Ulcerative colitis as a novel cause of increased need for levothyroxine
Open accessAbstract
Background: Thyroxine absorption takes place at small intestine level and several disorders affecting this intestinal tract lead to thyroxine malabsorption. An increased need for thyroxine was also observed in gastric disorders due to the variations in drug dissolution and/or in its ionization status. Ulcerative colitis (UC) is an inflammatory bowel disease that has been postulated as potential cause of increased need for thyroxine but there is a lack of evidence on this topic. This study was aimed at measuring the thyroxine requirement in hypothyroid patients bearing UC. Patients and Methods: Among 8573 patients with thyroid disorders consecutively seen in our referral center from 2010 to 2017, we found 34 patients with a definite diagnosis of UC. Thirteen of them were hypothyroid (12 F/1 M; median age=53 years), bearing UC during the remission phase and in need for thyroxine treatment thus representing the study group. The dose of T4 required by UC patients has been compared to the one observed in 51 similarly treated age- and weight-matched patients, compliant with treatment and clearly devoid from any gastrointestinal and /or pharmacological interference. Results: To reach the target serum TSH, the dose of thyroxine owed to be increased in twelve out of thirteen (92%) hypothyroid patients with ulcerative colitis. The median thyroxine dose required by UC patients was 1.54 µg/kg weight/day, that is 26% higher than in the control patients to reach a similar TSH (1.23 µg/kg weight/day; p=0.0002). Since half of our study group consisted of patients aged over 60 years we analyzed the effect of age upon subdivision in two classes. Six out of seven (86%) adult patients required more T4 than the one in the respective control group (1.61 vs 1.27 µg/kg weight/day; +27%; p<0.0001). An increased dose (+17%; p=0.0026) but to a lesser extent, was also required in all patients over 60 years as compared to the control group. Conclusions: In almost all hypothyroid patients with ulcerative colitis, the therapeutic dose of thyroxine is increased. Therefore, ulcerative colitis, even during clinical remission, should be included among the gastrointestinal causes of increased need for oral thyroxine.
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?
The levothyroxine requirement was 26% higher in 12 out of the 13 patients with ulcerative colitis examined, even if the disease was in clinical remission.
“The levothyroxine requirement was 26% higher in 12 out of the 13 patients with ulcerative colitis examined, even if the disease was in clinical remission.”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [118]
An increased need for levothyroxine has also been observed in patients with ulcerative colitis.
“An increased need for levothyroxine has also been observed in patients with ulcerative colitis (118).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [118]
Intestinal lymphangiectasia and ulcerative colitis have been revealed to cause impaired LT4 absorption, although the underlying mechanisms remain unclear.
“Some other intestinal dysfunctions, such as intestinal lymphangiectasia and ulcerative colitis, have been revealed to cause impaired LT4 absorption, although the underlying mechanisms remain unclear (58, 59).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [59]
To reach an equivalent TSH level, LT4 dose must be higher if the patient's intestinal tract is affected by ulcerative colitis, coeliac disease, lactose intolerance, gastritis (especially H. pylori-related and autoimmune gastritis), and Giardia lamblia infection.
“To reach an equivalent TSH level, the LT4 dose must be higher if the patient’s intestinal tract is affected by ulcerative colitis [ 49 ], coeliac disease [ 50 ], lactose intolerance [ 51 ], and gastritis (especially Helicobacter pylori –related gastritis and autoimmune gastritis) [ 43 , 52 – 54 ], and infections with Giardia lamblia (giardiasis) [ 55 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [49]
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
Ungaro, R. C., Mehandru, S., Allen, P. B., Peyrin‐Biroulet, L., & Colombel, J. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32126-2 · Cited by 3,656 · see citing works
Ford Alexander, C., Paul, M., Hanauer Steven, B., 谭蓓, & Dong, W. Z. (2001) · Cited by 3,021 · see citing works
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
Inflammatory bowel disease: clinical aspects and established and evolving therapies
Baumgart, D. C., & Sandborn, W. J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60751-x · Cited by 1,921 · see citing works
Bianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0455 · Cited by 1,853 · see citing works
Lewis, J. D., Chuai, S., Nessel, L. A., Lichtenstein, G. R., Aberra, F. N., & Ellenberg, J. H. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20520 · Cited by 965 · see citing works
Increased Circulating Pro-Inflammatory Cytokines and Th17 Lymphocytes in Hashimoto’s Thyroiditis
Figueroa‐Vega, N., Alfonso-Pérez, M., Benedicto, I., Sánchez‐Madrid, F., González‐Amaro, R., & Marazuela, M. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1719 · Cited by 268 · see citing works
Pathologic Features and Clinical Significance of ???Backwash??? Ileitis in Ulcerative Colitis
Haskell, H., Andrews, C. W., Reddy, S. I., Dendrinos, K., Farraye, F. A., Stucchi, A. F., Becker, J. M., & Odze, R. D. (2005) · The American Journal of Surgical Pathology · doi:10.1097/01.pas.0000176435.19197.88 · Cited by 247 · 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
Alternate Pathways of Thyroid Hormone Metabolism
Wu, S.-Y., Green, W. L., Huang, W.-S., Hays, M. T., & CHOPRA, I. J. (2005) · Thyroid · doi:10.1089/thy.2005.15.943 · Cited by 207 · see citing works
Salicylate-induced increases in free triiodothyronine in human serum
Larsen, P. R. (1972) · Journal of Clinical Investigation · doi:10.1172/jci106905 · Cited by 181 · 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
Self-citationGut microbiota and Hashimoto’s thyroiditis
Virili, C., Fallahi, P., Antonelli, A., Benvenga, S., & Centanni, M. (2018) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-018-9467-y · Cited by 157 · see citing works
Self-citationDelayed Intestinal Absorption of Levothyroxine
BENVENGA, S., BARTOLONE, L., SQUADRITO, S., GIUDICE, F. L., & TRIMARCHI, F. (1995) · Thyroid · doi:10.1089/thy.1995.5.249 · Cited by 156 · see citing works
Mucus Layers in Inflammatory Bowel Disease
Johansson, M. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000117 · Cited by 148 · see citing works
Localization of human thyroxine absorption
HAYS, M. T. (1991) · Thyroid · doi:10.1089/thy.1991.1.241 · Cited by 138 · 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
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
“Several pharmacokinetic and clinical studies enlightened the role of various drugs and gastrointestinal diseases in determining an increased need for LT4, by interfering with the steps key to the efficacy of this treatment (4).”
BackgroundSelf-citationMesalazine preparations for the treatment of ulcerative colitis: Are all created equal?
Ye, B. (2015) · World Journal of Gastrointestinal Pharmacology and Therapeutics · doi:10.4292/wjgpt.v6.i4.137 · Cited by 109 · see citing works
Small Intestinal Bacterial Overgrowth
Adike, A., & DiBaise, J. K. (2017) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2017.09.008 · Cited by 106 · see citing works
Virili, C., & Centanni, M. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.01.053 · Cited by 105 · see citing works
Primary and secondary thyroid hormone transporters
Kinne, A., Schülein, R., & Krause, G. (2011) · Thyroid Research · doi:10.1186/1756-6614-4-s1-s7 · Cited by 94 · 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
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-citationBüning, C., Geissler, N., Prager, M., Sturm, A., Baumgart, D. C., Büttner, J., Bühner, S., Haas, V. K., & Lochs, H. H. (2012) · Inflammatory Bowel Diseases · doi:10.1002/ibd.22909 · Cited by 82 · see citing works
When 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
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-citationL-Thyroxine Absorption in Patients with Short Bowel
STONE, E., LEITER, L. A., LAMBERT, J. R., SILVERBERG, J. D. H., JEEJEEBHOY, K. N., & BURROW, G. N. (1984) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-59-1-139 · Cited by 66 · see citing works
THYROXINE EXCRETION, A POSSIBLE CAUSE OF GOITER
Middlesworth, L. V. (1957) · Endocrinology · doi:10.1210/endo-61-5-570 · Cited by 65 · see citing works
Virili, C., Giovanella, L., Fallahi, P., Antonelli, A., Santaguida, M. G., Centanni, M., & Trimboli, P. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00010 · Cited by 61 · see citing works
Self-citationThyroxine 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., Ruffilli, I., & Antonelli, A. (2016) · BMC Gastroenterology · doi:10.1186/s12876-016-0439-y · Cited by 46 · see citing works
Ferrari, S. M., Fallahi, P., Santaguida, G., et al. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.07.006 · Cited by 38 · see citing works
Impairment of Small Intestinal Function in Ulcerative Colitis: Role of Enteric Innervation
Mourad, F. H., Barada, K. A., & Saadé, N. E. (2016) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjw162 · Cited by 34 · see citing works
Santaguida, M. G., Nardo, S. J. D., Duca, S. C. D., Lococo, E., Virili, C., Gargano, L., Lenti, L., & Centanni, M. (2011) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2011.04419.x · Cited by 31 · see citing works
Self-citationTHYROXINE METABOLISM IN UNTREATED AND TREATED PANCREATIC STEATORRHEA*
Hiss, J. M., & Dowling, J. T. (1962) · Journal of Clinical Investigation · doi:10.1172/jci104578 · Cited by 31 · 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
Seppel, T., Rose, F., & Schlaghecke, R. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1211442 · Cited by 30 · see citing works
Betterle, C., Garelli, S., Coco, G., & Burra, P. (2014) · Autoimmunity Highlights · doi:10.1007/s13317-013-0055-6 · Cited by 30 · see citing works
Abnormal Thyroid Function Test Results in Patients Taking Salsalate
McConnell, R. (1992) · JAMA · doi:10.1001/jama.1992.03480090090033 · 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
Canettieri, G., Franchi, A., Sibilla, R., Guzman, E., & Centanni, M. (2004) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0330051 · Cited by 19 · see citing works
Self-citationLobasso, A., Nappi, L., Barbieri, L., Peirce, C., Ippolito, S., Arpaia, D., Rossi, F. W., de Paulis, A., & Biondi, B. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00241 · Cited by 14 · see citing works
Drug Absorption in Gastrointestinal Disease and Surgery
Gubbins, P. O., & Bertch, K. E. (1989) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.1989.tb04140.x · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Optimal thyroid hormone replacement
Jonklaas, J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab031 · Cited by 89 · 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
Caron, 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
Levothyroxine therapy in thyrodectomized patients
Miccoli, P., Materazzi, G., & Rossi, L. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.626268 · Cited by 40 · see citing works
Castellana, M., Castellana, C., Giovanella, L., & Trimboli, P. (2020) · Endocrine · doi:10.1007/s12020-019-02185-4 · Cited by 41 · 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
“The hypothetical mechanism for the higher requirement is the small intestine reduced transit time that often characterizes these patients (118).”
Self-citationManaging 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
“For example, one study showed that people with ulcerative colitis and hypothyroidism required doses of LT4 that were 26% higher compared with those without ulcerative colitis [81].”
BackgroundRefractory 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
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
Self-citationAlhassan, A. A., Alidrisi, H. A., & Mansour, A. A. (2023) · Cureus · doi:10.7759/cureus.37776 · Cited by 6 · see citing works
Decreased expression of ileal thyroid hormone transporters in a hypothyroid patient: a case report
Chung, C. W., Mo, E. Y., Jung, G. S., Kim, Y. H., Cho, S. W., Park, D. J., Bae, J. M., & Park, Y. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.664839 · Cited by 5 · see citing works
“When persistent hypothyroidism despite oral LT4 therapy is encountered, the first step is to check possible causes including dietary or medicinal interference, gastrointestinal malabsorption, nephrotic syndrome, hepatic disease, cystic fibrosis, and pregnancy (7, 8, 29).”
Background
- Authors
- Virili, C., Stramazzo, I., Santaguida, M. G., Bruno, G., Brusca, N., Capriello, S., Cellini, M., Severi, C., Gargano, L., & Centanni, M.
- Affiliations
- Sapienza University of Rome (IT)
- Ospedale Santa Maria Goretti (IT)
- Corresponding author
- Virili, Camilla
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2019-04-16
- Volume
- 10
- Pages
- 233-233
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC6476912
- OpenAlex
- W2937453229
- Cited by
- 20
- References
- 49
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- ulcerative colitis, hypothyroidism, levothyroxine dose, gastrointestinal diseases, inflammatory bowel disease, thyroid function
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
