eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

3-Beta-Hydroxysteroid Dehydrogenase Deficiency: Treatment & Medication

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

Treatment

Medical Care

  • Classic 3-beta–hydroxysteroid dehydrogenase (3BHSD) deficiency: Patients with classic salt-losing 3-beta–hydroxysteroid dehydrogenase require replacement of glucocorticoids, mineralocorticoids, and sex steroids.
    • Exogenous orally administered hydrocortisone (or other glucocorticoid) suppresses adrenocorticotropic hormone (ACTH) secretion and decreases plasma concentrations of pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA).
    • Mineralocorticoid replacement is achieved by the oral administration of fludrocortisone acetate (9-alpha-fluorohydrocortisone, Florinef). Patients with non–salt-losing variants do not require mineralocorticoid replacement.
    • At puberty, patients with complete 3-beta–hydroxysteroid dehydrogenase deficiency require sex steroid replacement, including testosterone in males and cyclic estrogen-progesterone therapy in females. Such therapy promotes development of secondary sexual characteristics in both males and females, and cyclic menstrual bleeding in 46,XX females.
  • Late-onset (nonclassic) 3-beta–hydroxysteroid dehydrogenase deficiency: The need for replacement therapy varies, depending on the severity of the defect. Hydrocortisone (or other glucocorticoid) replacement suppresses excess androgens in children with premature pubarche and may correct menstrual irregularities and decrease hirsutism and acne in pubertal and postpubertal females.

Medication

Glucocorticoids

Exogenous glucocorticoid therapy suppresses adrenocorticotropic hormone (ACTH) secretion, decreasing pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA) levels. Doses used are somewhat empirical and must be individualized based on clinical findings, growth and skeletal maturation, and hormonal data, including monitoring of pregnenolone, 17-hydroxypregnenolone, and DHEA levels.


Hydrocortisone (A-Hydrocort, Cortef, Hydrocort)

Longer-acting preparations, such as prednisone and dexamethasone, are difficult to titrate and can lead to overtreatment and growth suppression.

Adult

Pediatric

15 mg/m2/d PO divided tid initially; adjust long-term dose on an individual basis

Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Administer with meals to decrease GI upset; early-onset adverse effects include glucose intolerance, hypertension, agitation, and indigestion; late-onset adverse effects observed in patients on large glucocorticoid doses include immune suppression and increased susceptibility to sepsis, hypertension, urinary calcium loss and osteopenia, and gastric irritation and bleeding (the above-listed adverse effects are not usually observed with the dosages used for physiologic replacement in 3BHSD deficiency)

Mineralocorticoids

Exogenous mineralocorticoid therapy is required in patients with salt-losing variants of CAH (21-hydroxylase deficiency and 3-beta–hydroxysteroid dehydrogenase [3BHSD] deficiency). Plasma renin levels are elevated in patients with untreated salt-losing variants, and the addition of mineralocorticoid replacement normalizes both renin and ACTH levels. Combination therapy of mineralocorticoid plus glucocorticoid replacement reduces total glucocorticoid dose required and improves statural growth.


Fludrocortisone acetate (Florinef)

Only drug available in this category. Promotes increased reabsorption of sodium and loss of potassium renal distal tubules. Dosages are adjusted to achieve suppressed plasma renin levels.

Adult

0.1-0.2 mg/d PO

Pediatric

0.05-0.1 mg/d (ie, one-half to one 100-mcg tab) PO initially; this dose may be sufficient in patients with milder forms of the disease; other patients with more severe defects may require higher doses (ie, 0.1-0.2 mg/d); if doses >0.1 mg/d are required, the dose may be divided bid; the addition of NaCl to the diet may also be required in patients with severe salt losing

Antagonizes effects of anticholinergics; rifampin, hydantoins, and barbiturates decrease effects of fludrocortisone; decreases salicylate levels

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Can cause elevation in blood pressure, salt and water retention, and excessive excretion of potassium

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

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  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].

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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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