Objective: IGF-1 receptor mutations (IGF1RM) are a rare abnormality; however, affected patients exhibit severe postnatal growth retardations without catch-up growth. Although several cases of IGF1RM have been described, a comprehensive retrospective analysis of the potential benefit of rhGH treatment is still missing. The aim of this study was therefore to investigate baseline auxology, response to rhGH therapy and potential metabolic effects in patients with IGF1RM in comparison to a cohort of children born small for gestational age (SGA).
Methods: Over the past 15 years we identified 23 patients with 17 different mutations within the IGF-1 receptor, with 17 being treated with rhGH. We compared these patients to 34 rhGH treated SGA children retrospectively. We analyzed birth parameters, growth before and under rhGH therapy, near final height, glucose homeostasis and insulin sensitivity. Additionally, health profiles of adult IGF1RM carriers were compared to those of former SGA patients.
Results: IGF1RM patients showed significantly decreased body growth both before and during rhGH treatment. In particular first-year response was diminished in IGF1RM patients (Δ height SDS of 0.29 vs. 0.65 for SGA), with many having very poor response (defined as growth <0.3 SDS; 53% of IGF1RM carriers vs. 17% in SGA patients). However, when first-year response was good, some patients showed catch-up to the level seen in SGA children when treated for a longer period (≥3 years). An association between IGF1R mutation and a disturbed glucose homeostasis has been suggested by some investigators. However, we observed no significant differences in glucose homeostasis before treatment (measured as fasting glucose, HbA1c and HOMA-IR) in IGF1RM carriers compared to SGA controls. In contrast - during rhGH treatment - there was a stronger decrease in insulin sensitivity (HOMA-IR of 2.1 for IGF1RM vs. 1.15 for SGA). No differences in health profile could be seen in adult IGF1RM carriers compared to SGA controls.
Conclusion: The presence of IGF1R mutations in SGA children correlates with a more severe growth phenotype and poor response to rhGH therapy. However, individual variability is high, with some patients being good responders. But causes for these differences remain unclear. Therefore, we conclude that IGF1RM carriers should not be excluded from treatment with rhGH, but a critical reevaluation of success should be performed after 23 years of treatment. In addition, we observed no significant influence of IGF1RM on glucose metabolism and health profile later in life. However, close monitoring during rhGH therapy is recommended.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology