title: ACTH-dependent precocious pseudopuberty in an infant with DAX1 gene mutation.
abstract: DAX1 gene (Xp21) expression is involved in the development of the hypothalamo-pituitary-gonadal and adrenal axes, and acts as a negative regulator of steroidogenesis. Mutations of this gene determine adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism. We report the case of a 9-month-old boy referred for the study of macrogenitosomia and pubic hair development. He had presented acute adrenal crises in the neonatal period and, later, a clinical picture of peripheral precocious puberty. A mutation in the DAX1 gene was found (Trp291Arg) and a diagnosis of AHC was made. Replacement doses of hydrocortisone (HC) (10 mg/m2/day) failed to produce a feedback inhibition of adrenocorticotropic hormone (ACTH), and testosterone levels remained high. Testosterone and ACTH values normalized after HC was progressively increased to 18 mg/m2/day. In conclusion, peripheral precocious puberty in patients with DAX1 gene mutations appears to be secondary to the stimulus exerted by ACTH on melanocortin receptors in Leydig cells and to the overexpression of testicular steroidogenesis activators by the loss of transcriptional repression.
authors.affiliation: Pediatric Endocrinology Department, Hospital Universitario Vall d'Hebron, Autonomous University Barcelona, Paseo Vall d'Hebron, 119-129, 08035, Barcelona, Spain. dyeste@vhebron.net
authors.forename: Diego
authors.initials: D
authors.lastname: Yeste
authors.forename: Cristina
authors.initials: C
authors.lastname: González-Niño
authors.forename: Guiomar
authors.initials: G
authors.lastname: Pérez de Nanclares
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pérez-Nanclares
authors.forename: Laura
authors.initials: L
authors.lastname: Audi
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrascosa
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007027:Hypothalamic Diseases / Q000235:genetics* / Q000378:metabolism*; D007223:Infant; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D000324:Adrenocorticotropic Hormone