ECEESPE2025 Rapid Communications Rapid Communications 5: Reproductive and Developmental Endocrinology Part 1 (6 abstracts)
Kisspeptin-54 accurately identifies the cause of delayed puberty
Maria Phylactou 1,2 , Kanyada Koysombat 1,2 , Megan Young 1,2 , Sandhi Nyunt 1,2 , Jovanna Tsoutsouki 1,2 , Arthur C. Yeung 1,2 , Pei Eng 1,2 , Sophie Clarke 3 , Edouard Mills 1,2 , Ruben H. Willemsen 4 , Jayanti Rangasami 5 , Evelien Gevers 4,6 , Alexander Comninos 1,2 , Sasha Howard 4,6 , Ali Abbara 1,2 & Waljit Dhillo 1,2
1Imperial College London, Metabolism, Digestion and Reproduction, London, United Kingdom; 2Imperial College Healthcare NHS Trust, Endocrinology, London, United Kingdom; 3University College London Hospital, Reproductive Endocrinology, London, United Kingdom; 4Barts Health NHS Trust, Paediatric Endocrinology, London, United Kingdom; 5Chelsea and Westminster NHS Foundation Trust, Paediatrics, London, United Kingdom; 6Queen Mary University of London, London, Centre for Endocrinology, William Harvey Research Institute, London, United Kingdom
JOINT1320
Background: Most young people with delayed puberty have self-limited delayed puberty (SLDP), but ~10% have congenital hypogonadotrophic hypogonadism (CHH). Differentiating between these two conditions is challenging, with the diagnosis typically made retrospectively, particularly in the absence of ‘red flag’ features of CHH e.g. anosmia. Kisspeptin stimulates hypothalamic GnRH neurons, and in turn LH release in healthy individuals, however patients with CHH have a minimal hormonal response to kisspeptin. Early evidence suggests that kisspeptin-10 could differentiate the cause of delayed puberty, however no data exists using kisspeptin-54, which could be advantageous. Kisspeptin-54 is reported to cross the blood brain barrier to access GnRH neuronal cell bodies, and a single bolus induces a greater LH rise than kisspeptin-10. We therefore investigated whether kisspeptin-54 could differentiate children with SLDP from those with CHH.
Methods: Fourteen young people with delayed puberty (12 boys and 2 girls) were categorised into three groups (Group 1: likely SLDP, Group 2: likely CHH, Group 3: indeterminate pending follow-up) according to pre-determined criteria including clinical history, auxology, and longitudinal Tanner staging. Participants received an intravenous bolus of kisspeptin-54 and GnRH on two separate occasions. Reproductive hormone levels were assessed every 15 min for 6 h (kisspeptin visit), and for 2 h (GnRH visit). LH rises between the three groups were compared by Kruskal Wallis test with post-hoc Dunn’s multiple comparisons. The LH rise between SLDP and CHH was compared by Mann Whitney U test.
Results: The mean age (±SD) of participants at time of assessment was 15.9±1.8 years. Five boys had likely diagnosis of SLDP, four young people (2 boys and 2 girls) had likely CHH, whilst the remaining five were indeterminate (Group 3). Kisspeptin-54 induced different maximal LH rises in the three groups (SLDP: 3.91±1.38, CHH: 1.29±0.91, Indeterminate 2.46±0.70 IU/l; P-value<0.0001). By contrast, the LH responses following GnRH were not significantly different between the groups (P-value=0.36). The LH-rise at two hours following administration of kisspeptin-54 fully differentiated participants with SLDP from those with CHH (area under ROC curve 1.0; P-value 0.0094). LH at both 30 and 60min post-GnRH had a poorer performance (auROC 0.58; P-value 0.72).Summary: Kisspeptin-54 demonstrates promise as a diagnostic test and performs better than GnRH, in young people with delayed puberty to help differentiate SLDP from CHH. Accurate and early identification of the cause of delayed puberty would remove uncertainty, aid in counselling, and could direct prompt appropriate management.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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