Effect of l‐thyroxine administration before breakfast vs at bedtime on hypothyroidism: A meta‐analysis

Abstract

Hypothyroidism is resulting from a deficiency of thyroid hormones, which is common condition with potentially devastating health consequences that affect all populations worldwide. 1 Thyroid hormones are essential for growth, neuronal development, reproduction and the regulation of energy metabolism. The prevalence of hypothyroidism varies considerably across the general population, ranging between 0.2% and 5.3% in Europe, 2 0.3% and 3.7% in the USA, 3 11% in India 4 and 17.8% in China (overt hypothyroidism: 1.1%; subclinical hypothyroidism: 16.7%). 5 Longitudinal studies from large UK cohorts report an incidence rate of spontaneous hypothyroidism of 3.5-5.0 per 1000 and 0.6-1.0 per 1000 in women and men, respectively. 6The clinical presentation of hypothyroidism is nonspecific and variable. Therefore, the diagnosis of hypothyroidism is based primarily on biochemical abnormalities. The pituitary hormone thyrotropin (TSH) has a complex inverse relationship with the thyroid hormones thyroxine (T4) and triiodothyronine (T3). 7 Accordingly, overt hypothyroidism is defined as serum TSH concentrations above the reference range with low free T4 (FT4) levels, while subclinical hypothyroidism is diagnosed when TSH levels are high and circulating Abstract Purpose: To compare the effects of l-thyroxine (L-T4) administration before breakfast and administration at bedtime on hypothyroidism. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing L-T4 administration before breakfast to the administration at bedtime in patients with hypothyroidism were included in the analysis. Results: Initially, 2884 articles were retrieved from the databases, and 10 articles were included in the quantitative analysis. The effect of L-T4 administration before breakfast compared with administration at bedtime had no statistically significant association with hormone thyrotropin (TSH) (Standardized mean differences [SMD] = 0.09, 95% confidence intervals (CI): −0.12, 0.30; P = .39), or free triiodothyronine (FT3) (SMD=−0.19, 95% CI: −0.53, 0.15; P = .28) in patients with hypothyroidism. However, the result of FT4 level was favourable for L-T4 bedtime administration group (SMD=−0.27, 95% CI: −0.52, −0.02; P = .03). Conclusion:Our meta-analysis revealed that L-T4 administration at bedtime is as effective as administration before breakfast for patients with hypothyroidism. Taking L-T4 at bedtime may be an attractive option for patients with hypothyroidism. K E Y W O R D Sadministration timing, hypothyroidism, l-thyroxine, meta-analysis How to cite this article: Pang X, Pu T, Xu L, Sun R. Effect of l-thyroxine administration before breakfast vs at bedtime on hypothyroidism: A meta-analysis. Clin Endocrinol (Oxf).

Comparative efficacy of early morning versus bedtime administration of levothyroxine in children with hypothyroidism: a prospective, open label, randomized, case-control study

“…The results are consistent with the only two previous studies in children [13,16]. Similar efficacy of bedtime levothyroxine has also been demonstrated in several studies in adults [15]. However, two previous studies in adult patient populations of hypothyroidism found a slightly lower efficacy of levothyroxine when administered in a non-fasting state [17,18].…”

Levothyroxine Interactions with Food and Dietary Supplements–A Systematic Review

“…The decrease in bowel movements at night, and the resulting increase in intestinal absorption of l -T4 may be a possible explanation of the described observations [ 31 ]. A recent meta-analysis [ 32 ] confirmed, that l -T4 ingestion at bedtime is as effective as the one before breakfast. An evening administration may reduce the risk of drug-food interactions and enhance the patient’s compliance with the treatment.…”

Levothyroxine treatment and gastric juice pH in humans: the proof of concept

“…Following the initial clinical examination, patients have been treated with the same brand of levothyroxine sodium in tablet formulation with an age- and weight-tailored dose. As previously described [ 34 , 35 ], all subjects were requested to follow a tight schedule of thyroxine ingestion, ensuring to take the tablet while in fasting condition and then abstaining from eating or drinking anything other than water for at least 1 h after T4 ingestion [ 16 , 19 ]. Patient’s compliance with treatment schedule was checked by a questionnaire, accepted at the first visit and confirmed at every examination.…”

“…Despite its narrow therapeutic window imposes a careful dose titration, an estimated rate of 30–60% treated patients still shows an out-of-target TSH [ 6 ], and side effects are described [ 7 , 8 ]. An individualized thyroxine treatment is therefore advisable and requires the knowledge of thyroxine biochemical and pharmacologic characteristics [ 9 – 13 ] as well as patients’ anthropometric data and habits [ 14 – 16 ]. The lean body mass is a major determinant of thyroxine dose [ 14 ] but, in clinical practice, the physicians usually choose the dose based on patient weight or BMI [ 5 ].…”