eted 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 patients with HIV(33.2), has occurred during recovery of low lymphocyte levels induced by therapy with CAMPATH in patients with Multiple sclerosis, has occurred after cessation of immune-suppressive treatment in patients with T1DM, and has developed during thyroid invasion by lymphoma(18).
|Table 4. Causes of Thyrotoxicosis|
Course of disease
|Graves’ disease||Familial, prolonged||Goiter||+ Ab, + RAIU, eye signs||Antithyroids, RAI, Surgery|
|Transient thyrotoxicosis||Brief||Small goiter||Low Ab, no eye signs, RAIU=0||Time, beta blocker, ? steroids|
|Subacute thyroiditis||Brief||Tender goiter||RAIU=0, elevated ESR, recent URI||Nothing, NSAID, steroids|
|Toxic multinodular goiter||Prolonged, mild||Nodular goiter||Typical scan||Antithyroids, RAI, surgery|
|Iodide induced||Recent, mild||Nodular goiter, occ.normal||Low RAIU, abnormal scan||Antithyroids, KClO4, time, stop I source|
|Toxic adenoma||Prolonged, mild||One nodule||“Hot” nodule on scan||Surgery, RAI, ? Sclerosis|
|Thyroid carcinoma||Recent||Variable, metastases||Functioning metastases||Surgery + RAI|
|Exogenous hormone||Variable||Small thyroid||RAIU and TG low, psychiatric illness||Withdrawal, counseling|
|Hydatiform mole||Recent, mild||Goiter||Pregnancy, bleeding,HCG||Surgery, chemotherapy|
|Choriocarcinoma||Recent, mild||Goiter||Increased HCG||Surgery, chemotherapy|
|Excess TRH||Goiter||Poor response to TRH||Not known||?|
|TSH-oma||Prolonged||Goiter||Excess alpha, TSH, adenoma||Op, somatostatin, thyroid ablation|
|Pituitary T3 resistance||Prolonged||Goiter||Elevated or normal TSH, no tumor, mod. thyrotox, no excess alpha||? Triac, somatostatin, thyroid ablation, beta blocker|
|Struma ovarii||Variable||+ / – goiter||Positive scan or US||Surgery|
|Hamburger toxicosis||Recent, self-limited||Small gland, no eye signs||Suppressed TSH and TG and RAIU||Avoid neck meat trimmings|
|Hyperemesis||Onset first trimester||Pregnancy, variably toxic||UP FTI, Low TSH, High HCG||ATD if severe, pregnancy termination|
|TSH-R mutation||Congenital||Typical thyrotoxicosis||+ FH, ger