Multiple endocrinopathies acquired using a checkpoint inhibitor - Pembrolizumab: A Case Report

Main Article Content

Gustavo César Sola Barreto Marcelino
https://orcid.org/0009-0000-8283-1737
Eduarda Lavínia Mota de Miranda
https://orcid.org/0000-0003-3240-7094
Fernando Sebastianes
https://orcid.org/0000-0001-6135-6332

Abstract

Immunotherapy with checkpoint inhibitors (ICIs) has been increasingly employed for the treatment of many malignancies, and endocrinopathies are one of their most frequent side effects. This case report describes a 70-year-old man who faced many endocrinopathies (primary hypothyroidism, secondary adrenal insufficiency, and diabetes mellitus) after initiation of immunotherapy with an ICI (pembrolizumab) for treatment of urothelial bladder cancer. We discuss the prevalence, physiopathology, screening, and diagnosis of each of these abnormalities. Clinicians need to be aware of these endocrine complications of ICI therapy and be ready for early diagnosis and appropriate management.

Article Details

How to Cite
Marcelino, G. C. S. B., Miranda, E. L. M. de, & Sebastianes, F. (2024). Multiple endocrinopathies acquired using a checkpoint inhibitor - Pembrolizumab: A Case Report. Brazilian Journal of Case Reports, 5(1), bjcr15. https://doi.org/10.52600/2763-583X.bjcr.2025.5.1.bjcr15
Section
Clinical Case Reports
Author Biographies

Gustavo César Sola Barreto Marcelino, Anhembi Morumbi University

Anhembi Morumbi University, Piracicaba, SP, Brazil.

Eduarda Lavínia Mota de Miranda, Anhembi Morumbi University

Anhembi Morumbi University, Piracicaba, SP, Brazil.

Fernando Sebastianes, Anhembi Morumbi University

Anhembi Morumbi University, Piracicaba, SP, Brazil.

References

Baxi S, Yang A, Gennarelli RL, Khan N, Wang Z, Boyce L, Korenstein D. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: Systematic review and meta-analysis. BMJ. 2018;360.

Xu C, Chen YP, Du XJ, Liu JQ, Huang CL, Chen L, et al. Comparative safety of immune checkpoint inhibitors in cancer: Systematic review and network meta-analysis. BMJ. 2018;363.

Kwok G, Yau TC, Chiu JW, Tse E, Kwong YL. Pembrolizumab (Keytruda). Hum Vaccin Immunother. 2016 Nov;12(11):2777-2789. doi: 10.1080/21645515.2016.1199310. Epub 2016 Jul 11. PMID: 27398650; PMCID: PMC5137544

Figueroa-Perez N, Kashyap R, Bal D, et al. (August 06, 2021) Autoimmune Myasthenia, Primary Adrenal Insufficiency, and Progressive Hypothyroidism Due to Pembrolizumab and Axitinib Combination Regimen. Cureus 13(8): e16933. doi:10.7759/cureus.16933

Hattersley R, Nana M, Lansdown AJ. Endocrine complications of immunotherapies: a review. Clin Med (Lond). 2021 Mar;21(2):e212-e222. doi: 10.7861/clinmed.2020-0827

Sankar K, Macfarlane M, Cooper O, et al. Pembrolizumab-induced diabetic ketoacidosis: A review of critical care case. Cureus. 2021;13(10).

Ayesh H, Burmeister C, Tomcho JC, Fatima R, Hejeebu SK. Pembrolizumab-induced thyroiditis. Am J Ther. 2023;30(3). doi: 10.1097/MJT.0000000000001367.

Montero Pérez O, Sánchez Escudero L, Guzmán Ramos MI, Aviñó Tarazona V. Hypophysitis secondary to pembrolizumab: a case report and review of the literature. Anticancer Drugs. 2022;33(1):94-99. doi:10.1097/CAD.0000000000001129

Kichloo A, Albosta MS, McMahon S, Movsesian K, Wani F, Jamal SM, et al. Pembrolizumab-induced diabetes mellitus pre-senting as diabetic ketoacidosis in a patient with metastatic colonic adenocarcinoma. J Investig Med High Impact Case Rep. 2020;8:2324709620951339. doi: 10.1177/2324709620951339.

Zhao S, et al. Clinical features, diagnosis, and management of pembrolizumab-induced myasthenia gravis. Clin Exp Immunol. 2023;211(2):85-92. doi: 10.1093/cei/uxac108.

Jeroen MK de Filette, Joeri J Pen, Lore Decoster, Thomas Vissers, Bert Bravenboer, Bart J Van der Auwera, Frans K Gorus, Bart O Roep, Sandrine Aspeslagh, Bart Neyns, Brigitte Velkeniers, Aan V Kharagjitsingh, Immune checkpoint inhibitors and type 1 diabetes mellitus: A case report and systematic review, European Journal of Endocrinology , Volume 181, Issue 3, September 2019, pages 363-374, https://doi.org/10.1530/EJE-19-0291

Joaquim Bellmunt, M.D., Ph.D., Ronald de Wit, M.D., Ph.D., David J. Vaughn, M.D., Yves Fradet, M.D., Jae-Lyun Lee, M.D., Ph.D., Lawrence Fong, M.D., Nicholas J. Vogelzang, M.D. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376:1015-1026. DOI: 10.1056/NEJMoa1613683

Schubert D, Bode C, Kenefeck R, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mu-tations. Nat Med. 2014;20(12):1410-1416. doi:10.1038/nm.3746

Paterson AM, Lovitch SB, Sage PT, et al. Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. J Exp Med. 2015;212(10):1603-1621. doi:10.1084/JEM.20141030

Girotra M, Hansen A, Farooki A, et al. The Current Understanding of the Endocrine Effects From Immune Checkpoint In-hibitors and Recommendations for Management. JNCI Cancer Spectr. 2018;2(3):1-9. doi:10.1093/jncics/pky021

Iglesias P, Sánchez JC, Díez JJ. Isolated ACTH deficiency induced by cancer immunotherapy: a systematic review. Pituitary. 2021 Aug;24(4):630-643. doi: 10.1007/s11102-021-01141-8. Epub 2021 Mar 24. PMID: 33761049.

Faje AT, Sullivan R, Lawrence D, et al. Ipilimumab-Induced Hypophysitis: A Detailed Longitudinal Analysis in a Large Cohort of Patients With Metastatic Melanoma. J Clin Endocrinol Metab. 2014;99(11):4078-4085. doi:10.1210/jc.2014-2306

Villa NM, Farahmand A, Du L, et al. Endocrinopathies with use of cancer immunotherapies. Clin Endocrinol (Oxf). 2018;88(2):327-332. doi:10.1111/cen.13483

Morganstein DL, Lai Z, Spain L, Diem S, Levine D, Mace C, Gore M, Larkin J (2017) Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf) 86:614-620

Osorio JC, Ni A, Chaft JE, Pollina R, Kasler MK, Stephens D, Rodriguez C, Cambridge L, Rizvi H, Wolchok JD, Merghoub T, Rudin CM, Fish S, Hellmann MD (2017) Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol 28:583-589

Kichloo A, Albosta MS, McMahon S, Movsesian K, Wani F, Jamal SM, Aljadah M, Singh J. Pembrolizumab-Induced Diabetes Mellitus Presenting as Diabetic Ketoacidosis in a Patient With Metastatic Colonic Adenocarcinoma. J Investig Med High Impact Case Rep. 2020 Jan-Dec;8:2324709620951339. doi: 10.1177/2324709620951339. PMID: 32830561; PMCID: PMC7448133

de Filette J, Andreescu CE, Cools F, Bravenboer B, Velkeniers B. A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors. Horm Metab Res. 2019;51:145-156. doi: 10.1055/a-0843-3366

Castinetti F, Albarel F, Archambeaud F, Bertherat J, Bouillet B, Buffier P, Briet C, Cariou B, Caron P, Chabre O, Chanson P, Cortet C, Do Cao C, Drui D, Haissaguerre M, Hescot S, Illouz F, Kuhn E, Lahlou N, Merlen E, Raverot V, Smati S, Verges B, Borson-Chazot F. French Endocrine Society Guidance on endocrine side effects of immunotherapy. Endocr Relat Cancer. 2019 Feb;26(2):G1-G18. doi: 10.1530/ERC-18-0320. PMID: 30400055; PMCID: PMC6347286.

Morganstein DL, Lai Z, Spain L, Diem S, Levine D, Mace C, et al. Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf). 2017;86:614-620.