The histopathology varies with etiology and age of the goiter. Initially, uniform follicular epithelial hyperplasia (diffuse goiter) is present, with an increase in thyroid mass. As the disorder persists, the thyroid architecture loses uniformity, with the development of areas of involution and fibrosis interspersed with areas of focal hyperplasia. This process results in multiple nodules (multinodular or adenomatous goiter). On nuclear scintigraphy, some nodules are hot, with high isotope uptake (autonomous) or cold, with low isotope uptake, compared with the normal thyroid tissue (as demonstrated in the images below).
The development of nodules correlates with the development of functional autonomy and reduction in thyroid-stimulating hormone (TSH) levels. Clinically, the natural history of a nontoxic goiter is growth, nodule production, and functional autonomy. However, abnormally high thyroid function resulting in thyrotoxicosisoccurs in a minority of patients. The risk of malignancy is the same in a patient with a nodular goiter as with a solitary nodule.