Postnatal Changes of T, LH, and FSH in 46,XY Infants with Mutations in the AR Gene

Androgen insensitivity syndromes (AIS) result from the incapacity for T and dihydrotestosterone to virilize male embryos and is mainly attributable to molecular defects of the AR gene. In normal males, T and LH rise during the first few months of life, and this physiological surge is commonly used to evaluate the gonadotropic axis at this age. This neonatal surge has not been evaluated in detail in newborns with AIS. We sequentially measured plasma T, LH, and FSH during the first 3 months of life in 15 neonates with AIS and AR mutation. A GnRH and an human CG stimulation test were also performed. Patients were divided in 2 groups with complete (n = 10) or partial (n = 5) AIS (CAIS or PAIS), based on the clinical phenotype. In patients with PAIS, T levels were in the high-normal range at d 30 (18.4 +/- 6.9 nM) and d 60 (12.8 +/- 3.8 nM). In contrast, plasma T values were below the normal range in 9 of 10 patients with CAIS at d 30 (1 +/- 0.3 nM) and d 60 (1.4 +/- 0.7 nM, both P < 0.004 vs. PAIS). Plasma LH values were low in CAIS at d 30 (0.7 +/- 0.1U/liter) and increased normally in PAIS (8.7 +/- 2.5 U/liter, P = 0.004). We conclude that the postnatal T and LH surge occurs expectedly in neonates with PAIS but is absent in those with CAIS and that the postnatal T rise requires the receptivity of the hypothalamo-pituitary axis to T.