ESPE Abstracts

Background: Steroidogenic factor 1 (SF-1/NR5A1) plays a crucial role in regulating adrenal development, gonad determination and differentiation, and in the hypothalamic-pituitary control of reproduction and metabolism. In men (46, XY) mutations in SF-1/NR5A1 gene cause a wide phenotypic spectrum that ranges from complete testicular dysgenesis with Müllerian structures and amenorrhea, through individuals with mild clitoromegaly or genital ambiguity, to severe penoscrotal hypospadias or even anorchia and oligospemia. In recent years the role of SF-1 in the ovarian function was controversially discussed, some reports suggesting a relationship of mutation in SF-1 with primary ovarian insufficiency.

Case presentation: We report the follow-up of the first case of a SF-1 deficient 46, XX girl in whom adrenal insufficiency was the only clinical sign of the loss-of-function mutation (AJHG 2000, 67:1563). During infancy ovarian development and function seemed normal on the base of normal ovarian morphology at US and repeatedly normal gonadotropins and ovarian markers. To date, this young woman aged 16.5 years shows normal growth, normal BMI and psychomotor development, has a normal puberty and regular menstruation. The current treatment of her adrenal insufficiency consists of hydrocortisone (17.4mg/m² per day) and fludrocortisone (0.05mg/day).

Conclusion: This report shows one, to date uniquely described phenotypic variant of SF-1 mutation in a 46, XX affected person with adrenocortical insufficiency but no ovarian dysfunction nor disturbance of pubertal development. By following the patient during adolescence and transition to adulthood, this case will help us to follow natural history of SF-1 mutation in 46, XX patient and will shed light on its role in the ovarian function.