Delayed TSH recovery after dose adjustment during TSH-suppressive levothyroxine therapy of thyroid cancer

Background: Delayed thyroid-stimulating hormone (TSH) recovery during treatment of Graves' disease is caused by long-term excessive thyroid hormone, which results in downregulation of pituitary thyrotrophs. However, it is unknown whether delayed TSH recovery exists after levothyroxine (LT4) dose reduction in patients with differentiated thyroid cancer (DTC) after long-term TSH suppression. Methods: We retrospectively reviewed 97 DTC patients with LT4 dose reduction after long-term TSH suppression. TSH levels at baseline (point 1), 6 months (point 2) and 12-18 months (point 3) after LT4 dose reduction were compared. A delayed TSH recovery group whose TSH levels changed to upper target TSH category (2015 revised ATA guidelines) from point 2 to point 3 was identified, and risk factors were analysed. Results: The median TSH level at point 3 was significantly higher than that of point 2 (0.17 vs 0.09 mIU/L; P<.001). The delayed TSH recovery group (44.3%) showed increased body weight (60.84 vs 62.73 kg; P=.01), while normal response group did not. Greater reduction (%) in the LT4 dose per weight [HR 1.10, 95% CI (1.00-1.22), P=.04] and higher BMI before thyroid surgery [1.19, 1.03-1.38, P=.01] predicted the occurrence of delayed TSH recovery, while higher dose of LT4 per weight after reduction showed preventive effect [HR 0.01, 95% CI (0.00-0.54); P=.02]. Conclusions: Delayed TSH recovery was common during LT4 dose reduction after long-term TSH suppression for DTC management. Six months may not be enough for TSH recovery and to evaluate thyroid hormone status by serum TSH.