What is the recommended treatment for toxic multinodular goiter (TMNG) with hyperthyroidism, characterized by elevated thyroxine (T4) and triiodothyronine (T3) levels, suppressed thyroid-stimulating hormone (TSH) levels, and thyroid nodules with a Thyroid Imaging, Reporting and Data System (TI-RADS) score of 4, in the absence of Graves' disease antibodies?

From the Guidelines

For toxic multinodular goiter confirmed by biopsy, the recommended treatment typically involves antithyroid medications, radioactive iodine therapy, or surgery, with radioactive iodine therapy often being the preferred definitive treatment, as it can effectively destroy overactive thyroid tissue with a single oral dose of I-131 1. The initial management may include antithyroid drugs like methimazole (starting at 10-30 mg daily) or propylthiouracil (100-300 mg daily divided into three doses) to control hyperthyroidism, along with beta-blockers such as propranolol (20-40 mg three to four times daily) to manage symptoms like palpitations and tremors. Following definitive treatment with radioactive iodine or surgery, lifelong thyroid hormone replacement with levothyroxine (typically 1.6 mcg/kg/day) is usually necessary to maintain normal thyroid hormone levels. The choice between radioactive iodine therapy and surgery depends on factors including goiter size, patient age, comorbidities, and preference, with surgery being preferred for large goiters causing compression symptoms or when malignancy is suspected, as indicated by your TI-RADS 4 nodules. Your significantly suppressed TSH with elevated T3 and T4 confirms hyperthyroidism, and the negative Graves' antibodies are consistent with toxic multinodular goiter rather than autoimmune disease, supporting the use of these treatment approaches 1. It's also important to consider the role of radionuclide uptake and scan in confirming that the entire goiter consists of thyroid tissue and identifying hypofunctioning or isofunctioning nodules for targeted biopsy, as suggested by the use of iodine-123 (I-123) for its superior imaging quality 1.

From the FDA Drug Label

In patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option. The treatment recommended for toxic multinodular goiter is methimazole 2.

• Methimazole is indicated for patients with hyperthyroidism due to toxic multinodular goiter when surgery or radioactive iodine therapy is not an appropriate treatment option.
• The goal of treatment with methimazole is to inhibit the synthesis of thyroid hormones and thus ameliorate symptoms of hyperthyroidism 2.

From the Research

Treatment Options for Toxic Multinodular Goiter

• The treatment of toxic multinodular goiter (TMNG) can be managed with various options, including antithyroid medications, radioactive iodine (RAI) ablation, and surgical thyroidectomy 3, 4, 5, 6, 7.
• According to a study published in 2008, surgery and RAI are both supported by level IV evidence in the treatment of solitary toxic nodules and toxic multinodular goiter, and treatment is determined by symptoms and co-morbidities 3.
• Another study published in 2019 compared the effectiveness and safety of long-term methimazole (MMI) and RAI in the treatment of TMNG, and found that long-term, low-dose MMI treatment is a safe and effective method for treatment of TMNG, and is not inferior to RAI treatment 4.

Radioactive Iodine Ablation

• RAI ablation is a commonly used treatment for TMNG, and has been shown to be effective in reducing thyroid volume and achieving euthyroidism 5.
• A study published in 1999 found that 92% of patients with TMNG were cured with 1 or 2 RAI treatments, and the thyroid volume was reduced by 43% with few side effects 5.

Surgical Thyroidectomy

• Surgical thyroidectomy is also a viable option for the treatment of TMNG, particularly for patients with large goiters or compressive symptoms 3.
• A study published in 2008 found that level IV evidence supports thyroidectomy over RAI for large goiters, and that thyroidectomy provides maximal symptom relief in patients at moderate risk 3.

Comparison of Treatment Options

• A study published in 2022 compared the efficacy and safety of long-term MMI versus RAI in the treatment of TMNG, and found that MMI therapy is superior to RAI treatment, with earlier achievement of euthyroidism and longer duration of sustained normal serum thyrotropin 7.
• Another study published in 2019 found that long-term MMI treatment is a safe and effective method for treatment of TMNG, and is not inferior to RAI treatment 4.