vert to normal after the attack(26). In most patients, the thyrotoxic episode occurs in the absence of circulating TSAb. This finding suggests that the pathogenesis is quite distinct from that in Graves’ disease. The thyrotoxicosis is caused by an inflammation-induced discharge of preformed hormone due to the thyroiditis. The T4/T3 ratio is higher than in typical Graves’ disease,and thyroid iodine stores are depleted. Since the thyrotoxicosis is due to an inflammatory process, therapy with antithyroid drugs or potassium iodide is usually to no avail, and RAI treatment of course cannot be given when RAIU is suppressed. Propranolol is usually helpful for symptoms. Glucocorticoids may be of help if the process — often transient and mild — requires some form of therapy. Propylthiouracil and/or ipodate can be used to decrease T4 to T3 conversion and will ameliorate the illness. Repeated episodes may be handled by surgery or by RAI therapy during a remission. Occasionally painless post-partum thyroiditis is followed by typical Graves’ Disease(27-29). Hyperemisis gravidarum is usually associated with elevated serum T4 , FTI, and variably elevated T3, and suppressed TSH. The abnormalities in thyroid function are caused by high levels of hCG. This molecule, or a closely related form, share enough homology with TSH so that it has about 1/1000 the thyroid stimulating activity of TSH, and can produce thyroid stimulation or thyrotoxicosis(29.4,29.5,30,32). It is typically self limited without specific treatment, disappears with termination of pregnancy, but may occasionally require anti-thyroid treatment temporarily or throughout pregnancy(29.3). Patients with minimal signs and symptoms, small or no goiter, and elevation of FTI up to 50 % above normal probably do not require treatment. Those with goiter, moderate or severe clinical evidence of thyrotoxicosis, highly elevated T4 and T3 and suppressed TSH are best treated with antithyroid drugs. If antibodies are positive or eye signs are present, the picture is usually interpreted as a form of Graves’ disease. Familial severe hyperemesis gravidarum with fetal loss has been reported with an activating germline mutation in the TSH-R, which made it specifically more sensitive to activation by hCG. Hyperthyroidism can be induced by “hyperplacentosis”, which is characterized by increased placental weight and circulating hCG levels higher than those in normal pregnancy(29.6). After hysterotomy, hCG levels declined in the one case reported and hyperthyroidism was corrected.
Congenital hyperthyroidism caused by a germ-line activating mutation in the TSH-R has recently been recognized . The mutations are usually single aminoacid transitions in the extracellular loops or transmembrane segments of the receptor trans-membrane domain. The diagnosis may be difficult to recognize in the absence of a family history. However the patients lack eye signs, and have negative assays for antibodies(29.1) (For interest, a similar syndrome occurs in cats(16.1)).
Hydatidiform moles, choriocarcinomas, and rarely seminomas secrete vast amounts of hCG. hCG, with an alpha subunit identical to TSH , and beta subunit related to TSH , binds to and activates the thyroid TSH receptor with about 1/1,000th the efficiency of TSH itself (Fig.-3)(31-33). Current evidence indicates that very elevated levels of native hCG or perhaps desialated hCG, cause the thyroid stimulation. Many patients have goiter or elevated thyroid hormone levels or both, but little evidence of thyrotoxicosis, whereas others are clearly thyrotoxic. Diagnosis rests on recognizing the tumor (typically during or after pregnancy) and measurement of hCG. Therapy is directed at the tumor.
Hyperthyroidism also is seen as one manifestation of autoimmune thyroid disease induced by interferon-alpha treatment of chronic hepatitis C. It can be self limiting, or severe enough to require cessation of IFN, or in some cases continue on after INF is stopped(33.1).
Hyperthyroidism also occurs during immune reconstitution seen after effective anti-viral therapy of pati