554 CHAPTER 15 Pediatric urology

Abnormal sexual differentiation

Disorders of sex development (DSD) are defined as congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical.

They are estimated to affect 1 in 4500 births, and have recently undergone changes in recommended nomenclature (Table 15.1).1

Sex chromosome DSD (disorders of gonadal differentiation)

These are subdivided into seminiferous tubule dysgenesis (Klinefelter syndrome XXY, 46XX males); Turner syndrome (45XO); true hermaphrodites (46XX or XY with both ovarian and testicular tissue); mixed gondal dysgenesis (streak gonads and a spectrum of ambiguous genitalia); and pure gonadal dysgenesis (females with streak gonads).

46XY DSD (previously male pseudohermaphroditism)

Individuals have 46XY karyotype with differentiated testes. They have defects of testosterone production (3A-hydroxysteroid dehydrogenase, 17A-hydroxylase enzyme deficiencies) or androgen resistance (testicular feminization, 5A-reductase deficiency), resulting in varying degrees of feminization.

46XX DSD (previously female pseudohermaphroditism)

Individuals have 46XX karyotype with ovaries, a partially masculinized phenotype, and ambiguous genitalia. The most common type is congential adrenal hyperplasia (CAH), due to 21-hydroxylase deficiency (in 95%; see Fig. 15.7). Formation of hydrocortisone is impaired, resulting in a compensatory increase in adrenocorticotrophin hormone (ACTH) and testosterone production.

Some forms have a salt-wasting aldosterone deficiency that can present in the first few weeks of life with adrenal crisis (severe vomiting and dehydration), requiring rehydration and steroid replacement therapy.

Evaluation

A detailed history may uncover a positive family history of intersex disorders. Maternal ingestion of drugs such as steroids or contraceptives during pregnancy should be ascertained.

General examination may show associated syndrome anomalies (Klinefelter and Turner syndromes) or failure to thrive and dehydration (salt-wasting CAH). Assess external genitalia for phallus size and location of urethral meatus. Careful palpation may confirm the presence of testes, excluding a diagnosis of female pseudohermaphroditism. Patients with bilateral undescended testes or unilateral undescended testis with hypospadias should be suspected of having an intersex disorder.

Pelvic US can help locate the gonads or, occasionally, laparotomy with gonadal biopsy is required for diagnosis.

1 Hughes IA, Houk C, Ahmed SF, et al. (2007). Consensus statement on management of intersex disorders. Arch Dis Child 554–563.

* Hughes IA, Houk C, Ahmed SF, et al. (2007). Consensus statement on management of intersex disorders. Arch Dis Child 554–563.

Cholesterol

17A-OH

Pregnenolone 17-OH Pregnenolone Dehydroepiandrosterone

Figure 15.7 Metabolic pathways for adrenal steroid synthesis.