The treatment of benign multinodular goitre (MNG) is controversial, but surgery is recommended in large compressive goitres. While some patients decline surgery others may have contraindications due to comorbidity, since MNG is prevalent in the elderly. Therefore, non-surgical treatment alternatives are needed. Until recently, levothyroxine therapy was the preferred non-surgical alternative, but due to low efficacy and potential side-effects, it is not recommended for routine use in recent international guidelines. Conventional radioiodine (131I)-therapy has been used for two decades as an effective and safe alternative to surgery in the treatment of symptomatic non-toxic MNG. Since much higher activities of 131I are employed when treating non-toxic than toxic MNG, there has been reluctance in many countries to use this treatment modality. Frequently the 131I -uptake in a non-toxic MNG is low, which makes 131I-therapy less feasible. Another challenge is the negative correlation between initial goitre size and goitre volume reduction (GVR). With its ability to more than double the thyroid 131I-uptake, recombinant human TSH (rhTSH) increases the absorbed radiation dose and thus enhances the GVR by 35-56% at the expense of an up to 5-fold higher rate of permanent hypothyroidism.. An alternative strategy is to reduce the administered 131I-activity with a factor corresponding to the rhTSH induced increase in 131I-uptake. Hereby the extra-thyroidal irradiation can be reduced without compromising efficacy. Thus, although in its infancy, and still experimental, rhTSH-augmented 131I-therapy may profoundly alter the nonsurgical treatment of benign non-toxic MNG.