title: Longitudinal evaluation of the hypothalamic-pituitary-testicular function in 8 boys with adrenal hypoplasia congenita (AHC) due to NR0B1 mutations.
abstract: BACKGROUND
  Boys carrying mutations in the NR0B1 gene develop adrenal hypoplasia congenita (AHC) and impaired sexual development due to the combination of hypogonadotropic hypogonadism (HH) and primary defects in spermatogenesis.
  
  
  METHODS
  We analysed the evolution of hypothalamic-pituitary-testicular function of 8 boys with AHC due to NR0B1 mutations. Our objective was to characterize and monitor the progressive deterioration of this function.
  
  
  RESULTS
  The first symptoms appeared in the neonatal period (n = 5) or between 6 months and 8.7 years (n = 3). Basal plasma adrenocorticotrophic hormone (ACTH) concentrations increased in all boys, whilst cortisol levels decreased in one case. The natremia was equal or below 134 mmol/L and kaliemia was over 5 mmol/L. All had increased plasma renin. In 3 of 4 patients diagnosed in the neonatal period and evaluated during the first year, the basal plasma gonadotropins concentrations, and their response to gonadotropin releasing hormone (GnRH) test (n = 2), and those of testosterone were normal. The plasma inhibin B levels were normal in the first year of life. With the exception of two cases these concentrations decreased to below the normal for age. Anti-Müllerian hormone concentrations were normal for age in all except one case, which had low concentrations before the initiation of testosterone treatment. In 3 of the 8 cases the gene was deleted and the remaining 5 cases carried frameshift mutations that are predicted to introduce a downstream nonsense mutation resulting in a truncated protein.
  
  
  CONCLUSIONS
  The decreases in testosterone and inhibin B levels indicated a progressive loss of testicular function in boys carrying NR0B1 mutations. These non-invasive examinations can help to estimate the age of the testicular degradation and cryopreservation of semen may be considered in these cases as investigational procedure with the aim of restoring fertility.
authors: Université Paris Descartes, Sorbonne Paris Cité, and Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Unité d'Endocrinologie Pédiatrique, Le Kremlin Bicêtre, France.
authors: Caroline
authors: C
authors: Galeotti
authors: Zineb
authors: Z
authors: Lahlou
authors: Domitille
authors: D
authors: Goullon
authors: Hélène
authors: H
authors: Sarda-Thibault
authors: Juliette
authors: J
authors: Cahen-Varsaux
authors: Joëlle
authors: J
authors: Bignon-Topalovic
authors: Anu
authors: A
authors: Bashamboo
authors: Ken
authors: K
authors: McElreavey
authors: Raja
authors: R
authors: Brauner
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics / Q000503:physiopathology*; D000309:Adrenal Insufficiency; D000595:Amino Acid Sequence; D001483:Base Sequence; D015331:Cohort Studies; D057137:DAX-1 Orphan Nuclear Receptor / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D000075262:Hypoadrenocorticism, Familial; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012189:Retrospective Studies; D013737:Testis / Q000503:physiopathology*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D017931:DNA Primers; C539965:NR0B1 protein, human