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Graves’ disease, the most common cause of hyperthyroidism, can also carry unique clinical features unrelated to thyrotoxicosis, such as ophthalmopathy and dermopathy.
Case
A 25-year-old, previously healthy woman presents with one month of anxiety, palpitations, intermittent loose non-dysenteriform stools, fine tremors, and hair loss. She has had a 20-pound weight loss in the previous four months, even though she reports an increased appetite. Her heart rate ranges from 115 to 130 beats per minute, and her temperature is 37.5oC. An exam is notable for mild bilateral proptosis, thin hair, and moist skin. A goiter is visible; it has increased consistency on palpation with an audible bruit over it. She has hyperreflexia and fine tremors. An EKG reveals sinus tachycardia. How should this patient be evaluated? What treatment should be initiated?
Overview
Graves’ disease, the most common cause of hyperthyroidism, is caused by autoimmune stimulation of the thyrotropin (TSH) receptor. It generally presents with a variety of signs and symptoms found with hyperthyroidism, but it can also carry unique clinical features unrelated to thyrotoxicosis, such as ophthalmopathy and dermopathy.
Graves’ disease diagnosis mainly is clinical, but also is supported by elevated free levels of thyroid hormones (mainly triiodothyronine [T3]) and suppressed TSH levels. Anti-thyrotropin receptor antibodies generally are present. Imaging in Graves’ disease is characterized by increased radioiodine uptake, as well as increased perfusion by Doppler ultrasonography.
Treatment can be pharmacologic, using anti-thyroid drugs, or ablative, with either radioiodine or thyroidectomy. Adjunctive therapy includes symptom control with beta-blocker agents, as well as steroid supplementation, especially in patients with orbitopathy undergoing radioablative treatment.
The Data
Epidemiology. Graves’ disease is the most common cause of hyperthyroidism, with a prevalence of ~0.5% of the population. Women are most commonly affected, with a prevalence five to 10 times higher than in male peers. The most common age of presentation is between the fifth and sixth decades of life.1-3
The fact that Graves’ disease occurs with higher incidence in patients with a family history of thyroid disease—and that concordance rates of up to 35% are seen with monozygotic twins—suggests that both genetic and environmental factors influence disease susceptibility.2,4
Pathophysiology. Graves’ disease occurs as a result of direct activation of the G-protein-coupled adenylate cyclase in the thyrotropin receptor by circulating IgG antibodies.2,3 Follicular hypertrophy and hyperplasia, and increased vascularity, cause goiter formation and an increased production of T3 and thyroxine (T4). The increase in T3 and T4 subsequently suppress TSH production.
Graves’ disease also is associated with unique clinical manifestations unrelated to the circulating levels of thyroid hormones, such as Graves’ ophthalmopathy and infiltrative dermopathy (localized or pretibial myxedema). Both of these occur as a result of local tissue infiltration by inflammatory cells and deposition of glycosaminglycanes.5
Clinical manifestations. Graves’ disease is characterized by a constellation of clinical findings and patient symptoms (see Table 1).1-3 The clinical presentation could differ in elderly patients, who present more commonly with weight loss or depression (also known as apathetic hyperthyroidism) and less commonly with tachycardia and tremor.2,3
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Table 1. Clinical Manifestations Of Hyperthyroidism
Although clinically apparent, exophtalmos is detected in 30% to 50% of patients; when using orbital imaging, it is identified in ≥80% of patients.5 Ophthalmopathy has a clinical course typically independent of the thyroid activity; its manifestations include proptosis, periorbital edema and inflammation, exposure keratitis, photophobia, extraocular muscle infiltration, and eyelid lag.5-8
Thyroid dermopathy (localized dermal myxedema) can occur in 0.5% to 4.3% of patients with Graves’ disease; it occurs most commonly among patients with Graves’ ophthalmopathy, in whom it occurs in up to 13% of cases. About 20% of patients with dermal myxedema have associated thyroid acropachy.3,9