eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

3-Beta-Hydroxysteroid Dehydrogenase Deficiency: Differential Diagnoses & Workup

Author: J Paul Frindik, MD, FACE, Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences
Contributor Information and Disclosures

Updated: Sep 18, 2008

Differential Diagnoses

Adrenal Insufficiency
Congenital Adrenal Hyperplasia
Dehydration
Familial Glucocorticoid Deficiency
Hypospadias
Precocious Pseudopuberty

Other Problems to Be Considered

Male pseudohermaphroditism

Workup

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.9  
    • Peripheral type I 3-beta–hydroxysteroid dehydrogenase activity may also increase androstenedione levels.9  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. 
    • Adrenocroticotropic 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.10
  • 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.

More on 3-Beta-Hydroxysteroid Dehydrogenase Deficiency

Overview: 3-Beta-Hydroxysteroid Dehydrogenase Deficiency
Differential Diagnoses & Workup: 3-Beta-Hydroxysteroid Dehydrogenase Deficiency
Treatment & Medication: 3-Beta-Hydroxysteroid Dehydrogenase Deficiency
Follow-up: 3-Beta-Hydroxysteroid Dehydrogenase Deficiency
Multimedia: 3-Beta-Hydroxysteroid Dehydrogenase Deficiency
References
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References

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

  2. 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. Dec 1999;84(12):4410-25. [Medline]. [Full Text].

  3. 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. Apr 1975;55(4):681-90. [Medline]. [Full Text].

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

  5. 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. Nov 1996;81(11):3961-5. [Medline].

  6. 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. Apr 2005;90(4):2076-80. [Medline]. [Full Text].

  7. 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). Jan 2000;52(1):67-75. [Medline].

  8. 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. Mar 1994;78(3):561-7. [Medline].

  9. 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].

  10. 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. Mar 2005;90(3):1287-93. [Medline]. [Full Text].

  11. 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. Sep 2007;157(3):339-44. [Medline].

  12. 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. Dec 2007;92(12):4583-9. [Medline].

  13. 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. Jul 22 2008;[Medline].

  14. 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].

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

  16. 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. Sep 1999;181(3):596-600. [Medline].

  17. 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. Jan 1997;62(1):176-84. [Medline].

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

  19. 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). Mar 2003;58(3):323-31. [Medline].

  20. 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. Jul 1992;1(4):239-45. [Medline].

  21. 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. Sep 1977;45(3):500-12. [Medline].

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Further Reading

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Keywords

3-beta–hydroxysteroid dehydrogenase, 3BHSD deficiency, 3b HSD deficiency, congenital adrenal hyperplasia, CAH, salt wasting, ambiguous genitalia, clitoromegaly, gynecomastia, hirsutism, salt-losing adrenal crisis, adrenal insufficiency

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Contributor Information and Disclosures

Author

J Paul Frindik, MD, FACE, Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences
J Paul Frindik, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists
Disclosure: Nothing to disclose.

Medical Editor

Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

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 Federation for Clinical Research, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Lawson-Wilkins Pediatric Endocrine Society, Pituitary Society, Society for Pediatric Research, Society for the Study of Reproduction, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and 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, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfiser, Inc. Honoraria Consulting

 
 
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