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Small changes in the dosing of levothyroxine (±25 mcg) are associated with large changes in serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentrations, but not with measurable changes in hypothyroid symptoms, well-being, or quality of life. (SOR: B, based on a single RCT.) Taking levothyroxine while fasting is associated with a higher serum FT4 and lower serum TSH compared with administration after a meal, but these differences are small. (SOR: C, based on a single RCT using disease-oriented outcomes.)