A 56-year-old woman comes to the office due to eye irritation, painful eye movements, and diplopia. Over the last few weeks, she has also experienced weight loss and fatigue. The patient smokes a pack of cigarettes a day and has a 25-pack-year history. Other medical problems include chronic obstructive pulmonary disease treated with an inhaled corticosteroid and bronchodilators. She also suffered a head injury in a motor vehicle accident 6 months ago. Blood pressure is 146/70 mm Hg, pulse is 110/min, and respirations are 18/min. On physical examination, the patient is unable to maintain eye convergence and experiences diplopia on upward gaze. Her eyes are shown in the image below.
Show Explanatory Sources
Which of the following is the most likely cause of this patient's examination findings?
Clinical manifestations of Graves disease | |
General | Heat intolerance, weight loss, sweating |
Eyes | Lid lag, proptosis, diplopia |
Skin | Hair loss, infiltrative dermopathy (pretibial myxedema) |
Cardiovascular | Tachycardia, hypertension, atrial fibrillation |
Nails | Onycholysis, clubbing (acropachy) |
Endocrine | Hyperglycemia, hypercalcemia, bone loss, menstrual irregularities |
Gastrointestinal | Diarrhea |
Neurology | Tremors, hyperreflexia, proximal muscle weakness |
This patient has clinical features of hyperthyroidism (ie, weight loss, tachycardia) with proptosis and impaired extraocular motion (decreased convergence, diplopia) consistent with Graves ophthalmopathy. Other common symptoms include irritation (eg, gritty or sandy sensation), redness, photophobia, pain, and tearing. Ophthalmopathy in Graves disease is typically diagnosed at the same time as hyperthyroidism but may occur before or after the onset of hyperthyroidism. Risk factors include female sex, advancing age, and smoking.
In Graves disease, thyrotropin (TSH) receptor autoantibodies (TRAB) stimulate thyroid hormone production, resulting in hyperthyroidism. Thyroid hormone increases sensitivity to catecholamines, and thyrotoxicosis of any etiology may cause lid lag and retraction due to sympathetic activation and contraction of the superior tarsal muscle. However, true exophthalmos with impaired extraocular motion is seen only in Graves disease and is due to T cell activation and stimulation of orbital fibroblasts and adipocytes by TRAB, resulting in orbital tissue expansion and lymphocytic infiltration.
(Choice A) Brain stem dysfunction can cause diplopia but not proptosis. Furthermore, because many neural tracts are tightly packed in the brain stem, other neurologic findings (eg, weakness, sensory deficits, altered sensorium) are usually present.
(Choice B) Increased intracranial pressure (eg, pseudotumor cerebri) can cause papilledema but would not cause proptosis.
(Choice C) Graves ophthalmopathy can cause increased intraocular pressure due to orbital tissue expansion and compression of the globe. However, increased intraocular pressure alone (eg, glaucoma) does not cause proptosis.
(Choices D and F) Myasthenia gravis (MG) is a disorder of the neuromuscular junction caused by autoantibodies against acetylcholine receptors on the motor end plate. Ocular involvement may cause fluctuating diplopia and ptosis. Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic syndrome that may also cause diplopia. However, ocular involvement by LEMS is less common than involvement of the proximal limb muscles, and neither MG nor LEMS would cause ocular irritation, painful movement, or proptosis.
Educational objective:
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 thyrotropin (TSH) receptor autoantibodies, leading to expansion of orbital tissues.