Background: Both genetic and environmental factors serve as the trigger of Hashimoto's thyroiditis (HT), but the exact mechanisms are still not fully understood. Increased intestinal permeability was shown to be a constant and early feature of several autoimmune disorders. Although HT is the most common autoimmune disorder worldwide, the role of intestinal permeability in its pathogenesis had received little attention. Human zonulin modulates intracellular tight junctions and controls intestinal permeability. Zonulin level in blood is considered as a useful marker of intestinal permeability.
Objective: To examine the hypothesis that patients with HT have increased intestinal permeability.
Methods: This was a case-control study on a group of 30 children and adolescents with HT, and age, gender and body mass index (BMI) matched 30 patients with congenital hypothyroidism (CH). Serum zonulin levels, free thyroxine (fT4), thyroid stimulating hormone (TSH), anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were measured.
Results: Zonulin levels were significantly higher in patients with HT than patients with CH (59.1±22.9 vs. 43.3±32.9, P=0.035). Age, gender, weight SDS, height SDS, BMI SDS and levothyroxine dose were not different between the groups. In patients with HT, zonulin levels were positively correlated with weight (r= 0.406, P=0.03), BMI (r= 0.486, P=0.006) and levothyroxine dose (r= 0.463, P=0.02). In patients with CH, zonulin levels were positively correlated with age (r= 0.475, P=0.008), weight (r= 0.707, P<0.001), BMI (r= 0.872, P<0.001) and levothyroxine dose (r= 0.485, P=0.007). After adjusting for age, weight, TSH and fT4 levels, zonulin level was only associated with levothyroxine dose in patients with HT (R2=0.36, P=0.05). When we put the patients with CH in the same regression model, only weight was associated with zonulin level (R2=0.62, P<0.001).
Conclusion: Results of this first study examining zonulin levels in patients with HT suggested increased intestinal permeability in these patients. In addition, the association between zonulin levels and levothyroxine dose might imply a relationship between serum zonulin and disease severity.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology