What is the management of Toxic Multinodular Goiter (TMNG)?

From the Guidelines

Toxic nodular goiter management should prioritize definitive treatment with radioactive iodine (RAI) therapy or surgical management, as medical therapy alone is often insufficient due to the autonomous nature of the thyroid nodules. Management of toxic nodular goiter involves treating hyperthyroidism and addressing the goiter itself. Initial treatment typically includes antithyroid medications such as methimazole (starting at 10-30 mg daily) or propylthiouracil (PTU, 100-300 mg daily in divided doses) 1. Beta-blockers like propranolol (40-120 mg daily) or atenolol (25-100 mg daily) can be added to control symptoms such as tachycardia and tremors.

Diagnostic Evaluation

The use of radionuclide uptake and scan can confirm that the entire goiter consists of thyroid tissue, and iodine-123 (I-123) is preferred over iodine-131 (I-131) due to its superior imaging quality 1. Ultrasound (US) is the best imaging study to evaluate thyroid morphology and can be a helpful adjunct study to a radioiodine uptake, providing thyroid dimensions for planning RAI treatment and evaluating for suspicious features of malignancy 1.

Treatment Options

RAI therapy at doses of 10-30 mCi is effective for most patients, though multiple treatments may be needed for larger goiters. Surgical management, typically total thyroidectomy, is appropriate for large goiters causing compressive symptoms, suspected malignancy, or when RAI is contraindicated (pregnancy, breastfeeding). Post-definitive treatment, patients require lifelong thyroid hormone replacement with levothyroxine (typically 1.6 mcg/kg/day). Regular monitoring of thyroid function tests is essential during treatment and afterward. The choice between RAI and surgery depends on patient factors including age, comorbidities, goiter size, and patient preference.

Key Considerations

Toxic nodular goiter results from autonomously functioning thyroid nodules that produce excess thyroid hormone independent of TSH regulation, making it less responsive to medical therapy alone compared to other causes of hyperthyroidism. Given the potential for malignancy and the need for definitive treatment, a thorough diagnostic evaluation with radionuclide uptake and scan, as well as US, is crucial in guiding treatment decisions 1.

From the FDA Drug Label

Propylthiouracil is indicated: in patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment option. Methimazole tablets, USP are indicated: In patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option.

Toxic Nodular Goiter Management options include:

• Propylthiouracil (PO) 2 for patients who are intolerant of methimazole
• Methimazole (PO) 3 for patients for whom surgery or radioactive iodine therapy is not an appropriate treatment option Key considerations:
• Surgery or radioactive iodine therapy may be considered when appropriate
• Medication selection depends on patient tolerance and treatment appropriateness

From the Research

Treatment Options for Toxic Nodular Goiter

• Medications: Antithyroid medications such as methimazole can be used to control hyperthyroidism in patients with toxic nodular goiter 4, 5.
• Radioactive Iodine (RAI): RAI ablation is a common treatment for toxic nodular goiter, especially in the United States 6, 5.
• Surgery: Thyroidectomy is a surgical option for patients with large goiters or compressive symptoms, and is supported by level IV evidence 7.
• Ethanol Ablation: Ethanol ablation of toxic nodules is a treatment option for patients who are unfit for surgery, supported by level III evidence 7.

Comparison of Treatment Options

• A study comparing long-term methimazole and RAI treatment found that methimazole was a safe and effective method for treating toxic multinodular goiter, and was not inferior to RAI treatment 4.
• Another study found that long-term methimazole therapy was superior to RAI treatment in achieving and maintaining euthyroidism in patients with toxic multinodular goiter 8.
• The choice of treatment depends on the underlying diagnosis, presence of contraindications, severity of hyperthyroidism, and patient preference 5.

Safety and Efficacy of Treatment Options

• Long-term methimazole treatment has been shown to be safe and effective, with minimal side effects 4, 8.
• RAI treatment can cause hypothyroidism in some patients, and the risk of malignancy and complications must be considered 7.
• Surgery and ethanol ablation are also effective treatment options, but may have associated risks and complications 6, 7.