Clinical Features Symptoms of thyrotoxicosis include fatigue, diarrhea, heat intolerance, palpitations, dyspnea, nervousness, and weight loss. In young patients there may be paradoxical weight gain from an increased appetite. Thyrotoxicosis may cause vomiting in pregnant women, which may be confused with hyperemesis gravidarum (50). Tachycardia, lid lag, tremor, proximal muscle weakness, and warm moist skin are classic physical findings. The most dramatic physical changes are ophthalmologic and include lid retraction, periorbital edema, and proptosis. These eye findings occur in less than one-third of women. In elderly adults, symptoms are often more subtle, with presentations of unexplained weight loss, atrial fibrillation, or new onset angina pectoris. Menstrual abnormalities span from regular menses to light ﬂow to anovulatory menses and associated infertility. Goiter is common in younger women with Graves disease, but may be absent in older women. Toxic nodular goiter is associated with nonhomogeneous glandular enlargement, whereas in subacute thyroiditis the gland is tender, hard, and enlarged.
Diagnosis Most thyrotoxic patients have elevated total and free T4 and T3 concentrations (measured by radioimmune assay). In thyrotoxicosis, serum TSH concentrations are virtually undetectable, even with very sensitive assays (sensitivity measured to 0.1 units). Sensitive serum TSH measurements may aid in the diagnosis of hyperthyroidism. Radioiodine uptake scans are useful in the differential diagnosis of established hyperthyroidism. Scans with homogeneous uptake of radioactive iodine are suggestive of Graves disease, whereas heterogeneous tracer uptake is suggestive of a diagnosis of toxic nodular goiter. Thyroiditis and medication-induced thyrotoxicosis have diminished glandular radioisotope concentration.
Therapy Antithyroid medications, either propylthiouracil (PTU 50–300 mg every 6–8 hours) or methimazole (10–30 mg per day) are used for initial therapy. After metabolic control is achieved, definitive therapy is obtained by thyroid ablation with radioiodine, which results in permanent hypothyroidism. Both antithyroid drugs block thyroid hormone biosynthesis and may have additional immunosuppressive effects on the gland. The primary difference in oral medications is that PTU partially inhibits extrathyroidal T4-to-T3 conversion, whereas methimazole does not. Methimazole has a longer half-life and permits single daily dosing, which may encourage compliance. Euthyroidism is typically restored in 3 to 10 weeks, and treatment with oral antithyroid agents is continued for 6 to 24 months, unless total ablation with radioiodine or surgical resection is performed. Surgery is less popular because it is invasive and may result in inadvertent parathyroid removal, which commits the patient to lifelong calcium therapy.
The relapse rate with oral antithyroid medications is 50% over a lifetime. Lifelong follow-up is important when medical therapy is used solely because of the high relapse rate. Both medications have infrequent (5%) minor side effects, which include fever, rash, or arthralgias. Major toxicity (e.g., hepatitis, vasculitis, and agranulocytosis) occurs in less than 1%. Agranulocytosis cannot be predicted by periodic complete blood counts; therefore, patients who have a sore throat or fever should stop taking the medication and call their physician immediately.
Therapy with iodine-131 provides a permanent cure of hyperthyroidism in 90% of patients.