Clinical and Biological Phenotypes in Late-Onset 21 Hydroxylase Deficiency
Abstract
We analyzed data from 20 patients with late-onset 21-hydroxylase deficiency (LOHD). Three clinical phenotypes could be distinguished among the 18 women. Seven (39%) presented with clinical features suggesting polycystic ovarian disease (PCOD). However, despite androgen levels similar to those of patients with typical PCOD, high serum LH to FSH ratios were not consistently found. Seven other women (39%) presented with isolated hirsutism, suggesting idiopathic hirsutism. The remaining 4 women (22%) had no manifestations of androgen excess and were considered to have the cryptic form of LOHD. Serum 17-hydroxyprogesterone (17-OHP) and androgen levels were similar in the 3 phenotypes, suggesting that the clinical expression of LOHD in women is modulated by individual factors, such as androgen sensitivity. The 2 men were detected by family study and were clinically normal. Since clinical diagnosis of LOHD is impossible, we concentrated on hormonal data with the aim of providing guidelines for the biological diagnosis of LOHD. Assay of basal serum 17-OHD at 0800 h in both sexes and in the early follicular phase in women was sufficient to establish the diagnosis of LOHD in most patients. If doubtful results are obtained, i.e. serum 17-OHP levels between 2 and 5 ng/ml, an ACTH test must be performed. Post-ACTH serum 17-OHP levels exceeding 10 ng/ml confirm the diagnosis of LOHD. Such results should avoid confusion with heterozygotes for 21-hydroxylase deficiency, whose frequency is high within the general population and may be even higher in patients with idiopathic hirsutism or PCOD.
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Diagnosis of NCCAH due to 21-hydroxylase deficiency is based on elevated baseline and ACTH-stimulated 17-hydroxyprogesterone levels.
“The diagnosis is based on elevated baseline and ACTH-stimulated 17-hydroxyprogesterone (17-OHP) levels.”
From Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche (2011) · cites this paper as [9]
Baseline 17-hydroxyprogesterone levels above 5 ng/ml (15 nmol/l) and ACTH-stimulated values above 10 ng/ml (30 nmol/l) are the established cutoffs for diagnosing NCCAH.
“Baseline 17-OHP levels O5 ng/ml (O15 nmol/l) and ACTH-stimulated 17-OHP values O10 ng/ml (O30 nmol/l) are the cutoffs established for the diagnosis of the disease (8,9).”
From Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche (2011) · cites this paper as [9]
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- Authors
- DEWAILLY, D., VANTYGHEM-HAUDIQUET, M.-C., SAINSARD, C., BUVAT, J., CAPPOEN, J. P., ARDAENS, K., RACADOT, A., LEFEBVRE, J., & FOSSATI, P.
- Affiliations
- Centre Hospitalier Universitaire de Lille (FR)
- ORCID
- DEWAILLY, DIDIER
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1986-08
- Volume
- 63
- Issue
- 2
- Pages
- 418-423
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2075590864
- Cited by
- 151
- References
- 22
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 3
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- congenital adrenal hyperplasia, polycystic ovary syndrome, idiopathic hirsutism, ACTH stimulation test, hyperandrogenism, androgen sensitivity, heterozygotes, women
- MeSH terms
- Adolescent, Adrenal Hyperplasia, Congenital, Adrenocorticotropic Hormone, Adult, Androgens, Follicle Stimulating Hormone, Hirsutism, HLA Antigens, Humans, Hydroxyprogesterones, Luteinizing Hormone, Male, Phenotype, Steroid Hydroxylases, 17-alpha-Hydroxyprogesterone
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