The gland-specific dosing method induces a euthyroid state with a calculated low dose of RAI based on the estimated weight of the patient’s thyroid. The optimal dosage may be difficult to calculate, but it is usually the preferred method for patients with Graves’ ophthalmopathy.
Adverse effects of RAI can include worsening of Graves’ ophthalmopathy and an acute rise in thyroid hormone that increases hyperthyroid symptoms or even causes a thyroid storm associated with increased cardiovascular risk.2 A negative pregnancy test result is a prerequisite for all women of childbearing age before taking RAI, and patients are advised to use contraception for 6 months after RAI administration.
Although RAI is often the initial treatment for hyperthyroidism, in some instances—eg, for older patients with comorbidities—pre-treatment with antithyroid drugs (ATD) is indicated to avoid transient worsening of hyperthyroid symptoms after RAI. However, always discontinue ATD 2 weeks before RAI administration; concomitant use is associated with a higher failure rate and persistent or recurrent hyperthyroidism.15
Antithyroid drugs
Two antithyroid medications are available for use in the United States: propylthiouracil (PTU) and methimazole (MMI). In the United Kingdom, carbimazole is also available.
MMI is the drug of choice.16 Compared with PTU, MMI costs less, has a longer half-life, and causes fewer adverse effects. A starting dose of 15 mg per day for MMI is suitable for mild and moderate hyperthyroidism. For more severe cases, 30 mg per day is the recommended starting dose.16 Reserve PTU for treating hyperthyroidism in pregnancy, during which MMI should be avoided, if possible.
Allergic reactions to ATDs appear in around 5% of patients and usually occur in the first 6 weeks of treatment.17 Agranulocytosis is the main concern, although it occurs in fewer than 1% of patients17 and is reversible by stopping the medication. Measure the leukocyte count 1 week after initiation of treatment and repeat the measurement at 1-month intervals.
Two methods are used to dose these medications: titration and block-and-replace. Titration is as effective as the block-and-replace method and is associated with fewer rashes (6% vs 10% of patients) and less agranulocytosis (0.4 % vs 1.4%). The 2 methods have similar relapse rates (around 50%).18
With titration, MMI is started at a dose of 15 mg per day and titrated upward to the lowest effective dose. Treatment for 12 to 18 months is associated with a lower relapse rate than treatment for 6 months (37% vs 58%).19
The block-and-replace method uses persistently high ATD doses in combination with L-thyroxin replacement to avoid hypothyroidism (MMI 30 mg and levothyroxine 80 mcg).
To monitor effectiveness initially, measure free T4 and T3 levels, because TSH concentration changes slowly and may stay low for a few months. Response to treatment is often temporary.8 More definitive treatment with RAI or surgery is usually necessary.
Surgery
Thyroidectomy creates permanent hypothyroidism, necessitating lifelong thyroxine replacement. In the United States, surgical intervention is reserved for special situations, such as pregnant women with severe disease who are allergic or not responding to antithyroid medications, removal of a clinically suspicious thyroid nodule coexisting with hyperthyroidism, or severe or recurrent Graves’ disease with severe ophthalmopathy.20 Surgical options are total or subtotal thyroidectomy. Hyperthyroidism persists or recurs in 8% of patients with subtotal thyroidectomy.21 Potential complications of thyroidectomy include adverse effects of anesthesia, hypoparathyroidism, and vocal cord paralysis.
Other treatment options
Iodides
Iodides inhibit thyroid hormone release and block conversion of T4 to T3. Use potassium iodide only in combination with ATDs, for patients with severe thyrotoxicosis or as pretreatment for urgent thyroidectomy in patients with Graves’ disease. It has been shown to improve the short-term control of Graves’ hyperthyroidism and is not associated with worsening hyperthyroidism;22 however, potassium iodide should not be used for more than 12 weeks as it can cause paradoxical hyperthyroidism.22
Beta-blockers
Hyperthyroidism is associated with an increased number of beta-adrenergic receptors,23 which explains the symptoms of palpitations, anxiety, and tremors. Nonselective beta-blockers are usually preferred for symptomatic treatment of hyperthyroid symptoms, and propranolol is the most widely used agent.24 If you decide to use a beta-blocker, start it with the ATD and continue it until the patient becomes euthyroid or asymptomatic, then taper it over a period of 4 to 6 weeks. Symptoms may persist, however, and require higher doses of propranolol (80-320 mg/d) given more frequently.
Treating Graves’ ophthalmopathy
Exophthalmos and other eye signs are the hallmark of Graves’ disease and may occur in the absence of hyperthyroidism. Smoking is a significant risk factor for developing ophthalmopathy due to increased orbital connective tissue volume,25 and smoking cessation is recommended.26