However, this also confirms that taking levothyroxine at bedtime is an effective alternative to taking it before breakfast. Further, bedtime may be better in patients who appear to have problems absorbing levothyroxine. TSH: Thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally.
Thyroid hormone therapy: patients with hypothyroidism are most often treated with Levothyroxine in order to return their thyroid hormone levels to normal. Replacement therapy means the goal is a TSH in the normal range and is the usual therapy.
Suppressive therapy means that the goal is a TSH below the normal range and is used in thyroid cancer patients to prevent growth of any remaining cancer cells. Twitter feed Tweets by thyroidfriends. Patient Publications. Despite levothyroxine being the treatment of choice for those with an underactive thyroid there are few guidelines in term of timing. Patients are usually advised that the drug should be taken on an empty stomach and preferable 30 minutes before breakfast.
But for some people this is tricky, particularly when they may be on several other medications requiring similar restrictions. Might thyroid hormone levels be optimised by taking levothyroxine just before bed on an empty stomach? A trial involving 90 patients with primary hypothyroidism saw them receiving levothyroxine either in the morning or in the evening with a switch after three months. Results showed that taking Levothyroxine at bedtime actually improved thyroid hormone levels compared to taking it in the morning.
There was a reduction in serum thyrotropin TSH of 1. In the group that received morning levothyroxine first, the mean SD TT 3 level increased from In the group that received bedtime levothyroxine first, the mean SD TT 3 level decreased from In this case, the direct treatment effect of bedtime levothyroxine was an increase in TT 3 level of 6.
No first-order carryover effect was found for thyrotropin, FT 4 , or TT 3 levels. There were no differences between the 2 study groups in serum creatinine or lipid levels, blood pressure, body mass index, or heart rate.
These results are summarized in Table 2. Hypothyroidism symptoms were unchanged between the 2 periods, despite improved thyroid hormone profiles, nor was there a difference in hyperthyroidism symptoms. When asked at the end of the trial before the randomization code was broken , 34 of 90 patients said that they felt better during the period of morning intake of levothyroxine, 31 patients preferred the period of bedtime intake, and 25 patients indicated no preference.
At 1 year after completion of the trial, more than half of the patients still preferred bedtime intake of levothyroxine.
We performed this large, randomized, double-blind crossover trial among 90 patients to address whether levothyroxine taken at bedtime instead of in the morning improves thyroid hormone levels. The primary outcomes show a decrease in thyrotropin level of 1.
Despite the change in thyroid hormone levels, the patient QOL did not differ. Bedtime levothyroxine intake could be more convenient for patients, as they do not have to postpone breakfast. After our study was completed, more than half of the patients decided to continue with bedtime intake of levothyroxine. How can the bioavailability effects of levothyroxine be explained? An interval of 30 minutes between taking levothyroxine and eating breakfast may be too short to prevent interference with gastrointestinal absorption of levothyroxine.
Moreover, many patients drink coffee in the morning, often instead of eating breakfast, 6 or may take other medications that interfere with levothyroxine absorption. In contrast, most patients in our study stated that they had eaten no food or snacks for several hours before bedtime, this being their usual routine. Bowel motility is slower at night, resulting in more prolonged exposure of levothyroxine to the intestinal wall and, consequently, in better bioavailability.
Thyroid hormone level changes did not translate into QOL changes. There are various explanations for this observation. Patients with hypothyroidism taking adequate doses of levothyroxine ie, those whose thyrotropin level is in the reference range can still have significant impairment in psychological well-being and cognitive function compared with control subjects.
Weight gain and inability to lose weight are known to occur in patients with treated hypothyroidism and hyperthyroidism. A trial investigating T 3 supplementation showed that improved QOL was limited to a subgroup of patients with suppressed thyrotropin levels who had lost weight.
In contrast, plasma thyroid hormone levels may not be representative of thyroid hormone levels at the tissue level eg, in the brain ; therefore, they would be unrelated to QOL. Primary outcomes of this study are consistent with results of an earlier pilot study. In a retrospective medical record review of 15 nursing home residents, Elliott 35 observed a nonsignificant decrease in thyrotropin levels when levothyroxine intake was switched from after breakfast to midnight.
The findings in that nonrandomized trial confirm the results of our study. A 3-period crossover design study 36 showed higher thyrotropin levels when levothyroxine was taken at bedtime instead of before breakfast, but there was no change in FT 4 or TT 3 levels, as in our study.
The study also included patients with thyroid cancer, whose thyrotropin levels were maintained at lower levels than those of the rest of the population.
Therefore, we believe that the findings in that study extend the generalizability of our study results to the treatment of primary hypothyroidism. Lower thyrotropin levels associated with levothyroxine intake before breakfast vs at bedtime intake in that study could be explained by the longer interval between levothyroxine intake and breakfast 60 minutes vs 30 minutes in our study.
Also, most patients in our study stated that they had nothing to eat or only a small snack for several hours before bedtime, which differs across cultures. In all studies performed on the timing of levothyroxine ingestion, intake on an empty stomach seems to result in maximal absorption of levothyroxine. Our study shows that if this fasting regimen can be achieved at bedtime, then resulting thyroid hormone levels are better than those associated with levothyroxine intake 30 minutes before breakfast.
The crossover design of our study has the advantage that each patient served as his or her own control. Therefore, a statistical difference in thyrotropin values at baseline will not influence primary and secondary outcomes of the study.
The study design has potential limitations, including order and sequence effects. We found no first-order carryover effect between the 2 periods, but we looked at no other order or sequence effects. It should also be noted that this was a single-site study in the Netherlands, where eating habits might be different from those in other countries or cultures. Based on the results of our study, clinicians should inform patients with hypothyroidism that levothyroxine intake at bedtime is a good alternative to levothyroxine intake in the morning, provided that levothyroxine is taken on an empty stomach.
For patients who do not attain normal thyrotropin or FT 4 levels with morning levothyroxine intake, a switch to bedtime is recommended. Recommendations on timing of levothyroxine intake and on uptake interference by food are found in few guidelines about the management of hypothyroidism.
In conclusion, bedtime intake of levothyroxine in our study significantly improved thyroid hormone levels. This may be explained by better gastrointestinal bioavailability at night or by less uptake interference by food or medications. As shown in this study, bedtime administration is more convenient for many patients.
Clinicians should inform their patients about the possibility of taking levothyroxine at bedtime. A prolonged period of bedtime levothyroxine therapy may be required for a change in QOL to occur. Authors Contributions: Dr Bolk had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design : Bolk, Visser, and Berghout. Acquisition of data : Bolk, Jongste, and Berghout. Critical revision of the manuscript for important intellectual content : Visser, Tijssen, and Berghout.
Statistical analysis : Nijman and Tijssen. Administrative, technical or material support : Nijman and Jongste. Study supervision : Berghout. Additional Contributions: Liesbeth Ruygrok, PhD, oversaw preparation of the levothyroxine and placebo capsules and randomization of the patients.
Maasstad Hospital Rotterdam laboratory technicians processed the blood samples, and employees of the Department of Internal Medicine assisted with patient assessment. We thank the patients who participated in this study for their cooperation. Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Download PDF Comment.
Figure 1. View Large Download. Table 1. The spectrum of thyroid disease in a community: the Whickham Survey. Liel YHarman-Boehm IShany S Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients. Altered intestinal absorption of L -thyroxine caused by coffee. The clinical spectrum of postpartum thyroid disease. Handbook of Statistics. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis.
Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism.
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