MON-246 Long-Term Impact of Recombinant Follicle Stimulating Hormone Treatment in Five Infants with Hypogonadotropic Hypogonadism

Background Severe congenital hypogonadotropic hypogonadism (CHH) in boys can be diagnosed during the minipuberty of infancy. Combined gonadotrophin treatment at that age is suggested to improve testicular function, yet long-term evidence is lacking. We describe the first long-term follow-up data on CHH boys treated with recombinant human follicle stimulating hormone [r-hFSH] as infants. Patients and Methods This is a retrospective patient chart review of five boys from two pediatric tertiary centers in Finland (2004-2016). Four patients had panhypopituitarism of yet unknown etiology, one had CHARGE syndrome due to a CHD7 mutation. The patients were treated at the age of 0.7 to 4.2 months with r-hFSH (from 16.6 IU to 33.4 IU s.c. per week for 3 to 4.3 months) combined with testosterone [T] (25 mg i.m. monthly for three months). Inhibin B levels and testicular development were followed for 1.9 to 12.2 years after the treatment. Results During the r-hFSH + T treatment, inhibin B increased from 76 ± 18 ng/L to 176 ± 80 ng/L (p = 0.04) and penile length increased by 81 ± 50% (p = 0.04). All boys underwent orchidopexy at 2.0 ± 0.7 years of age; one boy had testicular regression. Unexpectedly, two boys with robust inhibin B responses in infancy demonstrated low inhibin B values in peripuberty: from 290 ng/L (4 months) to 16 ng/L (12.4 years), and from 207 ng/L (6 months) to 21 ng/L (12.8 years). Conclusions This is the first report of the long-term effects of r-hFSH-treatment given during minipuberty. The data suggest that Sertoli-cell response to r-hFSH is transient and that testosterone, given concomitantly with r-hFSH at infancy, does not inhibit Sertoli cell activity. Our observations require confirmation from larger longitudinal patient series.