A 28-year-old woman comes to the office due to progressively worsening eye irritation and double vision over the last 2 months. She also reports unintentional weight loss, mood swings, and palpitations. The patient has no prior medical problems and takes no medications. She has no known drug allergies and does not use tobacco, alcohol, or illicit drugs. Blood pressure is 140/70 mm Hg, and pulse is 110/min and regular. Physical examination shows bilateral conjunctival redness and severe proptosis. Appropriate therapy is begun. On a follow-up visit 4 weeks later, her eye symptoms have improved, and examination reveals a small decrease in proptosis with no redness. The drug that improved her ocular symptoms most likely did so by affecting which of the following?

Question

A 28-year-old woman comes to the office due to progressively worsening eye irritation and double vision over the last 2 months.  She also reports unintentional weight loss, mood swings, and palpitations.  The patient has no prior medical problems and takes no medications.  She has no known drug allergies and does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 140/70 mm Hg, and pulse is 110/min and regular.  Physical examination shows bilateral conjunctival redness and severe proptosis.  Appropriate therapy is begun.  On a follow-up visit 4 weeks later, her eye symptoms have improved, and examination reveals a small decrease in proptosis with no redness.  The drug that improved her ocular symptoms most likely did so by affecting which of the following?

Quizplus · Accepted Answer

11ec160b_3bb8_7c1a_9249_b37520d67602_MD0001_00 This patient has Graves disease with hyperthyroidism (weight loss, palpitations, tachycardia) and significant ophthalmopathy (proptosis, diplopia). Graves disease is an autoimmune disorder triggered by thyrotropin receptor antibodies, which bind and activate the TSH receptor. In addition to the thyroid, the TSH receptor is present on fibroblasts, adipocytes, and other cell types. Graves ophthalmopathy is caused by stimulation of orbital fibroblasts by thyrotropin receptor antibodies, which leads to excess deposition of extracellular glycosaminoglycans; this is accompanied by T-cell activation and inflammatory infiltration. The resultant expansion of extraocular muscles and retro-orbital tissues with the orbit displaces the globe forward, and dysfunction of the extraocular muscles causes restricted extraocular movements and diplopia. Glucocorticoids (eg, prednisone) decrease peripheral conversion of T4 to T3, but it is their anti-inflammatory effects that improve Graves ophthalmopathy. Glucocorticoids decrease the severity of inflammation and reduce the excess extraocular volume. They also can prevent worsening of ophthalmopathy induced by radioactive iodine treatment. (Choices B, C, and E) Antithyroid drugs (eg, methimazole, propylthiouracil) inhibit thyroid peroxidase, leading to decreased iodine organification and coupling of iodotyrosines. Certain oxoanions (eg, perchlorate, pertechnetate) inhibit the sodium-iodide symporter and reduce iodine uptake by the thyroid. These agents ultimately lead to reduced production and release of thyroid hormone but do not alter the inflammatory process in Graves ophthalmopathy. (Choice D) Sympathetic activation secondary to hyperthyroidism is responsible for a number of symptoms, including palpitations and tremors. Beta blockers can provide rapid symptomatic relief while awaiting definitive therapy. Although lid lag (which is seen in hyperthyroidism of any cause) would improve with beta blockers, the specific features of Graves ophthalmopathy (eg, diplopia, proptosis) would not be affected. Educational objective: Graves ophthalmopathy is caused by stimulation of orbital fibroblasts by thyrotropin receptor antibodies and cytokines released by activated T-cells. Excess deposition of extracellular glycosaminoglycans and inflammatory infiltration lead to expansion of extraocular muscles and retro-orbital tissues. Glucocorticoids improve Graves ophthalmopathy by decreasing the severity of inflammation and reducing the excess extraocular volume. __________ References: Glucocorticoid regimens for prevention of Graves' ophthalmopathy progression following radioiodine treatment: systematic review and meta-analysis. (http://www.ncbi.nlm.nih.gov/pubmed/25068172)

A 28-Year-Old Woman Comes to the Office Due to Progressively