ECE2020 Audio ePoster Presentations Pituitary and Neuroendocrinology (217 abstracts)
Kisspeptin-54 accurately identifies hypothalamic dysfunction in men with congenital hypogonadotropic hypogonadism
Ali Abbara 1 , Pei Chia Eng 1 , Maria Phylactou 1 , Sophie Clarke 1 , Edouard Mills 1 , Germaine Chia 1 , Lisa Yang 1 , Chioma Izzi-Engbeaya 1 , Channa Jayasena 1 , Alexander Comninos 1 , Richard Ivell 2 , Ravinder Anand-Ivell 2 , Jesse Rademaker 3 , Xu Cheng 3 , Richard Quinton 4 , Nelly Pittelout 3 & Waljit Dhillo 1
1Imperial College London, United Kingdom; 2University of Nottingham, United Kingdom; 3University of Lausanne, Lausanne, Switzerland; 4Newcastle University, United Kingdom
Background: Hypogonadotrophic hypogonadism is characterised by hypogonadism in the context of low/inappropriately normal gonadotrophin levels. Congenital Hypogonadotrophic Hypogonadism (CHH) occurs due to disrupted GnRH neuronal migration, or impaired hypothalamic GnRH secretion or action. However, no direct test of hypothalamic GnRH neuronal function currently exists. Kisspeptin-54 is a neuropeptide that stimulates endogenous hypothalamic GnRH release. Thus, we investigated whether kisspeptin-54 could be used to interrogate hypothalamic function in men with CHH.
Methods: Men with CHH (low testosterone, low/inappropriately normal gonadotrophin levels, incomplete pubertal development; n = 21) and healthy eugonadal men (n = 21) received an intravenous bolus of either GnRH (100 mg), or kisspeptin-54 (6.4 nmol/kg), on two study visits at least one week apart. Serum gonadotrophins were measured every 15 mins for 6 hrs following injection. Increases in serum gonadotrophins from baseline following GnRH/kisspeptin in eugonadal men and CHH were compared by Mann Whitney U test.
Results: The maximal rise in LH following KP54 was significantly greater in healthy men (12.5 iU/l) than in men with CHH (0.4 iU/l; P < 0.0001). Following KP54, all men with CHH had an LH-rise <2 iU/l, whereas all healthy men had an LH-rise >4 iU/l. Thus, the LH-rise after KP54 more effectively discriminated men with CHH from healthy men (auROC 1.0) than GnRH (auROC 0.88). Anosmic men with CHH (ie Kallmann syndrome) had even lower LH-rises following KP54 than normosmic men with CHH (P = 0.017).
Conclusion: In summary, akisspeptin-54 test of hypothalamic GnRH neuronal function more accurately discriminated men with CHH from healthy men thana GnRH test. Consequently, a kisspeptin-54 test can be used to better identify patients with CHH to direct genetic testing, and to rapidly assess for evidence of spontaneous reversal of hypothalamic dysfunction in patients with known CHH. Thus, KP54 demonstrates potential as a specific test of hypothalamic GnRH function when assessing patients presenting with disorders of puberty.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more