ESPE Abstracts

Background: A decrease in random LH concentration is observed after initiation of treatment for central precocious puberty (CPP), but the suitability of random LH concentrations for assessing efficacy is controversial. Although Neely et al. reported that random LH values frequently fail to demonstrate suppression to prepubertal levels,¹ Lee et al. demonstrated that a cutoff of random LH <0.6 IU/l may be adequate for monitoring suppression.² We present secondary analyses of random LH data from the pivotal trial of the first small-volume, long-acting, subcutaneously administered GnRH agonist for CPP, approved in 2020.³

Methods: 62 children (60 girls, 2 boys) with treatment-naïve CPP received 2 doses of 45 mg subcutaneous leuprolide acetate at 24-week intervals over the 48-week study period. Luteinizing hormone concentrations were assessed using a validated central Cobas ECLIA assay with a lower limit of detection of 0.100 IU/L. Random LH was defined as LH at time 0 or another visit where a stimulation test was not performed. Blood samples for random LH measurement were taken at baseline and weeks 4, 12, 20, 24, 36, 44, and 48.

Results: Mean random LH decreased from 1.9 IU/l at screening to ≤0.6 IU/l from week 12 to 48. 63 to 71% of children achieved random LH <0.6 IU/l from week 12 to 48. Of patients who achieved both arrested growth (decreased bone age to chronological age ratio and no progression of Tanner stage) and peak LH <4 IU/l at week 24, 68% had random LH <0.6 IU/l at week 24. strong correlation was not seen between peak and random LH concentrations.

Conclusions: Random LH concentrations decreased significantly following treatment initiation and most children attained a random LH <0.6 IU/L.² There were insufficient data to suggest a strong correlation between peak and random LH concentrations. These data support further research into the use of random LH for monitoring CPP treatment efficacy. Physicians should continue to monitor all relevant hormone levels and clinical symptoms that confirm suppression of pubertal progression per standard of care.

References:

1. Neely EK, et al. Int J Pediatr Endocrinol. 2013.

2. Lee PA, et al. J Pediatr Endocrinol Metab. 2016.

3. Klein KO, et al. The Journal of Clinical Endocrinology & Metabolism. 2020.