The Thyroid Axis 'Setpoints' are Significantly Altered After Long-Term Suppressive LT4 Therapy

The aim of the study was to investigate the changes in the thyroid axis setpoint after long-term suppressive levothyroxine therapy for differentiated thyroid carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine differentiated thyroid cancer patients were reviewed. All patients had at least one known TSH-level >= 0.01 mU/l (lower detection limit) and <1.0mU/l within 2 years of initial treatment (time 1) and had at least one TSHvalue >= 0.01 mU/l and <1.0mU/l after continuous LT4 therapy for a minimum of 5 years (time 2). At time 2 the mean LT4 dosage/kg body weight, TSH, FT3, and FT4 levels were significantly lower than at time 1, while body weight was higher. At time 2, the FT3/FT4 ratio rate had dropped significantly (p < 0.001). At time 1, patients would require 2.96 mu g/kg body weight to reach total TSH suppression. The dose of levothyroxine/kg required for suppression can be lowered by about 0.05 mu g/kg body weight for each year of suppressive therapy. After a median of 12.7 years of continuous suppressive levothyroxine therapy, patients would require 2.25 mu g/kg body weight (-23.5%) to reach total TSH-suppression. At least part of this reduction was independent of aging. As a result of changes in thyroid hormone metabolism and thyroid axis setpoint, long-term TSH-suppressive therapy contributes to a reduction in the dosage of levothyroxine per kilogram body weight required for full TSH suppression over time.