A 14-year-old girl has primary amenorrhea. Karyotype is 46,XY. She has normal female external genitalia, absent uterus and fallopian tubes, and bilateral inguinal masses. Serum testosterone is in the male range, and serum LH is markedly elevated. Which hormonal and receptor abnormality is responsible?

• A Complete androgen insensitivity syndrome (CAIS): loss-of-function mutation in the androgen receptor (AR) → testosterone cannot act; MIF (anti-Müllerian hormone) from testes causes Müllerian regression → absent uterus; female external phenotype from DHT/T insensitivity; elevated LH from loss of androgen feedback ✓
• B Swyer syndrome (46,XY gonadal dysgenesis): mutation in SRY gene → gonads are streak; lack of MIF → Müllerian structures present; testosterone cannot be made
• C 5α-reductase deficiency: testosterone is normal but DHT is absent; external genitalia appear female at birth; uterus is absent because AMH was secreted by testes
• D Kallmann syndrome: GnRH deficiency causing absent LH/FSH → low testosterone → female phenotype in 46,XY individual

Explanation

The triad of 46,XY karyotype + female external genitalia + absent uterus + elevated testosterone + elevated LH + inguinal masses (cryptorchid testes) is pathognomonic of complete androgen insensitivity syndrome (CAIS). The testes are present (hence normal testosterone and AMH/MIF production); AMH from Sertoli cells causes Müllerian duct regression (absent uterus, fallopian tubes). Because the androgen receptor (AR) is non-functional, testosterone and DHT cannot act — male external genitalia do not develop and the default female phenotype appears. Elevated LH results from loss of androgen-mediated negative feedback on the hypothalamic-pituitary axis. Option B (Swyer) presents with female genitalia but the uterus IS present (no AMH from streak gonads). Option C (5α-reductase deficiency) presents with ambiguous genitalia and virilization at puberty, not full female phenotype. Option D (Kallmann) would show low LH and testosterone, not high.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.