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Abnormalities of 21-hydroxylase gene ratio and adrenal steroidogenesis in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to acute adrenal stimulation.
J Clin Endocrinol Metab. 1991 Dec; 73(6):1327-31.JC

Abstract

One to 2% of hyperandrogenic women demonstrate a 17-hydroxyprogesterone (17-HP) level greater than 36.3 nmol/L (1200 ng/dL) after acute ACTH-(1-24) adrenal stimulation, consistent with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia (LOAH). The following study was undertaken to endocrinologically and genetically define hyperandrogenic patients with an exaggerated 17-HP response to ACTH stimulation, and which do not represent LOAH. Of 265 consecutive patients suffering from hirsutism and/or hyperandrogenic oligomenorrhea, 23 (8.7%) demonstrated a 17-HP level 30 min post stimulation greater than 9.6 nmol/L or 316 ng/dL (the upper 95th percentile in 41 eumenorrheic nonhirsute healthy control women). Seven patients or five separate families (1.8% of total) demonstrated poststimulation 17-HP levels consistent with LOAH. Of the remaining 16 patients, the net increment in 17-HP (delta 17-HP0-30) was within normal limits in seven (2.6%) and these women were assumed to have a normal 17-HP adrenocortical response superimposed on an elevated basal level of nonadrenal (e.g. ovarian) origin. In the remaining nine hyperandrogenic patients (3.4%) various abnormalities of adrenal response were noted in all but one patient, consistent with adrenal hyper-responsiveness. One patient demonstrated an 11-deoxycortisol poststimulation level greater than 3-fold the upper 95th percentile of normal, consistent with 11-hydroxylase LOAH and was excluded from further study. Six of these women were available for further genetic characterization, all Caucasian and unrelated. Three were heterozygotes for HLA-B14, three for B40, and one for B35 antigen, HLA-types associated with the inheritance of 21-OH deficiencies. Although, normally there are two 21-OH genes (a pseudogene and a functional gene) present in a 1:1 ratio, we have previously reported a high frequency of 21-OH gene ratio abnormalities in LOAH. All but one of our patients demonstrated an abnormal 21-OH gene ratio. In conclusion, 3.4% of our hyperandrogenic population demonstrated an exaggerated 17-HP increment after ACTH stimulation, not consistent with LOAH or increased extraadrenal 17-HP production. The increased prevalence of HLA alleles known to be linked to inherited defects of 21-OH function and the increased frequency in 21-OH gene ratio abnormalities suggest that a majority of these individuals may be carriers for these genetic disorders. However, the adrenocortical abnormalities noted were more consistent with a generalized hyperreactivity of the adrenal to ACTH stimulation, than a specific enzyme deficiency, implying that carrier status for 21-OH deficiency may be incidental to the hyperandrogenism.

Authors+Show Affiliations

Azziz R
Department of Obstetrics and Gynecology, University of Alabama, Birmingham 35294.
Wells G
No affiliation info available
Zacur HA
No affiliation info available
Acton RT
No affiliation info available

MeSH

17-alpha-HydroxyprogesteroneAdrenal Cortex HormonesAdrenal GlandsAdultAndrogensCosyntropinFemaleGenesHirsutismHumansHydroxyprogesteronesHyperplasiaOligomenorrheaSteroid 21-Hydroxylase

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1955515

Citation

Azziz, R, et al. "Abnormalities of 21-hydroxylase Gene Ratio and Adrenal Steroidogenesis in Hyperandrogenic Women With an Exaggerated 17-hydroxyprogesterone Response to Acute Adrenal Stimulation." The Journal of Clinical Endocrinology and Metabolism, vol. 73, no. 6, 1991, pp. 1327-31.
Azziz R, Wells G, Zacur HA, et al. Abnormalities of 21-hydroxylase gene ratio and adrenal steroidogenesis in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to acute adrenal stimulation. J Clin Endocrinol Metab. 1991;73(6):1327-31.
Azziz, R., Wells, G., Zacur, H. A., & Acton, R. T. (1991). Abnormalities of 21-hydroxylase gene ratio and adrenal steroidogenesis in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to acute adrenal stimulation. The Journal of Clinical Endocrinology and Metabolism, 73(6), 1327-31.
Azziz R, et al. Abnormalities of 21-hydroxylase Gene Ratio and Adrenal Steroidogenesis in Hyperandrogenic Women With an Exaggerated 17-hydroxyprogesterone Response to Acute Adrenal Stimulation. J Clin Endocrinol Metab. 1991;73(6):1327-31. PubMed PMID: 1955515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Abnormalities of 21-hydroxylase gene ratio and adrenal steroidogenesis in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to acute adrenal stimulation. AU - Azziz,R, AU - Wells,G, AU - Zacur,H A, AU - Acton,R T, PY - 1991/12/1/pubmed PY - 1991/12/1/medline PY - 1991/12/1/entrez SP - 1327 EP - 31 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 73 IS - 6 N2 - One to 2% of hyperandrogenic women demonstrate a 17-hydroxyprogesterone (17-HP) level greater than 36.3 nmol/L (1200 ng/dL) after acute ACTH-(1-24) adrenal stimulation, consistent with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia (LOAH). The following study was undertaken to endocrinologically and genetically define hyperandrogenic patients with an exaggerated 17-HP response to ACTH stimulation, and which do not represent LOAH. Of 265 consecutive patients suffering from hirsutism and/or hyperandrogenic oligomenorrhea, 23 (8.7%) demonstrated a 17-HP level 30 min post stimulation greater than 9.6 nmol/L or 316 ng/dL (the upper 95th percentile in 41 eumenorrheic nonhirsute healthy control women). Seven patients or five separate families (1.8% of total) demonstrated poststimulation 17-HP levels consistent with LOAH. Of the remaining 16 patients, the net increment in 17-HP (delta 17-HP0-30) was within normal limits in seven (2.6%) and these women were assumed to have a normal 17-HP adrenocortical response superimposed on an elevated basal level of nonadrenal (e.g. ovarian) origin. In the remaining nine hyperandrogenic patients (3.4%) various abnormalities of adrenal response were noted in all but one patient, consistent with adrenal hyper-responsiveness. One patient demonstrated an 11-deoxycortisol poststimulation level greater than 3-fold the upper 95th percentile of normal, consistent with 11-hydroxylase LOAH and was excluded from further study. Six of these women were available for further genetic characterization, all Caucasian and unrelated. Three were heterozygotes for HLA-B14, three for B40, and one for B35 antigen, HLA-types associated with the inheritance of 21-OH deficiencies. Although, normally there are two 21-OH genes (a pseudogene and a functional gene) present in a 1:1 ratio, we have previously reported a high frequency of 21-OH gene ratio abnormalities in LOAH. All but one of our patients demonstrated an abnormal 21-OH gene ratio. In conclusion, 3.4% of our hyperandrogenic population demonstrated an exaggerated 17-HP increment after ACTH stimulation, not consistent with LOAH or increased extraadrenal 17-HP production. The increased prevalence of HLA alleles known to be linked to inherited defects of 21-OH function and the increased frequency in 21-OH gene ratio abnormalities suggest that a majority of these individuals may be carriers for these genetic disorders. However, the adrenocortical abnormalities noted were more consistent with a generalized hyperreactivity of the adrenal to ACTH stimulation, than a specific enzyme deficiency, implying that carrier status for 21-OH deficiency may be incidental to the hyperandrogenism. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/1955515/Abnormalities_of_21_hydroxylase_gene_ratio_and_adrenal_steroidogenesis_in_hyperandrogenic_women_with_an_exaggerated_17_hydroxyprogesterone_response_to_acute_adrenal_stimulation_ DB - PRIME DP - Unbound Medicine ER -