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% association 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.
Highlights
Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of spontaneous pubertal development in the face of low sex steroids and gonadotropin levels with otherwise normal pituitary function
Besides the 9 known mutations widely quoted for Kallmanns Syndrome (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., fibro blast growth factor (FGF) 17, ILRD, DUSP 6, SPRY4 and FLRT3 have been shown to be involved in CHH, mostly KS besides SEMA 7A
The very concept of classifying IHH into anosmic/hyposmic KS and normosmic IHH gets challenged by the study of Lewkowitz Shpunoff till we have been tuned to working on the basis of KS/nIHH
Summary
Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of spontaneous pubertal development in the face of low sex steroids and gonadotropin levels with otherwise normal pituitary function. In most patients with IHH, physiological GnRH response restores normal levels of pituitary and Gonadal hormones, allowing for testicular growth and spermatogenesis in men and ovulation in women [2]. Human studies in KS fetuses with olfactory bulb agenesis revealed that premature interruption of the olfactory, vomeronasal (VN), and terminal nerve fibers in the fronto nasal region disrupts the migration of GnRH-1 cells which normally migrate from the nose to the brain along these nerve fibers [4] [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
