Effects of levothyroxine treatment on serum thyroid hormone levels in euthyroid patients with papillary thyroid microcarcinoma

We recently reported that lowering serum thyroid stimulating hormone (TSH) levels with levothyroxine (LT4) may be associated with decreased tumor growth during active surveillance (AS) of papillary thyroid microcarcinoma (PTMC). Most clinicians might believe that low serum TSH levels following LT4 therapy indicate subclinical thyrotoxicosis. This study aimed to evaluate the effects of TSH-lowering therapy using small doses of LT4 on serum thyroid hormone levels in euthyroid patients with PTMC. We retrospectively analyzed data from 28 patients with low-risk PTMC who had undergone measurement of both FT4 and FT3 consecutively and received LT4 to achieve serum TSH levels of <0.5 μIU/mL and >0.05 μIU/mL between January 2012 and May 2018 at Kuma Hospital. There were 24 females and 4 males (aged 55±12 years [mean ± standard deviation {SD}]). We compared their serum FT4 and FT3 levels at diagnosis with those following TSH-lowering therapy with LT4. Following LT4 therapy, the patients’ serum FT4 levels were significantly increased (P < 0.001). Serum FT3 levels, however, remained unchanged (P = 0.10). The proportions of patients whose FT3 levels increased by more than 1SD, remained unchanged, and decreased by more than 1SD were 11%, 57%, and 32%, respectively. Our study indicated that mild TSH-lowering doses of LT4 for euthyroid patients with PTMC increased serum FT4 levels but did not increase serum FT3 levels in most cases, suggesting that a mild TSH-lowering therapy for euthyroid patients may not necessarily cause thyrotoxicosis.