Aetiology
Single toxic adenomas are benign monoclonal tumours that grow and produce thyroid hormones independently of thyroid-stimulating hormone (TSH).[8][10][11] 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.[8][12] Genetic and environmental factors (e.g., iodine deficiency) and thyrocyte heterogeneity may influence which clones eventually become autonomous nodules.[13]
Worldwide, iodine deficiency is the best-studied epidemiological risk factor for goitre.[14] 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).[15]
Pathophysiology
Growth and function of thyroid cells are normally stimulated by thyroid-stimulating hormone (TSH) via the TSH receptor.[8] TSH receptor activity is mediated through the alpha subunit of stimulating G-protein.[13][16] In the case of thyroid cells the effector is cyclic adenosine monophosphate (cAMP). Increased cAMP levels cause growth and excess function of thyrocytes, leading eventually to hyperthyroidism.[11][17][18] Other mechanisms, such as alterations of G-protein signaling, may also be involved in the evolution of toxic thyroid adenomas.[19] Euthyroidism is gradually followed by subclinical hyperthyroidism and finally overt hyperthyroidism.[20]
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