Faculty Bibliography

OBJECTIVE:To review the association of celiac disease and various endocrine disorders and present the related clinical experience of a 3-physician adult endocrinology practice. METHODS:We provide an overview of the pertinent literature, discuss the clinical manifestations, genetics, and pathogenesis of celiac disease, and describe our clinical experience during a 5-year period. RESULTS:Celiac disease has been associated with numerous disorders, including several conditions treated by endocrinologists-type 1 diabetes mellitus, autoimmune thyroid disease, Addison disease, osteomalacia, secondary hyperparathyroidism, vitamin D or iron deficiency, fertility problems, hypogonadism in men, and autoimmune hypopituitarism. After our clinical awareness was raised about these potential comorbidities, 18 patients were newly diagnosed with celiac disease in our clinical practice during a 5-year interval. All patients had been referred for endocrine evaluation or were undergoing follow-up for ongoing management of endocrine disorders. When a "celiac-associated" endocrine disorder coexists with other factors associated with celiac disease, we recommend performance of IgA class antibody testing, and either antiendomysial or anti-tissue transglutaminase antibodies provide high specificity and sensitivity for the diagnosis of celiac disease. CONCLUSION/CONCLUSIONS:Endocrinologists have an opportunity to diagnose celiac disease, a relatively common disorder with profound clinical implications that can often be associated with various endocrinopathies.

Interferon (IFN) alpha treatment for various conditions has been associated with thyroid autoimmunity. The incidence of interferon induced thyroid autoimmunity has been reported to range from 2.5% to 42%, possibly depending upon dose and duration of medical therapy and patient characteristics. It is not known whether IFN-alpha initiates autoimmune thyroid disease (AITD) or simply exacerbates AITD in individuals with subclinical AITD.

Alpha interferon (alphaIFN) therapy is known to induce thyroid autoimmunity in up to 40% of patients. The mechanism is unknown, but Th1 switching has been hypothesized. The aim of our study was to examine whether alphaIFN accelerated the development of thyroiditis in genetically susceptible mice. We took advantage of NOD-H2h4, a genetically susceptible animal model, which develops thyroiditis when fed a high iodine diet. Six to eight week old male NOD H2h4 mice were injected with mouse alphaIFN (200 units) or with saline three times a week for 8 weeks. All mice drank iodinated water (0.15%). Mice were sacrificed after 8 weeks of injection. Their thyroids were examined for histology and blood was tested for antithyroglobulin antibody levels. T4 and glucose levels were also assessed. In the IFN-injected group, 6/13 (46.2%) developed thyroiditis and/or thyroid antibodies while in the saline-injected group, only 4/13 (30.8%) developed thyroiditis and/or thyroid antibodies (p = 0.4). The grade of thyroiditis was not different amongst the two groups. None of the mice developed clinical thyroiditis or diabetes mellitus. Our results showed that alphaIFN treatment did not accelerate thyroiditis in this mouse model. This may imply that alphaIFN induces thyroiditis in a non-genetically dependent manner, and this would not be detected in a genetically susceptible mouse model if the effect were small. Alternatively, it is possible that alphaIFN did not induce thyroiditis in mice because, unlike in humans, in mice alphaIFN does not induce Th1 switching.