Levothyroxine liquid solution versus tablet form for replacement treatment in pregnant women
Open accessAbstract
OBJECTIVE: To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant women on liquid compared to tablet formulations. METHODS: Patients were recruited by searching our "thyroid patients" database. The selection criteria were as follows: a) pregnant women on treatment for hypothyroidism (both liquid and tablet LT4) who gave birth at our hospital between February 2012 and January 2014; b) thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels obtained at least 3 months before missed menstrual cycle, with a TSH value less than 2.5 mIU/L and c) TSH and FT4 obtained within 12 weeks of pregnancy, and each month subsequently. RESULTS: During pregnancy, 8/31 (25.5%) of the women had to increase the dosage of LT4. Of these, 7/17 (41.2%) were on LT4 replacement therapy with tablets, and 1/14 (7.1%) with liquid formulation (p = 0.038). Daily LT4 was significantly increased in the liquid group only (52.9 ± 19.5 versus 67.5 ± 19.2 mcg/day (p = 0.013). A logistic regression analysis showed that the treatment with LT4 tablets was the only predictor of LT4 increase (OR: 0.44; 95% CI: 0.04-0.83; p = 0.031). CONCLUSION: Pregnant women on optimal replacement therapy before pregnancy require an increase of LT4 dosage more often when on a tablet than liquid formulation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
A retrospective cohort study in 31 pregnant patients with hypothyroidism showed a decreased daily LT4 dose in 14 patients taking liquid solutions and 17 taking tablets, with no significant difference in age, weight, or TH levels.
“A retrospective cohort study by Cappelli et al in 31 pregnant patients with hypothyroidism showed a decreased daily LT4 dose in 14 patients taking liquid solutions and 17 taking tablets, with no significant difference in age, weight, or TH levels (200).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [200]
Better absorption of liquid LT4 is a possible explanation for the decreased daily LT4 dose in pregnant patients taking liquid solutions.
“Better absorption of liquid LT4 is a possible explanation.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [200]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stagnaro-Green, A., Abalovich, M., Alexander, E., Azizi, F., Mestman, J., Negro, R., Nixon, A., Pearce, E. N., Soldin, O. P., Sullivan, S., et al. (2011) · Thyroid · doi:10.1089/thy.2011.0087 · Cited by 2,942 · see citing works
DeGroot, L. J., Abalovich, M., Alexander, E. K., Amino, N., Barbour, L. A., Cobin, R. H., Eastman, C. J., Lazarus, J. H., Luton, D., Mandel, S. J., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2803 · Cited by 1,862 · 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
Lazarus, J., Brown, R. S., Daumerie, C., Hubalewska-Dydejczyk, A., Negro, R., & Vaidya, B. (2014) · European Thyroid Journal · doi:10.1159/000362597 · Cited by 742 · 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
Patra, J., Bakker, R., Irving, H., Jaddoe, V., Malini, S., & Rehm, J. (2011) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2011.03050.x · Cited by 555 · see citing works
Physiologic and pharmacokinetic changes in pregnancy
Costantine, M. M. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00065 · Cited by 526 · see citing works
Increased need for thyroxine during pregnancy in women with primary hypothyroidism
Mandel, S. J., Larsen, P. R., Seely, E. W., & Brent, G. A. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007123230204 · Cited by 360 · 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
Thyroid hormone early adjustment in pregnancy (the THERAPY) trial
Yassa, L., Marqusee, E., Fawcett, R., & Alexander, E. K. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0013 · Cited by 262 · see citing works
Procter, S. B., & Campbell, C. G. (2014) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2014.05.005 · Cited by 237 · see citing works
Dawes, M., & Chowienczyk, P. (2001) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1053/beog.2001.0231 · Cited by 212 · see citing works
What Happens to the Normal Thyroid During Pregnancy?
Glinoer, D. (1999) · Thyroid · doi:10.1089/thy.1999.9.631 · Cited by 199 · see citing works
Diagnosis and management of subclinical hypothyroidism in pregnancy
Negro, R., & Stagnaro‐Green, A. (2014) · BMJ · doi:10.1136/bmj.g4929 · Cited by 166 · see citing works
Shawe, J., Delbaere, I., Ekstrand, M., Hegaard, H. K., Larsson, M., Mastroiacovo, P., Stern, J., Steegers, E. A. P., Stephenson, J., & Tydén, T. (2014) · The European Journal of Contraception & Reproductive Health Care · doi:10.3109/13625187.2014.990088 · Cited by 141 · see citing works
Overt Hyperthyroidism and Hypothyroidism During Pregnancy
Stagnaro‐Green, A. (2011) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0b013e3182272f32 · Cited by 129 · see citing works
TRANSIT TIME IN THE SMALL INTESTINE IN PREGNANCY
Parry, E., Shields, R. C., & TURNBULL, A. C. (1970) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1970.tb03423.x · Cited by 125 · see citing works
GASTRIC AND DUODENAL ULCERS DURING PREGNANCY
Cappell, M. S., & García, A. S. (1998) · Gastroenterology Clinics of North America · doi:10.1016/s0889-8553(05)70352-6 · Cited by 117 · 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
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
The administration of l -thyroxine as soft gel capsule or liquid solution
Vita, R., Fallahi, P., Antonelli, A., & Benvenga, S. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.918101 · Cited by 93 · see citing works
Abalovich, M., Alcaraz, G., Kleiman-Rubinsztein, J., Pavlove, M. M., Cornelio, C., Levalle, O. A., & Gutierrez, S. (2010) · Thyroid · doi:10.1089/thy.2009.0457 · Cited by 88 · 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
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
Verga, U., Bergamaschi, S., CORTELAZZI, D., Ronzoni, S., Marconi, A. M., & Beck‐Peccoz, P. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03398.x · Cited by 56 · 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
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
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 · cited 2× · see citing works
“Many recent reports have clearly demonstrated that liquid LT4 formulation circumvents these problems, in patients taking proton pump inhibitors, those suffering from gastric related T4 malabsorption, those assuming T4 with coffee or fed by enteral tube, and also those submitted to bariatric surgery [24-28].”
BackgroundLevothyroxine liquid solution versus tablet for replacement treatment in hypothyroid patients
Negro, R., Valcavi, R., Agrimi, D., & Toulis, K. A. (2014) · Endocrine Practice · doi:10.4158/ep13378.or · Cited by 36 · cited 2× · see citing works
“Recent studies have shown a better absorption of soft gel\liquid formulation than tablet, hesitating in more stable TSH values [9-11].”
BackgroundKothari, A., & Girling, J. (2008) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2008.01901.x · Cited by 34 · see citing works
Cappelli, C., Pirola, I., Daffini, L., Gandossi, E., Agosti, B., & Castellano, M. (2014) · European Geriatric Medicine · doi:10.1016/j.eurger.2014.09.006 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Liquid 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
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
Fallahi, P., Ferrari, S. M., Ruffilli, I., Ragusa, F., Biricotti, M., Materazzi, G., Miccoli, P., & Antonelli, A. (2016) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2016.1227782 · Cited by 48 · see citing works
Levothyroxine Formulations: Pharmacological and Clinical Implications of Generic Substitution
Benvenga, S., & Carlé, A. (2019) · Advances in Therapy · doi:10.1007/s12325-019-01079-1 · Cited by 45 · 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
Precision Medicine in Autoimmune Thyroiditis and Hypothyroidism
Ferrari, S. M., Ragusa, F., Elia, G., Paparo, S. R., Mazzi, V., Baldini, E., Benvenga, S., Antonelli, A., & Fallahi, P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.750380 · Cited by 41 · see citing works
Antonelli, A., Elia, G., Ragusa, F., Paparo, S. R., Cavallini, G., Benvenga, S., Ferrari, S. M., & Fallahi, P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.633587 · Cited by 32 · see citing works
The exploration of Hashimoto's Thyroiditis related miscarriage for better treatment modalities
Min, Y., Wang, X., Chen, H., & Yin, G. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.48128 · Cited by 27 · see citing works
Increased requirement of replacement doses of levothyroxine caused by liver cirrhosis.
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
Ferrara, R., Ientile, V., Arcoraci, V., Ferrajolo, C., Piccinni, C., Fontana, A., Benvenga, S., & Trifirò, G. (2017) · Endocrine · doi:10.1007/s12020-017-1242-4 · Cited by 23 · see citing works
L-T4 Therapy in Enteric Malabsorptive Disorders
Fallahi, P., Ferrari, S. M., Elia, G., Ragusa, F., Paparo, S. R., & Antonelli, A. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.626371 · Cited by 23 · 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
Bornikowska, K., Gietka-Czernel, M., Raczkiewicz, D., Glinicki, P., & Zgliczyński, W. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10225233 · Cited by 17 · see citing works
Benvenga, S. (2019) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2019.100204 · Cited by 17 · see citing works
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
Seeking optimization of LT4 treatment in patients with differentiated thyroid cancer
Stramazzo, I., Capriello, S., Antonelli, A., Fallahi, P., Centanni, M., & Virili, C. (2022) · HORMONES · doi:10.1007/s42000-022-00376-9 · Cited by 9 · see citing works
Ruchała, M., Bossowski, A. T., Brzózka, M. M., Gietka‐Czernel, M., Hubalewska–Dydejczyk, A., Kos‐Kudła, B., Lewiñski, A., Syrenicz, A., & Zgliczyński, W. (2022) · Endokrynologia Polska · doi:10.5603/ep.a2022.0078 · Cited by 7 · see citing works
Are liquid levothyroxine formulations comparable? The LETI study
Gatta, E., Maltese, V., Pirola, I., Gandossi, E., Silvestrini, I., Ugoccioni, M., Morandi, R., Casella, C., & Cappelli, C. (2025) · Thyroid Research · doi:10.1186/s13044-025-00236-9 · Cited by 3 · see citing works
Matyjaszek‐Matuszek, B., Woźniak, M. M., Ochmańska, A., Sawicka‐Gutaj, N., Ruchała, M., & Czarnywojtek, A. (2021) · Endokrynologia Polska · doi:10.5603/ep.a2021.0013 · Cited by 3 · see citing works
Drug forms of levothyroxine. Is there room for innovation in hypothyroidism treatment?
Kolpakova, E. A., Voznesenskaya, А. А., Викторовна, Ф. Н., & Troshina, E. A. (2023) · Clinical and experimental thyroidology · doi:10.14341/ket12759 · Cited by 1 · see citing works
Scappaticcio, L., Martino, N. D., Ferrazzano, P., Nuzzo, M. D., Volatile, A., Caruso, P., Longo, M., Verde, M. L., Maiorino, M. I., FRANCISCIS, P. D., et al. (2025) · Endocrine Practice · doi:10.1016/j.eprac.2025.12.021 · Cited by 1 · see citing works
Hypothyroidism and pregnancy: Diagnostic and therapeutic dilemmas in modern management algorithms
Омариевна, У. Ф., Demidova, T. Y., & Расуловна, Б. А. (2025) · FOCUS Endocrinology · doi:10.62751/2713-0177-2025-6-3-09
Mohammadi, R., Imanpour, V., Ardian, N., & Goodarzi-Khoigani, M. (2026) · Iranian Journal of Nursing and Midwifery Research · doi:10.4103/ijnmr.ijnmr_308_23
Refractory hypothyroidism: Diagnostic evaluation and management strategies
Mavromati, M., Jarlborg, P., Demarchi, M. S., & Leboulleux, S. (2026) · Annales d Endocrinologie · doi:10.1016/j.ando.2026.102489
- Authors
- Cappelli, C., Negro, R., Pirola, I., Gandossi, E., Agosti, B., & Castellano, M.
- Affiliations
- University of Brescia (IT)
- Ospedale Vito Fazzi (IT)
- Corresponding author
- Cappelli, Carlo
- Venue
- Gynecological Endocrinology
- Publisher
- Informa UK Limited
- Published
- 2015-11-20
- Volume
- 32
- Issue
- 4
- Pages
- 290-292
- ISSN
- 0951-3590 (ISSN-L)
- 1473-0766
- OpenAlex
- W2177083183
- Cited by
- 24
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 2
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Gynecological Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion, other-oa)
- 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, hypothyroidism in pregnancy, liquid formulation, tablet formulation, thyroid hormone replacement, dose adjustment, thyroid-stimulating hormone, free thyroxine
- MeSH terms
- Adult, Female, Humans, Hypothyroidism, Pregnancy, Pregnancy Complications, Retrospective Studies, Thyroxine, Young Adult
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
