The Role of Insulin Resistance/Hyperinsulinism in the Evolution of Thyroid Nodular Disease in Humans

Nodular thyroid disease or nodular goiter is characterized by the presence of a single or multiple nodules within the thyroid parenchyma. The formation of thyroid nodules is thought to be the result of the intrinsic heterogeneity of thyroid follicular cells, in responding to low-grade or intermittent stimulus, regarding their growth potential and function [1,2]. This heterogeneity in growth and function of the thyroid cells appears to be the underlying primary factor for the development of thyroid nodular disease. On the other hand the various secondary factors that stimulate the growth of the thyroid appear to influence the evolution of the thyroid nodular disease. The main thyroid stimulatory factors are the TSH (induced by iodine deficiency, natural goitrogens or inborn errors of thyroid hormone synthesis), thyroid stimulating immunoglobulin’s, TSIs (in Graves disease) and thyroid growth stimulating factors ( including insulin, IGF-1 and other growth factors) [3]. It is likely that, when a mild or intermittent stimulus (e.g. mild iodine deficiency , light TSH increase) acts on this heterogeneous group of thyroid follicular cells, only the subpopulation of cells with the highest growth potential will respond ,leading to focal thyroid cell hyperplasia. If, on the other hand, the goitrogenic stimulus is strong and persistent (TSIs, in Graves’ disease), then the whole population of cells undergo replication resulting in diffuse thyroid hyperplasia [1,2]. This mini-review highlights the evolution of nodular thyroid disease and the role of insulin resistance/ hyperinsulinemia in this phenomenon.