Disorders and Differences of Sex Development
Classification
Differences of sex development are classified by karyotype: 46,XX DSD, 46,XY DSD, and sex chromosome DSD. 46,XX DSD includes CAH, aromatase deficiency, and maternal androgens. 46,XY DSD includes complete and partial androgen insensitivity, 5α-reductase deficiency, gonadal dysgenesis, and testosterone biosynthetic defects. Sex chromosome DSD includes Turner (45,X) and Klinefelter (47,XXY). Phenotype reflects gonadal development, androgen production, androgen receptor function, and Müllerian inhibiting substance. A newborn with atypical genitalia is a medical emergency only for salt-wasting CAH; otherwise proceed deliberately.
Evaluation and traps
Obtain karyotype, electrolytes, glucose, 17-hydroxyprogesterone, testosterone, LH/FSH, and pelvic ultrasound; hCG stimulation and DHT help assess androgen synthesis and action. Do not assign a sex of rearing before diagnosis and family discussion. In 46,XY complete androgen insensitivity, testes are present, Müllerian structures are absent, testosterone is high, and LH is high. In 5α-reductase deficiency, testosterone is normal or high and DHT is low. In Turner syndrome, look for coarctation, bicuspid aortic valve, renal anomalies, and autoimmune thyroid disease.
Worked example
A 46,XY newborn has female external genitalia, inguinal testes, and no uterus. Testosterone is high and LH is high after infancy. This points to complete androgen insensitivity; confirm with receptor testing or genetics and provide sensitive counseling.