Approach

The hyperthyroidism of toxic adenomas generally does not remit, and therefore definitive treatment is usually required.

Patient values and preferences

These are an important part of any therapeutic decision-making about definitive treatments. Patients choosing I-131 therapy would most likely favor avoidance of issues surrounding surgery, such as anesthesia or hospitalization, and their possible complications. Those choosing surgery may prefer avoidance of radioactivity; desire very rapid control of hyperthyroidism; or have a lower concern about risks of surgery.[1] Individual issues such as cardiovascular risk also play a role in choice of therapy.

Symptomatic treatment

Beta-blockers are generally recommended for older adults with symptoms or younger people with heart rate >90 bpm.[1] In the absence of contraindication, beta-blockers may be used, if needed, for symptomatic relief while awaiting results of definitive treatment. Propranolol has been most commonly used and also blocks thyroxine (T4) to triiodothyronine (T3) conversion, a theoretical advantage.[37] A selective beta-blocker such as atenolol may be used in patients who cannot tolerate propranolol or who prefer once-daily dosing. An alternative is a calcium-channel blocker if beta-blockers are contraindicated.

Radioactive iodine

I-131 therapy is a preferred treatment for most nonpregnant, nonlactating patients. Dose is generally either fixed; calculated based on goiter size; or computed based on amount of radiation to be delivered.[21] In patients with mild symptoms, I-131 can be administered as a one-time dose, along with symptomatic beta-blocker therapy. Occasionally a second dose of radioactive iodine is required after full therapeutic effect has been achieved at 3 to 6 months post-therapy. In elderly patients or those who have severe symptoms or comorbidities such as cardiac disease, a course of antithyroid drugs (e.g. methimazole) may be used to normalize thyroid function prior to I-131 therapy.[38]

Radioactive iodine is a less-preferred option than surgery in patients with large masses causing compressive symptoms, but can be utilized when surgery is contraindicated or refused. Nodule shrinkage may occur post-treatment.[39][40][41]

I-131 therapy is contraindicated in pregnancy and during lactation.

Antithyroid drugs

Antithyroid drugs are the preferred treatment for pregnant or lactating women.[3] Methimazole is the preferred drug (except during the first trimester of pregnancy), due to a higher risk of hepatotoxicity with propylthiouracil. Because of possible congenital defects (e.g., aplasia cutis, choanal atresia) associated with methimazole, propylthiouracil has been preferred during the first trimester.[42] However, more recent data suggest there may also be a rare propylthiouracil-associated embryopathy with defects of the urinary system and face/neck.[43] Methimazole also has the advantage of less-frequent dosing.

Drugs should also be considered for nonpregnant patients who are not candidates for, or who refuse, radioactive iodine or surgery. Indefinite treatment is generally required, but definitive therapy is appropriate for women after delivery and lactation. Rare but serious complications include agranulocytosis, hepatitis and vasculitis. A course of antithyroid drugs may also be used before I-131 therapy to attain euthyroidism, particularly in patients with severe symptoms or in those who are older or have comorbidities such as heart disease. Antithyroid drugs are used to normalize thyroid function prior to surgery.

Pregnant women should be managed by a multidisciplinary team. Maternal and fetal hypothyroidism must be avoided to prevent damage to fetal neural development, risk of miscarriage, or preterm delivery.[36] Generally doses of antithyroid drugs are lower in pregnancy, and maternal levels of free thyroid hormones are kept high-normal to slightly elevated. Low-to-moderate doses of antithyroid drugs can be safely used during lactation.[36]

Surgery

Subtotal thyroidectomy is an option for people who decline or are resistant to radioactive iodine, or who prefer surgery. Rarely, it is required for pregnant women whose hyperthyroidism cannot be controlled with antithyroid drugs. Rarely, it is an option for patients who remain hyperthyroid after radioactive iodine therapy but decline a second dose. It can also be used as first-line treatment for people with very large nodules causing obstructive symptoms. An experienced, high-volume surgeon is recommended.[1] Complications such as hypoparathyroidism or recurrent laryngeal nerve damage are uncommon when the surgeon is experienced.

Subclinical hyperthyroidism

Treatment of subclinical hyperthyroidism (isolated suppression of thyroid-stimulating hormone (TSH) with normal levels of free thyroid hormones) should be individualized. Treatment is controversial because of a lack of prospective randomized controlled trials regarding benefits, despite an increased risk of complications such as bone loss or dysrhythmia from prolonged TSH suppression.[44][45] Patients should undergo careful consideration of the possible risks and benefits of treatment, by an endocrinologist.

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