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Thyroid follicular cells, as well as adrenocortical cells, are endowed by an intrinsic heterogeneity regarding their growth potential, in response to various stimuli. This heterogeneity appears to constitute the underlying cause for the focal cell hyperplasia and eventually the formation of thyroid and adrenal nodules, under the influence of growth stimulatory factors. Among the main stimulatory factors are the pituitary tropic hormones, thyroid-stimulating hormone (TSH) or thyrotropin and adrenocorticotropic hormone (ACTH), which regulate the growth and function of their respective target cells, and the insulin/insulin-like growth factor system, that, through its mitogenic effects, can stimulate the proliferation of these cells. The predominance of one or the other of these growth stimulatory factors appears to determine the natural history of thyroid and adrenal nodular disease. Thus, iodine deficiency was, in the past, the main pathogenic factor responsible, through a transient rise in TSH secretion, for the endemic nodular goiter with the characteristic colloid thyroid nodules among the inhabitants in iodine deficient areas. The correction of iodine deficiency was followed by the elimination of endemic colloid goiter and the emergence of thyroid autoimmunity. The recent epidemic of obesity and metabolic syndrome (MS), or insulin resistance syndrome, has been associated with the re-emergence of nodular thyroid disease. A parallel rise in the incidence of benign, nonfunctional adrenocortical tumors, known as adrenal incidentalomas, has also been reported in association with the manifestations of the MS. It is likely that the compensatory to insulin resistance hyperinsulinemia may be responsible for the rising trend of thyroid and adrenal nodular disease in the current environment.

The Role of Insulin Resistance/Hyperinsulinism on the Rising Trend of Thyroid and Adrenal Nodular Disease in the Current Environment