Background: Peak growth hormone (GH) levels decrease with increasing BMI, which could lead to overdiagnosis of GH deficiency (GHD) in children with overweight and obesity. However, current guidelines do not guide how to interpret peak GH in these children. The aim of this systematic review and meta-analysis was to investigate and quantify the effect of BMI standard deviation score (SDS) on peak GH in children.

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

Results: Fifty-eight studies were included (n=5135 children of which 576 with individual participant data). A pooled r 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 showed 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 the impact of BMI SDS on peak GH in children. Based on this meta-analysis, we suggest the following weight status-adjusted cutoffs for GH stimulation tests that have cutoffs for children with normal weight of 5, 7, 10 and 20 µg/L: for overweight children: 4.6, 6.5, 9.3 and 18.6 µg/L; for children with obesity: 4.3, 6.0, 8.6 and 17.3 µg/L.