Effects of Evening vs Morning Levothyroxine Intake: A Randomized Double-blind Crossover Trial
Abstract
BACKGROUND: Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed. METHODS: To ascertain if levothyroxine intake at bedtime instead of in the morning improves thyroid hormone levels, a randomized double-blind crossover trial was performed between April 1, 2007, and November 30, 2008, among 105 consecutive patients with primary hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. Patients were instructed during 6 months to take 1 capsule in the morning and 1 capsule at bedtime (one containing levothyroxine and the other a placebo), with a switch after 3 months. Primary outcome measures were thyroid hormone levels; secondary outcome measures were creatinine and lipid levels, body mass index, heart rate, and quality of life. RESULTS: Ninety patients completed the trial and were available for analysis. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L (95% confidence interval [CI], 0.60-1.89 mIU/L; P < .001), an increase in free thyroxine level of 0.07 ng/dL (0.02-0.13 ng/dL; P = .01), and an increase in total triiodothyronine level of 6.5 ng/dL (0.9-12.1 ng/dL; P = .02) (to convert thyrotropin level to micrograms per liter, multiply by 1.0; free thyroxine level to picomoles per liter, multiply by 12.871; and total triiodothyronine level to nanomoles per liter, multiply by 0.0154). Secondary outcomes, including quality-of-life questionnaires (36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale, 20-Item Multidimensional Fatigue Inventory, and a symptoms questionnaire), showed no significant changes between morning vs bedtime intake of levothyroxine. CONCLUSIONS: Levothyroxine taken at bedtime significantly improved thyroid hormone levels. Quality-of-life variables and plasma lipid levels showed no significant changes with bedtime vs morning intake. Clinicians should consider prescribing levothyroxine intake at bedtime. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN17436693 (NTR959).
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a double-blind cross-over study, TSH values were 0.9-1.6 mIU/L higher with morning compared with bedtime LT4 ingestion.
“TSH values were 0.9-1.6 mIU/L higher with the morning compared with the bedtime LT4 ingestion (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 [129]
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 [129]
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 [129]
In a 2010 randomized, double-blind, crossover trial recruiting 90 patients, reduced TSH levels and elevated total T3 and total T4 (TT4) levels were observed in patients taking LT4 at bedtime, with no significant difference in quality of life or preference.
“In 2010, a randomized, double-blind, crossover trial recruiting 90 patients examined the efficacy of taking LT4 at bedtime (104). Reduced TSH levels and elevated total T3 and total T4 (TT4) levels were observed in patients taking LT4 at bedtime, with no significant difference in quality of life or preference.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [104]
Bolk et al. reported administration of LT4 at bedtime was associated with higher thyroid hormone concentrations and lower TSH concentrations than administration in the morning.
“Bolk et al. reported that administration of LT4 at bedtime was associated with higher thyroid hormone concentrations and lower TSH concentrations than administration in the morning [ 35 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [35]
Cites
The Hospital Anxiety and Depression Scale
Zigmond, A. S., & Snaith, R. P. (1983) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1983.tb09716.x · Cited by 47,139 · see citing works
Hollowell, J. G., Staehling, N. W., Flanders, W. D., Hannon, W. H., Gunter, E. W., Spencer, C. A., & Braverman, L. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.2.489 · Cited by 4,279 · see citing works
Smets, E. M. A., Garssen, B., Bonke, B., & de Haes, J. C. J. M. (1995) · Journal of Psychosomatic Research · doi:10.1016/0022-3999(94)00125-o · Cited by 3,622 · see citing works
THE SPECTRUM OF THYROID DISEASE IN A COMMUNITY: THE WHICKHAM SURVEY
Tunbridge, W. M. G., Evered, D. C., Hall, R., Appleton, D. R., BREWIS, M., CLARK, F., Evans, J. G., Young, E. T., Bird, T., & Smith, P. (1977) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1977.tb01340.x · Cited by 2,665 · see citing works
15 Design and Analysis of Cross-Over Trials
Kenward, M. G., & Jones, B. C. (2007) · Handbook of statistics · doi:10.1016/s0169-7161(07)27015-4 · Cited by 873 · see citing works
Hypothyroidism and Atherosclerosis
Cappola, A. R., & Ladenson, P. W. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030398 · Cited by 640 · see citing works
Saravanan, P., Chau, W. ‐., Roberts, N., Vedhara, K., Greenwood, R., & Dayan, C. M. (2002) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2002.01654.x · Cited by 514 · see citing works
Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study
Duyff, R. F. (2000) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.68.6.750 · Cited by 447 · see citing works
Treatment Guidelines for Patients With Hyperthyroidism and Hypothyroidism
Singer, P. A. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520340064038 · Cited by 427 · see citing works
Thyroxine in Goiter, <i>Helicobacter pylori</i> Infection, and Chronic Gastritis
Centanni, M., Gargano, L., Canettieri, G., Viceconti, N., Franchi, A., Fave, G. D., & Annibale, B. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa043903 · Cited by 329 · see citing works
Wekking, E. M., Appelhof, B. C., Fliers, E., Schene, A. H., Huyser, J., Tijssen, J. G. P., & Wiersinga, W. M. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.02025 · Cited by 299 · see citing works
Escobar-Morreale, H. F., Obregón, M. J., Escobar del Rey, F., & Morreale de Escobar, G. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118353 · Cited by 287 · see citing works
Correlation between severity of thyroid dysfunction and renal function
den Hollander, J. G., Wulkan, R. W., Mantel, M. J., & Berghout, A. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02236.x · Cited by 263 · see citing works
Circadian Rhythm of Gastric Acid Secretion in Man
Moore, J. G., & Englert, E. (1970) · Nature · doi:10.1038/2261261a0 · Cited by 240 · see citing works
SINGER, P. A. (1995) · JAMA · doi:10.1001/jama.273.10.808 · Cited by 235 · see citing works
Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism
Campbell, N. R. C., Hasinoff, B. B., Stalts, H., Rao, B., & Wong, N. C. W. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-12-1010 · Cited by 231 · see citing works
Effect of calcium carbonate on the absorption of levothyroxine
Singh, N. (2000) · JAMA · doi:10.1001/jama.283.21.2822 · Cited by 219 · see citing works
Timing of levothyroxine administration affects serum thyrotropin concentration
Bach-Huynh, T.-G., Nayak, B., Loh, J., Soldin, S., & Jonklaas, J. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0860 · Cited by 198 · see citing works
Altered intestinal absorption of L-thyroxine caused by coffee
Benvenga, S., Bartolone, L., Pappalardo, M. A., Russo, A., Lapa, D., Giorgianni, G., Saraceno, G., & Trimarchi, F. (2008) · Thyroid · doi:10.1089/thy.2007.0222 · Cited by 191 · see citing works
Appelhof, B. C., Fliers, E., Wekking, E. M., Schene, A. H., Huyser, J., Tijssen, J. G. P., Endert, E., van Weert, H. C. P. M., & Wiersinga, W. M. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2111 · Cited by 183 · see citing works
Aspects of the absorption of oral L-thyroxine in normal man
Wenzel, K. W., & Kirschsieper, H. E. (1977) · Metabolism · doi:10.1016/0026-0495(77)90121-4 · Cited by 151 · see citing works
Roos, A., Linn-Rasker, S. P., van Domburg, R. T., Tijssen, J. P., & Berghout, A. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.15.1714 · Cited by 150 · see citing works
The clinical spectrum of postpartum thyroid disease
Lazarus, J. H., Hall, R., Othman, S. B., Parkes, A. B., Richards, C. J., McCulloch, B., & Harris, B. L. (1996) · QJM · doi:10.1093/qjmed/89.6.429 · Cited by 147 · see citing works
Long-term weight regulation in treated hyperthyroid and hypothyroid subjects
Hoogwerf, B. J., & Nuttall, F. Q. (1984) · The American Journal of Medicine · doi:10.1016/0002-9343(84)90842-8 · Cited by 135 · see citing works
Liel, Y., Harman-Boehm, I., & Shany, S. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.2.8636317 · Cited by 129 · see citing works
Hamilton, T. E., Davis, S., Onstad, L., & Kopecky, K. J. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2300 · Cited by 120 · see citing works
Sachmechi, I., Reich, D. M., Aninyei, M., Wibowo, F., Gupta, G., & Kim, P. J. (2007) · Endocrine Practice · doi:10.4158/ep.13.4.345 · Cited by 112 · see citing works
Vonk, R., van der Schot, A. C., Kahn, R. S., Nolen, W. A., & Drexhage, H. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.08.041 · Cited by 110 · see citing works
Sucralfate causes malabsorption of L-thyroxine
Sherman, S. I., Tielens, E. T., & Ladenson, P. W. (1994) · The American Journal of Medicine · doi:10.1016/0002-9343(94)90093-0 · Cited by 105 · see citing works
Bolk, N., Visser, T. J., Kalsbeek, A., van Domburg, R. T., & Berghout, A. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02681.x · Cited by 96 · see citing works
Update on the Management of Hyperthyroidism and Hypothyroidism
Woeber, K. A. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.8.1067 · Cited by 84 · see citing works
The thyroid axis and mood disorders: overview and future prospects.
Esposito, S., Prange, A. J., & Golden, R. N. (1997) · PubMed · Cited by 80 · see citing works
Raloxifene Causing Malabsorption of Levothyroxine
Siraj, E. S., Gupta, M. K., & Reddy, S. S. K. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.11.1367 · Cited by 76 · see citing works
3-Iodothyronamine (T1AM): A New Player on the Thyroid Endocrine Team?
Scanlan, T. S. (2008) · Endocrinology · doi:10.1210/en.2008-1596 · Cited by 72 · see citing works
Serum lipids in hyper- and hypothyroidism before and after treatment
Friis, T., & Pedersen, L. R. (1987) · Clinica Chimica Acta · doi:10.1016/0009-8981(87)90447-5 · Cited by 71 · see citing works
Prolonged ambulatory antroduodenal manometry in humans.
Wilson, P., Perdikis, G., Hinder, R. A., Redmond, E. J., Anselmino, M., & Quigley, E. M. M. (1994) · PubMed · Cited by 58 · see citing works
Csako, G., McGriff, N. J., Rotman-Pikielny, P., Sarlis, N. J., & Pucino, F. (2001) · Annals of Pharmacotherapy · doi:10.1345/aph.1a031 · Cited by 40 · see citing works
Changes in cardiac function at rest before and after treatment in primary hypothyroidism
Tielens, E. T., Pillay, M., Storm, C. J., & Berghout, A. (2000) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00750-x · Cited by 21 · see citing works
Flagged first, then by citations
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 · see citing works
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 · see citing works
Chaker, L., Bianco, A. C., Jonklaas, J., & Peeters, R. P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30703-1 · Cited by 1,159 · see citing works
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 · see citing works
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 · see citing works
Léger, J., Olivieri, A., Donaldson, M., Torresani, T., Krude, H., van Vliet, G., Polak, M., Butler, G., & on behalf of ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE, A. T. C. H. C. C. G. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1891 · Cited by 569 · see citing works
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259 · see citing works
Hypothyroidism: etiology, diagnosis, and management
Almandoz, J. P., & Gharib, H. (2012) · Medical Clinics of North America · doi:10.1016/j.mcna.2012.01.005 · Cited by 216 · see citing works
Gaitonde, D., Rowley, K. D., & Sweeney, L. (2012) · South African Family Practice · doi:10.1080/20786204.2012.10874256 · Cited by 209 · see citing works
Léger, J., Olivieri, A., Donaldson, M., Torresani, T., Krude, H., van Vliet, G., Polak, M., Butler, G., & on behalf of ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE, A. T. C. H. C. C. G. (2014) · Hormone Research in Paediatrics · doi:10.1159/000358198 · Cited by 208 · see citing works
Treatment for primary hypothyroidism: current approaches and future possibilities
Vaidya, B., Chakera, A. J., & Pearce, S. H. S. (2011) · Drug Design Development and Therapy · doi:10.2147/dddt.s12894 · Cited by 202 · see citing works
Overt and Subclinical Hypothyroidism
Khandelwal, D., & Tandon, N. (2011) · Drugs · doi:10.2165/11598070-000000000-00000 · Cited by 199 · see citing works
Thyroid Dysfunction from Antineoplastic Agents
Hamnvik, O. R., Larsen, P. R., & Marqusee, E. (2011) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djr373 · Cited by 165 · see citing works
Gastrointestinal malabsorption of thyroxine
Virili, C., Antonelli, A., Santaguida, M. G., Benvenga, S., & Centanni, M. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00168 · Cited by 164 · see citing works
Clinical practice guidelines for the management of hypothyroidism
Brenta, G., Vaisman, M., Sgarbi, J. A., Bergoglio, L., de Andrada, N. C., Bravo, P. P., Orlandi, A. M., & Graf, H. (2013) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302013000400003 · Cited by 161 · see citing works
Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
Skelin, M., Lucijanić, T., Amidžić Klarić, D., Rešić, A., Bakula, M., Liberati-Čizmek, A.-M., Gharib, H., & Rahelić, D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.01.005 · Cited by 133 · see citing works
Thyroid Hormone Signaling and Homeostasis During Aging
Bowers, J., Terrien, J., Clerget-Froidevaux, M. S., Gothié, J. D., Rozing, M. P., Westendorp, R. G. J., van Heemst, D., & Demeneix, B. A. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1056 · Cited by 117 · see citing works
Thyroid hormone therapy for hypothyroidism
Biondi, B., & Cooper, D. S. (2019) · Endocrine · doi:10.1007/s12020-019-02023-7 · Cited by 110 · see citing works
Timing is important in medication administration: a timely review of chronotherapy research
Kaur, G., Phillips, C. L., WONG, K. K. H., & Saini, B. (2013) · International Journal of Clinical Pharmacy · doi:10.1007/s11096-013-9749-0 · Cited by 92 · see citing works
Optimal thyroid hormone replacement
Jonklaas, J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab031 · Cited by 89 · see citing works
Levothyroxine interactions with food and dietary supplements – a systematic review
Wiesner, A., Gajewska, D., & Paśko, P. (2021) · Pharmaceuticals · doi:10.3390/ph14030206 · Cited by 85 · see citing works
“Similar results were obtained in many other studies [26–30].”
ResultWhen thyroid hormone replacement is ineffective?
Benvenga, S. (2013) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000003 · Cited by 74 · see citing works
Gaitonde, D. Y., Rowley, K. D., & Sweeney, L. B. (2012) · PubMed · Cited by 73 · see citing works
Thyroxine replacement: a clinical endocrinologist’s viewpoint
Eligar, V, Taylor, P., Okosieme, O., Leese, G., & Dayan, C. (2016) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1177/0004563216642255 · Cited by 72 · see citing works
Quality of life in patients with primary hypothyroidism related to BMI
Bolk, N., Visser, T. J., Tijssen, J. G. P., & Berghout, A. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0395 · Cited by 87 · see citing works
A. Irving, S., Vadiveloo, T., & Leese, G. P. (2015) · Clinical Endocrinology · doi:10.1111/cen.12559 · Cited by 69 · see citing works
Thyroxine softgel capsule in patients with gastric-related T4 malabsorption
Santaguida, M. G., Virili, C., Duca, S. C. D., Cellini, M., Gatto, I., Brusca, N., De Vito, C., Gargano, L., & Centanni, M. (2015) · Endocrine · doi:10.1007/s12020-014-0476-7 · Cited by 68 · see citing works
Serum Thyrotropin Levels Following Levothyroxine Administration at Breakfast
Perez, C. L. S., Araki, F. S., Graf, H., & de Carvalho, G. A. (2013) · Thyroid · doi:10.1089/thy.2012.0435 · Cited by 63 · see citing works
McMillan, M., Rotenberg, K. S., Vora, K., Sterman, A. B., Thevathasan, L., Ryan, M. F., Mehra, M., & Sandulli, W. (2016) · Drugs in R&D · doi:10.1007/s40268-015-0116-6 · Cited by 64 · see citing works
New Formulations of Levothyroxine in the Treatment of Hypothyroidism: Trick or Treat?
Nagy, E. V., Perros, P., Papini, E., Katkó, M., & Hegedűs, L. D. (2020) · Thyroid · doi:10.1089/thy.2020.0515 · Cited by 65 · see citing works
Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
Levothyroxine therapy in elderly patients with hypothyroidism
Effraimidis, G., Watt, T., & Feldt-Rasmussen, U. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.641560 · Cited by 60 · see citing works
“a potentially useful dosing at bedtime, separate from other medication (71).”
BackgroundCaron, P., Grunenwald, S., Persani, L., Borson-Chazot, F., Leroy, R., & Duntas, L. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09691-9 · Cited by 53 · see citing works
Rajput, R., Chatterjee, S., & Rajput, M. (2011) · Journal of Thyroid Research · doi:10.4061/2011/505239 · Cited by 52 · see citing works
Circadian Variation in Efficacy of Medications
Walton, J. C., Walker, W. H., Bumgarner, J. R., Meléndez‐Fernández, O. H., Liu, J. A., Hughes, H. L., Kaper, A. L., & Nelson, R. J. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2073 · Cited by 51 · see citing works
Levothyroxine absorption in health and disease, and new therapeutic perspectives.
Ianiro, G., Mangiola, F., Rienzo, T. A. D., Bibbò, S., Franceschi, F., Greco, A. V., & Gasbarrini, A. (2014) · PubMed · Cited by 51 · see citing works
Levothyroxine therapy in gastric malabsorptive disorders
Virili, C., Brusca, N., Capriello, S., & Centanni, M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.621616 · Cited by 52 · see citing works
Diagnosis and Management of Hypothyroidism in Gulf Cooperation Council (GCC) Countries
Alzahrani, A. S., Mourad, M. A., Hafez, K. K., Almaghamsy, A. M., Alamri, F. A., Aljuhani, N. R., Alhazmi, A. S., Saeedi, M. Y., Alsefri, S. S., Alzahrani, M. D. A., et al. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01382-2 · Cited by 53 · see citing works
Guidelines for Mass Screening of Congenital Hypothyroidism (2014 revision)
Nagasaki, K., Minamitani, K., Anzo, M., Adachi, M., Ishii, T., Onigata, K., Kusuda, S., Harada, S., Horikawa, R., Minagawa, M., et al. (2015) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.24.107 · Cited by 46 · see citing works
Guglielmi, R., Frasoldati, A., Zini, M., Grimaldi, F., Gharib, H., Garber, J. R., & Papini, E. (2016) · Endocrine Practice · doi:10.4158/ep161308.or · Cited by 39 · see citing works
Thyroid hormone replacement: current status and challenges
Okosieme, O. E. (2011) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2011.600307 · Cited by 33 · see citing works
Guidelines for Newborn Screening of Congenital Hypothyroidism (2021 Revision)
Nagasaki, K., Minamitani, K., Nakamura, A., Kobayashi, H., Numakura, C., Itoh, M., Mushimoto, Y., Fujikura, K., Fukushi, M., & Tajima, T. (2022) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.2022-0063 · Cited by 38 · see citing works
Van Wilder, N., Bravenboer, B., Herremans, S., Vanderbruggen, N., & Velkeniers, B. (2017) · European Thyroid Journal · doi:10.1159/000452489 · Cited by 31 · see citing works
Morin, R., Forest, G., & Imbeault, P. (2025) · Frontiers in Sleep · doi:10.3389/frsle.2025.1544945 · Cited by 29 · see citing works
Diagnosis, Treatment and Outcome of Congenital Hypothyroidism
Vliet, G. V., & Deladoëy, J. (2014) · Endocrine development · doi:10.1159/000363155 · Cited by 28 · see citing works
Pang, X., Pu, T., Xu, L., & Sun, R. (2020) · Clinical Endocrinology · doi:10.1111/cen.14172 · Cited by 26 · see citing works
Update on the treatment of hypothyroidism
Jonklaas, J. (2015) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000242 · Cited by 25 · see citing works
Borson‐Chazot, F., Terra, J., Goichot, B., & Caron, P. J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10071386 · Cited by 27 · see citing works
The clinical impact of chronopharmacology on current medicine
Kaşkal, M., Sevım, M., Ülker, G., Keleş, C., & Bebi̇toğlu, B. T. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-03788-7 · Cited by 26 · see citing works
Levothyroxine treatment and gastric juice pH in humans: the proof of concept
Virili, C., Bruno, G., Santaguida, M. G., Gargano, L., Stramazzo, I., De Vito, C., Cicenia, A., Scalese, G., Porowska, B., Severi, C., et al. (2022) · Endocrine · doi:10.1007/s12020-022-03056-1 · Cited by 22 · see citing works
Effects of Commonly Prescribed Medications on Sleep: A Review of the Literature
Klugherz, L. J., Mansukhani, M. P., & Kolla, B. P. (2025) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2025.02.005 · Cited by 22 · see citing works
Guglielmi, V., Bellia, A., Bianchini, E., Medea, G., Cricelli, I., Sbraccia, P., Lauro, D., Cricelli, C. A., & Lapi, F. (2017) · Endocrine · doi:10.1007/s12020-017-1412-4 · Cited by 20 · see citing works
Environmental photochemical fate and UVC degradation of sodium levothyroxine in aqueous medium
Parizi, M. P. S., Lastre-Acosta, A. M., Ishiki, H. M., Rossi, R. C., Mafra, R. C., & Teixeira, A. C. S. C. (2018) · Environmental Science and Pollution Research · doi:10.1007/s11356-018-2907-0 · Cited by 18 · see citing works
Administration and pharmacokinetics of levothyroxine
Lipp, H.-P. (2021) · 70 Years of Levothyroxine · doi:10.1007/978-3-030-63277-9_2 · Cited by 18 · see citing works
Al-Qahtani, K. M., Aldeeri, I. A., Alshaibi, A. M., Alshabib, N. S., Barghouthi, R. M., Alyusuf, E. Y., & Jammah, A. A. (2022) · Thyroid · doi:10.1089/thy.2022.0110 · Cited by 15 · see citing works
Practical guidance for use of oral semaglutide in primary care: a narrative review
Morales, J., Shubrook, J. H., & SKOLNIK, N. (2020) · Postgraduate Medicine · doi:10.1080/00325481.2020.1788340 · Cited by 14 · see citing works
Ducharme, M., Scarsi, C., Bettazzi, E., Mautone, G., Lewis, Y., & Celi, F. S. (2022) · Thyroid · doi:10.1089/thy.2021.0604 · Cited by 13 · see citing works
Should We Treat for Subclinical Hypothyroidism?
Burns, R. B., Bates, C. K., Hartzband, P., & Smetana, G. W. (2016) · Annals of Internal Medicine · doi:10.7326/m16-0857 · Cited by 11 · see citing works
Kucharská, A., Beń‐Skowronek, I., Walczak, M., Ołtarzewski, M., Szalecki, M., Jackowska, T., Lewiñski, A., & Bossowski, A. T. (2016) · Endokrynologia Polska · doi:10.5603/ep.2016.0062 · Cited by 11 · see citing works
Dose administration time from before breakfast to before dinner affect thyroid hormone levels?
Ala, S., Akha, O., Kashi, Z., Asgari, H., Bahar, A., & Sasanpour, N. (2015) · PubMed Central · Cited by 11 · see citing works
Koehler, V. F., & Bojunga, J. (2021) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-1258-5674 · Cited by 10 · see citing works
Morning vs. bedtime levothyroxine administration: what is the ideal choice for children?
Akın, O. (2018) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2018-0168 · Cited by 10 · see citing works
Malabsorption of L-T4 due to drip coffee: a case report using predictors of causation
Wegrzyn, N. M. (2016) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2016.02.016 · Cited by 9 · see citing works
de Mello, R. B., Giassi, K., Stahl, G., Machado Assis, M. L., Flores, M. S., de Lima, B. C., Piccoli, V., & da Costa Rodrigues, T. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.828762 · Cited by 9 · see citing works
Ala, S., Akha, O., Kashi, Z., Bahar, A., Rad, H. A., Sasanpour, N., & Shiva, A. (2015) · International Journal of Endocrinology · doi:10.1155/2015/156375 · Cited by 9 · see citing works
Thyroid Disorders in Children and Adolescents
Rivkees, S. A., & Bauer, A. J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-62520-3.00013-0 · Cited by 9 · see citing works
Ali, Z. H., Abdulridha, M. K., & Alzajaji, Q. B. (2024) · Journal of Medicine and Life · doi:10.25122/jml-2023-0387 · Cited by 7 · see citing works
Causes of treatment failure in primary hypothyroidism
Manuylova, Y. A., Моргунова, Т. Б., & Fadeyev, V. V. (2019) · Clinical and experimental thyroidology · doi:10.14341/ket10163 · Cited by 7 · see citing works
Alternative schedules of levothyroxine administration
Geer, M., Potter, D. M., & Ulrich, H. (2015) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp140250 · Cited by 7 · see citing works
Thyroid disorders in children and adolescents
Rivkees, S. A. (2014) · Elsevier eBooks · doi:10.1016/b978-1-4557-4858-7.00021-4 · Cited by 7 · see citing works
Effect of Ramadan Fasting on Thyroid Hormone Levels in Patients on Levothyroxine Treatment
Dellal, F. D., Ogmen, B. E., Özdemir, D., Alkan, A., Neslihan, F., Polat, Ş. B., Ersoy, R., & Çakır, B. (2020) · Journal of College of Physicians And Surgeons Pakistan · doi:10.29271/jcpsp.2020.10.1009 · Cited by 7 · see citing works
Elsherbiny, T. M. (2021) · Dubai Diabetes and Endocrinology Journal · doi:10.1159/000513927 · Cited by 6 · see citing works
Tea consumption affects the absorption of levothyroxine
Lai, Y.-W., & Huang, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.943775 · Cited by 7 · see citing works
Hypothyroidism—should levothyroxine be taken at bedtime?
Vanderpump, M. P. J. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.29 · Cited by 6 · see citing works
Pineda, J., Galofré, J. C., Toni, M., & Anda, E. (2016) · Medicine - Programa de Formación Médica Continuada Acreditado · doi:10.1016/j.med.2016.06.002 · Cited by 6 · see citing works
Jonklaas, J. (2019) · Springer eBooks · doi:10.1007/978-3-319-72102-6_19 · Cited by 6 · see citing works
Bianchini, B. V., de Jesus, P. R., de Mello, R. G. B., Ziegelmann, P. K., Filion, K. B., & Pizzol, T. D. S. D. (2024) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2024.2313616 · Cited by 6 · see citing works
Andrade, C. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13f08668 · Cited by 5 · see citing works
2023 Korean Thyroid Association Management Guidelines for Patients with Subclinical Hypothyroidism
Chung, H. K., Ku, E. J., Yoo, W. S., Kang, Y. E., Kim, K. J., Kim, B. H., Kim, T. Y., Park, Y. J., Ahn, C. H., Yoon, J. H., et al. (2023) · International Journal of Thyroidology · doi:10.11106/ijt.2023.16.1.32 · Cited by 6 · see citing works
Guglielmi, R., Mian, C., Novizio, R., Paoletta, A., Persichetti, A., Samperi, I., Scoppola, A., Bagnasco, M., Menis, E. D., Rimini, M. L. D., et al. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02652-y · Cited by 6 · see citing works
Parakkal, S. A., Hakeem, F. A., Madathil, H., Alabidi, R. A., Alfaifi, A. Y., Nemr, H. S., & Al-Ghamdi, F. (2022) · Journal of Pharmacy Practice · doi:10.1177/08971900221111139 · Cited by 4 · see citing works
Evaluation of evening versus morning levothyroxine intake in elderly (MONIALE)
Giassi, K. D. S., Piccoli, V., Rodrigues, T. D. C., & de Mello, R. G. B. (2019) · Trials · doi:10.1186/s13063-019-3816-3 · Cited by 5 · see citing works
NHG-Standaard Schildklieraando eningen (tweede herziening)
van Lieshout, J., Felix-Schollaart, B., Bolsius, E., de Boer, A. C. F. P., Burgers, J. S., Bouma, M., & Sijbom, M. (2013) · Cited by 4 · see citing works
Factors Associated with Medicine Timing Effects: A Meta-analysisPreprint
Ruben, M. D., Francey, L. J., Wu, G., Smith, D. F., FitzGerald, G. A., Hughey, J., & Hogenesch, J. B. (2021) · medRxiv · doi:10.1101/2021.10.24.21265348 · Cited by 4 · see citing works
Tesař, O., Měrková, V., Doseděl, M., & Malý, J. (2020) · Klinická farmakologie a farmacie · doi:10.36290/far.2020.020 · Cited by 3 · see citing works
Eligar, V. S., Taylor, P. N., Okosieme, O. E., & Dayan, C. M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00077-8 · Cited by 3 · see citing works
Hypothyroidism and Subclinical Hypothyroidism in the Older Patient
Gurevitz, S. L., Snyder, J. A., Peterson, K. L., & Kelly, K. L. (2011) · The Consultant Pharmacist · doi:10.4140/tcp.n.2011.657 · Cited by 3 · see citing works
Quality of life in patients with overt hypothyroidism: a systematic review
Thvilum, M., Lind, S. M., Ebbehøj, E., Gregersen, S., & Grove‐Laugesen, D. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvaf179 · Cited by 4 · see citing works
Latrofa, F., & Vitti, P. (2012) · CRC Press eBooks · doi:10.1201/b12117-3 · Cited by 2 · see citing works
Lee, K. P., Ah, Y., & Choi, H. D. (2020) · Korean Journal of Clinical Pharmacy · doi:10.24304/kjcp.2020.30.2.87 · Cited by 2 · see citing works
A Case Report of Myxedema Coma in the Setting of Normal Thyroid Stimulating Hormone
Bally, K., Trusty, R.-K., & Naher, K. (2024) · Cureus · doi:10.7759/cureus.62695 · Cited by 1 · see citing works
Senotherapeutic approach to age-related endocrine diseases
Turgut, Ş., & Andican, G. (2025) · Advances in pharmacology · doi:10.1016/bs.apha.2025.02.009 · Cited by 1 · see citing works
da Rocha, B. S., Silveira, V. B., Rados, D. R. V., Zanella, A. B., Scheffel, R. S., Maia, A. L., & Dora, J. M. (2025) · Endocrine · doi:10.1007/s12020-025-04229-4 · Cited by 2 · see citing works
Circadian rhythm homeostasis biomarkers: current landscape and emerging frontiers
Li, S., Zhang, C., Lin, Y., & Wang, S. (2025) · Oral Science and Homeostatic Medicine · doi:10.26599/oshm.2025.9610028 · Cited by 1 · see citing works
Beshyah, S., Khalil, A., Beshyah, A. S., Benbarka, M., & Sherif, I. (2023) · Journal of Diabetes and Endocrine Practice · doi:10.1055/s-0043-176327 · Cited by 1 · see citing works
Koçakoğlu, Ş., ÇADIRCI, D., Çadırcı, M. Ş., & Eren, M. A. (2023) · Konuralp Tıp Dergisi · doi:10.18521/ktd.1328697 · Cited by 1 · see citing works
Seifert, R. (2023) · Springer eBooks · doi:10.1007/978-3-662-68371-2_37 · Cited by 1 · see citing works
Exploring the potential of thyroid hormone therapy: Recent advancements and controversies
Sai, Y. R. K. M. (2024) · International Journal of Clinical Endocrinology and Metabolism · doi:10.17352/ijcem.000059
2. Advances in the Diagnosis and Treatment for Thyroidal Function-associated Disorders
Mori, M. (2012) · Nihon Naika Gakkai Zasshi · doi:10.2169/naika.101.2468 · Cited by 1 · see citing works
Importance of Thyroid Hormone Replacement Therapy in Patients with Medullary Thyroid Cancer
Jonklaas, J. (2016) · Springer eBooks · doi:10.1007/978-3-319-39412-1_13 · Cited by 1 · see citing works
- Authors
- Bolk, N.
- Affiliations
- Maasstad Ziekenhuis (NL)
- Corresponding author
- Bolk, Nienke
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2010-12-13
- Volume
- 170
- Issue
- 22
- Pages
- 1996
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2167956101
- Cited by
- 128
- References
- 38
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 12 · 2020: 10 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 10 · 2015: 10 · 2014: 10 · 2013: 12 · 2012: 9
- FWCI
- 7.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- 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 › Adrenal Hormones and Disorders
- Keywords
- bedtime dosing, morning dosing, primary hypothyroidism, thyroid-stimulating hormone, free thyroxine, triiodothyronine, thyroid hormone levels, quality of life, fatigue, serum lipids, creatinine, heart rate, body mass index, crossover trial, medication adherence
- MeSH terms
- Adult, Aged, Creatinine, Double-Blind Method, Drug Administration Schedule, Female, Heart Rate, Humans, Hypothyroidism, Lipids, Male, Middle Aged, Netherlands, Quality of Life, Surveys and Questionnaires, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine, Body Mass Index, Cross-Over Studies, Hormone Replacement Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
