Ovarian steroidogenic responses to gonadotropin-releasing hormone agonist testing with nafarelin in hirsute women with adrenal responses to adrenocorticotropin suggestive of 3β-hydroxy-Δ5-steroid dehydrogenase deficiency

Randall B. Barnes*, David A. Ehrmann, Deborah F. Brigell, Robert L. Rosenfield

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Nonclassical 3 beta-hydroxy-Δ5-steroid dehydrogenase (3 β-HSD) deficiency type of congenital adrenal hyperplasia has been hypothesized to occur in as many as 10-40% of hirsute women, based on the adrenal steroidogenic responses to ACTH. However, diagnostic criteria for this "late-onset" 3 β-HSD deficiency are not clearly established. Among 40 successive hyperandrogenic women undergoing evaluation of adrenal steroidogenic responses to ACTH, 8 had responses suggestive of 3 β-HSD deficiency. Since 3 β-HSD is present in both the ovary and adrenal, we attempted to document the defect in the ovary by stimulating their ovarian function with a gonadotropin-releasing hormone agonist test using nafarelin (6-D-[2-naphthyl]alanine-gonadotropin-releasing hormone). The eight hirsute women had steroid responses to ACTH suggestive of 3 β-HSD deficiency, namely, the values of the Δ5-steroids, 17-hydroxypregnenolone and dehydroepiandrosterone, 30 and 60 min after ACTH in each hirsute woman were greater than 2 SD above the normal mean. Seven of the eight hirsute women had at least one elevated Δ54-steroid ratio; however, only three of the hirsute women had two abnormal ratios. Furthermore, the response of the Δ4-steroid androstenedione and the ratio of androstenedione to cortisol after ACTH were significantly increased in the hirsute women, findings not consistent with 3 β-HSD deficiency. After nafarelin, five and six hirsute patients had elevated values of the Δ4-steroids androstenedione and 17-hydroxyprogesterone, respectively. No patient had an elevated Δ54-steroid ratio after nafarelin. Thus, ovarian steroidogenic responses to nafarelin did not support the diagnosis of 3 β-HSD deficiency. Rather, they are consistent in most cases with polycystic ovary syndrome due to dysregulation of 17-hydroxylase and 17,20-lyase activities. We propose that increased activity of the enzyme P450c17 alpha in the adrenal cortex is responsible for most of what is often termed late-onset 3 β-HSD deficiency.

Original languageEnglish (US)
Pages (from-to)450-455
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume76
Issue number2
DOIs
StatePublished - Feb 1993

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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