Isolated Follicle-Stimulating Hormone (FSH) Deficiency in Male Sex: A Case Report

Follicle-stimulating hormone (FSH) is a glycoprotein hormone produced in the anterior pituitary, essential in the regulation of gonadal functions. Isolated FSH deficiency (IFD) is a rare inherited disorder, usually caused by β-subunit alterations. In men, it is frequently detected during infertility evaluation, commonly associated with spermatogenesis impairment and testicular atrophy with normal testosterone levels. We present the case of a 30-year-old male patient who was referred for breast pain and bilateral gynecomastia. Laboratory evaluation displayed primary hypothyroidism with positive thyroid autoantibodies and decreased FSH levels, with normal total testosterone and adequate luteinizing hormone (LH) levels. A gonadotropin-releasing hormone (GnRH) stimulation test demonstrated inadequate FSH response, highly suggestive of IFD. Genetic testing for <i>FSHB</i> mutations was negative, and whole exome sequencing revealed no recognized pathogenic variants. Semen analysis was postponed by the patient's choice. Although rare, IFD should be considered when evaluating patients with symptoms suggestive of hypogonadism. The overall prevalence of FSH-β mutations is unknown but probably underdiagnosed in male patients.