5-Alpha-Reductase Deficiency Workup

  • Author: Jill E Emerick, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Jul 29, 2010
 

Laboratory Studies

General laboratory evaluation for all newborns with ambiguous genitalia should begin with the following:

  • Karyotype with specific X and Y probes.
  • 17-hydroxyprogesterone, follicle-stimulating hormone (FSH), leuteinizing hormone (LH), testosterone, dihydrotestosterone (DHT), antimullerian hormone (AMH), electrolytes, and urinalysis
  • Abdominopelvic ultrasound to assess for presence of internal male/female structures

Results should be expedited, ideally available within 48-72 hours.

In neonates with Y material (46,XY or fluorescent in situ hybridization [FISH] results positive for sex-determining region [SRY]) and ambiguous genitalia, 5-alpha-reductase type 2 deficiency should be considered.

Elevated serum testosterone-to-DHT ratio (T/DHT) is the hallmark of 5-alpha-reductase type 2 deficiency. Typically, testosterone levels are normal to modestly elevated and DHT levels are low to undetectable. levels are detectable to diagnostic levels during the testosterone surge that occurs from birth to 1-3 months.

Human chorionic gonadotropin (hCG) stimulation is needed after this period in order to obtain adequate levels of testosterone and DHT for diagnosis. Multiple protocols, both short-term and long-term, have been established with varying sensitivities. Three common protocols include the following: (1) 1500 IU intermuscularly (IM) on days 1, 3, and 5 (short test); (2) 1500 IU IM every other day for 7 injections (prolonged test); or (3) 5000 IU/m2 IM as a single dose. Laboratory results are established prior to hCG (baseline) and 24 hours after the last dose (stimulated).

In healthy newborns and prepubertal children, the baseline T/DHT ratio is less than 8; in postpubertal patients, the baseline is less than 17. Following hCG stimulation, the ratio is less than 17. In patients with 5-alpha-reductase type 2 deficiency, the post-hCG ratio is typically more than 27.[11]

Other methods not commonly used in clinical practice include mutation analysis and gas chromatography–mass spectrometry. Mutation analysis of the 5-alpha-reductase type 2 gene (SRD5A2) located at band 2p23 is only available through research laboratories. Gas chromatography–mass spectrometry of urinary steroids shows reduced 5-alpha to 5-beta metabolites.

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Imaging Studies

Ultrasonography

Although not diagnostic for 5-alpha-reductase type 2 deficiency, ultrasonography of the pelvis is useful.

Ultrasonography can verify the location of the testes and other wolffian structures as well as the absence of mullerian structures, to include the cervix and uterus.

The ultrasonographer, and other members of the radiographic and laboratory evaluation team, should be cognizant of the suspected diagnosis and be trained on how to properly discuss findings with gender-neutral terms.

Genitography

A genitogram (ie, dye introduced into the urogenital (UG) sinus via small catheter or feeding tube) is a useful tool to assess urethral anatomy, UG sinus length, or evidence of mullerian remnants.

This study can verify that no fistulous connections are present between the urinary tract and UG sinus.

CT and MRI

CT or MRI are usually not necessary but may be useful to more accurately assess internal anatomy.

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Histologic Findings

The testes exhibit Leydig cell hyperplasia and decreased spermatogenesis. However, testicular biopsy is not part of the routine evaluation.

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Contributor Information and Disclosures
Author

Jill E Emerick, MD  Fellow, Pediatric Endocrinology, Uniformed Services University of the Health Sciences, Pediatrics Department, Walter Reed Army Medical Center/National Naval Medical Center

Jill E Emerick, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Noelle Summers Larson, MD  Fellow, Pediatric Endocrinology, Uniformed Services University of the Health Sciences, Pediatrics Department, Walter Reed Army Medical Center/National Naval Medical Center

Noelle Summers Larson, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Andrew J Bauer, MD  Program Director, Pediatric Endocrinology Fellowship, Uniformed Services University of the Health Sciences

Andrew J Bauer, MD is a member of the following medical societies: American Academy of Pediatrics, American Thyroid Association, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Phyllis W Speiser, MD  Chief, Division of Pediatric Endocrinology, The Children's Hospital, North Shore LIJ Health System; 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.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

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 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.

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: Nothing to disclose.

References

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  18. Vardi Y, Har-Shai Y, Gil T, Gruenwald I. A critical analysis of penile enhancement procedures for patients with normal penile size: surgical techniques, success, and complications. Eur Urol. Nov 2008;54(5):1042-50. [Medline].

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Biochemical effects of 5-alpha-reductase type 2 deficiency in testosterone biosynthesis. Typically levels of testosterone are elevated, whereas levels of dihydrotestosterone (DHT) are significantly decreased, leading to male undervirilization.
Prader scale reflecting the degree of virilization of the external genitalia. The internal genitalia reflect the changes in the urogenital sinus in response to the presence or absence of mullerian inhibiting hormone (MIH)
 
 
 
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