eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

3-Beta-Hydroxysteroid Dehydrogenase Deficiency: Follow-up

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

Follow-up

Further Outpatient Care

  • Follow up with infants and young children about every 3-4 months for evaluation of height and weight, blood pressure, and laboratory monitoring (ie, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone [DHEA], plasma renin levels). Individualize adjustment of hydrocortisone and fludrocortisone acetate dosages based on the results of the physical examination and laboratory studies.
  • A left-hand radiograph may be obtained yearly for evaluation of skeletal maturation.
  • Sex hormone replacement may be required at the time of expected puberty in patients with complete 3-beta–hydroxysteroid dehydrogenase (3BHSD) deficiency. Because commercial estrogen preparations in the United States contain high doses of estradiol that induce rapid epiphyseal maturation, replacement therapy is often delayed until the bone age is 12 years or more to preserve linear growth. Ideally, testosterone or estrogen should begin at very low doses and gradually increase as the child ages and matures.

Inpatient & Outpatient Medications

  • Approximately 15 mg/m2/d of oral hydrocortisone divided 3 times daily may be used as an initial dose. Hydrocortisone is the drug of choice in infants and children. Longer-acting preparations, such as prednisone and dexamethasone, are difficult to titrate and can lead to overtreatment and growth suppression. Fludrocortisone acetate, 50 mcg (newborns and infants) to 200 mcg (older children) per day, is also required in patients with salt-losing variants of 3-beta–hydroxysteroid dehydrogenase deficiency. Adjust long-term dosages on an individual basis.
  • Exogenous glucocorticoid therapy suppresses adrenocorticotropic hormone (ACTH) secretion and decreases pregnenolone, 17-hydroxypregnenolone, and DHEA levels. Exogenous mineralocorticoid therapy normalizes both renin and ACTH levels. Combination therapy of mineralocorticoid plus glucocorticoid replacement reduces total glucocorticoid dose required and improves statural growth.

Complications

  • Benign testicular adrenal rest tumors are found in adult men in association with poorly controlled congenital adrenal hyperplasia (CAH). Such men may have gonadal dysfunction and infertility, perhaps due to obstruction of seminiferous tubules.11
  • High-resolution ultrasonography has recently been used to estimate the prevalence of testicular adrenal rest tumors in male children with CAH, with a reported incidence ranging from 21-24%.12,11
  • Although the testes are by far the most common location for such rest tumors, ectopic adrenal rest tumors may be present elsewhere.13

Prognosis

  • Prognosis is usually good-to-excellent with adequate replacement glucocorticoid and mineralocorticoid (if needed) therapy and monitoring.
  • Sex steroid replacement may be necessary for the development of secondary sexual characteristics in both males and females and cyclic menstrual bleeding in females. In postpubertal females with late-onset 3-beta–hydroxysteroid dehydrogenase deficiency, menstrual irregularity and infertility may correct with glucocorticoid replacement alone.

Patient Education

  • Patients with complete 3-beta–hydroxysteroid dehydrogenase deficiency are at risk for acute adrenal insufficiency when ill. Patients and their families should be instructed in the use of stress doses of glucocorticoids for acute illness (eg, temperature >101°F) or major trauma. If medication can be taken orally, the patient should double or triple the usual dose of glucocorticoid for 3 days. Mineralocorticoid doses do not need to be increased. If the patient cannot take the medication orally because of vomiting, altered state of consciousness, or surgery, parenteral glucocorticoids, preferably hydrocortisone, should be administered.
  • Patients should wear MedicAlert identification and be taken to their local health care provider as soon as possible when acutely ill for evaluation.

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize ambiguous genitalia or mild clitoromegaly in newborn infants: Ambiguous genitalia should be obvious on initial physical examination, but less severe abnormalities of the genitals in newborns (such as first-degree hypospadias or mild clitoromegaly) may also indicate possible adrenal abnormalities.
  • Failure to diagnosis adrenal insufficiency in a sick patient: The combination of circulatory collapse plus ambiguous genitalia, low serum sodium, high potassium, and/or low glucose suggests adrenal insufficiency requiring exogenous steroid administration in addition to standard resuscitation.

Special Concerns

  • Although the literature and experience regarding treatment of pediatric patients is extensive, little has been published regarding treatment of adults with congenital adrenal hormone deficiencies. Certainly, no consensus or published guidelines are available regarding types, dosages, or timing of steroid replacement in adult patients. 
  • A survey in the United Kingdom demonstrated that the most widely used glucocorticoid in adult patients was hydrocortisone, followed by dexamethasone and prednisolone.14 Sixty percent of physicians surveyed used larger doses of glucocorticoids at night (reverse circadian pattern) to achieve adrenocorticotropic hormone (ACTH) suppression, and only 16% of treating physicians used body weight or surface area to determine dosage.
  • Adult patients must be continuously and carefully treated, using body size or weight-related dosages (in a manner analogous to pediatric treatment) to avoid extremes of overtreatment and undertreatment.
 


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
[ CLOSE WINDOW ]

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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

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

[ CLOSE WINDOW ]

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

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.