Adherence to levothyroxine treatment among patients with hypothyroidism: a northeastern Italian survey
Open accessAbstract
Background: A significant number of patients showed sub-optimal adherence to LT4 therapy, mainly due to the fact that they had to postpone their breakfast of at least 30 minutes. The aim of this observational cross-sectional study was to assess the therapeutic compliance of patients on LT4 treatment and secondly to verify the preference of a lifetime treatment in tablets or liquid formulation. Patients and Methods: To all the participant (ambulatory care patients had to be eighteen or older, affected by hypothyroidism on LT4 substitutive treatment both in tablet or liquid solution) was administered the eight-item Morisky Medication Adherence Scale (MMAS-8). The MMAS-8 questionnaire has been supplemented with other three items in order to specifically evaluate medication preference between tablet and liquid LT4 formulation for long life treating. Results: A total of 320 patients (272 female) with median age of 47.9±15.6 yrs (range 20-78) completed the MMAS-8 questionnaire. We showed a high adherence (87% of the subjects) to therapeutic compliance both for patients on tablets than those on liquid LT4 formulation, although significant difference are emerged. Patients assuming LT4 in tablet forgot more frequently medication(s) (p<0.001), felt hassled about sticking to their treatment plan (p<0.001) and had difficulty to remember to take all their medication(s) (p<0.001) than those on liquid LT4 treatment. Conclusions: We showed a high adherence to levothyroxine treatment both for tablets than for liquid formulation. The possibility to take LT4 treatment at breakfast represent the best convenience for the majority of patients.
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 database study conducted in the United States and a questionnaire study conducted in Italy showed that the low and medium adherence rates were 54.1% and 64.5%, respectively.
“Similarly, a database study conducted in the United States and a questionnaire study conducted in Italy showed that the low and medium adherence rates were 54.1% and 64.5%, respectively (124, 125).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [124]
Liquid LT4 might improve patient compliance compared with tablets.
“Cappelli et al revealed that liquid LT4 might improve patient compliance compared with tablets (124).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [124]
Patients taking solution adhered much better to LT4 treatment than patients taking tablet (P < .001).
“As discussed under “Pseudomalabsorption,” patients taking solution adhered much better to LT4 treatment than patients taking tablet (P < .001) (124).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [124]
The major factor contributing to the discrepancy in compliance is the coingestion of breakfast and liquid LT4.
“The major factor contributing to the discrepancy is the coingestion of breakfast and liquid LT4.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [124]
Taken together, the convenience of the liquid preparation improves patient compliance.
“Taken together, these data show that the convenience of the liquid preparation improves patient compliance.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [124]
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
1 retracted
Retracted: Predictive Validity of a Medication Adherence Measure in an Outpatient Setting
Morisky, D. E., Ang, A., Krousel‐Wood, M., & Ward, H. J. (2008) · The Journal of Clinical Hypertension · doi:10.1111/j.1751-7176.2008.07572.x · Cited by 2,877 · see citing works
RetractedConcurrent and Predictive Validity of a Self-reported Measure of Medication Adherence
Morisky, D. E., Green, L. W., & Levine, D. M. (1986) · Medical Care · doi:10.1097/00005650-198601000-00007 · Cited by 5,304 · see citing works
The Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824 · 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
Thyroid Status, Disability and Cognitive Function, and Survival in Old Age
Gussekloo, J. (2004) · JAMA · doi:10.1001/jama.292.21.2591 · Cited by 899 · see citing works
Comparison of drug adherence rates among patients with seven different medical conditions
Briesacher, B. A., Andrade, S. E., Fouayzi, H., & Chan, K. A. (2008) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.28.4.437 · Cited by 587 · see citing works
Fade, J. V., Franklyn, J. A., Cross, K. W., Jones, S. C., & Sheppard, M. C. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb01739.x · Cited by 567 · see citing works
The Spectrum of Thyroid Disorders in an Iodine-Deficient Community: The Pescopagano Survey 1
Aghini-Lombardi, F., Antonangeli, L., Martino, E., Vitti, P., Maccherini, D., Leoli, F., Rago, T., Grasso, L., Valeriano, R., Balestrieri, A., et al. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.2.5508 · Cited by 362 · see citing works
Moon, S. J., Lee, W.-Y., Hwang, J. S., Hong, Y. P., & Morisky, D. E. (2017) · PLOS ONE · doi:10.1371/journal.pone.0187139 · Cited by 293 · see citing works
The Spectrum of Thyroid Disorders in an Iodine-Deficient Community: The Pescopagano Survey
Aghini-Lombardi, F. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.2.561 · Cited by 288 · 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
(1993) · Europe PMC (PubMed Central) · Cited by 167 · see citing works
Vita, R., Saraceno, G., Trimarchi, F., & Benvenga, S. (2013) · Endocrine · doi:10.1007/s12020-012-9772-2 · Cited by 91 · 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
Self-citationWhen 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
Guglielmi, R., Grimaldi, F., Negro, R., Frasoldati, A., Misischi, I., Graziano, F., Cipri, C., Guastamacchia, E., Triggiani, V., & Papini, E. (2018) · Endocrine, Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530318666180125155348 · Cited by 57 · see citing works
Adherence to thyroid hormone replacement therapy: a retrospective, claims database analysis
Hepp, Z., Wyne, K. L., Manthena, S. R., Wang, S., & Gossain, V. V. (2018) · Current Medical Research and Opinion · doi:10.1080/03007995.2018.1486293 · Cited by 48 · 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
Randomised controlled trial of a hypothyroid educational booklet to improve thyroxine adherence.
Crilly, M., & Esmail, A. (2005) · Europe PMC (PubMed Central) · Cited by 37 · see citing works
Delea, T. E., Hagiwara, M., Dalal, A. A., Stanford, R. H., & Blanchette, C. M. (2008) · Current Medical Research and Opinion · doi:10.1185/03007990802534020 · Cited by 31 · see citing works
Juch, H., Lupattelli, A., Ystrøm, E., Verheyen, S., & Nordeng, H. (2016) · Patient Education and Counseling · doi:10.1016/j.pec.2016.04.006 · Cited by 30 · see citing works
Fallahi, P., Ferrari, S. M., & Antonelli, A. (2016) · Endocrine Practice · doi:10.4158/ep161545.or · Cited by 28 · see citing works
Pirola, I., Gandossi, E., Brancato, D., Marini, F., Cristiano, A., Delbarba, A., Agosti, B., Castellano, M., & Cappelli, C. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-018-0867-3 · Cited by 21 · see citing works
Self-citationAn Italian Survey of Compliance With Major Guidelines for L-Thyroxine of Primary Hypothyroidism
Vezzani, S., Giannetta, E., Altieri, B., Barbonetti, A., Bellastella, G., Certo, R., Cignarelli, A., Cinti, F., D’Andrea, S., Dalmazi, G. D., et al. (2018) · Endocrine Practice · doi:10.4158/ep-2017-0159 · Cited by 20 · see citing works
Liquid levothyroxine and its potential use
Formenti, A. M., Daffini, L., Pirola, I., Gandossi, E., Cristiano, A., & Cappelli, C. (2015) · HORMONES · doi:10.14310/horm.2002.1579 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
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
Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2019) · Drugs in Context · doi:10.7573/dic.212597 · Cited by 40 · see citing works
Update of hypothyroidism and its management in Unani medicine
Alam, M. A., Quamri, M. A., Sofi, G., & Ansari, S. (2020) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2020-0121 · Cited by 31 · see citing works
Adherence to Levothyroxine Tablet in Patients with Hypothyroidism
Kumar, R., & Shaukat, F. (2019) · Cureus · doi:10.7759/cureus.4624 · Cited by 32 · see citing works
Medication Adherence Measurement in Chronic Diseases: A State-of-the-Art Review of the Literature
Dunbar‐Jacob, J. M., & Zhao, J. (2025) · Nursing Reports · doi:10.3390/nursrep15100370 · Cited by 28 · see citing works
Yavuz, D. G., Yazan, C. D., Hekimsoy, Z., Aydın, K., Gökkaya, N., Ersoy, C., Akalın, A., Topaloğlu, Ö., Aydoğan, B. İ., Dilekçi, E. N. A., et al. (2022) · Clinical Endocrinology · doi:10.1111/cen.14787 · Cited by 19 · see citing works
Hallit, S. R., Haddad, C., Sacre, H., Rahme, C., Akel, M., Saleh, N., Chalhoub, C., & Salameh, P. (2020) · Clinical Epidemiology and Global Health · doi:10.1016/j.cegh.2020.08.014 · Cited by 16 · see citing works
Managing symptoms in hypothyroid patients on adequate levothyroxine: a narrative review
Razvi, S., Mrabeti, S., & Luster, M. (2020) · Endocrine Connections · doi:10.1530/ec-20-0205 · Cited by 15 · see citing works
“In addition, the likelihood of sub-optimal adherence to LT4 appears to vary according to the preparation prescribed [75,77].”
BackgroundMehuys, E., Lapauw, B., T'Sjoen, G. G., Christiaens, T. C., Sutter, A. D., Steurbaut, S., Tongelen, I. V., & Boussery, K. (2023) · Thyroid · doi:10.1089/thy.2023.0066 · Cited by 17 · 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
Gottwald‐Hostalek, U., & Razvi, S. (2022) · Current Medical Research and Opinion · doi:10.1080/03007995.2022.2071059 · Cited by 10 · 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
Alofi, R. M., Alrohaily, L. S., Jan, R. A., Alsaedi, S. L., Mahrous, F. A., & Alreefi, M. M. (2023) · Cureus · doi:10.7759/cureus.40686 · Cited by 9 · see citing works
Heim, M., Nixon, I. J., Emmerson, E., & Callanan, A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.997288 · Cited by 10 · see citing works
Díez, J. J., Iglesias, P., & Gómez-Mateos, M. Á. (2021) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2021.04.010 · Cited by 9 · see citing works
Long-Term Adherence to Levothyroxine Replacement Therapy in Thyroidectomized Patients
Bocale, R., Desideri, G., Barini, A., D’Amore, A., Boscherini, M., Necozione, S., & Lombardi, C. P. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11154296 · Cited by 8 · see citing works
Kindi, R. M. A., Riyami, R. A. A., Juma, S. Y., & Kiyumi, M. I. A. (2023) · Current Medical Research and Opinion · doi:10.1080/03007995.2023.2250256 · Cited by 6 · see citing works
Díez, J. J., Iglesias, P., & Gómez-Mateos, M. Á. (2022) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2022.03.001 · Cited by 5 · see citing works
The Relationship Between Brain Fog and Medication Adherence for Individuals With Hypothyroidism
Haskard‐Zolnierek, K. B., Wilson, C., Pruin, J., Deason, R. G., & Howard, K. J. (2021) · Clinical Nursing Research · doi:10.1177/10547738211038127 · Cited by 5 · see citing works
Cappelli, C., Pirola, I., & Castellano, M. (2020) · Case Reports in Endocrinology · doi:10.1155/2020/8858887 · Cited by 5 · see citing works
Self-citationWillems, J. I. A., van Twist, D. J. L., Helmich, F., Sluiter, T., Medici, M., Peeters, R. P., & van Wijngaarden, R. F. A. T.-D. L. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf686 · Cited by 4 · see citing works
Topaloğlu, Ö., Yavuz, A., & Aylıkcı, A. B. T. (2021) · International Journal of Clinical Practice · doi:10.1111/ijcp.14312 · Cited by 4 · see citing works
Díez, J. J., Anda, E., Alcázar, V., Galofré, J. C., Familiar, C., Pamplona, M. J., Martínez, S. G., Ruiz, A. H., Alhambra, M. R., Planas, A., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1652862 · Cited by 3 · see citing works
Dirikoç, A., Genç, B., Özdemir, D., Tam, A. A., Topaloğlu, O., Ersoy, R., & Çakır, B. (2021) · Ankara Medical Journal · doi:10.5505/amj.2021.24572 · Cited by 3 · see citing works
Breakfast Habits in Patients Using Levothyroxine: Patient Experiences and Preferences
Willems, J. I. A., van Twist, D. J. L., Luu, I. H. Y., Bianchi, R., Peeters, R. P., & van Wijngaarden, R. F. A. T.-D. L. (2024) · Journal of the Endocrine Society · doi:10.1210/jendso/bvae180 · Cited by 3 · see citing works
Kim, J. H., Shin, J., Kim, M. S., & Moon, J. H. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae751 · Cited by 1 · 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
Poojary, B., Wilson, M. M., Jose, R., Sam, S. P., & George, A. E. (2023) · Indonesian Journal of Pharmacology and Therapy · doi:10.22146/ijpther.9375 · Cited by 1 · see citing works
Comparison of tablet versus liquid ethanol-free Levothyroxine in thyroidectomised patients
Croce, L., Chytiris, S., Teliti, M., Bertini, J., Pizzuto, L., Molin, M. D., Limiroli, M., Calì, B., Magri, F., & Rotondi, M. (2025) · Endocrine · doi:10.1007/s12020-025-04375-9 · Cited by 1 · see citing works
Valladales‐Restrepo, L. F., Londoño‐Cano, D. A., Muñoz-Velez, C. M., Soto-Romero, L. M., Tafur, M., Rojas-Varón, M. J., & Machado‐Alba, J. E. (2026) · Endocrine · doi:10.1007/s12020-025-04488-1 · Cited by 1 · see citing works
Nagendiran, A., Kalaimani, K., & Anantharani, K. (2021) · International journal of Nutrition Pharmacology Neurological Diseases · doi:10.4103/ijnpnd.ijnpnd_7_21 · Cited by 1 · see citing works
Hằng, P. T., & Bảy, N. Q. (2022) · Tạp chí Y học Việt Nam · doi:10.51298/vmj.v508i2.1603
Song, Y., Tao, M., & Wang, L. (2023) · PubMed Central
Not What the Doctor Ordered: A Real-World Analysis of Levothyroxine Use
Kawkgi, O. M. E. (2023) · Clinical Thyroidology · doi:10.1089/ct.2023;35.495-497
Medication-Nonadherent Hypothyroidism Requiring Frequent Primary Care Visits to Achieve Euthyroidism
Kaul, S. (2024) · Federal Practitioner · doi:10.12788/fp.0461
Kamrul-Hasan, A. B. M., Mustari, M., Hannan, M. A., Hoque, M. A., Chowdhury, E. U. R., Kabir, M. L., Kabir, M. A., Asaduzzaman, M., Hannan, M. A., Mondal, E., et al. (2024) · Bangladesh Journal of Endocrinology and Metabolism · doi:10.4103/bjem.bjem_17_24 · Cited by 1 · see citing works
Hoermann, R., & Dietrich, J. W. (2025) · Springer eBooks · doi:10.1007/978-981-96-3682-2_11
Awareness of Thyroid Disorders and Newborn Screening in Primigravida – A Questionnaire-based Study
Gupta, D., Hegde, A., Kollampare, S., Shenoy, R., & Rao, S. (2025) · Journal of Nature and Science of Medicine · doi:10.4103/jnsm.jnsm_213_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
Kartal, Ş., Emre, N., & Okta, M. (2026) · Eurasian Journal of Family Medicine · doi:10.33880/ejfm.2026150106 · Cited by 1 · see citing works
Gao, H., Chen, H., Chen, X., Lu, X., Bai, D., Yuan, Y., Hou, C., & Gao, J. (2026) · Health Psychology Review · doi:10.1080/17437199.2026.2667533
Razvi, S. (2026) · Current Medical Research and Opinion · doi:10.1080/03007995.2026.2740285
- Authors
- Cappelli, C., Castello, R., Marini, F., Paoletta, A., Marchetti, M., Saullo, M., Cristiano, A., Pirola, I., Gandossi, E., Ferlin, A., & Castellano, M.
- Affiliations
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- Ospedale San Bassiano (IT)
- Corresponding author
- Cappelli, Carlo
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-11-23
- Volume
- 9
- Pages
- 699-699
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC6265311
- OpenAlex
- W2900804332
- Cited by
- 43
- References
- 25
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 5 · 2020: 4 · 2019: 3
- FWCI
- 3.44
- 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)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacy and Medical Practices
- Keywords
- levothyroxine, hypothyroidism, medication adherence, Morisky Medication Adherence Scale, drug preference, breakfast timing, forgetfulness, treatment burden
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
