TSH suppression, especially with levels <0.1 mIU/L, can lead to many significant adverse events, including secondary osteoporosis and increased fracture risk from increased mobilization of bone mineral and increased cortical osteoclastic resorption [28–32]. Atrial fibrillation risk can increase by up to 20% [33, 34] with increased risk of cardiomyopathy and heart failure [35–37, 32]. Exercise intolerance with dyspnea and peripheral edema may also occur [38]. Increased morbidity and mortality, from TSH over-suppression, have been described [39, 40] along with decrements in health status, mood, and decision-making [41–43]. Practitioners should be aware of these risk factors when considering therapeutic strategies and goals of therapy when treating benign thyroid nodules.

While the recent literature is against the use of LT4-suppressive therapy to shrink thyroid nodules, clinical practice seems to lag behind recommendations. To evaluate current practice, Bennedbaek et al., surveyed members of the European Thyroid Association (ETA), in 1999 [44], and the American Thyroid Association (ATA), in 2000 [45], asking how to manage a “42-year-old woman with a solitary 2 × 3 cm thyroid nodule and no clinical suspicion of malignancy.” While everyone agreed that FNA biopsy, to rule out malignancy, was the best initial step, 60% of respondents from the ETA and 53% of ATA advocated against TSH-suppressive therapy to shrink a benign solitary nodule. Of note, these studies were conducted more than 16 years ago, and we believe that current practice suggests even less enthusiasm for suppressive therapy. Accordingly, both recent guidelines by the ATA [46] and the American Association of Clinical Endocrinologists (AACE) /Associazione Medici Endocrinologi (AME) [47] recommend against TSH-suppressive therapy to reduce the volume of cytologically negative thyroid nodules.