CONICET | Buscador de Institutos y Recursos Humanos

Childhoodonset AHC is associated with variable degrees of impaired sexual development due to hypogonadotropic hypogonadism (HH). We report three (15 to 20 years old) patients from two families (mutations Y214X, I361T in the DAX1 gene) with childhood onset AHC. The three patients developed adrenal insufficiency at 4 to 8 years of age. All had an incomplete HH reaching a Tanner stage II to III. Nocturnal spontaneous gonadotropin secretion using cluster analysis showed in all a marked reduction in mean LH levels (0.02 to 2.2 mIU/ml , normal 4.9 ± 0.38 mIU/ml) as well as LH pulse amplitude (0.2 to 0.88 mIU/ml, normal 3.5 ± 0.5 mIU/ml). Serum testosterone (T) ranged from prepubertal (10 ng/dl) to low pubertal (210 ng/dl) levels. Mean serum FSH was low in 2 patients (0.79 ± 0.07 and 0.85 ± 0.05 mIU/ml, normal 5.3 ± 0.60 mIU/ml), and high in the remaining (11.3 ± 1.11 mIU/ml). Serum antimullerian hormone (AMH) was relatively low in 2 patients (185 and 205 pmol/l, reference levels for boys with serum T < 50 ng/dl: 250 800 pmol/l), concomitantly with low FSH, indicating hypogonadotropic hypogonadism. In these two patients serum inhibin B were moderately low (67 and 118 pg/ml) compared to prepubertal normal levels. Finally, in the third patient in Tanner stage III, with serum testosterone between 208 to 211 ng/dl, serum AMH and inhibin B were low (21 pmol/l and 94 pg/ml, respectively), concomitantly with high serum levels of serum FSH, reflecting a primary impairment of seminiferous epithelial function already during adolescence. In summary, we believe these cases expand the clinical spectrum of the potential disorders at the hypothalamicpituitarygonadal axis in patients with incomplete HH due to childhood-onset Xlinked AHC.