Gonadal histology with testicular carcinoma in situ in a 15-year-old 46,XYfemale patient with a premature termination is the steroidogenic acute regulatory protein causing congenital lipoid adrenal hyperplasia

Mutations in the steroidogenic acute regulatory protein (StAR) gene cause c ongenital Lipoid adrenal hyperplasia, characterized by diminished or absenc e of adrenal and gonadal steroids, resulting in severe adrenal insufficienc y and ambiguous or complete female external genitalia in genetic males. We report on a 15-yr-old 46,XY phenotypic female, referred because of lack of pubertal development. ACTH and gonadotropin concentrations were elevated ; and aldosterone, cortisol and its precursors, and sex steroids before and after stimulation were below the lower limit of detection. In the StAR gen e, a homozygous nonsense mutation (TGG --> TAG) in exon 7 (W250X) was ident ified. Histologic examination after gonadectomy showed seminiferous tubules containing immature Sertoli cells and a few single germ cells with positiv e placental-like alkaline phosphatase immunoreactivity, indicating carcinom a in situ. This is the first report on testicular morphology, at a pubertal age, in a female patient with 46,XY karyotype and a mutation in the StAR gene, in who m gonadal neoplasia had developed.