SFEBES2018 Oral Communications Clinical highlights (6 abstracts)
Kisspeptin- a novel clinical test of hypothalamic function in men with hypogonadotrophic hypogonadism
Pei Chia Eng , Ali Abbara Sophie Clarke , Maria Phylactou , Edouard Mills , Muralidhara Koteshwara , Germaine Chia , Lisa Yang , C Pratibha Machenahalli , Deborah Papadopoulou , Chioma Izzy-Engbeaya , Channa Jayasena , Alexander N Comninos & Waljit S Dhillo
Imperial College London, London, UK.
Background: Hypogonadotrophic Hypogonadism (HH) is characterised by hypogonadism in the context of low gonadotrophin levels, frequently due to a defect in hypothalamic function e.g. Kallman’s syndrome. However, no direct test of hypothalamic function currently exists. Kisspeptin is a hypothalamic neuropeptide that stimulates endogenous GnRH release. Thus, we investigated whether kisspeptin could be used to interrogate hypothalamic function in men with HH.
Methods: Men with HH (low testosterone/LH/FSH, normal MRI pituitary, absent puberty, unprimed by pulsatile GnRH; n=4) and healthy eugonodal men (n=20) received either an intravenous bolus of GnRH (100mcg), or kisspeptin-54 (6.4 nmol/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 HH were compared by unpaired t test.
Results: Mean increase in serum LH from baseline was +8.2±3.8i U/L in eugonadal men and +0.12±0.13 iU/L in HH (P=0.0003) following kisspeptin. All men with HH had an LH-increase <1.5i U/L following kisspeptin, whereas all eugonadal men had an LH-increase >1.5i U/L. By contrast, mean increase in serum LH from baseline following GnRH was +6.2±3.2i U/L in eugonadal men and +2.2±3.8 iU/L in HH (P=0.062). Whilst kisspeptin-induced mean LH increase effectively discriminated men with HH from eugonadal men (area under ROC 1.0), GnRH-induced mean LH increase was less discriminatory (area under ROC 0.82). In eugonadal men, the maximal increase in LH following kisspeptin significantly predicted the maximal increase in LH following GnRH (univariate linear regression, r2=0.45; P=0.0013), however this relationship was lost in men with HH (r2=0.03; P=0.83).
Conclusion: This provides ‘proof of concept’ that a novel kisspeptin test of hypothalamic function better discriminate men with HH from eugonadal men than GnRH. These findings have significant implications for managing patients with HH.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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