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Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration

Division of Endocrinology (T.-G.B.-H., B.N., J.L., S.S., J.J.), and Bioanalytic Core Laboratory, General Clinical Research Center (S.S.), Georgetown University Medical Center, Washington, D.C. 20007

Address all correspondence and requests for reprints to: Jacqueline Jonklaas, Division of Endocrinology and Metabolism, Georgetown University Medical Center, Suite 232, Building D, 4000 Reservoir Road NW, Washington, D.C. 20007. E-mail: jj{at}bc.georgetown.edu.

Context: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action.

Objective: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels.

Design: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T₄, and total T₃ during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens.

Setting: The study was conducted in an academic medical center.

Participants: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer.

Results: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 ± 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 ± 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 ± 2.66 mIU/liter).

Conclusion: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range.

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