Kisspeptin-stimulation test response predicts delayed puberty outcome

medwireNews: Research suggests that a single challenge with the neuropeptide kisspeptin can distinguish between children with pubertal delay who will or will not require long-term gonadotropin-releasing hormone (GnRH) therapy.

The kisspeptin stimulation test “has the potential to be a significant advance in evaluating delayed puberty”, say Yee-Ming Chan, from Boston Children’s Hospital in Massachusetts, USA, and co-authors who believe that this test could help physicians and families choose between sex steroid therapy and watchful waiting as a management approach.

As reported in The Journal of Clinical Endocrinology & Metabolism, the team followed up 13 boys and three girls aged from 13.9 to 17.5 years old with delayed or stalled puberty at 6-month intervals until age 18 years.

Six boys and two girls achieved a luteinising hormone (LH) increase of 0.8 mIU/mL or more in response to a single dose of kisspeptin 0.313 µg/kg; these patients all experienced a progressive testicular volume increase or breast development without exogenous therapy.

By contrast, six boys and one girl had little or no response to kisspeptin (LH 0.0–0.1 mIU/mL), and one boy achieved an intermediate LH increase of 0.4 mIU/mL; these patients showed “persistent sexual immaturity” with a testicular volume below 4 mL, and no breast progression until exogenous oestradiol therapy.

Thus, the kisspeptin challenge significantly predicted puberty progression with 100% sensitivity and specificity for this outcome, the authors say.

By contrast, unstimulated LH levels measured at day or night did not significantly predict spontaneous puberty, and while all six patients who had at least one pulse of sleep-detected LH secretion progressed through puberty, “variable outcomes” were found for the 10 children without such a pulse.

Although GnRH-stimulated LH level has also been suggested as a predictor of puberty outcome, the team found that levels overlapped between children who did (1.2–15.4 mIU/mL) and did not (0.2–7.5 mIU/mL) progress through puberty.

Baseline levels of serum LH and follicle-stimulating hormone levels in boys and girls, and inhibin levels in boys also failed to predict puberty outcome, and genetic analysis did not identify any pathogenic or likely pathogenic variants associated with puberty outcome, including in the IGSF10 gene linked to constitutional delay.

“Future work will undoubtedly enhance our understanding of the contribution of both rare and common genetic variation to [idiopathic hypogonadotropic hypogonadism] and constitutional delay, and clinical genetic testing may eventually come to have a valuable role in the evaluation of delayed puberty”, the team predicts.

They conclude: “Coupling the kisspeptin-stimulation test with other tests may provide the greatest accuracy in predicting outcomes for patients presenting with delayed puberty and, in turn, guiding appropriate management of these patients to optimize health outcomes in adolescence and adulthood.”

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

J Clin Endocrinol Metab 2020;doi:10.1210/clinem/dgaa162
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