Biochemistry of thyroid regulation under normal and abnormal conditions.
Perhaps in an oversimplified view, abnormal thyroid growth can be classified into two main categories: a) those cases due to excess of thyroid stimulators extrinsic to the gland; b) situations in which an intrinsic alteration in the gland occurs: Extrinsic (excess thyroid stimulation) Iodide deficiency with elevated TSH Goitrogens Graves' immunoglobulins Thyroid stimulating factors produced by tumors Dishormonogenesis with hypothyroidism Intrinsic (normal TSH) Increased sensitivity to TSH (iodine depletion) Altered autoregulation (?) Abnormal TSH receptor Other biochemical abnormalities From the studies performed in animals it can be concluded that since goiter appears before a detectable increase in serum TSH occurs, an intrinsic alteration in the thyroid gland would be responsible for the onset of growth. Under these conditions TSH would play a permissive role in promoting and maintaining the gland enlargement. In some aspects this situation is similar to that of certain endemic goiter areas. It may be postulated that under a mild iodine deficiency a decrease in thyroidal iodine concentration occurs (and/or in certain iodocompounds), thus rendering the gland more sensitive to the stimulatory action of TSH, and leading to the appearance of goiter. If this mechanism is able to maintain an euthyroid status no further alterations will occur. In more severely iodine deficient areas, or when additional factors such as dietary goitrogens are present, hypothyroidism develops and TSH is clearly elevated. A similar localized mechanism can be postulated for the development of nodular goiter. It is more difficult to explain the pathogenesis of goiter and tumors in nonendemic areas, since the biochemical findings so far reported are not conclusive. It seems likely that an alteration of the TSH receptor is a common factor to many tumors in man and animals. However, some contradictory results would preclude us from making a general statement. The wide variety of biochemical alterations reported would perhaps indicate, that there is not a single cause for the rise of abnormal thyroid growth and that different factors may play a role in the regulation of growth under such circumstances. It is to be hoped that future studies will provide a better comprehension of this problem.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004247:DNA / Q000378:metabolism; D006801:Humans; D007455:Iodine / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D011989:Receptors, Thyrotropin; D013959:Thyroid Diseases / Q000378:metabolism / Q000503:physiopathology; D013961:Thyroid Gland / Q000502:physiology* / Q000503:physiopathology; D013963:Thyroid Hormones / Q000502:physiology; D013972:Thyrotropin / Q000378:metabolism / Q000502:physiology
D009696:Nucleic Acids; D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D013972:Thyrotropin; D004247:DNA; D007455:Iodine; D000262:Adenylyl Cyclases