Medical treatment options generally employ either TSH suppression with levothyroxine (LT4) administration or radioactive iodine thyroid ablation . In the setting of hypothyroidism, excess TSH production can result in hyperplasia, nodular growth, and a general increase in goiter size. Here, the use of LT4 to induce a euthyroid state has been clearly documented to decrease goiter size [9, 10]. However, in the circumstance of the euthyroid MNG, simple LT4 administration is unlikely to have any meaningful effect. Therefore, some groups have advocated high-dose LT4 administration in suppressive doses to significantly lower TSH. Moalem and Duh [27] provide an evidence-based review of the literature on its effectiveness. They reviewed two large meta-analyses, including over 13 major studies and nine randomized trials. In 2002, Castro et al. [28] found six randomized trials comprising almost 350 patients who had a benign solitary thyroid nodule treated with high-dose suppressive LT4. And 22 % of patients treated with LT4 had a 50 % decrease in nodule volume compared to only 10 % of patients treated with placebo; however, p values were not significant. In a follow-up study, Sdano et al. [29] expanded on this work by including nine randomized trials (650 patients and some with MNG) . 22 % of patients who underwent suppressive LT4 therapy had a 50 % decrease in nodular size, whereas patients who received no treatment or placebo therapy only had a 10 % rate of significant decrease in nodular volume. These results were statistically significant, but as Moalem et al. indicated, “eight patients (with nodular thyroid disease) would need to be treated in order to have one patient benefit,” from suppressive LT4 therapy. While these data do hold some promise, there is a concern with LT4 medical treatment that should be raised. This treatment method may often be employed in patients who are poor surgical candidates (elderly, cardiac disease, pulmonary disease, etc.). These are the very patients who may also experience complications due to high-dose LT4 treatment, including osteoporosis [30], atrial fibrillation, and other cardiac arrhythmias. Based on these complications, the American Thyroid Association issued a concern regarding long-term treatment of nontoxic MNG with LT4 therapy and stated, that it is, “generally not recommended.” The medical community has also commented that, “as a result of poor efficacy and potential side effects from the induction of subclinical hyperthyroidism,” LT4 treatment of MNG has fallen out of favor [31, 32] . Finally, it must be noted that if LT4 therapy is chosen for the management of MNG, it must be continued indefinitely as it is has been shown that the goiter and nodules may return to their original size within as little as 3 months after discontinuation of suppressive treatment [33].

Another option for the medical treatment of MNG is the use of radioactive iodine (I-131) in ablative doses. This treatment modality is often used for Graves’ disease or for toxic MNG. In addition, it has been successfully used to treat MNG for more than 25 years, where it has been shown to cause a decrease in overall thyroid volume of up to 40 % in the first year and 50–60 % 2 years after treatment [34, 35] . However, its effects are dependent on the ability of the thyroid and its nodules to both uptake and organify iodine. Many nontoxic MNG contain “cold” nonfunctional nodules which can limit the effectiveness of I-131 treatment. Therefore, several groups have employed an off-label use for recombinant human TSH (RhTSH) to increase the uptake of I-131 (radioactive iodine uptake, RAIU) up to two- to threefold [36]. Several trials have demonstrated this improved RAIU with RhTSH pretreatment. These studies have also shown that with RhTSH pretreatment, you can use a decreased dose of I-131, still leading to improved reduction of compressive goiters [37, 38] and even lessen the degree of tracheal compression from SG [39] .

While these results are impressive, the advocates of medical treatment of MNG freely admit that it cannot be used in all circumstances and acknowledge that it has potential side effects and drawbacks. I-131 treatment +/− RhTSH is considered contraindicated for patients with an MNG with suspicion of malignancy, goiter during pregnancy, and in patients with severe tracheal compression and overt symptoms. I-131 can lead to acute swelling of MNG which could worsen tracheal compression or other symptoms. RAI use should also be considered a relative contraindication for young patients with large goiter, in patients requiring rapid decompression of compressive goiter, or if prior I-131 treatment has failed to provide adequate relief of symptoms. Its best use may be for patients with mild to moderate compressive symptoms, elderly patients with comorbid conditions that preclude surgery, or in patients who have undergone prior thyroidectomy in which reoperative surgery is considered too risky. This should only be done once cancer has been excluded by biopsy .