Thyroid Disease in Diabetes Mellitus

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The most frequent autoimmune disease in type 1 diabetes affects the thyroid. The etiology of autoimmunity in pancreas and thyroid is a T cell-mediated disease and seems to be due to common genetic susceptibility. Two immune regulatory genes (HLA = human leukocyte antigen and CTLA-4 = cytotoxic T lymphocyte-associated protein 4) contribute to the susceptibility for both diseases [5, 23]. This locus, also known as the IDDM 12 gene, seems to play a major role in development of autoimmune polyglandular syndrome type 2 (APS-2).

Autoimmunthyroiditis describes a group of thyroid diseases with destruction of thyroid tissue due to an autoimmune reaction. Classification of these diseases is not consistent in the literature. Most frequently, Hashimoto thyroidi-tis with antibodies against thyroid antigens is found. These antibodies are directed towards thyroid peroxidase (TPO-Ab), thyreoglobulin (TG-Ab) and/or TSH-receptor antigen (TRAK).

Positivity for thyroid auto antibodies in children with type 1 diabetes shows considerable variability in different countries. Incidence and prevalence numbers vary between 3 and 50% [3, 18, 19, 33, 36] compared to a suggested rate of 3-10% in non diabetic children and adolescents [17, 26, 38]. The largest cohort analysis was published by Kordonouri et al. [19] reporting a rate of 21.6% of thyroid antibodies in a group of 7,097 children and adolescents with type 1 diabetes. In this study patients with antibody positivity were older, had longer diabetes duration and had developed diabetes later in life. 63% of patients with positive thyroid antibodies were female.

The majority of patients with positive thyroid antibodies have normal thyroid function. Elevated TSH levels as a marker for subclinical hypothyroidism are found in about 15% in the antibody positive patient group. Overt primary hypothyroidism due to autoimmune thyroiditis is seen in 3-5% of patients [3, 8, 19]. Clinical findings of hypothyroidism like goiter, weight gain, fatigue, cold intolerance and bradycardia are rare because of screening for TSH and autoantibodies in patients with type 1 diabetes (table 1).

In the study of Kaspers et al. [16], evidence for thyroid disease was significantly more often observed in patients when celiac disease was present (6.3 vs. 2.3%).

Since screening is both efficient and cost effective there is no controversy about thyroid antibody screening in patients with type 1 diabetes anymore. Screening is performed in our institution once a year. In case of significant antibody levels (especially thyroperoxidase antibodies) a longitudinal survey of diabetic children over 5 years showed a higher risk of later development of TSH elevation and subclinical or clinical hypothyroidism [18]. These data were confirmed by a recently published study from Australia over a follow-up period of 13 years [9]. Therefore, in patients with elevated TPO/TGA antibodies thyroid

Table 1. Prevalence of hypothyroidism or hyperthyroidism in patients with type 1 diabetes mellitus in different countries

Country

Number of patients (age, years)

Hypothyroidism male:female

Hyperthyroidism male:female

Follow-up years

Reference

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