Isolated 17,20-lyase (desmolase) deficiency in a 46,XX female presenting with delayed puberty

To investigate the cause of hypergonadotropic hypogonadism.

Case report and literature review.

University Departments of Pediatric Endocrinology and Obstetrics and Gynecology.

A 13.5-year-old girl with absent puberty and growth retardation.

None.

Detailed biochemical, radiological, and molecular analysis, including pelvic ultrasound, basal steroid hormone analysis in serum and aspirated follicle fluid, serum steroid measurement after ACTH (Synachten) and human chorionic gonadotropin (hCG) stimulation, and molecular analysis of CYP17.

This girl with hypergonadotropic hypogonadism (LH 65 U/L, FSH 50 U/L) had a 46,XX karyotype, small uterus and enlarged cystic ovaries, and markedly delayed bone age (9 years). Basal (serum, follicular) and stimulated (serum) steroid hormone levels were consistent with isolated 17,20-lyase deficiency whereas relatively normal P and 17-hydroxyprogesterone concentrations were detected together with very low androstenedione, T, and E(2) levels.

Isolated 17,20-lyase deficiency should be considered in the differential diagnosis of hypergonadotropic hypogonadism in 46,XX females, and follicular fluid steroid analysis is a useful adjuvant test. Failure to detect mutations in CYP17 raises the possibility of a novel association of these phenotypes.