A Crossover Study Evaluating Effect of Timing of Levothyroxine on Thyroid Hormone Status in Patients of Hypothyroidism.

Objective: Current literature shows a definite benefit of fasting state Levothyroxine administration. However, superiority of any specific timing is not yet established. Our study was designed to compare the effect of timing of levothyroxine administration, morning versus evening dose, on thyroid profile control in patients of hypothyroidism.

Methodology: :A randomized double-blind crossover study was performed on 60 patients with primary hypothyroidism, euthyroid on stable levothyroxine regime of 100 µg daily, randomized into two sequence groups, morning dose first (AB sequence) versus evening dose first (BA sequence) with switch over after 6 weeks. Primary endpoints were change in thyroid function tests.

Results: There was an insignificant rise in TSH in morning dose first group (AB) at 6 weeks which reduced significantly in evening dose, [2.36(1.11) to 2.45(1.19) mIU/L (p=0.56)], [2.07(0.99) (p=0.006)] respectively. Levothyroxine evening dose first group (BA) showed significant reduction of TSH levels at 6 weeks followed by non significant increase [2.63(0.96) to 1.85(1.35) mIU/L, (p=0.002)], [2.14(1.16), (p=0.15)]. Group AB showed mild followed by significant rise in FT4 at 6 and 12 weeks respectively, [1.06(0.30) to 1.14(0.33) ng/dl (p=0.18)], [1.24(0.36) (p=0.008)]. FT4 of BA sequence significantly increased at 6 weeks followed by mild increase, [1.10(0.29) to 1.20(0.28) ng/dl (p=0.01)] [1.23(0.31) ng/dl (p=0.58)]. FT3 of AB revealed initial reduction (p=0.87), followed by significant rise (p=0.02). Group BA showed a significant rise (p=0.04) in FT3 followed by fall (p=0.63).

Conclusion: Bedtime dosing of Levothyroxine showed improved thyroid hormone status control and could be a viable option in treatment of patients with hypothyroidism.