this diagnosis is likely. Usually the erythrocyte sedimentation rate (ESR) and CRP are greatly elevated, and the leukocyte count may also be increased. Occasionally the goiter is non-tender. Antibody titers are low or negative. Many patients have the HLA-B35 antigen, indicating a genetic predisposition to the disease.
The rare TSH secreting pituitary adenoma will be missed unless one measures the plasma TSH level, or until the enlargement is sufficient to produce deficiencies in other hormones, pressure symptoms, or expansion of the sella turcica(20). These patients have thyrotoxicosis with inappropriately elevated TSH levels and may/or may not secrete more TSH after TRH stimulation. The characteristic finding is a normal or elevated TSH, and an elevated TSH alpha subunit level in blood, measured by special RIA. TRAbs are not present. Exophthalmos, family history, and antibodies of Graves’ disease are absent. Demonstration of a suppressed TSH level excludes these rare cases.
The category of patients with thyrotoxicosis and inappropriately elevated TSH levels also includes the very rare persons with excess TRH secretion, or pituitary “T3 resistance” as a part of the Resistance to Thyroid Hormone syndrome caused usually by TH Receptor mutations. TRH hypersecretion, a possible cause of thyrotoxicosis , is marked by an absence of pituitary tumor, elevated TSH levels, and failure to respond to TRH. The syndrome of Pituitary Thyroid Hormone Resistance is usually marked by mild thyrotoxicosis, mildly elevated TSH levels, absence of pituitary tumor, a generous response to TRH, no excess TSH alpha subunit secretion [19,21],and by TSH suppression if large doses of T3 are administered. Final diagnosis depends on laboratory demonstration of a mutation in the TR gene, if possible.
Administration of large amounts of iodide in medicines, for roentgenographic examinations, or in foods can occasionally precipitate thyrotoxicosis in patients with multinodular goiter or functioning adenomas. This history is important to consider since the illness may be self-limiting. Induction of thyrotoxicosis has also been observed in apparently normal individuals following prolonged exposure to organic iodide containing compounds such as antiseptic soaps and amiodarone. Amiodarone is of special importance since the clinical problem often is the presentation of thyrotoxicosis in a patient with serious cardiac disease including dysrythmia. Amodarone can induce thyrotoxicosis in patients without known prior thyroid disease, or with multinodular goiter. The illness appears to come in two forms. In one the RAIU may be low or normal. In the second variety , which appears to be more of a thyroiditis-like syndrome, the RAIU is very suppressed, and IL-6 may be elevated. In either case TSH is suppressed, FTI may be normal or elevated, but T3 is elevated if the patient is toxic. Antibodies are usually negative.
An increasingly recognized form of thyrotoxicosis is the syndrome described variously as painless thyroiditis, transient thyrotoxicosis, or “hyperthyroiditis“. Its hallmarks are self-limited thyrotoxicosis, small painless goiter, and low or zero RAIU(22,23). The patients usually have no eye signs, a negative family history, and low antibody titers. This condition is due to autoimmune thyroid disease, and is considered a variant of Hashimoto’s Thyroiditis. It occurs sporadically, usually in young adults. It frequently occurs 3 – 12 weeks after delivery, sometimes representing the effects of immunologic rebound from the immunosuppressive effects of pregnancy in patients with Hashimoto’s thyroiditis or prior Graves’ Disease, and is called Post Partum Thyroiditis(12,24,25). The course typically includes development of a painless goiter, mild to moderate thyrotoxicosis, no eye signs, remission of symptoms in 3 -20 weeks, and often a period of hypothyroidism before return to euthyroid function. The cycle may be repeated several times. Histologic examination shows chronic thyroiditis, but it is not typical of Hashimoto’s disease or subacute thyroiditis and may re