Prolonged activation of the hypothalamus– pituitary–gonadal axis in a child with X‐linked adrenal hypoplasia congenita

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Abstract
X‐linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder of the human adrenal cortex that is caused by a mutation of the DAX‐1 gene, a member of the nuclear hormone receptor superfamily. Hypogonadotrophic hypogonadism is frequently associated with this disease and the DAX‐1 mutation is known to impair gonadotrophin production by acting at both the hypothalamic and pituitary levels. However, three recent studies reported that the hypothalamic–pituitary–gonadal axis was active in six infants with AHC, suggesting that a difference exists in the central regulation of hypothalamic–pituitary–gonadal activity between infant boys and pubertal boys. To determine the effect of the DAX‐1 gene mutation on the axis in early childhood, we measured testosterone, LH, and FSH and performed LH‐releasing hormone tests on a boy with AHC from birth to 3 years of age. Surprisingly, our findings showed that the axis was active from the infantile period to 3 years of age. This delayed initiation of the prepubertal pause, or prolonged activation of the axis, indicates that the DAX‐1 gene is related to the control mechanism of the prepubertal restraint of gonadotrophin secretion.