A 32-year-old previously healthy woman comes to the office due to several weeks of anxiety, palpitations, excessive sweating, and thinning hair. The symptoms have progressively worsened and interfered significantly with her daily activities. The patient does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/70 mm Hg and pulse is 104/min. On physical examination, there is lid lag, moderate exophthalmos, and fine tremors of the outstretched hands. After the diagnosis is made, she is prescribed propranolol for immediate symptom control. Which of the following findings is most likely to persist in this patient despite this therapy?
General manifestations of hyperthyroidism | |
Symptoms |
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Physical examination |
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Graves disease is an autoimmune disorder characterized by autoantibodies that bind to and activate the TSH receptor (thyrotropin receptor antibodies [TRAb]). In the thyroid, TRAb triggers release of thyroid hormones, leading to thyrotoxicosis. Hyperthyroidism causes increased expression of beta-adrenergic receptors in various organs, and the subsequent hyperadrenergic state can result in hypertension, tremor, heat intolerance, palpitations/tachycardia, and hyperreflexia (Choices D, E, and F). Patients with Graves disease are frequently given beta-adrenergic blocking medications (eg, propranolol) to control these manifestations while awaiting definitive management.
TSH receptors are also present on fibroblasts, adipocytes, and other tissues. Graves ophthalmopathy results from stimulation of orbital fibroblasts and adipocytes by TRAb and activated T cells. The fibroblasts secrete excess amounts of glycosaminoglycans, leading to expansion of the ground substance of retro-orbital tissues. This, along with excess adipose deposition, displaces the globe forward (exophthalmos) and leads to restricted movement of the extraocular muscles (eg, diplopia). These manifestations are not mediated by thyroid hormone or adrenergic stimulation and do not respond to beta blockers. However, as they are immune mediated, the manifestations of Graves ophthalmopathy usually respond to glucocorticoid therapy.
(Choice A) Although beta blockers can cause fatigue and depressive symptoms, they help reduce fatigue and mood lability in patients with Graves disease by ameliorating sympathetic overactivation. Beta blockers can also help blunt the physical manifestations of anxiety.
(Choice B) Apocrine sweat glands are stimulated primarily by catecholamines; beta blockers can reduce secretory activity. By contrast, eccrine sweat glands are directly innervated by cholinergic fibers. However, centrally acting beta blockers (eg, propranolol) can modulate eccrine activity and reduce emotionally driven (eg, anxiety) stimulation of eccrine sweating.
Educational objective:
Hyperthyroidism causes a hyperadrenergic state characterized by hypertension, palpitations/tachycardia, sweating, heat intolerance, tremor, and hyperreflexia. Beta blockers can relieve these symptoms. Exophthalmos in Graves disease is due to an immune-mediated increase in orbital soft tissue mass and does not improve with beta blockers.