Background: Congenital hypogonadotropic hypogonadism (CHH) is a group of rare disorders responsible for insufficient secretion of the pituitary gonadotropins LH and FSH. We have observed CHH in men with poorer responses to human chorionic gonadotropin (hCG), or combined FSH and hCG for testicular maturation and fertility after adolescence.
Objective and hypotheses: The purpose of this research is to clarify how best to tailor-make treatment according to the genotype by retrospectively analyzing the results of a treatment method based on exact gene diagnosis. rFSH pretreatment may become a successful means of treatment for men with CHH.
Method: We investigated the clinical course of 11 male patients (aged 425 years) with CHH, including eight patients with Kallmann syndrome and two patients with CHARGE syndrome. All male patients with CHH were subjected to mutation assessment in 48 CHH-associated genes, using Ion Torrent next-generation sequencing. We then confirmed these mutations using Sanger sequencing.
Results: Seven of the patients had bilateral cryptorchidism and micropenis, and three patients had micropenis only. All patients had no olfactory blub. Abnormal delay of secondary sexual characteristics was noted in the eight patients older than 15 years, who revealed no response in the hCG test. We discovered KAL1, FGF1R mutations during the study. In one adolescence man with Kallmann syndrome and FGF1R mutation, testicular maturation was absent during continuous hCG injections for 6 months. His testes volume was <1 ml. We administered rFSH 75 IU S.C. daily for 2 months, following which hCG 1000 IU S.C. and rFSH 75 IU S.C. were administered every other day. Consequently, his testes became larger and his serum testosterone value reached a normal range.
Conclusion: rFSH pretreatment followed by GnRH may be useful in enhancing testicular growth in men with CHH including Kallmann syndrome. However, further studies are needed to clarify whether rFSH pretreatment results in fertility.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology