ESPE Abstracts

Background: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M and the transmembrane 6 superfamily member 2 (TM6SF2) E167K polymorphisms have been recognized as the major risk polymorphisms for Non-Alcoholic Fatty Liver Disease (NAFLD). Data supported a close relationship of NAFLD with thyroid function both in adults and children. To investigate the influence of NAFLD and of its genetics on thyroid function.

Methods: We examined 2275 children and adolescents with obesity. Both clinical and biochemical evaluations were conducted. Subclinical hypothyroidism (SH) was defined by thyroid stimulating hormone (TSH)>4.2μUI/ml with normal fT3 and fT4. NAFLD was defined by ultrasound detected liver steatosis and/or ALT levels >40IU/l.

Results: Patients with NAFLD had higher TSH levels than those without NAFLD (3.04±1.57 vs. 2.80±1.34 µUI/ml, P<0.0001). Significant differences in SH prevalence were also found in these subjects compared to peers without NAFLD (15.4% vs. 7.4%, P=0.001). They also showed an odds ratio (OR) to have SH of 1.68 (95% CI 1.01-2.80, P=0.04) adjusted for age, BMI-SDS, and sex. Subjects with NAFLD carrying the TM6SF2 167K allele showed lower TSH levels than noncarriers (P=0.03), while no differences were found for TSH levels in patients with NAFLD carrying the PNPLA3 148M allele (2.97±1.43 vs 3.01±1.36, P=0.73). Carriers of the TM6SF2 167K allele with NAFLD presented with an OR to have SH of 0.10 (95% CI 0.01-0.79, P=0.02). Patients carrying the TM6SF2 167K allele in the Study Population also had lower TSH levels than noncarriers (2.60±1.41 vs 3.04±1.39, P=0.04). A general linear model for TSH variance (including gender, duration of obesity, NAFLD, PNPLA3, and TM6SF2 genotypes, BMI-SDS, HOMA, LDl, and triglycerides) was run in the study population and TSH levels were found to be inversely associated with TM6SF2 genotypes (r² 0.09, adjusted r² 0.05, P=0.03). The same analysis (including gender, duration of obesity, PNPLA3, and TM6SF2 genotypes, BMI-SDS, HOMA, LDl, and triglycerides) was conducted both in patients with and without NAFLD. It confirmed an inverse and significant association of TSH with TM6SF2 genotypes only in the NAFLD group (P=0.001).

Conclusion: NAFLD negatively affects thyroid function determining an increase in TSH levels and in SH prevalence. While the PNPLA3 I148M polymorphism does not have any influence on thyroid function, the TM6SF2 E167K exerts a protective role against the increase of TSH levels and SH in children with obesity and NAFLD, by expanding its influence on cardiometabolic health of these patients.