Timing of levothyroxine administration affects serum thyrotropin concentration

Bach-Huynh, Thien-Giang; Nayak, Bindu; Loh, Jennifer; Soldin, Steven; Jonklaas, Jacqueline

doi:10.1210/jc.2009-0860

Cited by 198Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Timing of levothyroxine administration affects serum thyrotropin concentration

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Bach-Huynh, Thien-Giang, Nayak, Bindu, Loh, Jennifer, Soldin, Steven, Jonklaas, Jacqueline·2009·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2009-0860PMC PMC2758731

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Abstract

CONTEXT: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action. OBJECTIVE: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels. DESIGN: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T(4), and total T(3) during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens. SETTING: The study was conducted in an academic medical center. PARTICIPANTS: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer. RESULTS: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 +/- 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 +/- 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 +/- 2.66 mIU/liter). CONCLUSION: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range.

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In a study comparing three timing regimens in 65 patients with primary hypothyroidism, with-breakfast dosing resulted in highest and most variable TSH levels, one hour before breakfast was associated with lowest and least variable TSH, and bedtime LT4 produced values and variability in-between.
“In a study which compared three timing regimens in 65 patients with primary hypothyroidism, a with-breakfast dosing resulted in the highest and most variable TSH levels, while a regimen of LT4 being administered an hour before breakfast was associated with the lowest and least variable TSH; the bedtime LT4 regimen produced values and variability that was in-between the other two dosing regimens (4”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [41]
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Two recent cross-over studies had different findings, with lowest serum TSH values seen either 1 hour before breakfast or at bedtime.
“Two recent cross-over studies had different findings with the lowest serum TSH values being seen either 1 hour before breakfast or at bedtime (128,129).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [128]
In one cross-over study, mean TSH values were 1.06, 2.93, and 2.19 mIU/L for LT4 taken at least 1 hour before breakfast, with breakfast, or at bedtime, respectively.
“The mean TSH values seen with these different conditions were 1.06, 2.93, and 2.19 mIU/L respectively (128).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [128]
Four of six studies examining timing of LT4 administration showed that timing influences serum TSH values in hypothyroid patients receiving treatment.
“Four studies (121,126,128,129), out of the six studies examining this issue (121,128-131), have shown that the timing of LT4 administration influences the serum TSH values of hypothyroid patients receiving treatment.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [128]
Coingestion with breakfast or coffee can reduce and delay LT4 absorption.
“Coingestion with breakfast or coffee can reduce and delay absorption (21, 22).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [21]

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Authors: Bach-Huynh, T.-G., Nayak, B., Loh, J., Soldin, S., & Jonklaas, J.
Affiliations: Georgetown University Medical Center (US)
Corresponding author: Jonklaas, Jacqueline
ORCID: Jonklaas, Jacqueline
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2009-10-01
Volume: 94
Issue: 10
Pages: 3905-3912
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2009-0860
PMC: PMC2758731
OpenAlex: W2110073453
Cited by: 198
References: 30
Citations by year: 2026: 5 · 2025: 10 · 2024: 10 · 2023: 7 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 11 · 2018: 19 · 2017: 10 · 2016: 21 · 2015: 16 · 2014: 12 · 2013: 11 · 2012: 14
FWCI: 6.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsches Krebsforschungszentrum
National Center for Research Resources (K23 RR16524, M01RR020359, MO1-RR-020359, K23RR016524)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: levothyroxine, timing of drug administration, serum thyrotropin, thyroid-stimulating hormone, dietary intake, fasting, hypothyroidism, thyroid cancer, free thyroxine, total T3, drug absorption
MeSH terms: Administration, Oral, Adult, Aged, Drug Administration Schedule, Fasting, Female, Humans, Hypothyroidism, Male, Middle Aged, Thyroid Hormones, Thyroid Neoplasms, Thyrotropin, Thyroxine, Time Factors, Cross-Over Studies, Hormone Replacement Therapy

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Timing of levothyroxine administration affects serum thyrotropin concentration

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