Most effects of hyperthyroidism are obvious from the preceding discussion of the various physiologic effects of thyroid hormone. However, some specific effects should be mentioned in connection especially with the development, diagnosis, and treatment of hyperthy-roidism.
Causes of Hyperthyroidism (Toxic Goiter, Thyrotoxicosis, Graves’ Disease). In most patients with hyperthyroidism, thethyroid gland is increased to two to three times normal size, with tremendous hyperplasia and infolding of the follicular cell lining into the follicles, so that the number of cells is increased greatly. Also, each cell increases its rate of secretion severalfold; radioactive iodine uptake studies indicate that some of these hyper-plastic glands secrete thyroid hormone at rates 5 to 15 times normal.
The changes in the thyroid gland in most instances are similar to those caused by excessive TSH. However, plasma TSH concentrations are less than normal rather than enhanced in almost all patients and often are essentially zero. However, other substances that have actions similar to those of TSH are found in the blood of almost all these patients. These substances are immunoglobulin antibodies that bind with the same membrane receptors that bind TSH. They induce continual activation of the cAMP system of the cells, with resultant development of hyperthyroidism. These antibodies are called thyroid-stimulating immunoglobu-lin and are designated TSI. They have a prolongedstimulating effect on the thyroid gland, lasting for as long as 12 hours, in contrast to a little over 1 hour for TSH. The high level of thyroid hormone secretion caused by TSI in turn suppresses anterior pituitary for-mation of TSH.
The antibodies that cause hyperthyroidism almost certainly occur as the result of autoimmunity that has developed against thyroid tissue. Presumably, at some time in the history of the person, an excess of thyroid cell antigens was released from the thyroid cells, and this has resulted in the formation of antibodies against the thyroid gland itself.
Thyroid Adenoma. Hyperthyroidism occasionally resultsfrom a localized adenoma (a tumor) that develops in the thyroid tissue and secretes large quantities of thyroid hormone. This is different from the more usual type of hyperthyroidism, in that it usually is not associated with evidence of any autoimmune disease. An interesting effect of the adenoma is that as long as it continues to secrete large quantities of thyroid hormone, secretory function in the remainder of the thyroid gland is almost totally inhibited because the thyroid hormone from the adenoma depresses the production of TSH by the pitu-itary gland.