Adrenal hypoplasia congenita - an uncommon reason of primary adrenal insufficiency.

Adrenal hypoplasia congenita (AHC) is a rare inherited condition characterised by primary adrenal failure and hypogonadotropic hypogonadism. Most cases arise from mutations in the NR0B1 gene (Xp21.3), which encodes an orphan nuclear receptor DAX-1. A 20-year-old patient was recently diagnosed with AHC. Adrenal failure had been recognized and treated since his infancy. During adolescence, gradual decrease in growth velocity and low body mass were noted. Lack of puberty and skeletal immaturity were observed. Serum DHEA-S and testosterone were undetectable. Low gonadotropin levels failed to rise after stimulation. Neither dysfunction of the somatotropic nor pituitary-thyroid axis was found and no hypothalamo-pituitary pathology was visible on MRI. Androgen replacement therapy induced the development of secondary sexual characteristics, remarkably improved patient's growth and advanced his bone age. NR0B1 mutation screening revealed nucleotide transversion C>A, resulting in premature stop codon (Y399X). Same mutation was previously identified in a Scottish family, however, phenotypic differences suggest the role of additional factors modifying the disease course. Although it does not change therapeutic strategy, accurate molecular diagnosis allows genetic counselling in family members. Autoimmunity remains the major cause of adrenal failure; however, other rare conditions should always be considered.