Idiopathic Hypogonadotropic Hypogonadism— An Update on the Aetiopathogenesis, Management of IHH in Both Males and Females—An Exhaustive Review

Abstract

Methods: Asystematic literature search was performed using PUBMED for all English articles up to April 2014. Although this review mainly focuses on published human studies, it also draws attention to where future research should be directed based on animal studies. Results: Besides the 9 known mutations widely quoted for KS namely KAL1, Fibroblast growth factor 8 (FGF8), fibroblast growth factor receptor 1 (FGFR1), prokineticin 2 (PROK2), PROK receptor 2 (PROKR2), WDR11, heparin sulfate-6-O-Transferase (HS6T1), chromodomain helicase DNA binding protein 7 (CHD7) and semaphorin 3A (SEMA 3A), additional mutations in "FGF8 synexpression" group e.g., FGF 17, ILRD, DUSP 6, SPRY4 and FLRT3 have been shown to be involved in CHH, mostly KS besides SEMA 7A. Although traditionally division has been based on anosmic/normosnic criteria, further genes found to cause so called nIHH like Gonadotropin releasing hormone receptor (GNRHR). KISS1, TAC3, TACR3 have also been found to be associated with hyposmia on detailed testing on UPSIT and MRI for olfactory structures revealed absent OB. Further detailed examination of transcription factor genes have revealed involvement of HESX1, TSHZ1, AXL, SOX10 with a strong overlap of in transcription factors in development of septooptic dysplasia (SOD), combined pituitary hormone deficiency (CHPD) and KS. Treatment with rFSH/-hCG gives almost similar results to pulsatile GnRH therapy and should be based on cost factor, availability and in occasional cases specific treatment like kisspeptin therapy. Conclusions: Contrary to the traditional thinking, one shoud reconsider classifying cases of IHH simply on basis of anosmia/normosmia. Deafness calls for looking for mutations in Sox 10/CHD7/ILRD7 considering 38% associ-Open Access K. K. Kulvinder et al. 51 ation of former. Therapy should be individualized based on availability of pulsatile GnRH, cost factor and in recalcitrant cases kp therapy may be of use with kp mutations and NKB mutations.

Untitled

“…Hence role of surgery in endometriosis is highlighted here besides the articles on medical treatment of endometriosis, aetiopathogenesis, endometriosis associated pain and role of dienogest and GnRH -a in Em treatment described earlier [4][5][6].…”

Clinical Presentation of Hypogonadotropic Hypogonadism in 18-Year-Old Man: Case Report

“…The absence of spontaneous pubertal development characterizes idiopathic hypogonadotropic hypogonadism (IHH) as a result of low levels of sex steroids and gonadotropins with normal pituitary function. 1 Idiopathic hypogonadotropic hypogonadism is divided into two categories, namely Kallmann Syndrome and normosmic IHH. 2 Incident varies from 1: 10,000 -140,000 with a ration of male: female of 4: 1 with men every 1: 8000.…”

“…In most patients with IHH, the physiological response to GnRH restores normal levels of the pituitary and gonadal hormones, allowing testicular growth and spermatogenesis in men. 1 Hypogonadotropic hypogonadism can cause micropenis. Hypogonadotropic hypogonadism is the most common cause of micropenis.…”