Abstract

Background. Spontaneous serum TSH variations during levothyroxine replacement therapy and multiple dose changes in athyreotic patients seem to be frequent in clinical practice. Aim. To describe the rate and extent of spontaneous serum TSH variations in patients after total thyroidectomy for differentiated thyroid cancer (DTC) in real-life practice, and the number of resulting levothyroxine (LT4) dose adjustments. Methods. Data of DTC patients were prospectively collected at a single referral center between January 2005 and May 2019. TSH and fT4 serum levels, LT4 dose and formulation, and concomitant medications were recorded at 1, 3, and 12 months after primary treatment (surgery ± radioiodine therapy), and then yearly; the data were retrospectively evaluated for this study. Visit at one month was used to tailor LT4 dose and was not considered into the data analysis. Patients with structural evidence of disease or during pregnancy were excluded. Results. Data of 2883 evaluations (472 patients) were collected; at baseline, the median age was 49.7 years, 73.5% were females. The LT4 formulation administered at baseline were tablets (84.9%), liquid solution (11.4%), or soft-gel capsule (3.7%). Overall, in 27.5% of clinical evaluation with unchanged levothyroxine dose (341/1243), there were meaningful spontaneous TSH variations (defined as delta TSH > 1.5 mcUI/ml) at yearly follow-up visit. It is clinically significant: in 6.6% of visits, overt thyrotoxicosis was recorded. Furthermore, the treating clinicians decided to change the LT4 dose in 37.1% of cases. These figures were not significantly higher in the first years, and a rate above 25% persist even after ten years of follow-up. The median maintenance dose needed was 1.61 (interquartile range [IQR] 1.41-1.92) mcg/Kg/day for tablets, 1.54 (IQR 1.39-1.79) mcg/Kg/day for liquid solution, and 1.46 (IQR 1.23-1.71) mcg/Kg/day for soft-gel capsules. After correction for daily dose, there was no difference in the rate of TSH variations > 1.5 mcUI/ml, or in the absolute value of median delta of TSH between the three formulations. In 20.1% of patients, the LT4 formulation was changed during the follow-up: it was more common in patients with a known gastroenteric disease (OR 1.76, p=0.03). Conclusions. TSH spontaneous variations and dose adjustments are very common in patients after total thyroidectomy, even during long-term follow-up: wide variations happen in more than 1/4 of all visits, and dose changes are needed in more than 1/3 of all evaluations. We were more inclined to change LT4 formulation in patients with known interference in LT4 absorption: however, no difference in TSH variations was recorded between users of three different formulations, even if soft-gel capsules seem to have a lower maintenance dose.

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