Approach

The hyperthyroidism of toxic multinodular goitre (MNG) generally does not remit spontaneously, and therefore definitive treatment such as radioactive iodine (I-131) is usually required. A secondary goal of treatment may be to decrease goitre size, mainly in relationship to large goitres, which are common in many areas of the world.

Patient values and preferences

These are an important part of any therapeutic decision-making about definitive treatments. Patients choosing I-131 therapy would most probably favour avoidance of issues surrounding surgery, such as anaesthesia or hospitalisation, and their possible complications, and hope to remain euthyroid. Those choosing surgery may prefer avoidance of radioactivity; desire very rapid control of hyperthyroidism; or have a lower concern about risks of surgery or the likelihood of immediate permanent hypothyroidism.[14] 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 a heart rate >90 bpm.[14]

In the absence of contra-indication, beta-blockers may be used if needed for symptomatic relief while awaiting results of definitive treatment. However, toxic MNGs generally cause milder symptoms than Graves' disease. Beta-blockers may be appropriate for patients with atrial fibrillation and rapid ventricular response. Older patients may have contra-indications to beta-blockers, such as bradycardia or heart block. If beta-blockers are contra-indicated, a calcium-channel blocker may be useful.

Radioactive iodine (I-131)

I-131 therapy is a preferred treatment for most non-pregnant and non-lactating patients.[3] A nuclear medicine consultant referral is indicated. Full effect of therapy is achieved after several weeks to months. Persistent hyperthyroidism may require a second dose.

Higher doses of I-131 are generally needed for toxic MNG than for Graves' disease, because of radio-resistance.[1] Uptake is also usually lower than in patients with Graves' disease.

I-131 therapy of toxic MNG has been associated with about a 40% reduction in goitre size 2 years after last dose.[32]

Antithyroid drugs

Antithyroid drugs are the preferred treatment during pregnancy.[33] They should also be considered for patients who are not candidates for, or who refuse, definitive treatment. Indefinite treatment is generally required.

Antithyroid drugs may also be used to restore euthyroidism prior to definitive therapy. A course of antithyroid drugs may be used to normalise thyroid function prior to I-131 therapy in patients with severe symptoms, older age, or comorbidities such as heart disease. Antithyroid drugs can also be withdrawn to produce a higher rebound uptake prior to I-131. They should be withdrawn 3 to 5 days before I-131 therapy and restarted 3 to 5 days after treatment. A course of antithyroid drugs is also used before surgery to achieve euthyroidism.

Both thiamazole and propylthiouracil have been associated with birth defects when used during the first trimester of pregnancy, although the defects associated with thiamazole use tend to be more severe. Propylthiouracil does, however, have more frequent dosing compared with thiamazole, and its use may rarely cause fulminant hepatic failure. Thiamazole is, therefore, the preferred antithyroid drug outside the first trimester of pregnancy; when antithyroid drugs are needed in the first trimester propylthiouracil is recommended.

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.[34] Generally, doses of antithyroid drugs are lower in pregnancy, and maternal levels of free T4 are kept high-normal to slightly elevated.[34] Low-to-moderate doses of antithyroid drugs can be used during lactation.[34]

Surgery

Surgery is indicated for patients with large goitres that cause obstructive symptoms such as choking or dyspnoea, or for patients who decline or are resistant to radioactive iodine, or who prefer surgery.[1][35] Surgery may also be indicated based on fine needle aspiration findings when a suspicious cold nodule occurs in a toxic MNG.[27][28]

In pregnancy, surgery is occasionally indicated for uncontrolled hyperthyroidism due to adverse reaction or non-adherence to antithyroid drugs and is preferably performed in the second trimester.

An experienced, high-volume surgeon is recommended to reduce the risk of complications.

Sub-clinical hyperthyroidism

Treatment of sub-clinical hyperthyroidism (isolated suppression of thyroid-stimulating hormone [TSH] with normal levels of free thyroid hormones) should be individualised. Treatment is controversial because of a lack of prospective randomised controlled trials regarding benefits, despite an increased risk of complications such as bone loss or dysrhythmia from prolonged TSH suppression.[36][37] Patients should undergo careful consideration of the possible risks and benefits of treatment, by an endocrinologist.[36]

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