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. CONCLUSION: We demonstrated for the first time that the clinical spectrum of NNT deficiency may consist of mineralocorticoid deficiency and testicular involvement as well.
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. CONCLUSION: We demonstrated for the first time that the clinical spectrum of NNT deficiency may consist of mineralocorticoid deficiency and testicular involvement as well.
Authors: A S Tresoldi; N Betella; V Hasenmajer; C Pozza; W Vena; B Fiamengo; L Negri; M Cappa; A G A Lania; A Lenzi; A M Isidori; A Pizzocaro Journal: J Endocrinol Invest Date: 2020-07-20 Impact factor: 4.256