title: Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency.
abstract: OBJECTIVE
  The nicotinamide nucleotide transhydrogenase (NNT) enzyme is the main generator of nicotinamide adenine dinucleotide phosphate-oxidase in the mitochondrion. Mutations of the NNT gene have been recently implicated in familial glucocorticoid deficiency. We describe the long-term clinical course of a NNT-deficient 20-year-old patient with combined adrenal failure who had developed a testicular adrenal rest tumor and precocious puberty.
  
  
  METHODS
  The patient's medical records were reviewed. Whole-exome sequencing was performed on DNA obtained from the patient and family members.
  
  
  RESULTS
  The patient experienced Addisonian crisis at 10 months of age. Enlarged testicular volume and precocious puberty, accompanied by increased testosterone levels, were noted at 6 years. Testicular biopsy revealed a adrenal rest tumor, which regressed after intensification of glucocorticoid treatment. Genetic studies disclosed a c.1163A>C, p.Tyr388Ser substitution on the NNT gene. This mutation is predicted to be damaging to NNT function.
  
  
  CONCLUSIONS
  We demonstrated for the first time that the clinical spectrum of NNT deficiency may consist of mineralocorticoid deficiency and testicular involvement as well.
authors: Eli
authors: E
authors: Hershkovitz
authors: Maram
authors: M
authors: Arafat
authors: Neta
authors: N
authors: Loewenthal
authors: Alon
authors: A
authors: Haim
authors: Ruti
authors: R
authors: Parvari
mesh_terms: D000309:Adrenal Insufficiency / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D000314:Adrenal Rest Tumor / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009250:NADP Transhydrogenases / Q000172:deficiency*; D013736:Testicular Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D009250:NADP Transhydrogenases