Etiology
Single toxic adenomas are benign monoclonal tumors that grow and produce thyroid hormones independently of thyroid-stimulating hormone (TSH).[5][7][8] These arise after activating (gain of function) germline mutations in thyroid cells. The mutations most commonly affect the TSH receptor and less commonly the alpha subunit of stimulating G-protein.[5][9] Genetic and environmental factors (e.g., iodine deficiency) and thyrocyte heterogeneity may influence which clones eventually become autonomous nodules.[10]
Worldwide, iodine deficiency is the best-studied epidemiologic risk factor for goiter.[11] In individuals with autonomous nodules, an iodine load (e.g., from iodinated radiographic contrast, amiodarone, or a change in diet) may also cause iodine-induced hyperthyroidism (the Jod-Basedow phenomenon).[12]
Pathophysiology
Growth and function of thyroid cells are normally stimulated by thyroid-stimulating hormone (TSH) via the TSH receptor.[5] TSH receptor activity is mediated through the alpha subunit of stimulating G-protein.[10][13] In the case of thyroid cells the effector is cAMP. Increased cAMP levels cause growth and excess function of thyrocytes, leading eventually to hyperthyroidism.[8][14][15] Other mechanisms, such as alterations of G-protein signaling, may also be involved in the evolution of toxic thyroid adenomas.[16] Euthyroidism is gradually followed by subclinical hyperthyroidism and finally overt hyperthyroidism.[17]
Use of this content is subject to our disclaimer