Laboratory Studies

The studies described below may be indicated in patients with androgen insensitivity syndrome (AIS).

A karyotype is essential to differentiate an undermasculinized male from a masculinized female. Alternatively, the presence of a Y chromosome can be confirmed by fluorescent in situ hybridization (FISH) probes for either the SRY region of the Y chromosome or a subtelomeric Y chromosome probe. These offer a much quicker turnaround time than conventional karyotypes.

Levels of testosterone and dihydrotestosterone (DHT) establish the presence of normal steroidogenesis. If the testosterone level is low for age, obtain levels of dehydroepiandrosterone (DHEA), androstenedione, and their precursors, 17-hydroxypregnenolone and 17-hydroxyprogesterone. These levels allow identification of errors in the steroid biosynthetic pathways. An elevated ratio of testosterone to DHT indicates a 5-alpha reductase deficiency, a possible differential for patients with partial androgen insensitivity syndrome but usually not for complete androgen insensitivity syndrome. Low levels of testosterone in the absence of evidence of defective steroidogenesis suggest testicular dysgenesis or Leydig cell aplasia/hypoplasia.

Mutation analysis of the androgen receptor gene is now commercially available. It detects upwards of 95% of the mutations for complete androgen insensitivity syndrome and partial androgen insensitivity syndrome. The analysis is performed on DNA obtained from buccal swabs. However, the testing is slow (about 6 wk for results) and expensive (not covered by some insurance companies).

For patients with Kennedy disease, an elevated testosterone level can be found in approximately 70% of cases. More than 40 CAG tandem repeats in exon 1 of the AR are diagnostic.^[13]

Imaging Studies

A pelvic ultrasound examination is frequently useful. Identification of any müllerian structures, such as uterus or fallopian tubes, is inconsistent with a diagnosis of complete androgen insensitivity syndrome or partial androgen insensitivity syndrome.

Histologic Findings

Histologic examination of the testes in patients with complete androgen insensitivity syndrome or partial androgen insensitivity syndrome should show fairly normal testicular structure, although the numbers of spermatogonia and/or sperm may be reduced markedly in postpubertal patients.

Given current management recommendations, a histologic examination may be impossible to perform until the patient is in late adolescence or early adulthood.

Treatment & Management

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Media Gallery

Penoscrotal hypospadias is shown. Note the associated ventral chordee and true urethral meatus located at the scrotal level.

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Author

Christian A Koch, MD, PhD, FACP, MACE Professor, University of Oldenburg and Dresden, Germany; Past Professor With Tenure, Division of Endocrinology, University of Mississippi Medical Center

Christian A Koch, MD, PhD, FACP, MACE is a member of the following medical societies: American Academy of Neurology, American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Society for Clinical Pharmacology and Therapeutics, American Society for Dermatologic Surgery, Endocrine Society, German Diabetes Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Novartis<br/>Received income in an amount equal to or greater than $250 from: Springer Publisher and Elsevier Publisher.

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.

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Robert P Hoffman, MD Professor and Program Director, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Division of Pediatric, Endocrinology, Diabetes, and Metabolism, Nationwide Children's Hospital

Robert P Hoffman, MD is a member of the following medical societies: American College of Pediatricians, American Diabetes Association, American Pediatric Society, Christian Medical and Dental Associations, Endocrine Society, Midwest Society for Pediatric Research, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, Florida Chapter of The American Academy of Pediatrics, Florida Pediatric Society, International Society for Pediatric and Adolescent Diabetes

Disclosure: Nothing to disclose.

Acknowledgements

Bruce E Wilson, MD Associate Professor, Department of Pediatrics and Human Development, Michigan State University College of Human Medicine at East Lansing

Bruce E Wilson is a member of the following medical societies: American Diabetes Association, Association of Clinical Scientists, Lawson-Wilkins Pediatric Endocrine Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.