The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration
Open accessAbstract
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 the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“Bach-Huynh et al. three-period crossover study of 65 LT4-treated stable hypothyroid patients found that non-fasting LT4 administration was associated with higher and more variable serum TSH concentrations [ 33 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [33]
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Citations
Cites
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“Additional factors affecting the absorption of LT4 are food (1–4, 22, 23), including high-fiber diets (24), soy (25), and beverages (26).”
BackgroundDelayed Intestinal Absorption of Levothyroxine
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Use Of Soy Protein Supplement And Resultant Need For Increased Dose Of Levothyroxine
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Flagged first, then by citations
1 of the 30 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Lamson, 2004, Quantitation of a substantial reduction in levothyroxine (T4) absorption by food, Thyroid, 14, 876
- Elliott, 2001, Effect of levothyroxine administration time on serum TSH in elderly patients., Ann Pharmacother, 35, 529, 10.1345/aph.10286 · DOI · Paper page
Cited by
Sorted by citations
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
“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).”
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber, K. A. (2012) · Endocrine Practice · doi:10.4158/ep12280.gl · Cited by 1,567
“Another study showed that taking it 60 minutes before breakfast on an empty stomach was better than taking it within 2 hours of the last meal of the day, which in turn was better than taking it within 20 minutes of breakfast (166).”
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber for the American Association, K. A. (2012) · Thyroid · doi:10.1089/thy.2012.0205 · Cited by 1,053
“Another study showed that taking it 60 minutes before breakfast on an empty stomach was better than taking it within 2 hours of the last meal of the day, which in turn was better than taking it within 20 minutes of breakfast (166).”
2013 ETA Guideline: Management of Subclinical Hypothyroidism
Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013) · European Thyroid Journal · doi:10.1159/000356507 · Cited by 877
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259
“of the difference in receiving L-T4 in either a fasting state, at bedtime, or with breakfast (266).”
Background
Metadata
- 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
- 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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