OR32-3 Kisspeptin- a Novel Clinical Test of Hypothalamic Function in Men with Hypogonadotrophic Hypogonadism

• Published in: Journal of the Endocrine Society 2019-04, Vol.3 (Supplement_1)
• Main Authors: Phylactou, Maria, Abbara, Ali, Eng, Pei, Clarke, Sophie, Mills, Edouard, Koteshwara, Muralidhara, Chia, Germaine, Yang, Lisa, Machenahalli, Pratibha, Papadopoulou, Deborah, Izzi-Engbeaya, Chioma, Jayasena, Channa, Comninos, Alexander, Dhillo, Waljit
• Format: Article
• Language: English
• Subjects: Neuroendocrinology and Pituitary
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/js.2019-OR32-3

Background: Hypogonadotrophic Hypogonadism is characterised by hypogonadism in the context of low / inappropriately normal gonadotrophin levels. Congenital HH (CHH) occurs due to defective hypothalamic GnRH neuronal migration (e.g. Kallman’s syndrome), or secretion. However, no direct test of hypothalamic GnRH neuronal function currently exists. Kisspeptin is a neuropeptide that stimulates endogenous hypothalamic GnRH release. Thus, we investigated whether kisspeptin could be used to interrogate hypothalamic function in men with CHH. Methods: Men with CHH (low testosterone, low LH/FSH, normal MRI pituitary / baseline pituitary function, absent puberty, unprimed by pulsatile GnRH; n=4) and healthy eugonadal men (n=20) received an intravenous bolus of GnRH (100mcg), or kisspeptin-54 (6.4nmol/kg), on two study visits ≥1 week apart. Serum gonadotrophins were measured every 15mins for 6hrs following injection. Increases in serum gonadotrophins from baseline following GnRH / kisspeptin in eugonadal men and CHH were compared by unpaired t test. Results : Mean increase in serum LH from baseline was 8.2±3.8iU/L in eugonadal men and 0.12±0.13iU/L in CHH (P=0.0003) following kisspeptin administration. All eugonadal men had an LH increase >1.5iU/L, whereas all men with CHH had an LH increase