A 32-year-old woman comes to the office due to a persistent sensation of warmth. For the last 6 months she has felt unusually warm compared to others in the room. The patient has no medical problems and takes no medications or supplements. She does not use tobacco, alcohol, or illicit drugs. Family history is significant for hypothyroidism in her mother. Temperature is 36.7 C (98 F), blood pressure is 130/60 mm Hg, and pulse is 104/min. BMI is 20 kg/m². On physical examination, the patient appears anxious and has a staring gaze. There is exophthalmos, lid lag, and a diffusely enlarged thyroid with an audible thyroid bruit. The patient has a fine tremor on outstretched arms, and the skin is warm and moist. Antibodies directed against which of the following are most likely to be found in this patient?

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11ec160b_3cac_ee0e_9249_3f51377df38b_MD0001_00 This patient has signs of hyperthyroidism, including heat intolerance, tachycardia, and lid lag. In light of her diffuse goiter and exophthalmos this is very likely due to Graves disease. Graves disease is an autoimmune disorder triggered by thyrotropin receptor antibodies (TRAb), which bind and activate the TSH receptor. In addition to the thyroid, the TSH receptor antigen is present on other cell types, including fibroblasts and adipocytes. Graves ophthalmopathy is characterized by ocular irritation, impaired extraocular motion, and proptosis; it is caused by T-cell activation and stimulation of orbital fibroblasts by TRAb, leading to expansion of extraocular muscles and retro-orbital tissues. TRAb binds to extracellular domains on the TSH receptor, a transmembrane G protein-coupled receptor. The G_s alpha subunit activates adenylate cyclase and subsequently the adenylate cyclase second messenger system. Serum TRAb immunoassays have a high sensitivity (97%) and specificity (99%) for Graves disease, although they detect both activating and blocking anti-TSH receptor antibodies. Activating antibodies can be confirmed with a functional bioassay (thyroid-stimulating immunoglobulin) that measures cyclic AMP production by a TSH-receptor-expressing cell line in response to patient serum. (Choice A) Antibodies to thyroglobulin are thought to reflect disruption of thyroid follicles, which exposes thyroglobulin to the bloodstream. They are present in a number of autoimmune thyroid disorders but are most common in autoimmune hypothyroidism and are present in only a minority of patients with Graves disease. (Choice B) Thyroid peroxidase antibodies are most closely associated with Hashimoto thyroiditis and related disorders (eg, silent thyroiditis, postpartum thyroiditis). Hyperthyroidism with exophthalmos is most consistent with Graves disease. (Choices D and E) Antibodies to thyroxine and triiodothyronine (ie, anti-T4 and anti-T3 immunoglobulins, respectively) can be detected by adding radiolabeled thyroid hormone to the patient's serum followed by precipitation of the antigen-antibody complexes with polyethylene glycol. These antibodies can be seen in a variety of autoimmune thyroid disorders, but are rare. Educational objective: Graves disease is an autoimmune disorder triggered by thyrotropin receptor antibodies (TRAb) that bind and activate the TSH receptor. Serum TRAb immunoassays have a high sensitivity and specificity for Graves disease. __________ References: Thyrotropin receptor epitope and human leukocyte antigen in Graves disease. (http://www.ncbi.nlm.nih.gov/pubmed/27602020)

A 32-Year-Old Woman Comes to the Office Due to a Persistent