Increased thyroidal fat and goitrous hypothyroidism induced by interferon-γ

Hashimoto's thyroiditis is associated with a diffuse lymphocytic infiltration of the stroma and a production of several cytokines, such as interferon-γ (IFN-γ). We previously reported that transgenic mice expressing IFN-γ under the control of the thyroglobulin promoter develop primary hypothyroidism. In order to determine the long-term changes induced by IFN-γ in the thyroid gland, we analysed cross-sectionally 202 mice (96 transgenic mice and 106 controls) of 0-650 days of age. Multiple linear regression analysis showed that, after adjusting for age and sex, thyr-IFN-γ transgenic mice were 14% (3g) smaller (P < 0.0001) and had a 5- to 6-fold bigger thyroid (P < 0.0001) than wild-type littermates. Transgenic thyroids showed striking histopathological changes in follicles, thyrocytes and stroma. Follicles were enlarged, irregular and were lined by thickened, granular and oxyphilic thyrocytes. The stroma contained a moderate and diffuse mononuclear infiltrate - mainly composed of macrophages - and, interestingly, a clear increase in the content of fat. These findings indicate that, in addition to hypothyroidism, chronic exposure of the thyroid to IFN-γ leads also to macrophage infiltration and subsequent adipocyte expansion, suggesting a link between inflammation and fat accumulation.