Gastrointestinal Malabsorption of Thyroxine

Virili, Camilla; Antonelli, Alessandro; Santaguida, Maria Giulia; Benvenga, Salvatore; Centanni, Marco

doi:10.1210/er.2018-00168

Cited by 118 publications

(177 citation statements)

References 239 publications

(308 reference statements)

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“…Moreover, no recommendations are reported by other specialized societies about the indications for the use of these novel LT4 formulations [14][15][16]. Giving the high level of evidence on the efficacy and safety of LT4 LS/SG formulations [9,12,13] subsequent to these guidelines [1,[14][15][16] and considering the worldwide prevalence of gastrointestinal disorders that considerably impact on LT4 tablet absorption [17,18], the indications of LT4 nontablet formulations should be reappraised.…”

Section: Discussionmentioning

confidence: 99%

Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study

Trimboli

Scappaticcio

Bellis

et al. 2020

International Journal of Endocrinology

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Objective. Hypothyroid patients are treated by sodium levothyroxine (LT4). Tablet is the mostly used LT4 formulation, and the fasting regimen is required for the absorption of active principle. Also, gastrointestinal diseases and drugs may impair the LT4 bioavailability when tablet is used. Nonsolid LT4 formulations (i.e., liquid solution (LS) and soft gel (SG) capsule) were manufactured to overcome the limitations of LT4 tablet. This study was conceived to evaluate the performance of nonsolid LT4 formulations in a real-life scenario. Methods. Two institutions participated in the study that was conducted in two phases (i.e., enrollment and re-evaluation). Adults with autoimmune or postsurgical hypothyroidism and on LT4 from a few months were selected. A nonparametric statistical analysis for paired or unpaired data was performed. Results. 121 consecutive cases were included. At the enrollment phase, a 52% of patients took the therapy at least 30 min before breakfast with no difference between tablet and SG/LS users. TSH was 1.65 mIU/L (0.86–2.70) in patients on LT4 tablet and 1.70 mIU/L (1.10–2.17) in those on SG/LS (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.22) and significantly reduced in SG/LS group (p=0.004); among the patients using incorrect LT4 assumption, TSH was significantly increased in those on tablet (p=0.0029) and stable in those on SG/LS (p=0.36). Conclusion. The performance of nonsolid LT4 formulations is not influenced by correct or incorrect use of therapy. On the contrary, LT4 tablet does not guarantee euthyroidism when it is ingested without waiting for at least 30 minutes before breakfast. These new data, obtained in a real-life scenario, suggest that LT4 SG/LS should be regarded as first-line therapy for treating adults with newly diagnosed hypothyroidism.

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Section: Discussionmentioning

confidence: 99%

Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study

Trimboli

Scappaticcio

Bellis

et al. 2020

International Journal of Endocrinology

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“…Nonadherence to medications is a major challenge in the management of thyroxine treatment. When patients do not take L‐T4 regularly or do not comply with timing in relation to food ingestion and fail to report such behaviours to the endocrinologist, the clinician may wonder about the cause of a persistently elevated TSH, despite a high L‐T4 dose . Guidelines suggest that L‐T4 should be taken well before 1 hour of eating breakfast.…”

Section: Discussionmentioning

confidence: 99%

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

Pang

et al. 2020

Clinical Endocrinology

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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).

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“…5 The small bowel is the principal site of levothyroxine absorption by a process of translocation across the mucosa that remains uncertain. [6][7][8] There is a prolonged exposure of the levothyroxine to the intestinal wall due to slow bowel motility at night, resulting in improved uptake. When greater than regular dose is required to maintain TSH in the normal range in post total thyroidectomy patients, it's vital for the surgeon to find out the reason behind it.…”

Section: Discussionmentioning

confidence: 99%

The dilemma of levothyroxine replacement timing: comparison of bedtime versus early-morning replacement of levothyroxine in post total thyroidectomy patients

et al. 2019

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Background: Following total thyroidectomy levothyroxine replacement is imperative and required lifelong. There are many studies done to assess the effectiveness of levothyroxine administration in hypothyroid patients with intact thyroid gland. This study was intended to evaluate if bedtime dose of levothyroxine is same as early-morning replacement of levothyroxine in post total thyroidectomy patients. Methods: A randomized study was conducted on patients who underwent total thyroidectomy for benign thyroid disorders from September 2017 to August 2018 at endocrine surgery department in a tertiary care institute (South India). Patients were randomly assigned into two groups by chit method, Group A received levothyroxine early morning one hour before food and the Group B received levothyroxine at bedtime two hours after food up to 3 months. 6 weeks and 12 weeks fT4 (freeT4) and TSH (thyroid stimulating hormone) were measured during follow up. Results: A total of 123 patients were recruited and randomized into either of the study groups. 58 patients in Group A and 53 patients in Group B were considered for statistical evaluation. At 6th and 12th week assessment mean TSH level of early-morning group and bedtime group had no statistical difference. At 6th week assessment, mean fT4 level of bedtime group was insignificantly than the early morning group. At 12th week assessment, mean fT4 level of bedtime group was higher than early-morning group, and the difference was also statistically significant (p=0.0005). Conclusions: Clinicians may consider prescribing levothyroxine at bedtime as an alternative to the conventional morning dose.

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Gastrointestinal Malabsorption of Thyroxine

Cited by 118 publications

References 239 publications

Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study

Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study

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

The dilemma of levothyroxine replacement timing: comparison of bedtime versus early-morning replacement of levothyroxine in post total thyroidectomy patients

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