ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Journal of clinical endocrinology and metabolism vol. 105,8 (2020): dgaa162. doi: https://academic.oup.com/jcem/article/105/8/dgaa162/5813981

This longitudinal study (n =16) suggests that responses to kisspeptin administration could predict later pubertal outcomes for patients with delayed puberty.

The management of delayed puberty still represents a clinical challenge given the difficulty to differentiate between patients with constitutional delay, who require only watchful waiting, and those with idiopathic hypogonadotropic hypogonadism (IHH) who will not attain adult reproductive function. Measurement of baseline and GnRH stimulated serum LH and FSH levels, and inhibin B have been suggested to differentiate those clinical entities (1–3) but none of these tests has sufficient sensitivity and/or specificity to accurately predict pubertal outcomes.

The premise of this physiological study was based on previous findings in adults showing that a bolus of kisspeptin increases LH release in reproductively-intact but not IHH individuals (4–6). Here, responsiveness to kisspeptin was measured in 16 patients with delayed or stalled puberty. All of those patients (n =8) who showed a rise in LH >0.8 mUI/ml after kisspeptin stimulation progressed spontaneously through puberty during the follow-up period, while all patients with an LH response <0.4 mUI/ml (n =8) failed to enter puberty. Furthermore, the kisspeptin stimulation test outperformed inhibin B, LH after GnRH stimulation, or basal or overnight LH and genetic testing to predict pubertal outcome.

These findings suggest that the kisspeptin stimulation test, coupled with others tests, may provide a more informative management for patients with delayed puberty and optimize later-life health outcomes.

References:

1. Adan L, Lechevalier P, Couto-Silva AC, et al. (2010). Plasma inhibin B and antimüllerian hormone concentrations in boys: discriminating between congenital hypogonadotropic hypogonadism and constitutional pubertal delay. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 16(11):CR511–7.

2. Binder G, Schweizer R, Blumenstock G, Braun R. (2015). Inhibin B plus LH vs GnRH agonist test for distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism in boys. Clin Endocrinol (Oxf). 82(1):100–105.

3. Rohayem J, Nieschlag E, Kliesch S, Zitzmann M. (2015). Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism. Andrology. 3(5):882–887.

4. Dhillo WS, Chaudhri OB, Patterson M, et al. (2005). Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 90(12):6609–6615.

5. Yee-Ming Chan, James P. Butler, Valerie F. Sidhoum, Nancy E. Pinnell, Stephanie B. Seminara. (2012). Kisspeptin Administration to Women: A Window into Endogenous Kisspeptin Secretion and GnRH Responsiveness across the Menstrual Cycle. The Journal of Clinical Endocrinology & Metabolism 97(8):E1458–E1467.

6 Chan YM, Lippincott MF, Butler JP, et al. (2014). Exogenous kisspeptin administration as a probe of GnRH neuronal function in patients with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 99(12):E2762–E2771.