Lean Body Mass Is a Major Determinant of Levothyroxine Dosage in the Treatment of Thyroid Diseases
Abstract
Total body weight is usually employed to calculate the amount of l-T(4) to be administered in patients with thyroid diseases. The aim of this study was to evaluate the effect of body composition on l-T(4) requirements. Body composition was assessed by dual energy x-ray absorptiometry in 75 patients on TSH-suppressive l-T(4) therapy after conventional thyroid ablation for differentiated cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3 mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There was a much stronger association between the l-T(4) dosage and lean body mass (P < 0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of regional tissue composition showed peripheral lean mass as the best correlate with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was observed with peripheral fat mass. In conclusion, individual l-T(4) requirements are dependent on lean body mass. Age- and gender-related differences in l-T(4) needs reflect different proportions of lean mass over the total body weight. An estimate of lean mass may be helpful to shorten the time required to attain a stable dose of l-T(4), particularly in subjects with high body mass index values that may be due either to increased muscular mass or to obesity.
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?
Ideal body weight is a better predictor of LT4 dose than actual body weight, suggesting LT4 dose requirement may depend on lean body mass.
“Two studies have shown that ideal body weight is a better predictor of LT 4 dose than actual body weight (214,225), thus suggesting that LT4 dose requirement may depend on lean body mass.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [225]
A more accurate predictor of daily LT4 dose would be lean body mass; its limited availability in most routine clinical settings makes normalization of LT4 dose based on actual body weight easier.
“Despite that, a more accurate predictor of daily LT4 dose would be the lean body mass (62); its limited availability in most routine clinical settings makes normalization of LT4 dose based on actual body weight easier.”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [62]
Lean body mass is a major determinant of LT4 treatment.
“Lean body mass is a major determinant of LT4 treatment (62).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [62]
Lean body mass is a key predictor of LT4 requirements because of its role in T4 metabolic processes.
“Lean body mass is a key predictor of LT4 requirements due to its role in T4 metabolic processes.97,98”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [97]
Studies suggest lean body mass is a better predictor of LT4 requirements, with around 2.3 mg/kg per day.
“While there are no specific guidelines for hypothyroidism and obesity, studies suggest lean body mass is a better predictor, with around 2.3 mg/kg per day.97,99,100”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [97]
Cites
Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons
Sawin, C. T., Geller, A., Wolf, P. A., Belanger, A. J., Baker, E., Bacharach, P., Wilson, P., Benjamin, E. J., & D'Agostino, R. B. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411103311901 · Cited by 1,259 · see citing works
Alexander, E. K., Marqusee, E., Lawrence, J., Jarolim, P., Fischer, G. A., & Larsen, P. R. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040079 · Cited by 633 · see citing works
Fish, L. H., Schwartz, H. L., Cavanaugh, J., Steffes, M. W., Bantle, J. P., & Oppenheimer, J. H. (1987) · New England Journal of Medicine · doi:10.1056/nejm198703263161302 · Cited by 353 · see citing works
Levothyroxine Therapy in Patients with Thyroid Disease
Mandel, S. J., Brent, G. A., & Larsen, P. R. (1993) · Annals of Internal Medicine · doi:10.7326/0003-4819-119-6-199309150-00009 · Cited by 324 · see citing works
Wolf, M., Weigert, A., & Kreymann, G. (1996) · European Journal of Endocrinology · doi:10.1530/eje.0.1340168 · Cited by 69 · see citing works
Role for inner ring deiodination preventing transcutaneous passage of thyroxine
Santini, F., Vitti, P., Chiovato, L., Ceccarini, G., Macchia, M., Montanelli, L., Gatti, G., Rosellini, V., Mammoli, C., Martino, E., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021439 · Cited by 37 · see citing works
Self-citation
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
“daily LT4 dose is more dependent on lean body mass than total body weight (225), which explains why the elderly often require lower doses of LT4 (219).”
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
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
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259 · see citing works
Santini, F., Marzullo, P., Rotondi, M., Ceccarini, G., Pagano, L., Ippolito, S., Chiovato, L., & Biondi, B. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0067 · Cited by 240 · see citing works
Self-citationHypothyroidism: 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
European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity
Pasquali, R., Casanueva, F., Haluzik, M., van Hulsteijn, L., Ledoux, S., Monteiro, M. P., Salvador, J., Santini, F., Toplak, H., & Dekkers, O. M. (2020) · European Journal of Endocrinology · doi:10.1530/eje-19-0893 · Cited by 180 · see citing works
Self-citationThyroid Hormones and Their Relation to Weight Status
Reinehr, T., Isa, A., de Sousa, G., Dieffenbach, R., & Andler, W. (2008) · Hormone Research in Paediatrics · doi:10.1159/000129678 · Cited by 185 · see citing works
A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism
Colucci, P., Yue, C. S., Ducharme, M., Benvenga, S., Principal Scientist, L. A. C. I., Principal Scientist, L. A. C. I. A. P. C., President and CEO, L. A. C. I., & Professor of Medicine, D. (2010) · European Endocrinology · doi:10.17925/ee.2013.09.01.40 · Cited by 167 · 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
Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report
Centanni, M., Benvenga, S., & Sachmechi, I. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0706-y · Cited by 113 · see citing works
“In a case series of 75 consecutive post-thyroidectomy patients, an inverse relationship between the dose of levothyroxine required to normalize TSH levels and body weight was reported [71].”
BackgroundTorlontano, M., Durante, C., Torrente, I., Crocetti, U., Augello, G., Ronga, G., Montesano, T., Travascio, L., Verrienti, A., Bruno, R., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1067 · Cited by 92 · see citing works
Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age
Devdhar, M., Drooger, R., Pehlivanova, M., Singh, G., & Jonklaas, J. (2011) · Thyroid · doi:10.1089/thy.2011.0029 · Cited by 90 · see citing works
Optimal thyroid hormone replacement
Jonklaas, J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab031 · Cited by 89 · see citing works
Thyroid dysfunction in the elderly
Boelaert, K. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.30 · Cited by 84 · see citing works
Sex and Age Differences in Levothyroxine Dosage Requirement
Jonklaas, J. (2010) · Endocrine Practice · doi:10.4158/ep09257.or · Cited by 72 · 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
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
Morris, J. C. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03536.x · Cited by 59 · see citing works
Improved Levothyroxine Pharmacokinetics After Bariatric Surgery
Gkotsina, M., Michalaki, M., Mamali, I., Markantes, G., Sakellaropoulos, G. C., Kalfarentzos, F., Vagenakis, A. G., & Markou, K. B. (2013) · Thyroid · doi:10.1089/thy.2011.0526 · Cited by 57 · see citing works
Rubio, I. G. S., Galrão, A. L., Santo, M. A., Zanini, A. C., & Medeiros-Neto, G. (2012) · Obesity Surgery · doi:10.1007/s11695-011-0452-8 · Cited by 58 · see citing works
The economic impact of levothyroxine dose adjustments: the CONTROL HE study
Ernst, F. R., Barr, P., Elmor, R., Sandulli, W., Thevathasan, L., Sterman, A. B., Goldenberg, J., & Vora, K. (2017) · Clinical Drug Investigation · doi:10.1007/s40261-016-0462-3 · Cited by 53 · see citing works
Ward, L. S. (2010) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302010000500002 · Cited by 53 · see citing works
Di Donna, V., Santoro, M. G., de Waure, C., Ricciato, M. P., Paragliola, R. M., Pontecorvi, A., & Corsello, S. M. (2014) · Thyroid · doi:10.1089/thy.2014.0111 · Cited by 52 · see citing works
Predicting thyroxine requirements following total thyroidectomy: Thyroxine dose prediction
Mistry, D., Atkin, S., Atkinson, H., Gunasekaran, S., Sylvester, D., Rigby, A. S., & England, R. J. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2010.03940.x · Cited by 50 · see citing works
Fierabracci, P., Martinelli, S., Tamberi, A., Piaggi, P., Basolo, A., Pelosini, C., Ricco, I., Magno, S., Querci, G., Ceccarini, G., et al. (2016) · Thyroid · doi:10.1089/thy.2015.0473 · Cited by 51 · see citing works
Pirola, I., Daffini, L., Gandossi, E., Lombardi, D., Formenti, A., Castellano, M., & Cappelli, C. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0082-9 · Cited by 47 · see citing works
Novel thyroxine formulations: a further step toward precision medicine
Virili, C., Trimboli, P., & Centanni, M. (2019) · Endocrine · doi:10.1007/s12020-019-02049-x · Cited by 41 · see citing works
Levothyroxine dosing following bariatric surgery
Gadiraju, S., Lee, C. J., & Cooper, D. S. (2016) · Obesity Surgery · doi:10.1007/s11695-016-2314-x · Cited by 39 · see citing works
Levothyroxine dose following thyroidectomy is affected by more than just body weight
Baehr, K. M., Lyden, E., Treude, K., Erickson, J., & Goldner, W. (2012) · The Laryngoscope · doi:10.1002/lary.23186 · Cited by 36 · see citing works
Robertson, H. M. A., Narayanaswamy, A. K. P., Pereira, O., Copland, S. A., Herriot, R., McKinlay, A. W., Bevan, J. S., & Abraham, P. (2014) · Thyroid · doi:10.1089/thy.2013.0661 · Cited by 35 · see citing works
Papoian, V., Ylli, D., Felger, E. A., Wartofsky, L., & Rosen, J. E. (2019) · Thyroid · doi:10.1089/thy.2019.0251 · Cited by 35 · see citing works
Impaired Pharmacokinetics of Levothyroxine in Severely Obese Volunteers
Michalaki, M. A., Gkotsina, M. I., Mamali, I., Markantes, G. K., Faltaka, A., Kalfarentzos, F., Vagenakis, A. G., & Markou, K. B. (2011) · Thyroid · doi:10.1089/thy.2010.0149 · Cited by 34 · see citing works
Centanni, M., Duntas, L., Feldt-Rasmussen, U., Koehrle, J., Peeters, R. P., Razvi, S., Trimboli, P., & Virili, C. (2025) · European Thyroid Journal · doi:10.1530/etj-25-0123 · Cited by 38 · see citing works
“Lean body mass is a major determinant of LT4 treatment (62).”
Del Duca, S. C., Santaguida, M. G., Brusca, N., Gatto, I., Cellini, M., Gargano, L., Verga Falzacappa, C., Frattaroli, F. M., Virili, C., & Centanni, M. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0314 · Cited by 31 · see citing works
Timing of breakfast does not influence therapeutic efficacy of liquid levothyroxine formulation
Morelli, S., Reboldi, G., Moretti, S., Menicali, E., Avenia, N., & Puxeddu, E. (2016) · Endocrine · doi:10.1007/s12020-015-0788-2 · Cited by 30 · see citing works
Midgley, J. E. M., Larisch, R., Dietrich, J. W., & Hoermann, R. (2015) · Endocrine Connections · doi:10.1530/ec-15-0056 · Cited by 31 · see citing works
The clinical utility of free thyroxine in oral levothyroxine absorption testing
Ching Sun, G. E., Pantalone, K. M., Faiman, C., Gupta, M., Olansky, L., & Hatipoglu, B. (2014) · Endocrine Practice · doi:10.4158/ep13487.or · Cited by 27 · see citing works
Ernst, F. R., Sandulli, W., Elmor, R., Welstead, J., Sterman, A. B., & Lavan, M. (2017) · Drugs in R&D · doi:10.1007/s40268-016-0150-z · Cited by 23 · 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
Midgley, J. E. M., Larisch, R., Dietrich, J. W., & Hoermann, R. (2015) · Endocrine Connections · doi:10.1530/ec-150056 · Cited by 31 · see citing works
Levothyroxine sodium pentahydrate tablets – formulation considerations
Kaur, N., & Suryanarayanan, R. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.08.006 · Cited by 19 · see citing works
Is levothyroxine requirement the same for tablet and soft gel formulations?
Di Donna, V., Paragliola, R. M., de Waure, C., Papi, G., Pontecorvi, A., & Corsello, S. M. (2018) · Endocrine · doi:10.1007/s12020-017-1311-8 · Cited by 17 · see citing works
The performance of levothyroxine tablet is impaired by bariatric surgery
Trimboli, P., Ossola, N., Torre, A., Mongelli, F., Quarenghi, M., Camponovo, C., Lucchini, B., Rotondi, M., Ruinelli, L., & Garofalo, F. (2022) · Endocrine · doi:10.1007/s12020-022-03289-0 · Cited by 17 · see citing works
Refractory hypothyroidism: unraveling the complexities of diagnosis and management
Quiroz-Aldave, J. E., Concepción-Zavaleta, M. J., Durand-Vásquez, M. D. C., Concepción-Urteaga, L. A., Gamarra-Osorio, E. R., Suárez-Rojas, J., Rafael-Robles, L. D. P., Paz-Ibarra, J., & Román-González, A. (2023) · Endocrine Practice · doi:10.1016/j.eprac.2023.09.003 · Cited by 14 · see citing works
Identifying predictors of prolonged levothyroxine dose adjustment after thyroidectomy
Atruktsang, T. S., Zaborek, N. A., Imbus, J. R., Long, K., Pitt, S. C., Sippel, R. S., & Schneider, D. F. (2019) · Journal of Surgical Research · doi:10.1016/j.jss.2019.03.049 · Cited by 13 · see citing works
Adams, R., & Mammen, J. S. (2025) · Thyroid · doi:10.1089/thy.2024.0604 · Cited by 12 · see citing works
Oteri, V., Volpe, S., Lopes, M., Sceusa, G., Tumminia, A., Belfiore, A., Frasca, F., & Gullo, D. (2024) · Endocrine · doi:10.1007/s12020-024-04016-7 · Cited by 9 · see citing works
Soldin, O. P., Soldin, S. J., Vinks, A. A., Younis, I., & Landy, H. J. (2010) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e3181f12fe5 · Cited by 9 · see citing works
- Authors
- Santini, F., Pinchera, A., Marsili, A., Ceccarini, G., Castagna, M. G., Valeriano, R., Giannetti, M., Taddei, D., Centoni, R., Scartabelli, G., Rago, T., Mammoli, C., Elisei, R., & Vitti, P.
- Affiliations
- University of Pisa (IT)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-01
- Volume
- 90
- Issue
- 1
- Pages
- 124-127
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2147794245
- Cited by
- 226
- References
- 6
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 12 · 2023: 12 · 2022: 19 · 2021: 12 · 2020: 10 · 2019: 14 · 2018: 6 · 2017: 16 · 2016: 16 · 2015: 14 · 2014: 13 · 2013: 7 · 2012: 14
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Use Siena air (University of Siena) (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 › Thyroid Cancer Diagnosis and Treatment
- Keywords
- levothyroxine dosage, lean body mass, body composition, TSH suppression, thyroid cancer, thyroid ablation, obesity, body mass index, fat mass, dose titration
- MeSH terms
- Body Composition, Female, Humans, Male, Thinness, Thyroid Diseases, Thyrotropin, Thyroxine, Leptin
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
