Hyperandrogenism and manifesting heterozygotes for 21-hydroxylase deficiency

Selma F. Witchel, Peter Lee, Makiko Suda-Hartman, Eric P. Hoffman

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Premature adrenarche and functional adolescent androgen excess are common disorders which may evolve into polycystic ovary syndrome (PCOS). In all three disorders, ACTH-stimulated 17-hydroxyprogesterone concentrations are often somewhat elevated. To determine the role of 21-hydroxylase (CYP21) gene mutations in these disorders, we performed molecular genotype analysis on 48 children and adolescents referred for evaluation of hyperandrogenic findings and diagnosed as having premature adrenarche or functional androgen excess. For comparison, DNA samples from 80 healthy adults were genotyped. Seventeen of the 48 hyperandrogenic patients were found to be heterozygotic carriers of CYP21 mutations. The frequency of heterozygosity was significantly greater among symptomatic patients (35%) than among the healthy controls (6%), P < 0.001. Seven mutation-positive patients (50%) and only one mutation-negative patient had ACTH-stimulated 17-hydroxyprogesterone concentrations typical for heterozygotic carriers of 21-hydroxylase deficiency, 400-1000 ng/d1. The significant difference in heterozygote frequency between symptomatic patients and healthy controls suggests that heterozygosity for 21-hydroxylase deficiency may be associated with premature adrenarche and functional adolescent hyperandrogenism. Longitudinal studies are necessary to determine if heterozygosity for 21-hydroxylase deficiency predicts risk for PCOS.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalBiochemical and Molecular Medicine
Volume62
Issue number2
DOIs
StatePublished - Jan 1 1997

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Hyperandrogenism
Steroid 21-Hydroxylase
Adrenarche
Heterozygote
17-alpha-Hydroxyprogesterone
Mutation
Adrenocorticotropic Hormone
Androgens
Polycystic Ovary Syndrome
Genes
Longitudinal Studies
Genotype
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Witchel, Selma F. ; Lee, Peter ; Suda-Hartman, Makiko ; Hoffman, Eric P. / Hyperandrogenism and manifesting heterozygotes for 21-hydroxylase deficiency. In: Biochemical and Molecular Medicine. 1997 ; Vol. 62, No. 2. pp. 151-158.
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Hyperandrogenism and manifesting heterozygotes for 21-hydroxylase deficiency. / Witchel, Selma F.; Lee, Peter; Suda-Hartman, Makiko; Hoffman, Eric P.

In: Biochemical and Molecular Medicine, Vol. 62, No. 2, 01.01.1997, p. 151-158.

Research output: Contribution to journalArticle

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