Journal of Clinical Endocrinology & Metabolism, Vol 60, 428-439, Copyright © 1985 by Endocrine Society

ARTICLES

Late-onset adrenal steroid 3 beta-hydroxysteroid dehydrogenase deficiency. I. A cause of hirsutism in pubertal and postpubertal women

SY Pang, AJ Lerner, E Stoner, LS Levine, SE Oberfield, I Engel and MI New

To investigate the adrenal cause of hyperandrogenism in peri- and postpubertal hirsute women, baseline and ACTH-stimulated serum concentrations of delta 5-17-hydroxypregnenolone (delta 5-17P), dehydroepiandrosterone (DHEA) and its sulfate, 17-hydroxyprogesterone (17-OHP), cortisol, delta 4-androstenedione, and testosterone were determined in 116 women with hirsutism or acne of peri- and postpubertal onset with or without menstrual abnormalities. The results were compared with the same steroid concentrations in 30 normal age- matched women. Sixteen of the 116 women with hirsutism whose ACTH- stimulated 17-OHP levels (mean +/- SD, 5404 +/- 3234 ng/dl; normal, 334 +/- 194) were markedly elevated while their ratios of delta 5-17P to 17- OHP (0.4 +/- 0.2; normal, 3.4 +/- 1.5) were low were diagnosed as having nonclassical symptomatic 21-hydroxylase deficiency. Seventeen other hirsute women, including 3 siblings, had very high responses of delta 5-17P (2276 +/- 669 ng/dl; normal, 985 +/- 327) and DHEA (2787 +/- 386 ng/dl; normal, 1050 +/- 384) to ACTH stimulation, with significantly elevated ratios of delta 5-17P to 17-OHP (11 +/- 2.0; normal, 3.4 +/- 1.5) and DHEA to delta 4-androstenedione (7.5 +/- 2.3; normal, 4.6 +/- 1.5). In these hirsute women, the morning serum delta 5- 17P and DHEA concentrations were elevated, had a diurnal variation, and were suppressed with dexamethasone administration. We propose that partial adrenal 3 beta-hydroxysteroid dehydrogenase deficiency is the cause of hirsutism in these women. This may represent an allelic variant at the genetic locus for 3 beta-hydroxysteroid dehydrogenase deficiency similar to that reported for symptomatic nonclassical 21- hydroxylase deficiency producing peripubertal excess androgen syndrome.

This article has been cited by other articles:

				J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family Endocr. Rev., June 1, 2005; 26(4): 525 - 582. [Abstract] [Full Text] [PDF]

				D. Keen-Kim, J. B. Redman, R. U. Alanes, M. M. Eachus, R. C. Wilson, M. I. New, J. M. Nakamoto, and R. G. Fenwick Validation and Clinical Application of a Locus-Specific Polymerase Chain Reaction- and Minisequencing-Based Assay for Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) J. Mol. Diagn., May 1, 2005; 7(2): 236 - 246. [Abstract] [Full Text] [PDF]

				H. F. Escobar-Morreale, M. Luque-Ramirez, and J. L. San Millan The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome Endocr. Rev., April 1, 2005; 26(2): 251 - 282. [Abstract] [Full Text] [PDF]

				T. H. Johannsen, D. Mallet, H. Dige-Petersen, J. Muller, K. M. Main, Y. Morel, and M. G. Forest Delayed Diagnosis of Congenital Adrenal Hyperplasia with Salt Wasting Due to Type II 3{beta}-Hydroxysteroid Dehydrogenase Deficiency J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2076 - 2080. [Abstract] [Full Text] [PDF]

				L. M. Mermejo, L. L. K. Elias, S. Marui, A. C. Moreira, B. B. Mendonca, and M. de Castro Refining Hormonal Diagnosis of Type II 3{beta}-Hydroxysteroid Dehydrogenase Deficiency in Patients with Premature Pubarche and Hirsutism Based on HSD3B2 Genotyping J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1287 - 1293. [Abstract] [Full Text] [PDF]

				G. Carbunaru, P. Prasad, B. Scoccia, P. Shea, N. Hopwood, F. Ziai, Y. T. Chang, S. E. Myers, J. I. Mason, and S. Pang The Hormonal Phenotype of Nonclassic 3{beta}-Hydroxysteroid Dehydrogenase (HSD3B) Deficiency in Hyperandrogenic Females Is Associated with Insulin-Resistant Polycystic Ovary Syndrome and Is Not a Variant of Inherited HSD3B2 Deficiency J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 783 - 794. [Abstract] [Full Text] [PDF]

				C. Lutfallah, W. Wang, J. I. Mason, Y. T. Chang, A. Haider, B. Rich, M. Castro-Magana, K. C. Copeland, R. David, and S. Pang Newly Proposed Hormonal Criteria via Genotypic Proof for Type II 3{beta}-Hydroxysteroid Dehydrogenase Deficiency J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2611 - 2622. [Abstract] [Full Text] [PDF]

				S. Lajic, S. Clauin, T. Robins, P. Vexiau, H. Blanche, C. Bellanne-Chantelot, and A. Wedell Novel Mutations in CYP21 Detected in Individuals with Hyperandrogenism J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2824 - 2829. [Abstract] [Full Text] [PDF]

				M. E. Silfen, A. M. Manibo, M. Ferin, D. J. McMahon, L. S. Levine, and S. E. Oberfield Elevated Free IGF-I Levels in Prepubertal Hispanic Girls with Premature Adrenarche: Relationship with Hyperandrogenism and Insulin Sensitivity J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 398 - 403. [Abstract] [Full Text] [PDF]

				L. Ibáñez, J. DiMartino-Nardi, N. Potau, and P. Saenger Premature Adrenarche--Normal Variant or Forerunner of Adult Disease? Endocr. Rev., December 1, 2000; 21(6): 671 - 696. [Abstract] [Full Text]

				P. C. White and P. W. Speiser Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency Endocr. Rev., June 1, 2000; 21(3): 245 - 291. [Abstract] [Full Text]

				New Insight into the Molecular Basis of 3{beta}-Hydroxysteroid Dehydrogenase Deficiency: Identification of Eight Mutations in the HSD3B2 Gene in Eleven Patients from Seven New Families and Comparison of the Functional Properties of Twenty-Five Mutant Enzymes J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4410 - 4425. [Abstract] [Full Text]

				S. Banerjee, S. Raghavan, E. J. Wasserman, B. L. Linder, P. Saenger, and J. DiMartino-Nardi Hormonal Findings in African-American and Caribbean Hispanic Girls With Premature Adrenarche: Implications for Polycystic Ovarian Syndrome Pediatrics, September 1, 1998; 102(3): e36 - e36. [Abstract] [Full Text] [PDF]

				H. W. Jones and J. P. Toner The Infertile Couple N. Engl. J. Med., December 2, 1993; 329(23): 1710 - 1715. [Full Text]

				T. Yalcinkaya, P. Siiteri, J. Vigne, P Licht, S Pavgi, L. Frank, and S. Glickman A mechanism for virilization of female spotted hyenas in utero Science, June 25, 1993; 260(5116): 1929 - 1931. [Abstract] [PDF]