Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism [published erratum appears in Endocr Rev 1994 Aug;15(4):438]

Abstract

NORMAL growth and neurological development are dependent on a normal metabolic state, conditioned by an adequate supply of thyroid hormones. Synthesis of T₃ and T₄ follows a metabolic pathway that depends on the integrity of the thyroglobulin (T_g) structure. This large glycoprotein, a dimer of 660,000 daltons, is synthesized and secreted by the thyroid cells into the lumen of the thyroid follicle. T_g serves two main purposes in the function of the thyroid gland. The first is related to the process of hormone production. Thus T_g provides for the efficient coupling of the hormone precursors, mono- and diiodotyrosine to form T₃ and T₄. The second function is that of a repository within the gland of a large supply of iodine and of hormone for secretion at a steady rate or upon demand (1). These two properties of Tg seem to permit the organism to operate in an environment that is usually deficient in iodine and to adapt to wide variations in iodine supply. The efficiency of hormone synthesis in T_g depends on structural factors intrinsic to the protein matrix that favors the coupling reaction. We may assume that genetic mutations resulting in a structurally defective protein would severely impair the functional ability of T_g to serve as a matrix for T₃ and T₄ generation.