Thyroid autoimmunity in childhood celiac disease.

Abstract

Celiac Disease is associated with other autoimmune disorders, but much greater emphasis has been put on the association of celiac disease with Type 1 Diabetes Mellitus (T1DM) than on its association with autoimmune thyroiditis even though the high prevalence of anti-thyroid antibodies (1–3) and thyroid disorders (4) in celiac patients suggests that this association may be clinically more important. From Medline (1980–2001) we found 176 papers on the association between CD and T1DM but only 36 on its association with thyroid disorders. We prospectively studied the prevalence of anti-thyroid antibodies in celiac children. In children with increased titers we measured thyroid hormones and TSH and performed thyroid ultrasonography. PATIENTS AND METHODS We studied 66 children with CD (35 females, 31 males) diagnosed with jejunal biopsy according to the European Society of Paediatric Gastroenterology and Nutrition criteria. Forty-one children were untreated and on a gluten-containing diet. Serum samples were obtained the same day of the first duodenal biopsy. Nineteen children were on a gluten-free diet and 6 children were on a short (median 3 months) gluten-challenge to confirm the diagnosis. Serum titres of TPO and TG were measured, and when raised we measured FT3, FT4, and TSH, and performed thyroid ultrasonography using a 7.5-MHz linear probe. Thyroid patterns were classified according to Sostre criteria (5). Follow up sera after a gluten-free diet of 3 months to 15 years were retested for TPO and TG in 30 children. RESULTS AND CONCLUSION Of the 41 untreated celiac children, six (14.6%) had raised TPO, three raised TG titers, and one had elevated TSH (Table 1). Ultrasonography showed a normal thyroid gland in three children, multiple hypoechoic foci in a normoechoic gland (grade 2) in two children, and an enlarged gland with diffuse but mild hypoechogenicity (grade 3) in one child. FT3 and FT4 were always normal.TABLE 1: Characteristics of children with anti-thyroid antibodiesFollow-up sera of these 6 children were obtained after a strictly conducted gluten-free diet of variable duration (range 1–5 years) with serial determination of anti-gliadin and anti-endomysium antibodies that were always negative. TPO became negative in two, but titers increased in the other four, and TSH was elevated in one more child (Table 1). There was an associated T1 DM in one child, a family history of type T1 DM in another, and a celiac mother in two children, suggesting that association with autoimmune disease in the family may be a risk factor. Interestingly, at diagnosis untreated children with anti-thyroid antibodies were significantly older (median age 7.5 vs. 2.0 years in children without antibodies, P = 0.03 Mann-Whitney U test) and of those younger than 6 years only 1/23 (4.3%) had anti-thyroid antibodies, whereas over 6 years 5/18 were positive (27.7%, P = 0.04), suggesting that duration of gluten exposure may be another important risk factor for the development of thyroid autoimmunity. Of the children with anti-thyroid antibodies, the younger three had lower titres. Ultrasound showed a normal gland in all, and in two, TPO became negative after instituting a gluten-free diet. The older three children with anti-thyroid antibodies had higher TPO titres which increased after a gluten-free diet. Ultrasonography showed structural damage of the gland, and two became sub-clinically hypothyroid with an elevated TSH, and were given replacement treatment with L-thyroxin. Of the 25 treated celiac children, on gluten-free diet or after a short challenge, none had anti-thyroid antibodies. Their median age at diagnosis was 1.5 years. We also had a chance to diagnose CD in seven young adults, four medical students, and three mothers of our celiac children (age-range 23–33 years) and four of them had anti-thyroid antibodies. Our data are in agreement with other studies reporting a correlation between a late diagnosis of CD, which mirrors longer gluten exposure, and the prevalence of autoimmune thyroid antibodies (1,2), but suggest that a gluten-free diet is not sufficient to suppress thyroid autoimmunity when it has already started. Perhaps an early diagnosis and an early gluten withdrawal may be preventive for thyroiditis.