Snapshot A 34-year-old woman presents to the physician's office with complaints of weight loss and sweatiness. She states that despite a ravenous appetite, she has lost 4 pounds this past month. In addition she states that she has been more sweaty lately, and unable to cool down in rooms that others find comfortable. On physical exam you see an anxious and fidgety woman who has a very prominent gaze with protuberant eyes. Introduction An autoimmune disease with stimulating anti-TSH receptor antibodies a type II hypersensitivity anti-microsomal and anti-thyroglobulin antibodies also present (more commonly associated with Hashimoto's thyroiditis and hypothyroidism) anti-TSH antibodies also stimulate retroorbital fibroblasts → exopthalmos Epidemiology most common cause of hyperthyroidism female dominant HLA-B8, -DR3 association often incited during stress e.g., childbirth, infection, and steroid withdrawal Presentation Symptoms hyperthyroidism Physical exam symmetrical, non-tender thyroid enlargement ophthalmopathy (proptosis and exopthalmos) due to glycosaminoglycan deposition pretibial myxedema digital swelling Evaluation Serology ↑ total serum T4 ↑ free T4 ↑ 123I uptake diffusely on radioactive iodine uptake scan ↓ serum TSH Histology not a routine part of evaluation, but on histology may see scalloping of the colloid increased activity of the epithelium to produce increased thyroid hormone Treatment Pharmacologic β-blockers symptomatic relief via blockade of beta-1 adrenergic receptors propranolol inhibits peripheral T4 to T3 conversion by deiodinase thiocyanate inhibits the Na-I symporter located on the basolateral membrane of thyroid epithelial cells decreased iodide uptake leads to decreased hormone synthesis thionamides inhibits thyroid peroxidase result in reduced hormone synthesis 131I ablation glucocorticoids treatment of exophthalmos Prognosis, Prevention, and Complications Complications stress-induced catecholamine surge may be fatal by arrhythmia pregnancy complications anti-TSH receptor antibodies may cross placenta and produce hyperthryoidism in the fetus may present with tachycardia, goiters, growth delays, microcephaly, or craniosynostosis High Yield Presentation a female patient with weight loss, tachycardia, irritability, pretibial myxedema and exopthalmos Pathophysiology TSH stimulating antibodies stimulate TSH receptors (-->hyperthyroidism) associated with other autoimmune disorders and HLA B8 and DR3 stimulation of thyroid gland leads to increased T4 and T3 decreased TSH diffuse increase in radioactive iodine uptake exophthalmos caused by lymphocytic infiltration TSH stimulating antibodies can stimulate retro-orbital fibroblasts antithyroid medications will not improve/reverse glucocorticoids may help decrease inflammation Management best initial step: propranolol and propylthiouracil be aware of agranulocytosis with thionamides definitive management: radioactive iodine ablation (in general) or surgical removal of the thyroid in extreme cases (pregnancy)