ESPE Abstracts

Background: Peak stimulated growth hormone (GH) levels are known to decrease with increasing BMI, possibly leading to overdiagnosis of GH deficiency (GHD) in children with overweight and obesity. However, current guidelines do not provide guidance how to interpret peak GH values of these children. The aim of this systematic review and meta-analysis was to study the effect of BMI standard deviation score (SDS) on stimulated peak GH values in children, to identify potential moderators of this association, and to quantify to which extent peak GH in children with obesity is decreased.

Methods: This systematic review was performed in accordance with PRISMA guidelines. Medline, Embase, Cochrane, Web-of-Science, and Google Scholar were searched for studies reporting impact of weight status on peak GH in children. Where possible, individual participant data was extracted or obtained from authors. Primary outcome was the association between peak GH and BMI SDS. The pooled correlation coefficient, 95% confidence interval (CI) and heterogeneity statistic I² were calculated under a multilevel, random effects model and exploratory moderator analyses and meta-regressions were performed. For the individual participant dataset, linear mixed-models regression analysis was performed with ln(peakGH) as outcome, accounting for used GH stimulation agent.

Results: Fifty-eight studies were included, providing data on n = 5135 children (576 with individual participant data). A pooled correlation of -0.32 (95% CI -0.41 to -0.23, n = 2434 patients, k=29 cohorts, I²=75.2%) was found. In meta-regressions, larger proportions of males included were associated with weaker negative correlations (P = 0.04). Pubertal status, presence of syndromic obesity, mean age and BMI SDS did not moderate the pooled r (all P > 0.05). Individual participant data analysis revealed a beta of -0.123 (95% CI -0.160 to -0.086, P < 0.0001), i.e., per 1 point increase in BMI SDS, peak GH decreases by 11.6% (95% CI 8.3 to 14.8%).

Conclusions: To our knowledge, this is the first systematic review and meta-analysis to investigate and quantify the impact of BMI SDS on peak GH values in children. Importantly, this relation is already present in the normal range of BMI SDS and could lead to overdiagnosis of GHD in children with overweight and obesity. With ever-rising prevalence of pediatric obesity, BMI-specific cut-off values for GH stimulation tests in children are needed. Based on this meta-analysis, we suggest weight status-adjusted cut-offs for children with overweight and obesity of 9.3 µg/L and 8.6 µg/L, respectively, in stimulation tests that have a normal weight cut-off of 10 µg/L.