Childhood Onset X-Linked Adrenal Hypoplasia Congenita (AHC) Associated with Variants of Incomplete Hypogonadotropic Hypogonadism

BERGADA I; REY R; ROPELATO G; ANDREONE L; CAMPO S; COPELLI S

Boston, Ma, USA

Congreso; 88th Annual Meeting of the Endocrine Society; 2006

Endocrine Society

Childhood onset AHC is associated with variable degrees of impaired sexual development due to hypogonadotropic hypogonadism (HH). We report three (15 – 20 years old) patients from two families  (mutations Y214X, I361T in the DAX-1 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 gonadotropins 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 (147 and 185 pmol/l, reference levels for boys with serum T < 50 ng/dl: 250-800 pmol/l), concomitantly with low FSH, indicating hypogonadotropic hypogonadism. Finally, AMH was extremely low in the third (17 pmol/l), 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  hypothalamic-pituitary-gonadal axis in patients with incomplete HH due to childhood onset X-linked AHC