How is Graves’ Disease Diagnosed and Evaluated?

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This CT image from a patient with Graves disease shows bilateral proptosis and orbital fat deposition.

Hospitalists should be aware of thyroid storm. Although rare, occurring in only 1% to 2% of patients with hyperthyroidism, it can be a medical emergency. It is generally manifested by fever (due to severe thermogenesis), atrial tachyarrhythmias (due to hyperadrenergic response), mental status changes, and liver dysfunction.

In addition, patients with thyroid storm might present with hyperglycemia, hypercalcemia, hypocortisolism, and hypokalemia.¹⁰ Thyroid storm requires prompt treatment of both the clinical manifestations and the underlying condition.

Differential Diagnosis from Other Causes of Thyroiditis

Laboratory. The classic presentation of Graves’ disease is a suppressed TSH and elevated serum T3 and T4 levels.^1-3 Generally, T3 is higher than T4, which also occurs in toxic multinodular goiter, solitary hyperfunctioning nodule, and iodine-induced hyperthyroidism.^2,6 The free T3 and T4 levels should be obtained, as these are useful for monitoring response to therapy.^1-3

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Table 2. Differential diagnosis of thyroiditis

Most patients with Graves’ disease also have anti-thyroid antibodies (see Table 2), although these are not required for the diagnosis.^1-3,11

Following initiation of treatment, TSH levels remain suppressed for approximately two to three months, even after free T3 and T4 levels return to normal or below normal. After this period of suppression is over, TSH levels can be used to adjust therapy.^1-3

Imaging. A thyroid radioiodine-uptake study provides a measure of iodine uptake, as well as an image of functioning thyroid tissue; the imaging is done 24 hours after the intake of iodine-123 or iodine-131. Generalized increased uptake is characteristic of Graves’ disease.^1-3,12 In comparison, patients with thyroiditis have decreased radioiodine uptake as well as low blood flow in Doppler ultrasonography.¹³

In patients with large goiters, when there are signs or symptoms of upper airway or thoracic outlet obstruction, imaging with a neck and upper-chest CT scan is recommended.² In patients with unilateral proptosis, asymmetric ophthalmopathy, or visual loss, orbital imaging is advised (CT scan or MRI).^2,5 In patients with tachyarrhythmias, an electrocardiogram should evaluate for the presence of atrial fibrillation.² Table 2 illustrates how Graves’ disease can be distinguished from other causes of thyroiditis.^1-3

Initial Treatment

Treatment of Graves’ disease has two main tenets: treating the underlying thyroid disorder and quickly controlling symptoms. The underlying thyroid disorder can be treated with such anti-thyroid drugs as thionamides (methimazole or propylthiouracil), ablative radioiodine, or surgical excision of the thyroid. Adjunct symptom therapy can include beta-blockers, organic iodide, and glucocorticoids.^11,14 Thionamides are preferred in young patients, pregnant women, and cases with orbital involvement.¹⁴

In pregnancy, treatment with propylthiouracil is preferred, especially during the first two trimesters due to the risk of teratogenicity with methimazole (there have been associated case reports of choanal atresia, aplasia cutis, and facial malformations).¹⁵

Steroid prophylaxis is used in patients with prominent ocular symptoms who undergo radioiodine ablation to minimize risk of worsening of ophthalmopathy.¹⁶

Back to the Case

The patient was admitted; free T3 and T4 levels were elevated, TSH was suppressed, and anti-thyroid antibodies (anti-TPO, anti-TG, and anti-TRAb) were positive. An I-123 radioiodine uptake scan showed diffuse thyroid gland uptake. Beta-blockers were initiated for heart-rate control (atenolol 25 mg) with adequate response.

Given the patient’s young age, it was decided to initiate thionamides. A pregnancy test was negative, so methimazole was initiated at a dose of 10 mg orally once daily.

Dr. Auron is a hospitalist in the Department of Hospital Medicine and the Center for Pediatric Hospital Medicine at Cleveland Clinic. Dr. Hamilton is a hospitalist in the Department of Hospital Medicine at Cleveland Clinic.