Medscape is available in 5 Language Editions – Choose your Edition here.


3-Beta-Hydroxysteroid Dehydrogenase Deficiency Workup

  • Author: J Paul Frindik, MD, FACE; Chief Editor: Stephen Kemp, MD, PhD  more...
Updated: Jun 16, 2016

Laboratory Studies

No biochemical differences between male and female patients are recognized.

  • Classic 3-beta–hydroxysteroid dehydrogenase (3BHSD) deficiency
    • Plasma concentrations of pregnenolone, 17-hydroxypregnenolone, and DHEA are elevated.
    • 17-Hydroxyprogesterone levels may be increased because of conversion of 17-hydroxypregnenolone to 17-hydroxyprogesterone by peripheral type I 3-beta–hydroxysteroid dehydrogenase isoenzyme and may be detected by neonatal screening for 21-hydroxylase deficiency.[15, 16]
    • Peripheral type I 3-beta–hydroxysteroid dehydrogenase activity may also increase androstenedione levels.[15] However, in 3-beta–hydroxysteroid dehydrogenase deficiency, the plasma ratio of 17-hydroxypregnenolone to 17-hydroxyprogesterone is markedly elevated. Plasma cortisol and aldosterone levels are low in 3-beta–hydroxysteroid dehydrogenase.
    • Adrenocorticotropic hormone (ACTH) levels are elevated because of the lack of cortisol secretion, and gonadotropin follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are elevated secondary to deficient sex steroid production.
  • Late-onset or nonclassic 3-beta–hydroxysteroid dehydrogenase deficiency: Baseline (unstimulated) measurements of pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA) may be unremarkable in patients with late-onset or nonclassic 3-beta–hydroxysteroid dehydrogenase deficiency. In such patients, diagnosis is based on an excessive response of 17-hydroxypregnenolone (delta 5-17Preg) and delta 5-17Preg-to-F ratios at or greater than 201 nmol/L and 487 nmol/L, respectively; this is equivalent to or greater than 36 standard deviations (SD) and 52 SD above matched control mean, respectively.[19]
  • Carriers: Carriers of type II 3-beta–hydroxysteroid dehydrogenase deficiency can have hormone profiles (both stimulated and unstimulated) within the reference range and, therefore, can only be detected by genotype studies.

Imaging Studies

Imaging studies may reveal polycystic ovaries in older patients or enlarged adrenal glands; such findings are nonspecific and not diagnostic for any particular type of enzyme deficiency.


Other Tests

Genotyping is not routinely required for diagnosis but may be helpful if hormone testing is inconclusive. Molecular genetic studies are indicated, as noted above, to detect carriers as well as for genetic counseling of the individual and family.[20]

Contributor Information and Disclosures

J Paul Frindik, MD, FACE Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences College of Medicine

J Paul Frindik, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

  1. Grumbach MM, Conte FA. Disorders of sex differentiation. Williams Textbook of Endocrinology. 8th ed. Philadelphia, PA: WB Saunders Co; 1992. 853-951.

  2. Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009 Apr. 23(2):181-92. [Medline].

  3. Moisan AM, Ricketts ML, Tardy V, et al. New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzym. J Clin Endocrinol Metab. 1999 Dec. 84(12):4410-25. [Medline]. [Full Text].

  4. Subramaniam P, Clayton PT, Portmann BC, Mieli-Vergani G, Hadzic N. Variable clinical spectrum of the most common inborn error of bile acid metabolism--3beta-hydroxy-Delta 5-C27-steroid dehydrogenase deficiency. J Pediatr Gastroenterol Nutr. 2010 Jan. 50(1):61-6. [Medline].

  5. Simard J, Ricketts ML, Gingras S, Soucy P, Feltus FA, Melner MH. Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. Endocr Rev. 2005 Jun. 26(4):525-82. [Medline].

  6. Simard J, Moisan AM, Morel Y. Congenital adrenal hyperplasia due to 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase deficiency. Semin Reprod Med. 2002 Aug. 20(3):255-76. [Medline].

  7. Welzel M, Wustemann N, Simic-Schleicher G, et al. Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2008 Apr. 93(4):1418-25. [Medline].

  8. Schneider G, Genel M, Bongiovanni AM, et al. Persistent testicular delta5-isomerase-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) deficiency in the delta5-3beta-HSD form of congenital adrenal hyperplasia. J Clin Invest. 1975 Apr. 55(4):681-90. [Medline]. [Full Text].

  9. Steiner AZ, Chang L, Ji Q, et al. 3alpha-Hydroxysteroid dehydrogenase type III deficiency: a novel mechanism for hirsutism. J Clin Endocrinol Metab. 2008 Apr. 93(4):1298-303. [Medline].

  10. Al-Jurayyan NA. Ambiguous genitalia: two decades of experience. Ann Saudi Med. 2011 May-Jun. 31 (3):284-8. [Medline].

  11. Benkert AR, Young M, Robinson D, Hendrickson C, Lee PA, Strauss KA. Severe Salt-Losing 3β-Hydroxysteroid Dehydrogenase Deficiency: Treatment and Outcomes of HSD3B2 c.35G>A Homozygotes. J Clin Endocrinol Metab. 2015 Aug. 100 (8):E1105-15. [Medline].

  12. Sakkal-Alkaddour H, Zhang L, Yang X, et al. Studies of 3 beta-hydroxysteroid dehydrogenase genes in infants and children manifesting premature pubarche and increased adrenocorticotropin-stimulated delta 5-steroid levels. J Clin Endocrinol Metab. 1996 Nov. 81(11):3961-5. [Medline].

  13. Burckhardt MA, Udhane SS, Marti N, Schnyder I, Tapia C, Nielsen JE, et al. Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature. Eur J Endocrinol. 2015 Nov. 173 (5):K1-K12. [Medline].

  14. Johannsen TH, Mallet D, Dige-Petersen H, et al. Delayed diagnosis of congenital adrenal hyperplasia with salt wasting due to type II 3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 2005 Apr. 90(4):2076-80. [Medline]. [Full Text].

  15. Nordenström A, Forest MG, Wedell A. A case of 3beta-hydroxysteroid dehydrogenase type II (HSD3B2) deficiency picked up by neonatal screening for 21-hydroxylase deficiency: difficulties and delay in etiologic diagnosis. Horm Res. 2007. 68(4):204-8. [Medline].

  16. Jeandron DD, Sahakitrungruang T. A novel homozygous Q334X mutation in the HSD3B2 gene causing classic 3ß-hydroxysteroid dehydrogenase deficiency: an unexpected diagnosis after a positive newborn screen for 21-hydroxylase deficiency. Horm Res Paediatr. 2012. 77(5):334-8. [Medline].

  17. Marui S, Castro M, Latronico AC, et al. Mutations in the type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature pubarche in girls. Clin Endocrinol (Oxf). 2000 Jan. 52(1):67-75. [Medline].

  18. Sanchez R, Rheaume E, Laflamme N, et al. Detection and functional characterization of the novel missense mutation Y254D in type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene of a female patient with nonsalt-losing 3 beta HSD deficiency. J Clin Endocrinol Metab. 1994 Mar. 78(3):561-7. [Medline].

  19. Mermejo LM, Elias LL, Marui S, Moreira AC, Mendonca BB, de Castro M. Refining hormonal diagnosis of type II 3beta-hydroxysteroid dehydrogenase deficiency in patients with premature pubarche and hirsutism based on HSD3B2 genotyping. J Clin Endocrinol Metab. 2005 Mar. 90(3):1287-93. [Medline]. [Full Text].

  20. [Guideline] Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Sep. 95(9):4133-60. [Medline]. [Full Text].

  21. Han TS, Conway GS, Willis DS, Krone N, Rees DA, et al. Relationship between final height and health outcomes in adults with congenital adrenal hyperplasia: United Kingdom congenital adrenal hyperplasia adult study executive (CaHASE). J Clin Endocrinol Metab. 2014 Aug. 99 (8):E1547-55. [Medline].

  22. Han TS, Krone N, Willis DS, Conway GS, Hahner S, et al. Quality of life in adults with congenital adrenal hyperplasia relates to glucocorticoid treatment, adiposity and insulin resistance: United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE). Eur J Endocrinol. 2013 Jun. 168 (6):887-93. [Medline].

  23. Ross RJ, Rostami-Hodjegan A. Timing and type of glucocorticoid replacement in adult congenital adrenal hyperplasia. Horm Res. 2005. 64 Suppl 2:67-70. [Medline].

  24. Claahsen-van der Grinten HL, Sweep FC, Blickman JG, Hermus AR, Otten BJ. Prevalence of testicular adrenal rest tumours in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol. 2007 Sep. 157(3):339-44. [Medline].

  25. Martinez-Aguayo A, Rocha A, Rojas N, et al. Testicular adrenal rest tumors and Leydig and Sertoli cell function in boys with classical congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2007 Dec. 92(12):4583-9. [Medline].

  26. Claahsen H, Duthoi K, Otten B, d'Ancona F, Hulsbergen C, Hermus A. An adrenal rest tumour in the perirenal region in a patient with congenital adrenal hyperplasia due to congenital 3{beta}-hydroxysteroid dehydrogenase deficiency. Eur J Endocrinol. 2008 Jul 22. [Medline].

  27. Bentsen D, Schwartz DS, Carpenter TO. Sonography of congenital adrenal hyperplasia due to partial deficiency of 3beta-hydroxysteroid dehydrogenase: a case report. Pediatr Radiol. 1997 Jul. 27(7):594-5. [Medline].

  28. Moran C, Potter HD, Reyna R, et al. Prevalence of 3beta-hydroxysteroid dehydrogenase-deficient nonclassic adrenal hyperplasia in hyperandrogenic women with adrenal androgen excess. Am J Obstet Gynecol. 1999 Sep. 181(3):596-600. [Medline].

  29. Morel Y, Mebarki F, Rheaume E, et al. Structure-function relationships of 3 beta-hydroxysteroid dehydrogenase: contribution made by the molecular genetics of 3 beta-hydroxysteroid dehydrogenase deficiency. Steroids. 1997 Jan. 62(1):176-84. [Medline].

  30. Nakamura Y, Suzuki T, Inoue T, et al. 3beta-Hydroxysteroid dehydrogenase in human aorta. Endocr J. 2005 Feb. 52(1):111-5. [Medline].

  31. Pang S, Carbunaru G, Haider A, et al. Carriers for type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) deficiency can only be identified by HSD3B2 genotype study and not by hormone test. Clin Endocrinol (Oxf). 2003 Mar. 58(3):323-31. [Medline].

  32. Rheaume E, Simard J, Morel Y, et al. Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene. Nat Genet. 1992 Jul. 1(4):239-45. [Medline].

  33. Rosler A, Levine LS, Schneider B, et al. The interrelationship of sodium balance, plasma renin activity and ACTH in congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1977 Sep. 45(3):500-12. [Medline].

Normal adrenal steroid biosynthesis results in 3 products: mineralocorticoid (aldosterone), glucocorticoids (cortisol), and androgens (androstenedione). Cortisol production is regulated by feedback with adrenocorticotropic hormone (ACTH). ACTH stimulates the enzyme P-450scc (20,22 desmolase) with subsequent increased production of all adrenal steroids.
Representation of typical congenital adrenal hyperplasia (CAH). In this example, both the mineralocorticoid and glucocorticoid pathways are deficient. Decreased serum cortisol levels stimulate adrenocorticotropic hormone (ACTH) release via negative feedback. Increased ACTH secretion results in overproduction of adrenal steroids preceding the missing enzyme as well as those not requiring the missing enzyme. In this example, a deficiency of 21-hydroxylase results in deficient mineralocorticoid and glucocorticoid production and excessive androgen production.
3-beta-hydroxysteroid dehydrogenase (3BHSD) is required for the synthesis of all three groups of adrenal steroids: mineralocorticoids, glucocorticoids, and sex steroids. 3BHSD catalyzes the conversion of pregnenolone to progesterone (mineralocorticoid pathway), 17-alpha-hydroxypregnenolone to 17-alpha-hydroxyprogesterone (glucocorticoid pathway), and dehydroepiandrosterone to androstenedione (sex steroid pathway). Complete absence of this enzyme thus impairs all steroid production. 17OH Preg = 17-alpha-hydroxypregnenolone; DHEA = Dehydroepiandrosterone; 17OH Prog = 17-alpha-hydroxyprogesterone; Andros = Androstenedione; DOC = Deoxycorticosterone; Cmp S = Compound S.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.