Assays for Thyroid Growth Immunoglobulins and Their Clinical Implications: Methods, Concepts, and Misconceptions

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Abstract
GRAVES' disease is characterized by thyroid hyperfunction and hyperplasia which lead to thyrotoxicosis and goiter. Hyperthyroidism has been clearly related to the presence in plasma of immunoglobulins which stimulate the TSH receptor via its adenylate cyclase, the thyroid stimulatory immunoglobulins (TSI) (1–4). With regard to growth, several facts have suggested that additional mechanisms may be involved. There is no simple relationship between level of function in Graves' disease and goiter size; indeed there are cases of hyperthyroidism with little increase in thyroid size and others with slight thyrotoxicosis and large goiters. Moreover, the presence of circulating growth-stimulating factors in euthyroid and hypothyroid patients with goiter has been reported (5–10). On the other hand, depending on the species, several biochemical pathways may be involved in the regulation of thyroid cell proliferation: 1) the TSH-activated adenylate cyclase-cAMP cascade (11–13); 2) the cAMP-independent epidermal growth factor mechanism, probably involving protein tyrosine phosphorylation (11,13); and 3) as in other types of cells, the phosphatidylinositol-Ca2+ cascade (14).

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