Levothyroxine therapy: changes of TSH levels by switching patients from tablet to liquid formulation. a systematic review and meta-analysis
Open accessAbstract
Background. In the last years, levothyroxine (LT4) has been commercialized also in liquid formulation which is less sensitive to the factors known to reduce the absorption of tablet LT4. To date, there is not robust information that liquid LT4 can improve pharmacologic thyroid homeostasis of patients with reduced efficacy of tablet LT4. This analysis aimed at achieving solid evidence that switching thyroxine treatment from tablet to liquid preparation improves patients’ TSH levels. Methods. The search was performed in PubMed/MEDLINE and Scopus database based on the terms “thyroid”, “levothyroxine” and “liquid”, and updated until September 25, 2017. Studies were included only if they described patients with suboptimal TSH on tablet LT4, subsequently switched to liquid LT4. Results. The literature search retrieved 462 articles and six were finally included. The pooled mean difference of TSH value between tablet and liquid LT4 was 4.23 mIU/L (95%CI from 3.69 to 4.77). Mild heterogeneity was found (I2 60%). Overall mean difference of TSH was significant (p<0.0001). Conclusions. The present meta-analysis showed that patients with suboptimal TSH on tablet LT4 can have a significantly improved TSH by switching to liquid LT4 formulation at unchanged dose.
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In a meta-analysis, six studies were included and the pooled mean reduction of TSH value was 4.23 mU/L (95% CI 3.69 to 4.77) after switching from tablet to LS, with mild heterogeneity among the studies.
“Six studies were included and the pooled mean reduction of TSH value was 4.23 mU/L (95% CI 3.69 to 4.77) after switching from tablet to LS, with mild heterogeneity among the studies.”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [129]
A meta-analysis including 6 prospective studies confirmed that patients administered liquid LT4 had reduced TSH levels (4.23 mIU/L, 95% CI 3.69-4.77) compared with the tablet group taking the same dose.
“A meta-analysis including 6 prospective studies confirmed that patients administered liquid LT4 had reduced TSH levels (4.23 mIU/L, 95% CI 3.69-4.77) compared with the tablet group taking the same dose (190).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [190]
Taken together, liquid solutions have higher absorption, faster Tmax, and lower and more stable TSH levels than solid formulations, partially due to better intestinal absorption.
“Taken together, these results show that liquid solutions have higher absorption, faster Tmax, and lower and more stable TSH levels than solid formulations, partially due to better intestinal absorption.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [190]
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Cites
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 · cited 1× · see citing works
“8 mcg/kg/day of LT4 should be satisfactory to treat hypothyroid patients (6), a non-negligible rate of them would require a dose increased up to 30–40% (7, 8).”
BackgroundThe Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418 · 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
Conditions and drugs interfering with thyroxine absorption
Liwanpo, L., & Hershman, J. M. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2009.06.006 · Cited by 222 · see citing works
Hashimoto’s Thyroiditis and Autoimmune Gastritis
Cellini, M., Santaguida, M. G., Virili, C., Capriello, S., Brusca, N., Gargano, L., & Centanni, M. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00092 · Cited by 120 · see citing works
Self-citationAtypical celiac disease as cause of increased need for thyroxine: a systematic study
Virili, C., Bassotti, G., Santaguida, M. G., Iuorio, R., Del Duca, S. C., Mercuri, V., Picarelli, A., Gargiulo, P., Gargano, L., & Centanni, M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1851 · Cited by 114 · see citing works
Self-citationDiagnosis 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 · cited 1× · see citing works
“, chronic atrophic gastritis, Helicobacter pylori infection) (7, 14), and concomitant intake of some drugs or ingestion of food or beverages (15, 16) can interfere with the LT4 absorption, thus reducing its efficacy.”
BackgroundSelf-citationVirili, C., & Centanni, M. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.01.053 · Cited by 105 · see citing works
Vita, R., Saraceno, G., Trimarchi, F., & Benvenga, S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2684 · Cited by 99 · see citing works
Does microbiota composition affect thyroid homeostasis?
Virili, C., & Centanni, M. (2014) · Endocrine · doi:10.1007/s12020-014-0509-2 · Cited by 85 · see citing works
Self-citationTablet Splitting of a Narrow Therapeutic Index Drug: A Case with Levothyroxine Sodium
Shah, R. B., Collier, J. S., Sayeed, V. A., Bryant, A., Habib, M. J., & Khan, M. A. (2010) · AAPS PharmSciTech · doi:10.1208/s12249-010-9515-8 · Cited by 83 · see citing works
Yue, C., Scarsi, C., & Ducharme, M. P. (2012) · Arzneimittelforschung · doi:10.1055/s-0032-1329951 · Cited by 81 · see citing works
Fallahi, P., Ferrari, S. M., Camastra, S., Politti, U., Ruffilli, I., Vita, R., Navarra, G., Benvenga, S., & Antonelli, A. (2017) · Obesity Surgery · doi:10.1007/s11695-016-2247-4 · Cited by 81 · see citing works
Cappelli, C., Pirola, I., Daffini, L., Formenti, A., Iacobello, C., Cristiano, A., Gandossi, E., Agabiti Rosei, E., & Castellano, M. (2016) · Thyroid · doi:10.1089/thy.2015.0422 · Cited by 80 · see citing works
Pirola, I., Formenti, A. M., Gandossi, E., Mittempergher, F., Casella, C., Agosti, B., & Cappelli, C. (2013) · Obesity Surgery · doi:10.1007/s11695-013-1015-y · Cited by 74 · see citing works
Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine
Cellini, M., Santaguida, M. G., Gatto, I., Virili, C., Del Duca, S. C., Brusca, N., Capriello, S., Gargano, L., & Centanni, M. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1217 · Cited by 72 · see citing works
Self-citationLiquid and softgel levothyroxine use in clinical practice: state of the art
Virili, C., Trimboli, P., Romanelli, F., & Centanni, M. (2016) · Endocrine · doi:10.1007/s12020-016-1035-1 · Cited by 71 · see citing works
Self-citationThyroxine 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
Self-citationThe emergence of levothyroxine as a treatment for hypothyroidism
Hennessey, J. V. (2017) · Endocrine · doi:10.1007/s12020-016-1199-8 · Cited by 66 · see citing works
Thyroxine treatment: absorption, malabsorption, and novel therapeutic approaches
Centanni, M. (2013) · Endocrine · doi:10.1007/s12020-012-9814-9 · Cited by 56 · see citing works
Self-citationHelicobacter pyloriinfection and drugs malabsorption
Lahner, E. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i30.10331 · Cited by 53 · see citing works
Fallahi, P., Ferrari, S. M., & Antonelli, A. (2016) · Endocrine · doi:10.1007/s12020-015-0836-y · Cited by 53 · see citing works
Self-citationThe 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
Benvenga, S., Di Bari, F., & Vita, R. (2017) · Endocrine · doi:10.1007/s12020-017-1244-2 · Cited by 51 · see citing works
Vaisman (2014) · PubMed · doi:10.3275/8810 · Cited by 49 · see citing works
Fallahi, P., Ferrari, S. M., Ruffilli, I., & Antonelli, A. (2016) · BMC Gastroenterology · doi:10.1186/s12876-016-0439-y · Cited by 46 · see citing works
Brancato, D., Scorsone, A., Saura, G., Ferrara, L., Di Noto, A., Aiello, V., Fleres, M., & Provenzano, V. (2014) · Endocrine Practice · doi:10.4158/ep13418.or · Cited by 44 · see citing works
Vita, R., Di Bari, F., & Benvenga, S. (2017) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2017.1290604 · Cited by 43 · see citing works
Oral liquid levothyroxine treatment at breakfast: a mistake?
Cappelli, C., Pirola, I., Gandossi, E., Formenti, A., & Castellano, M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-0693 · Cited by 41 · see citing works
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
Patients with lactose intolerance absorb liquid levothyroxine better than tablet levothyroxine
Fallahi, P., Ferrari, S. M., Marchi, S., De Bortoli, N., Ruffilli, I., & Antonelli, A. (2017) · Endocrine · doi:10.1007/s12020-016-1090-7 · Cited by 31 · see citing works
Self-citationTiming 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
Cappelli, C., Pirola, I., Gandossi, E., Cristiano, A., Daffini, L., Agosti, B., Casella, C., & Castellano, M. (2016) · International Journal of Endocrinology · doi:10.1155/2016/9043450 · Cited by 29 · see citing works
Fallahi, P., Ferrari, S. M., & Antonelli, A. (2016) · Endocrine Practice · doi:10.4158/ep161545.or · Cited by 28 · see citing works
Self-citationUtility of a Liquid Formulation of Levo-thyroxine in Differentiated Thyroid Cancer Patients
Giusti, M., Mortara, L., Machello, N., Monti, E., Pera, G., & Marenzana, M. (2014) · Drug Research · doi:10.1055/s-0034-1384535 · Cited by 24 · see citing works
Peirce, C., Ippolito, S., Lanas, A., Pesce, M., Pontieri, G., Arpaia, D., Sarnelli, G., & Biondi, B. (2018) · Endocrine · doi:10.1007/s12020-017-1367-5 · Cited by 16 · see citing works
Marina, M., Ceda, G. P., Aloe, R., Gnocchi, C., & Ceresini, G. (2016) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 12 · see citing works
Resistance to levothyroxine in a bariatric surgery patient: an indication for liquid formulation?
Hommel, C., & Delgrange, E. (2016) · Acta Clinica Belgica · doi:10.1080/17843286.2016.1196861 · Cited by 8 · see citing works
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Wiesner, A., Gajewska, D., & Paśko, P. (2021) · Pharmaceuticals · doi:10.3390/ph14030206 · Cited by 85 · see citing works
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BackgroundOvert and Subclinical Hypothyroidism in the Elderly: When to Treat
Calsolaro, V., Niccolai, F., Pasqualetti, G., Calabrese, A. M., Polini, A., Okoye, C., Magno, S., Caraccio, N., & Monzani, F. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00177 · Cited by 68 · see citing works
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Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
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Self-citationCastellana, M., Castellana, C., Giovanella, L., & Trimboli, P. (2020) · Endocrine · doi:10.1007/s12020-019-02185-4 · Cited by 41 · see citing works
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Ghosh, S., Pramanik, S., Biswas, K., Bhattacharjee, K., Sarkar, R., Chowdhury, S., & Mukhopadhyay, P. (2020) · European Thyroid Journal · doi:10.1159/000504218 · Cited by 39 · 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
Self-citationTanguay, M., Girard, J., Scarsi, C., Mautone, G., & Larouche, R. (2019) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.608 · Cited by 33 · see citing works
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Trimboli, P., Scappaticcio, L., De Bellis, A., Maiorino, M. I., Knappe, L., Esposito, K., Bellastella, G., & Giovanella, L. (2020) · International Journal of Endocrinology · doi:10.1155/2020/4524759 · Cited by 27 · see citing works
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Benvenga, S., Capodicasa, G., Perelli, S., Ferrari, S. M., Fallahi, P., & Antonelli, A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00150 · Cited by 25 · see citing works
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Gietka-Czernel, M., Hubalewska-Dydejczyk, A., Kos-Kudła, B., Lewiński, A., Ruchała, M., Syrenicz, A., & Zgliczyński, W. (2020) · Endokrynologia Polska · doi:10.5603/ep.a2020.0065 · Cited by 13 · 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
Morini, E., Catalano, A., Lasco, A., Morabito, N., & Benvenga, S. (2019) · Endocrine · doi:10.1007/s12020-019-01908-x · Cited by 12 · see citing works
Tuli, G., Munarin, J., & de Sanctis, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.860775 · Cited by 9 · see citing works
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Analysis of dose-TSH response effect of levothyroxine soft-gel formulation
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- Authors
- Virili, C., Giovanella, L., Fallahi, P., Antonelli, A., Santaguida, M. G., Centanni, M., & Trimboli, P.
- Affiliations
- Sapienza University of Rome (IT)
- Istituto Oncologico della Svizzera Italiana (CH)
- University of Pisa (IT)
- Corresponding author
- Virili, Camilla
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-01-26
- Volume
- 9
- Pages
- 10-10
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC5790785
- OpenAlex
- W2788457030
- Cited by
- 61
- References
- 38
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 1 · 2022: 8 · 2021: 11 · 2020: 6 · 2019: 14 · 2018: 6
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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, liquid formulation, tablet formulation, TSH levels, thyroid hormone replacement, formulation switching, drug absorption, hypothyroidism
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