Androgen Insensitivity (Resistance) Syndrome

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Chapter 163 Androgen Insensitivity (Resistance) Syndrome

INTRODUCTION

Description: Patients with androgen insensitivity have a normal male karyotype but a genetic alteration that results in somatic cells that cannot recognize or respond to testosterone. This results in a normal female phenotype, absent uterus, and scant (or absent) body hair. The syndrome was known at one time as “testicular feminization.”

Prevalence: Uncommon, 10% of patients with primary amenorrhea (third most common cause).

Predominant Age: Generally discovered in middle to late teens.

Genetics: Absence of an X-chromosome gene that encodes for cytoplasmic or nuclear testosterone receptor protein, X-linked recessive.

ETIOLOGY AND PATHOGENESIS

Causes: Testosterone and gonadotropin levels are essentially normal (there may be a slight increase in luteinizing hormone [LH]), but the testosterone is biologically ineffective because of the body’s inability to use it. Consequently, masculinization does not take place, and the normal production of Müllerian-inhibiting factor results in regression of the upper genital tract and a blind vaginal pouch.

Risk Factors: None known.

DIAGNOSTIC APPROACH

Differential Diagnosis

• Pregnancy before first cycle

• Obstructed outflow tract (making menstruation cryptic)

• Gonadal dysgenesis

• Uterine agenesis

• Complete lack of Müllerian development (MayerRokitansky-Küster-Hauser syndrome)

Associated Conditions: Infertility, amenorrhea, mildly impaired visual–spatial ability, horseshoe kidney.

Workup and Evaluation

Laboratory: Measurement of gonadotropins, estrogen, and testosterone (not required for diagnosis).

Imaging: Ultrasonography may be used to confirm the absence of the uterus, although it is not required for diagnosis.

Special Tests: Chromosomal analysis confirms the diagnosis.

Diagnostic Procedures: History and physical examination should provide the suggestion, confirmed by chromosomal analysis.

Pathologic Findings

The presence of testicular tissue in the labioscrotal folds.

MANAGEMENT AND THERAPY

Nonpharmacologic

General Measures: Evaluation and reassurance.

Specific Measures: Surgical extirpation of the gonads must be performed because of a 25% to 30% risk of malignant gonadal tumor formation. This should not be performed until complete breast development has occurred and there has been epiphyseal closure (age 18). Genetic counseling should be offered to siblings.

Diet: No specific dietary changes indicated.

Activity: No restriction.

Patient Education: Frank discussion about the syndrome and its effects (infertility and amenorrhea). Patients should be informed that they carry an abnormal sex chromosome without mentioning the Y chromosome specifically because of the “male” connotations this carries. In addition, the term gonads should be used rather than testes when discussing the need for removal. Refer patients to the Androgen Insensitivity Syndrome Support Group (www.aissg.org)

Drug(s) of Choice

None. (Estrogen replacement therapy is generally not necessary after removal of the gonads; the insensitivity of the peripheral tissues to the effects of circulating androgens results in unopposed estrogen effects from the low levels of estrogen that come from adrenal and peripheral conversion sources.)

FOLLOW-UP

Patient Monitoring: Normal health maintenance once the diagnosis is established and the gonads are removed (at the appropriate time).

Prevention/Avoidance: None.

Possible Complications: There is a 25% to 30% risk of malignant gonadal tumor formation if the testes are not removed (rare before age 25).

Expected Outcome: These patients are phenotypically, behaviorally, and psychologically female and continue to lead normal lives with the exception of infertility and amenorrhea.

MISCELLANEOUS

Pregnancy Considerations: These patients are infertile.

ICD-9-CM Codes: 257.8.

American College of Obstetricians and Gynecologists. Vaginal agenesis: diagnosis, management, and routine care. ACOG Committee Opinion 355. Obstet Gynecol. 2006;108:1605.

Evans BA, Hughes IA, Bevan CL, et al. Phenotypic diversity in siblings with partial androgen insensitivity syndrome. Arch Dis Child. 1997;76:529.

Golditch IM. Vaginal aplasia. Surg Gynecol Obstet. 1969;129:361.

Griffin JE, Wilson JD. The syndromes of androgen resistance. N Engl J Med. 1980;302:198.

Hyun G, Kolon TF. A practical approach to intersex in the newborn period. Urol Clin North Am. 2004;31:435. viii.

Lentz SS, Cappellari JO. Postmenopausal diagnosis of testicular feminization. Am J Obstet Gynecol. 1998;179:268.

Lobo RA. Primary and secondary amenorrhea and precocious puberty. In: Katz VL, Lentz GM, Lobo RA, Gershenson DM, editors. Comprehensive Gynecology. 5th ed. Philadelphia: Mosby/Elsevier; 2007:937.

Savage MO, Grant DB. The incomplete male. Arch Dis Child. 1978;53:701.

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