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Context: Several studies demonstrated that obese children have higher TSH than normal-weight children. The polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene showed an association with TSH. Objectives: i) To assess the effect of PDE8B on TSH in obese children; ii) to dissect the role of obesity degree in modulating this association; and iii) to stratify the individual risk to show hyperthyrotropinaemia according to PDE8B genotype. Methods: Eight hundred and sixty-seven Italian obese children were investigated. Clinical data and thyroid hormones were evaluated and the PDE8B rs4704397 was genotyped. Results: PDE8B A/A homozygous subjects showed higher TSH (PZ0.0005) compared with A/G or G/G. No differences were found for peripheral thyroid hormones. Among A/A children, 22% had hyperthyrotropinaemia, compared with 11.6% of heterozygotes and 10.8% of G/G (PZ0.0008). Consistently, A/A had an odds ratio (OR) to show abnormal TSH level of 2.25 (PZ0.0004). Body mass index (BMI) appeared correlated with TSH (PZ0.0001), but the strength of the effect of PDE8B on TSH was independent of BMI (PZ0.1). Children were subdivided into six groups according to obesity degree and genotypes. PDE8B A/A with BMI SDS above 3 had the highest OR (OR 2.6, PZ0.0015) to have hyperthyrotropinaemia, whereas G/G with BMI SDS below 3 showed the lowest possibilities (OR 0.3, PZ0.005). Conclusions: We have shown: i) in obese children, PDE8B is associated with TSH; ii) the interaction between adiposity and PDE8B on TSH is not synergistic, but follows an additive model; and iii) impact of this association in the stratification of individual risk to have hyperthyrotropinaemia.

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