Ovotesticular Disorder of Sexual Development Workup

  • Author: Molina B Dayal, MD, MPH; Chief Editor: Richard Scott Lucidi, MD   more...
 
Updated: Jan 10, 2012
 

Laboratory Studies

  • Cytogenetic investigation
    • 46,XX peripheral karyotype: Diagnostic possibilities include adrenogenital syndrome (ie, CAH), maternal androgen ingestion, excess maternal androgen production (eg, from maternal adrenocortical tumor), multiple congenital anomalies, and ovotesticular disorder of sexual development. This is the most common karyotype, constituting anywhere from 60-80% of patients.
    • 46,XY peripheral karyotype: Diagnostic possibilities include enzymatic defects in testosterone synthesis, such as 5-alpha reductase deficiency, complete or partial androgen insensitivity syndrome, gonadotropin deficiency, structural testicular abnormalities such as gonadal dysgenesis, and ovotesticular disorder of sexual development. This karyotype is found in about 10-15% of patients.
    • 46,XX/46,XY peripheral karyotype: Diagnostic possibilities include ovotesticular disorder of sexual development in a chimeric individual.
    • 45,X/46,XY, other mosaic patterns in peripheral karyotype: Diagnostic possibilities include mixed gonadal dysgenesis or ovotesticular disorder of sexual development.
    • Molecular studies: Fluorescent in situ hybridization for occult Y-DNA is used clinically today to enhance cytogenetic results. Probing for evidence of the Y-centromere (Y97 probe) and SRY is currently used on an investigational basis. Both peripheral lymphocytes and gonadal tissue samples can be studied. Several cases have been published showing discordance between the peripheral karyotype and the gonadal tissue.
  • Hormonal evaluation
    • Serum 17-hydroxyprogesterone: CAH must be ruled out with the use of serum 17-hydroxyprogesterone measurements. Individuals with ovotesticular disorder of sexual development have levels of this hormone that are within the reference range. In the newborn period, supportive management must be provided for those suspected of having the salt-wasting forms of CAH and pituitary insufficiency.
    • Basal and stimulated serum androgens: The presence of functional testicular tissue can be determined with the use of a human chorionic gonadotropin (HCG) stimulation test. In this test, basal levels of testosterone, dehydroepiandrosterone sulfate, androstenedione, and dihydrotestosterone (DHT) should be obtained. HCG (3000-5000 IU/m2/d IM) is then administered for 5 days. On the day 6, the serum hormone levels tests are repeated. A rise in serum testosterone demonstrates the presence of functioning Leydig cells. Elevated testosterone precursors may suggest a specific defect of testosterone synthesis. Failure of testosterone to reduce to DHT may suggest a 5-alpha hydroxylase deficiency.
    • Basal and stimulated estrogen levels: The presence of functional ovarian tissue can be determined with the use of gonadotropin or clomiphene citrate administration. An estradiol response to gonadotropin stimulation is a reliable test to differentiate ovotesticular disorder of sexual development from other disorders.
  • Study of androgen target cells: Defects in peripheral sensitivity to androgens may be responsible for genital ambiguity in male individuals with partial androgen insensitivity. Androgen receptor activity can be determined in fibroblasts grown from a genital skin biopsy sample; 5-alpha reductase activity also may be determined by this method.
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Imaging Studies

  • Ultrasonography, genitogram, and intravenous pyelogram studies have traditionally been used prior to definitive surgery.
    • A scrotal ultrasonography may be used to detect occult gonads.
    • A genitogram is used to evaluate the structure of the urethra and to confirm the presence of a vagina.
    • An intravenous pyelogram is important to rule out any associated urinary tract anomalies.
  • Today, pelvic or abdominal ultrasonography, CT scan, or MRI may aid in the identification of gonads and duct structures.
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Other Tests

The diagnosis of ovotesticular disorder of sexual development can sometimes be made prenatally. An amniocentesis following prenatal ultrasonography showing ambiguous genitalia may reveal a 46,XX, 46,XX/46,XY or 46,XX/47,XXY karyotype, providing a hint to the diagnosis.[6]

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Procedures

  • Laparoscopy or laparotomy with gonadal biopsy/gonadectomy allows for histologic confirmation of both ovarian and testicular tissue.
  • Conservative gonadal surgery is the procedure of choice for individuals with ovotesticular disorder of sexual development.[7] This approach entails partial resection of ovotestes guided by intraoperative histologic examination, preservation of gonadal tissue concordant with sex of rearing, and removal of all discordant tissue.
  • Cystoscopy may be used to determine the position of entry of the vagina into the urethra or urogenital sinus.
  • Prophylactic gonadectomy should be considered in those who manifest signs of virilization or are at an increased risk of gonadal malignancy.
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Histologic Findings

Ovotestis, ovary and/or testis, and associated duct structures may be recovered on surgical exploration.

Ovotestes contain both ovarian follicles and testicular tubular elements. They usually are compartmentalized, with connective tissue separating the ovarian from the testicular components. However, on rare occasions, an intermixture of these elements may occur.

Ovaries and ovarian portions of ovotestes appear normal and demonstrate follicular growth capable of estradiol production.

In true hermaphroditism, testicular elements show degeneration and hyalinization of the seminiferous tubules with poor germ cell development. Leydig cell hyperplasia also may occur. Spermatogenesis in the testes is rare.

Internal duct development usually corresponds to the adjacent gonad so that wolffian duct structures are observed on the gonad side(s) containing functioning testicular tissue. Müllerian duct structures are observed on the gonad side not containing testicular tissue.

This histologic section of an ovotestis demonstratThis histologic section of an ovotestis demonstrates both seminiferous tubules and ovarian follicles.
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Contributor Information and Disclosures
Author

Molina B Dayal, MD, MPH  Associate Professor, Medical Director of Egg Donation Program, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Medical Faculty Associates, George Washington University School of Medicine

Molina B Dayal, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and Society for Reproductive Endocrinology and Infertility

Disclosure: Nothing to disclose.

Coauthor(s)

Candice B O'Hern, MD  Resident Physician, Department of Obstetrics and Gynecology, George Washington University Hospital

Candice B O'Hern, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists and American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Richard Scott Lucidi, MD  Associate Professor of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Richard Scott Lucidi, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists and American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Additional Contributors

A David Barnes, MD, PhD, MPH, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)

A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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This histologic section of an ovotestis demonstrates both seminiferous tubules and ovarian follicles.
 
 
 
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