Association between non-alcoholic fatty liver disease and subclinical hypothyroidism in children with obesity

PurposeWe aimed (i) evaluating the relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function tests, (ii) testing if the relationship between NAFLD and thyroid dysfunction could be driven by the obesity and the IR degree, and (iii) exploring the influence of the patatin-like phospholipase domain-containing protein-3 (PNPLA3) I148M and the transmembrane 6 superfamily member 2 (TM6SF2) E167K polymorphisms on the association between NAFLD and thyroid function in children.MethodsWe examined 2275 children and adolescents with obesity. Subclinical hypothyroidism (SH) was defined by thyroid-stimulating hormone (TSH) > 4.2 mu UI/ml with normal fT3 and fT4.ResultsChildren with NAFLD showed higher SH prevalence than those without NAFLD (15.7% Vs 7.4%;p = 0.001) and showed an adjusted odds ratio (aOR) to have SH of 1.68 (95% CI:1.01-2.80;p = 0.04) while patients with SH had an aOR to show NAFLD of 2.13(95% CI:1.22-3.73;p = 0.008). Patients having severe obesity and IR degree presented an aOR to show both NAFLD and SH of 3.61 (95% CI:1.78-7.33;p < 0.0001). Subjects with NAFLD carrying the TM6SF2 167 K allele had lower TSH levels than non-carriers (p = 0.03) and showed an aOR to have SH of 0.10 (95% CI: 0.01-0.79;p = 0.02). No differences were found in carriers of the PNPLA3 148 M allele. A general linear model for TSH variance showed a significant association of TSH with TM6SF2 genotypes only in the NAFLD group (p = 0.001).ConclusionChildren with obesity and NAFLD presented increase risk of SH and vice versa likely due to the adverse effect of duration of obesity, obesity degree, and IR. The TM6SF2 E167K exerts a protective role against SH in children with obesity and NAFLD.

Automated summary

The study aimed to evaluate the relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function tests, testing if the relationship could be driven by obesity and insulin resistance (IR), and to explore the influence of PNPLA3 I148M and TM6SF2 E167K polymorphisms on the association between NAFLD and thyroid function in children with obesity. The results showed that children with NAFLD had a higher prevalence of subclinical hypothyroidism (SH), and patients with SH had a higher risk of NAFLD. Severe obesity and IR degree were associated with both NAFLD and SH. The TM6SF2 E167K polymorphism was found to have a protective role against SH in children with obesity and NAFLD.