Evaluating the roles of follicle-stimulating hormone receptor polymorphisms in gonadal hyperstimulation associated with severe juvenile primary hypothyroidism

Context: Rare activating mutations of the human (h)FSHR have been reported in some women with spontaneous ovarian hyperstimulation in pregnancy, where follicular growth is inappropriately stimulated by elevated concentrations of human chorionic gonadotropin acting through the hFSHR. It is not known whether ovarian hyperstimulation in peripubertal girls with untreated primary hypothyroidism is caused by hFSHR mutations and/or influenced by hFSHR allelic variants, rendering the hFSHR more sensitive to circulating TSH. Objective: The aim of the study was to determine whether mutations of the hFSHR and/or hFSHR allelic variants are associated with greater sensitivity of the hFSHR to TSH. Design: The hFSHR gene was sequenced from eight pediatric patients displaying gonadal hyperstimulation due to primary hypothyroidism. HEK293 cells expressing different hFSHR allelic combinations were studied for their responsiveness to recombinant (r)hTSH. Setting: The study was conducted at university research centers. Patie...