Clinical History:
- A 30-year-old woman presented to her physician with a 3 month history of weakness, 3 kg weight loss, and nervousness. Further questioning revealed that she experienced insomnia, excess perspiration, frequent bowel movements, infrequent menses, and heat intolerance during that time. Physical examination reveals a restless woman with warm, moist skin, palmar erythema, fine hair, and a resting pulse rate of 110/minute. On palpation of the neck, the thyroid is diffusely enlarged but nontender. A fine tremor is noted of her outstretched fingers. Deep tendon reflexes are 3+ bilaterally.
- Laboratory data reveal a serum T4 of 14.0 micrograms/ml (normal 4.8 to 11.2). A thyroid scan reveals increased uptake in both lobes. A subtotal thyroidectomy is performed. The tissue removed weighs 60 grams (normal thyroid is up to 30 grams) and is symmetrical and soft.
- What is the diagnosis?
This is Graves disease. The major differential diagnosis is Plummer's disease (toxic multinodular goiter). Note the hyperplastic pattern at low power (image 3.1). At medium power (image 3.2), pink colloid is present within the follicles, and the epithelium has papillary infoldings. At high power (image 3.3) the epithelial cells are tall and columnar, and there is scalloping of the colloid, as though the epithelial cells were scooping out large amounts of it.
- What immunologic mechanism may be at work here?
There may be anti-TSH receptor antibodies. These come in two varieties: thyroid-stimulating immunoglobulins (TSI) that increase hormone production and thyroid-growth immunoglobulins (TGI) that cause the hyperplasia.
- What neoplasms could produce similar findings?
A toxic thyroid adenoma could produce hyperthryoidism. Rarely, a thyroid carcinoma or a pituitary adenoma secreting TSH could be eitiologies. Even more rarely, struma ovarii (thyroid tissue in an ovarian teratoma) or choriocarcinoma could do the same.
- What therapies are available for this condition?
Pharmacologic therapy is available in the form of antithyroid agents, including the thionamides such as propylthiouracil and carbimazole (and its active metabolite methimazole) which inhibit thyroid peroxidase to reduce the oxidation and organification of iodide. These drugs may reduce antithyroid antibodies by unknown mechanisms. Propranolol is a beta-blocker that can work to alleviate the adrenergic effects of Graves disease, and it is effective in treating "thyroid storm" in which there is a life-threatening exacerbation of hyperthyroidism with fever, delirium, seizures, coma, vomiting, diarrhea, and jaundice. Radioactive iodine 131 is selectively taken up by the thyroid and causes progressive destruction of thyroid cells, but calculating an optimal dose for a resultant euthyroid state is difficult. Subtotal thyroidectomy can be considered in patients for whom the above therapies are not possible or do not work.
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