Combination therapy of ipilimumab and nivolumab induced thyroid storm in a patient with Hashimoto’s disease and diabetes mellitus: a case report
Open accessAbstract
Recently, immune checkpoint inhibitors have widely been used for the management of advanced melanoma. However, high-grade immune-related adverse events can occur, particularly with combination immunotherapy. We report a case of a patient with melanoma who developed thyroid storm following treatment with ipilimumab and nivolumab. An 85-year-old Japanese man with a history of malignant melanoma presented to our department with severe thyrotoxicosis and poor blood glucose control. He was already being treated for Hashimoto’s disease and type 2 diabetes mellitus before the treatment for the melanoma. During admission, laboratory investigations revealed the following thyroid functions: thyroid-stimulating hormone below sensitivity, free triiodothyronine 31.7 pg/ml, and thyroglobulin 48,000 IU/ml. Thyroid-stimulating hormone receptor antibody was negative, and a 99m Tc-labeled thyroid scan revealed a markedly decreased uptake. He was treated with beta-blocker, orally administered potassium iodine, a relatively low dose of prednisolone, and insulin injection therapy to control his blood glucose, resulting in an improvement in thyroid function and his symptoms. It might be important to be aware of the possibility of thyroid storm induced by immune checkpoint inhibitors.
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?
Immune checkpoint inhibitor-associated diabetes mellitus occurs in just under 1% of patients receiving immune checkpoint inhibitors.
“occurs in slightly less than 1% of patients treated with ICI 65”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [65]
Elevated amylase and lipase were present in about one-third of patients presenting with immune checkpoint inhibitor-associated diabetes mellitus.
“elevated amylase and lipase were present in about one-third of patients presenting with ICI-DM65”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [65]
There is a particularly strong association between immune checkpoint inhibitor-associated diabetes mellitus and HLA-DR4.
“with a particularly strong association with HLA-DR465”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [65]
Patients with islet autoantibodies developed diabetes sooner after immune checkpoint inhibitor treatment than those without.
“Individuals with islet auto-antibodies developed diabetes earlier after ICI treatment than those without65”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [65]
Exocrine pancreatic inflammation may contribute to the pathogenesis of immune checkpoint inhibitor-associated diabetes mellitus.
“exocrine pancreatic inflammation may also be involved in ICI-DM pathogenesis”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [65]
About 40-50% of patients with immune checkpoint inhibitor-associated diabetes mellitus have detectable islet autoantibodies at diagnosis, compared with more than 90% in type 1 diabetes.
“Approximately 40-50% of individuals with ICI-DM have detectable islet auto-antibodies at diagnosis, compared to >90% in T1D 64,65”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [65]
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
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,314 · see citing works
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · see citing works
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157 · see citing works
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma
Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., Linette, G. P., Meyer, N., Giguere, J. K., Agarwala, S. S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414428 · Cited by 2,781 · see citing works
Horvat, T. Z., Adel, N. G., Dang, T.-O., Momtaz, P., Postow, M. A., Callahan, M. K., Carvajal, R. D., Dickson, M. A., D'Angelo, S. P., Woo, K. M., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.60.8448 · Cited by 1,064 · see citing works
Life-Threatening Thyrotoxicosis: Thyroid Storm
Burch, H. B., & Wartofsky, L. (1993) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(18)30165-8 · Cited by 852 · see citing works
The Programmed Death-1 (PD-1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice
Ansari, M. J., Salama, A. D., Chitnis, T., Smith, R. N., Yagita∥, H., Akiba, H., Yamazaki, T., Azuma, M., Iwai, H., Khoury, S. J., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022125 · Cited by 806 · see citing works
Immune Modulation in Cancer with Antibodies
Page, D. B., Postow, M. A., Callahan, M. K., Allison, J. P., & Wolchok, J. D. (2013) · Annual Review of Medicine · doi:10.1146/annurev-med-092012-112807 · Cited by 516 · see citing works
Precipitation of Autoimmune Diabetes With Anti-PD-1 Immunotherapy
Hughes, J. W., Vudattu, N. K., Sznol, M., Gettinger, S. N., Kluger, H. M., Lupsa, B. C., & Herold, K. C. (2015) · Diabetes Care · doi:10.2337/dc14-2349 · Cited by 347 · see citing works
Satoh, T., Isozaki, O., Suzuki, A., Wakino, S., Iburi, T., Tsuboi, K., Kanamoto, N., Otani, H., Furukawa, Y., Teramukai, S., et al. (2016) · Endocrine Journal · doi:10.1507/endocrj.ej16-0336 · Cited by 259 · see citing works
Chen, T. W., Razak, A. R. A., Bedard, P. L., Siu, L. L., & Hansen, A. R. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv182 · Cited by 246 · see citing works
Morganstein, D. L., Lai, Z., Spain, L., Diem, S., Levine, D., Mace, C., Gore, M., & Larkin, J. (2017) · Clinical Endocrinology · doi:10.1111/cen.13297 · Cited by 190 · see citing works
Anti-PD1 Pembrolizumab Can Induce Exceptional Fulminant Type 1 Diabetes
Gaudy‐Marqueste, C., Clévy, C., Monestier, S., Dubois, N., Préau, Y., Mallet, S., Richard, M. A., Grob, J., Valéro, R., & Béliard, S. (2015) · Diabetes Care · doi:10.2337/dc15-1331 · Cited by 159 · see citing works
BIANCO, A. C., NUNES, M. T., HELL, N. S., & MACIEL, R. M. B. (1987) · Endocrinology · doi:10.1210/endo-120-3-1033 · Cited by 104 · see citing works
McMillen, B., Dhillon, M. S., & Yong-Yow, S. (2016) · BMJ Case Reports · doi:10.1136/bcr-2016-214603 · Cited by 87 · see citing works
Treatment of Ipilimumab Induced Graves’ Disease in a Patient with Metastatic Melanoma
Azmat, U., Liebner, D., Joehlin-Price, A., Agrawal, A., & Nabhan, F. (2016) · Case Reports in Endocrinology · doi:10.1155/2016/2087525 · Cited by 59 · see citing works
A novel melanoma therapy stirs up a storm: ipilimumab-induced thyrotoxicosis
Yu, C. H., CHOPRA, I. J., & Ha, E. L. (2015) · Endocrinology Diabetes and Metabolism Case Reports · doi:10.1530/edm-14-0092 · Cited by 49 · see citing works
Jaberi‐Douraki, M., Liu, S. W. S., Pietropaolo, M., & Khadra, A. (2014) · Pediatric Diabetes · doi:10.1111/pedi.12148 · Cited by 25 · see citing works
Case of Sorafenib-Induced Thyroid Storm
Haraldsdóttir, S., Li, Q., Villalona-Calero, M. A., Olencki, T. E., Kendra, K. L., & Ing, S. W. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.7142 · Cited by 23 · see citing works
Life-threatening thyrotoxicosis induced by amiodarone in patients with benign heart disease
Georges, J., Jp, N., Lenormand, M. E., & Schwob, J. (1992) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a060032 · Cited by 21 · see citing works
Ikeda, M., Shiina, S., Nakachi, K., Mitsunaga, S., Shimizu, S., Kojima, Y., Ueno, H., Morizane, C., Kondo, S., Sakamoto, Y., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.4_suppl.262 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Endocrine toxicities of immune checkpoint inhibitors
Wright, J. J., Powers, A. C., & Johnson, D. B. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00484-3 · Cited by 441 · see citing works
Thyroid Toxicity Following Immune Checkpoint Inhibitor Treatment in Advanced Cancer
Muir, C. A., Menzies, A. M., Clifton-Bligh, R. J., & Tsang, V. (2020) · Thyroid · doi:10.1089/thy.2020.0032 · Cited by 81 · see citing works
Immune checkpoint inhibitor-related thyroid dysfunction
Iwama, S., Kobayashi, T., Yasuda, Y., & Arima, H. (2022) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2022.101660 · Cited by 76 · see citing works
Self-citationZhan, L., Feng, H.-F., Liu, H., Guo, L., Chen, C., Yao, X.-L., & Sun, S. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.649863 · Cited by 60 · see citing works
Endocrine side effects of immune checkpoint inhibitors
Cardona, Z., Sosman, J. A., Chandra, S., & Huang, W. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1157805 · Cited by 55 · see citing works
Coureau, M., Meert, A., Berghmans, T., & Grigoriu, B. D. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00137 · Cited by 46 · see citing works
Deligiorgi, M. V., Sagredou, S., Vakkas, L., & Trafalis, D. T. (2021) · Cancers · doi:10.3390/cancers13215277 · Cited by 22 · see citing works
Endocrine Side Effects in Patients Treated with Immune Checkpoint Inhibitors: A Narrative Review
Profili, N. I., Castelli, R., Gidaro, A., Merella, A., Manetti, R., Palmieri, G., Maioli, M., & Delitala, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12155161 · Cited by 18 · see citing works
Basek, A., Jakubiak, G. K., Cieślar, G., & Stanek, A. (2023) · Cancers · doi:10.3390/cancers15245786 · Cited by 19 · see citing works
Immunotherapy-induced thyroid dysfunction: an updated review
Baraka, B., Abosheaishaa, H. M., & Nassar, M. (2023) · The Egyptian Journal of Internal Medicine · doi:10.1186/s43162-023-00210-7 · Cited by 14 · see citing works
Percik, R., Liel, Y., Urban, D., Bar, J., Ben‐Ami, E., & Tailakh, M. A. (2021) · Acta Oncologica · doi:10.1080/0284186x.2021.1958006 · Cited by 13 · see citing works
Elmenyar, E., Aoun, S., Saadi, Z. A., Barkumi, A., Cander, B., Al-Thani, H. A. S., & El-Menyar, A. A. (2023) · Diagnostics · doi:10.3390/diagnostics13193028 · Cited by 11 · see citing works
Anti PD-1 monoclonal antibody induced autoimmune diabetes mellitus: a case report and brief review
Li, W., Wang, H., Chen, B., Zhao, S., Zhang, X., Jia, K., Deng, J., He, Y., & Zhou, C. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr.2020.03.05 · Cited by 9 · see citing works
Dai, X., Cao, H., Li, J., Zhang, T., & Hou, Y. (2025) · Scientific Reports · doi:10.1038/s41598-025-07287-w · Cited by 8 · see citing works
Li, A., Jiang, X., Zhong, M., Li, N., Tao, Y., Wu, W., Yang, C., Wang, H., Min, L., Ma, Y., et al. (2020) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018820934307 · Cited by 8 · see citing works
Lassoued, N., Alaya, W., Senda, R., Sondos, A., Zantour, B., & Sfar, M. H. (2023) · Endocrinology Diabetes and Metabolism Case Reports · doi:10.1530/edm-21-0152 · Cited by 5 · see citing works
Meng, Z., Song, L., Wang, S., & Duan, G. (2025) · Clinical Epidemiology · doi:10.2147/clep.s494215 · Cited by 5 · see citing works
Pembrolizumab-Induced Thyroid Storm in a Patient With Triple-Negative Breast Cancer
Mohammed, S., Park, E. Y., Asad, R., & Tadisina, S. (2025) · AACE Endocrinology and Diabetes · doi:10.1016/j.aed.2025.04.008 · Cited by 4 · see citing works
Thyroid disorders associated with immune control point inhibitors
Fidilio, E., Navarro-González, E., Romero-Lluch, A. R., Iglesias, P., Gómez, J. J. D., Apiñániz, E. A., Mazo, E. S., & Zafón, C. (2021) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2021.10.004 · Cited by 4 · see citing works
Sajid-ur-Rehman, M., Ishtiaq, S., Khan, M. S., Jabeen, Q., Youssef, F. S., Ahmed, S. A., Elhady, S. S., & Ashour, M. L. (2023) · ACS Omega · doi:10.1021/acsomega.3c06630 · Cited by 4 · see citing works
Hayakawa, G., Leibowitz, M. M., Datta, S., & Oyibo, S. O. (2023) · Cureus · doi:10.7759/cureus.39439 · Cited by 2 · see citing works
Ramburuth, V., & Rajkanna, J. (2023) · Cureus · doi:10.7759/cureus.46985 · Cited by 2 · see citing works
Hagiwara, R., Suzuki, D., Tonezawa, S., Saikawa, R., Funazaki, S., Yoshida, M., Washino, S., Miyagawa, T., Hara, K., & Yamada, H. (2021) · Clinical Case Reports · doi:10.1002/ccr3.4781 · Cited by 2 · see citing works
Li, R., Liu, T., Li, T., Zhao, Z., Zhao, F., Chen, D., Huang, J., Xu, W., & Jin, P. (2025) · Endocrine Practice · doi:10.1016/j.eprac.2025.12.018 · Cited by 1 · see citing works
Thyroid storm triggered by immune checkpoint inhibitor therapy
Hagiwara, J., Sekine, M., Sakawaki, E., Sakawaki, S., & Takeyama, Y. (2026) · BMJ Case Reports · doi:10.1136/bcr-2026-272027 · Cited by 1 · see citing works
Li, X., Xiang, Q., Gong, Y., Long, Y., He, Y., Wu, Z., & Xiang, T. (2026) · Clinical Therapeutics · doi:10.1016/j.clinthera.2026.06.020 · Cited by 1 · see citing works
Alteraciones tiroideas asociadas con los inhibidores de los puntos de control inmunitario
Fidilio, E., Navarro-González, E., Romero-Lluch, A. R., Iglesias, P., Gómez, J. J. D., Anda, E., Mazo, E. S., & Zafón, C. (2020) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2020.04.007 · Cited by 1 · see citing works
Severe Thyrotoxicosis and Thyroid Storm
Lechner, M. G., & Angell, T. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-76097-3.00001-6 · Cited by 1 · see citing works
Severe Thyrotoxicosis and Thyroid Storm
Lechner, M. G., & Angell, T. E. (2020) · Springer eBooks · doi:10.1007/978-3-030-38976-5_4 · Cited by 1 · see citing works
Geng‐Ramos, G., Wang, M., & Mudd, P. A. (2021) · Springer eBooks · doi:10.1007/978-3-030-72551-8_19
Amiodarone/ipilimumab/nivolumab
(2019) · Reactions Weekly · doi:10.1007/s40278-019-59194-8
Endocrine Consequences Following Immune Checkpoint Inhibitors Therapy
Lavrentaki, A., & Ntali, G. (2023) · Springer eBooks · doi:10.1007/978-3-030-80962-1_172-1
Cancer immunotherapy-associated endocrine complications and treatment strategies
Sen, K., Adhikari, M., Biswas, C., Maity, S., Chatterjee, A., & Pramanick, K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95114-2.00010-8
Endocrine Consequences Following Immune Checkpoint Inhibitors Therapy
Lavrentaki, A., & Ntali, G. (2025) · Springer eBooks · doi:10.1007/978-3-032-00765-0_172
- Authors
- Yonezaki, K., Kobayashi, T., Imachi, H., Yoshimoto, T., Kikuchi, F., Fukunaga, K., Sato, S., Ibata, T., Yamaji, N., Lyu, J., Dong, T., & Murao, K.
- Affiliations
- Kagawa University (JP)
- Corresponding author
- Kobayashi, Toshihiro
- Murao, Koji
- Venue
- Journal of Medical Case Reports
- Published
- 2018-06-19
- Volume
- 12
- Issue
- 1
- Pages
- 171-171
- ISSN
- 1752-1947 (ISSN-L)
- PMC
- PMC6006841
- OpenAlex
- W2808713704
- Cited by
- 34
- References
- 22
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 10 · 2022: 1 · 2021: 8 · 2020: 6 · 2019: 1
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Medical Case Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- thyroid storm, ipilimumab, nivolumab, immune checkpoint inhibitors, combination immunotherapy, immune-related adverse events, melanoma, Hashimoto's thyroiditis, type 2 diabetes, thyrotoxicosis, prednisolone, insulin therapy, potassium iodide, beta-blockers
- MeSH terms
- Antineoplastic Agents, Immunological, Ipilimumab, Nivolumab, Aged, 80 and over, Diabetes Mellitus, Type 2, Humans, Male, Melanoma, Skin Neoplasms, Thyroid Crisis, Comorbidity, Hashimoto Disease
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
