Effects of Evening vs Morning Levothyroxine Intake A Randomized Double-blind Crossover Trial

Department of Internal Medicine, Maasstad Hospital Rotterdam, Rotterdam, The Netherlands.
Archives of internal medicine (Impact Factor: 17.33). 12/2010; 170(22):1996-2003. DOI: 10.1001/archinternmed.2010.436
Source: PubMed


Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed.
To ascertain if levothyroxine intake at bedtime instead of in the morning improves thyroid hormone levels, a randomized double-blind crossover trial was performed between April 1, 2007, and November 30, 2008, among 105 consecutive patients with primary hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. Patients were instructed during 6 months to take 1 capsule in the morning and 1 capsule at bedtime (one containing levothyroxine and the other a placebo), with a switch after 3 months. Primary outcome measures were thyroid hormone levels; secondary outcome measures were creatinine and lipid levels, body mass index, heart rate, and quality of life.
Ninety patients completed the trial and were available for analysis. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L (95% confidence interval [CI], 0.60-1.89 mIU/L; P < .001), an increase in free thyroxine level of 0.07 ng/dL (0.02-0.13 ng/dL; P = .01), and an increase in total triiodothyronine level of 6.5 ng/dL (0.9-12.1 ng/dL; P = .02) (to convert thyrotropin level to micrograms per liter, multiply by 1.0; free thyroxine level to picomoles per liter, multiply by 12.871; and total triiodothyronine level to nanomoles per liter, multiply by 0.0154). Secondary outcomes, including quality-of-life questionnaires (36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale, 20-Item Multidimensional Fatigue Inventory, and a symptoms questionnaire), showed no significant changes between morning vs bedtime intake of levothyroxine.
Levothyroxine taken at bedtime significantly improved thyroid hormone levels. Quality-of-life variables and plasma lipid levels showed no significant changes with bedtime vs morning intake. Clinicians should consider prescribing levothyroxine intake at bedtime. Identifier: ISRCTN17436693 (NTR959).

Download full-text


Available from: Nienke Bolk
  • Source
    • "One possible proposed mechanism is that dinner content may have more impact on levothyroxine absorption versus breakfast, even if eaten an hour after ingestion of the tablet. Rajput et al. [17] found equal efficacy of the two administration times but this contradicted the results obtained by Bolk et al. [14] [15]. This inconsistency might be in part due to the nutrition regimen in different patients and the effects of food intake on the absorption and oral bioavailability of levothyroxine. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Levothyroxine is commonly used in the treatment of patients with hypothyroidism. Levothyroxine is most often administered in the morning, on an empty stomach, in order to increase its oral absorption. However, many patients have difficulties taking levothyroxine in the morning. Aim. The aim of this study was evaluating the effect of changing levothyroxine administration time from before breakfast to before dinner on the serum levels of TSH and T4. Subjects and Methods. Fifty patients between 18 and 75 years old with hypothyroidism were included in the study and were randomly divided into two groups. Each group received two tablets per day (one levothyroxine tablet and one placebo tablet) 30 minutes before breakfast and 1 hour before dinner. After two months, the administration time for the tablets was changed for each group, and the new schedule was continued for a further two-month period. The serum TSH and T4 levels were measured before and after treatment in each group. Results. Changing the levothyroxine administration time resulted in 1.47 ± 0.51 í µí¼‡IU/mL increase in TSH level (í µí± = 0.001) and 0.35 ± 1.05 í µí¼‡g/dL decrease in T4 level (í µí± = 0.3). Conclusions. Changing the levothyroxine administration time from before breakfast to before dinner reduced the therapeutic efficacy of levothyroxine.
    Full-text · Article · May 2015 · International Journal of Endocrinology
  • Source
    • "and an increase in free T4 of 0.07 ng/dL (95% CI 0.02–0.13) and total T3 of 6.5 ng/dL (95% CI 0.9–12.1).34 However, there were no improvements in quality of life scores, blood pressure, or lipid profile. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism.
    Full-text · Article · Jan 2012 · Drug Design, Development and Therapy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Up to one-third of patients treated with levothyroxine for primary hypothyroidism have biochemical evidence of inadequate thyroid hormone replacement. Could treatment effects of levothyoxine be optimized by bedtime administration on an empty stomach? A new study reveals the answer and also sheds light on other possible benefits of this alternative timing.
    Full-text · Article · Mar 2011 · Nature Reviews Endocrinology
Show more