Timing of levothyroxine administration affects serum thyrotropin concentration

Abstract

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 T(4), and total T(3) 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.

Figure 1

A, Serum TSH concentrations of participants according to their LT₄ timing regimen (fasting, with breakfast, or at bedtime) for subjects who completed the study. Patients are displayed in the order and the same color in each of the three levothyroxine timings (each patient is not a unique color). B, Scatter plot showing TSH values during each LT₄ timing regimen for subjects who completed the study.

Figure 2

Change in serum TSH between a fasting regimen and either a WB regimen (left sided chart) or HS regimen (right sided chart). Pie chart showing percentage of patients whose serum TSH level decreased by more than 1 mIU/liter (white), remained within 1 mIU/liter (gray), and increased by more than 1 mIU/liter (black) when changing from a fasting regimen to a WB regimen and from a fasting regimen to an HS regimen.