Nodular goiter and goiter nodules: Where iodine deficiency falls short of explaining the facts.
While the concept of iodine deficiency (ID) still dominates most discussions about the pathogenesis of multinodular goiter (MNG), the present review focuses on those mechanisms that may cause MNG in the absence of ID. Among the many facets of MNG that cannot simply be explained by ID, are the frequent occurrence of the disease in patients not exposed to ID, the autonomous growth of goiters - often accompanied by subclinical or even overt thyrotoxicosis -, the inverse relationship between goiter size and serum TSH, the multifocal, heterogeneous and nodular growth pattern, the heterogeneity of function with the familiar patchy iodine metabolism on scintiscans, the growth of clonal and polyclonal nodules, the prominent genetic predisposition. Even the notoriously low intrathyroidal iodine concentration - common to endemic as well as to sporadic goiter - is a secondary, rather than a primary event. Thus, the fundamental process of goitrogenesis, is independent from ID but operates through mechanisms innate to the hereditary and acquired heterogeneity among the thyrocytes themselves. In this view, goiter nodules and nodular goiters are true benign neoplasias arising by mechanisms common to all benign endocrine and nonendocrine neoplasms. However, superimposed iodine shortage greatly enhances the incidence of MNG and shifts its clinical appearance toward younger ages by adding one more growth factor - presumably enhanced TSH secretion - to an intrinsically activated growth regulating network.
Derwahl
M
M
Department of Medicine, St. Hedwig Hospital and Humboldt University Berlin, Germany. M.Derwahl@alexius.de
Studer
H
H
D005260:Female; D006044:Goiter, Nodular / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D006965:Hyperplasia; D007455:Iodine / Q000032:analysis / Q000172:deficiency*; D008297:Male; D013961:Thyroid Gland / Q000737:chemistry / Q000473:pathology; D013964:Thyroid Neoplasms / Q000473:pathology; D013972:Thyrotropin / Q000097:blood
D012739:Gonadal Steroid Hormones; D013972:Thyrotropin; D007455:Iodine