FPIN's Clinical Inquiries

Morning vs. Evening Administration of Levothyroxine


Am Fam Physician. 2018 Oct 15;98(8):532-534.

Clinical Question

Does taking levothyroxine in the evening vs. morning reduce its effectiveness for reducing thyroid-stimulating hormone (TSH) levels?

Evidence-Based Answer

The effectiveness of levothyroxine for reducing TSH levels is most dependent on the timing of meals in relation to drug administration. (Strength of Recommendation: C, disease-oriented outcome.) There is conflicting evidence. In two studies, levothyroxine taken at least two hours after eating in the evening maintained or improved TSH levels compared with morning administration. However, another study found that evening administration was less effective than administration at least 60 minutes before breakfast.

Evidence Summary

A 2010 randomized, double-blind, placebo-controlled, crossover study of 90 adults with primary hypothyroidism compared whether taking levothyroxine 30 minutes before breakfast vs. at bedtime affected TSH levels.1 Patients had been receiving a stable levothyroxine dosage for at least six months before the study, and those with thyroid carcinoma were excluded. Patients received each regimen for three months, and reported not eating for several hours before bedtime administration. Bedtime administration significantly decreased TSH levels by 1.25 mIU per L compared with morning administration (95% confidence interval, 0.60 to 1.89). In a 24-week period, patients missed a mean of 1.3 capsules in the morning and 1.9 capsules in the evening (P = .54).

A 2009 randomized crossover study compared the effects of administering levothyroxine in the morning at least one hour before breakfast, within 20 minutes of breakfast, and at bedtime (at least two hours after eating).2 TSH levels were measured in 65 adults with primary hypothyroidism who had been on stable levothyroxine dosages for at least six months. All patients received each levothyroxine regimen for eight weeks. Bedtime administration resulted in significantly higher mean TSH levels compared with before-breakfast (fasting) administration

Address correspondence to Linda Contillo Garufi, MD, MEd, at linda_c.garufi@lvhn.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


show all references

1. Bolk N, Visser TJ, Nijman J, Jongste IJ, Tijssen JG, Berghout A. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med. 2010;170(22):1996–2003....

2. Bach-Huynh TG, Nayak B, Loh J, Soldin S, Jonklaas J. Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab. 2009;94(10):3905–3912.

3. Ala S, Akha O, Kashi Z, et al. Changes in serum TSH and T4 levels after switching the levothyroxine administration time from before breakfast to before dinner. Int J Endocrinol. 2015;2015:156375.

4. Rajput R, Chatterjee S, Rajput M. Can levothyroxine be taken as evening dose? Comparative evaluation of morning versus evening dose of levothyroxine in treatment of hypothyroidism. J Thyroid Res. 2011;2011:505239.

5. Jonklaas J, Bianco AC, Bauer AJ, et al.; American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism. Thyroid. 2014;24(12):1670–1751.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or e-mail: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, Associate Medical Editor.

A collection of FPIN's Clinical Inquiries published in AFP is available at https://www.aafp.org/afp/fpin.



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