Toxic multinodular goiter is a heterogeneous disease producing hyperthyroidism frequently found in iodine-deficient areas. The aim of this study was to evaluate the gene expression profile of functioning and non-functioning thyroid nodules present in the same thyroid gland from two patients affected by autonomous multinodular goiter by using the Affymetrix technology.
Total RNA was extracted from nodular and non nodular tissues, retrotranscribed, and the double strand cDNA was synthesized. Biotinylated cRNA was hybridized on U133 set arrays. The acquired images were analyzed to obtain the expression levels of transcripts. The expression levels of a subset of genes were also evaluated by real time PCR.
In functioning nodules about 16% of genes were modulated while in non-functioning nodules only 9% of genes were modulated. In functioning nodules of both patients an up-regulation of cyclin D1 was observed. Interestingly the cyclin-dependent kinase inhibitor 1 gene was also up-regulated, suggesting a feedback from increased proliferation. In functioning nodules a marked decrease in blood cells (suggested from a decrease in blood cell antigens like FY and CXCR4) and a decrease of complement components (suggesting a decrease of macrophages) were observed. An increase of cellular fibronectin preculsor gene was also found in functioning nodules suggesting an increase of endothelial cells. In both functioning nodules a reduced expression of Frizzled 1 gene of the Wnt signaling was observed.
In conclusion, the gene expression profile of functioning and non-functioning thyroid nodules co-existing inside the same gland demonstrated that these profiles are very similar, with an increase of genes implicated in cell proliferation, a decrease of blood cells and an increase of endothelial cells in functioning nodules.
01 - 05 Apr 2006
European Society of Endocrinology