Graves Disease

David L. Steward

History

A 33-year-old woman has thyroid enlargement, palpitations, tremor, and weight loss. She denies visual changes. She is otherwise healthy and is on no medications. She reports a family history of a maternal aunt who had radioiodine therapy and her mother who is on thyroid hormone.

Physical examination reveals diffuse and doughy thyromegaly, mild asymmetric exophthalmos with bilateral lagophthalmos, tachycardia, and mild tremor. Extraocular motion is preserved.

Differential Diagnosis—Key Points

This patient has a fairly classic presentation for Graves disease with signs and symptoms of hyperthyroidism, diffuse thyroid enlargement, and ophthalmopathy. The family history suggests both hyperthyroidism and hypothyroidism on her mother’s side. Current understanding of autoimmune thyroid disease suggests that Hashimoto thyroiditis and Graves disease are genetically related. Initial workup should focus on biochemical confirmation of the hyperthyroidism and amelioration of symptoms, with further workup focusing on the cause of the hyperthyroidism, which could include Graves, thyroiditis (Hashimoto or viral), or toxic adenoma or toxic multinodular goiter. The treatment and prognosis depend on the cause of the hyperthyroidism.

Test Interpretation

Biochemical diagnosis of hyperthyroidism includes thyroid-stimulating hormone (TSH), tri-iodothyronine (T₃), and free thyroxine (T₄) levels, with low TSH and high free T₃ or free T₄ levels being diagnostic. Subclinical hyperthyroidism is associated with low TSH with normal free T₃ and free T₄ levels.

The cause of hyperthyroidism can be evaluated using serum antithyroid antibody testing or with radioiodine uptake and scan. Thyroid ultrasound, especially if coupled with antibody testing, may be an alternative to the radioiodine scan in patients with Graves disease. Elevated anti-TSH receptor antibody levels are diagnostic of Graves disease. Elevated antithyroglobulin or antithyroid peroxidase (TPO) antibodies are consistent with chronic lymphocytic thyroiditis (Hashimoto). In the absence of positive antibody testing, elevated erythrocyte sedimentation rate (>60) is consistent with viral subacute thyroiditis (DeQuervan).