Impact of Lithium on Efficacy of Radioactive Iodine Therapy for Graves’ Disease: A Cohort Study on Cure Rate, Time to Cure, and Frequency of Increased Serum Thyroxine After Antithyroid Drug Withdrawal
Abstract
CONTEXT: Radioactive iodine (RAI) is a common therapy for hyperthyroidism due to Graves' disease. A small but significant proportion of patients have recurrence of hyperthyroidism after RAI therapy. Lithium might increase RAI effectiveness by increasing RAI retention in the thyroid. However, whether lithium favorably affects the long-term outcome of RAI therapy is still a matter of argument. OBJECTIVE: The objective of the study was to compare the efficacy of RAI given with or without concomitant lithium treatment. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted at a tertiary university center. PATIENTS: Six hundred fifty-one patients with newly diagnosed Graves' disease participated in the study. INTERVENTION: Two hundred ninety-eight patients were treated with RAI plus lithium (900 mg/d for 12 d) and 353 with RAI alone. MAIN OUTCOME MEASURES: Proportion of cured patients and time to achieve cure of hyperthyroidism during 1 yr of follow-up was measured. RESULTS: PATIENTS treated with RAI plus lithium had a higher cure rate (91.0%) than those treated with RAI alone (85.0%, P = 0.030). In addition, patients treated with RAI plus lithium were cured more rapidly (median 60 d) than those treated with RAI alone (median 90 d, P = 0.000). Treatment with lithium prevented the serum free T(4) increase after methimazole withdrawal and RAI therapy. Side effects after RAI therapy occurred in a subset of patients and were mild, transient, and without differences in the two groups. CONCLUSIONS: RAI combined with lithium is safe and more effective than RAI alone in the cure of hyperthyroidism due to Graves' disease.
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Over several decades, reports have indicated that pretreatment with lithium reduces the activity of RAI necessary for cure of Graves' hyperthyroidism and may prevent the thyroid hormone increase seen upon ATD withdrawal.
“Over several decades, there have been reports that pretreatment with lithium reduces the activity of RAI necessary for cure of Graves' hyperthyroidism and may prevent the thyroid hormone increase seen upon ATD withdrawal (81)(82)(83).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [83]
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“It has been reported that several factors may contribute to the treatment outcome of GH besides thyroid weight and 24-h 131I uptake, such as patient’s age, coexisting thyroid nodules, prior anti-thyroid drugs, duration and severity of hyperthyroidism, titer of TRAb, iodine uptake peak, and complications [3,10-18].”
BackgroundIs lithium an effective adjunct therapy for radioiodine therapy for hyperthyroidism?
Vanderpump, M. P. J. (2012) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2012.04425.x · Cited by 4 · see citing works
Ahmed, F. W., Kirresh, O. Z., Majeed, M. S., Iftikhar, M., & Sajid, M. S. (2021) · Endocrine Research · doi:10.1080/07435800.2021.1924769 · Cited by 4 · see citing works
Lithium Therapy and Thyroid Disorders
Cheng, D. T. D. (2013) · Journal of Thyroid Disorders & Therapy · doi:10.4172/2167-7948.1000125 · Cited by 5 · see citing works
“[44] determined that in patients who were given lithium (900 mg/ day x 12 days) starting five days prior to iodine-131 therapy, there was a higher cure rate than those treated with radioactive iodine alone [44].”
BackgroundSekulić, V., Rajic, M., Mž, V., Ilić, S., Stević, M., & Kojić, M. (2015) · PubMed · doi:10.1967/s002449910300 · Cited by 4 · see citing works
Kim, K. J., Song, E., Kim, M., Kwon, H., Ku, E. J., Kwon, H. W., Yoon, J. H., Lee, E. K., Lee, W. W., Park, Y. J., et al. (2025) · Endocrinology and Metabolism · doi:10.3803/enm.2025.2464 · Cited by 3 · see citing works
“In cases where ATD use is not feasible and rapid control of thyroid function is required, alternative approaches such as inorganic iodine [55], lithium [56,57], or therapeutic plasma exchange [58-60] have been suggested.”
Wang, Y., Hong, L., Yang, C., Lv, G., Wang, K., Huang, X., & Shen, H. (2023) · Endocrine Connections · doi:10.1530/ec-23-0429 · Cited by 3 · see citing works
“Previous studies explored factors such as age, sex, GD disease duration, history of ATD before RAI therapy, RAI dose, half-life, and TRAb positivity before treatment (10, 11).”
BackgroundTachibana, S., Yamashita, H., & Yanase, T. (2017) · Journal of Endocrinology and Metabolism · doi:10.14740/jem394w · Cited by 3 · see citing works
The evolution and hotspots of radioactive iodine therapy in hyperthyroidism: a bibliometric analysis
Chen, S., Gou, R.-Q., & Zhang, Q. (2024) · Nuclear Medicine Communications · doi:10.1097/mnm.0000000000001940 · Cited by 3 · see citing works
Graves’ Disease and Toxic Nodular Goiter (Plummer’s Disease)
Barczyński, M. (2021) · Springer eBooks · doi:10.1007/978-3-030-84737-1_3 · Cited by 2 · see citing works
LITHIUM AS AN ADJUVANT IN THE POSTOPERATIVE ABLATION OF REMNANT TISSUE IN LOW RISK THYROID CARCINOMA
Yamazaki, C. A., Padovani, R. D. P., Biscolla, R. P. M., Ikejiri, E. S., Matsumura, L. K., Maciel, R. M. B., Furlanetto, R. P., Marchetti, R. R., & Castiglioni, M. L. V. (2012) · Thyroid · doi:10.1089/thy.2011-0372 · Cited by 2 · see citing works
Lu, J., Chen, K., Shih, S., Wen, F.-Y., Wu, W.-C., Chen, T.-C., & Hu, F. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.11.005 · Cited by 2 · see citing works
Radioiodine Therapy of Hyperthyroidism in Graves’ Disease
Wong, W. Y., & Goh, A. S. W. (2012) · Medical radiology · doi:10.1007/174_2012_674 · Cited by 2 · see citing works
Lithium and the application of its compounds in different fields of medicine
Kiełczykowska, M., & Musik, I. (2014) · Journal of Elementology · doi:10.5601/jelem.2014.19.3.736 · Cited by 2 · see citing works
“Owing to its ability to inhibit secretion of thyroid hormones, lithium has been studied as a possible adjuvant in patients with thyroid diseases subjected to radioiodine therapy (bAl et al. 2002, liu et al. 2006, boGAZZi et al. 2010, oSZukoWSkA et al. 2010).”
Background131I Radioiodine therapy in Graves’ disease: Us et coutumes, controversies and guidelines
Bardet, S. (2020) · Médecine Nucléaire · doi:10.1016/j.mednuc.2020.06.001 · Cited by 1 · see citing works
Safety and Effectiveness of Lithium Therapy in Patients With Graves' Disease
Çavdar, Ü., Eren, Ö., Karaıslı, S., Ertürk, M. S., & Pamuk, B. Ö. (2025) · Clinical Endocrinology · doi:10.1111/cen.70022 · Cited by 1 · see citing works
Surgical Management of Hyperthyroidism
Orloff, L. A., & Shindo, M. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-66127-0.00008-9 · Cited by 2 · see citing works
Płazińska, M. T., Czarnywojtek, A., Sawicka‐Gutaj, N., Woliński, K., Krela‐Kaźmierczak, I., Zgorzalewicz-Stachowiak, M., Miechowicz, I., Gut, P., Florek, E., Skonieczna‐Żydecka, K., et al. (2021) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/126287 · Cited by 1 · see citing works
Abd‐ElGawad, M., Abdelgalil, M. S., Mabrouk, M. A., Saed, S. A. A., Salama, M. K., & Gadelmawla, A. F. (2025) · BMC Endocrine Disorders · doi:10.1186/s12902-024-01821-z · Cited by 1 · see citing works
“For example, Vannucchi et al. [46] tested the effect of lithium as an add-on treatment in a multinodular goiter, while Bogazz et al. (2010) [47], Sekulić et al. [37], and Tham-charoenvipas et al. [41] Included patients with Graves’ disease.”
Kim, K. J., Song, E., Kim, M., Kwon, H., Ku, E. J., Kwon, H. W., Yoon, J. H., Lee, E. K., Lee, W. W., Park, Y. J., et al. (2025) · International Journal of Thyroidology · doi:10.11106/ijt.2025.18.1.65 · Cited by 1 · see citing works
The Use of Lithium as an Adjuvant to Radioiodine in the Treatment of Thyroid Cancer
Zemskova, M., & Skarulis, M. C. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3314-3_61 · Cited by 1 · see citing works
Bartalena, L. (2018) · Endocrinology · doi:10.1007/978-3-319-45013-1_17
Self-citationPitlick, J. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-79007-9.00054-4
Antithyroid Drugs for Thyrotoxicosis
Bartalena, L. (2022) · doi:10.1093/med/9780198870197.003.0059
Self-citationBartalena, L. (2016) · Endocrinology · doi:10.1007/978-3-319-29195-6_17-1
Self-citationLe, T., & Francis, G. L. (2016) · Encyclopedia of Inflammatory Diseases · doi:10.1007/978-3-0348-0620-6_200-1
Le, T., & Francis, G. L. (2016) · Compendium of Inflammatory Diseases · doi:10.1007/978-3-7643-8550-7_200
El‐Mallakh, R. S., & Gao, Y. (2012) · Side effects of drugs annual · doi:10.1016/b978-0-444-59499-0.00003-9
Zannat, R., Lee, J., Muzaffar, J., Read, M. L., Brookes, K., Sharma, N., Boelaert, K., McCabe, C. J., & Nieto, H. T. (2022) · Endocrine Abstracts · doi:10.1530/endoabs.86.p281
Wang, Y., Hong, L., Lu, G., Yang, S., Li, L., Huang, X., & Shen, H. (2022) · PubMed Central · doi:10.12122/j.issn.1673-4254.2022.12.21
Gestione clinica dell’ipertiroidismo refrattario
Gallo, D., Bianchi, F. M., Barbera, F. M. L., Clementi, I., Lai, A., Piantanida, E., & Tanda, M. L. (2023) · L Endocrinologo · doi:10.1007/s40619-023-01238-1
“In tali casi, la somministrazione adiuvante con sali di litio incrementa il trapping del radioisotopo ed è in grado di migliorare l’efficacia del trattamento radiometabolico [18].”
BackgroundSelf-citationZhang, M., Lou, B., & Huang, W. (2023) · Research Square · doi:10.21203/rs.3.rs-2391421/v1
Khreish, F., Schaefer-Schuler, A., Roth, L., Burgard, C., Rosar, F., & Ezziddin, S. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1382024
Challenges in Managing Graves’ Disease with Coexisting Acute-on-chronic Liver Disease
Jabir, S., Kiran, B. S., Neelaveni, K., & Thomas, R. T. (2025) · Bangladesh Journal of Endocrinology and Metabolism · doi:10.4103/bjem.bjem_36_24
Shen, H., Wang, Y., Liao, J., Zuo, X., Zhang, B., & Yang, X. M. (2025) · Health care science · doi:10.1002/hcs2.70021
Abd‐ElGawad, M., Abdelmonem, M., Ahmed, A. E., Mohammed, O. M., Zaazouee, M. S., Assar, A., Gadelkarim, M., & Afifi, A. M. (2021) · Figshare · doi:10.6084/m9.figshare.14399476
Treatment of different inflammatory thyroid gland diseases utilizing advanced nanocarriers
Abdelbari, M. A., Mosallam, S., & Ahmed, S. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.109048
- Authors
- Bogazzi, F., Giovannetti, C., Fessehatsion, R., Tanda, M. L., Campomori, A., Compri, E., Rossi, G., Ceccarelli, C., Vitti, P., Pinchera, A., Bartalena, L., & Martino, E.
- Affiliations
- University of Pisa (IT)
- University of Insubria (IT)
- Istituto di Fisiologia Clinica (IT)
- Corresponding author
- Bogazzi, Fausto
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-01
- Volume
- 95
- Issue
- 1
- Pages
- 201-208
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2067436135
- Cited by
- 88
- References
- 35
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 4 · 2018: 4 · 2017: 2 · 2016: 10 · 2015: 8 · 2014: 9 · 2013: 4 · 2012: 13
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- IrInSubria (University of Insubria) (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
- Graves' disease, radioiodine therapy, lithium, hyperthyroidism, cure rate, time to cure, serum thyroxine, antithyroid drug withdrawal, methimazole, treatment side effects
- MeSH terms
- Adolescent, Adult, Aged, Female, Graves Disease, Humans, Hyperthyroidism, Iodine Radioisotopes, Lithium, Male, Middle Aged, Recurrence, Remission Induction, Retrospective Studies, Antithyroid Agents, Thyroxine, Time Factors, Cohort Studies, Incidence, Treatment Outcome, Withholding Treatment, Young Adult
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