of 19-nor-DOC. Urinary steroid fractions of appropriate polarity were examined by high resolution gas chromatography and gas chromatography/mass spectrometry (GC/MS) but no tetrahydro-19-nor-DOC was found. The high selectivity of the GC/MS technique ensured that the excretion of this compound could not exceed about 1% of the excretion of tetrahydroDOC. Assuming that tetrahydro-19-nor-DOC is a major metabolite of 19-nor-DOC, it can be stated that 19-nor-DOC production is not a significant feature of 17 alpha-hydroxylase deficiency. This assumption may not be valid if 19-nor-DOC is formed from DOC in the kidney and is excreted unmetabolized soon after synthesis.

Topics: Adrenal Hyperplasia, Congenital; Chromatography, Gas; Desoxycorticosterone; Gas Chromatography-Mass Spectrometry; Humans; Steroid Hydroxylases; Steroids