Introduction: Checkpoint inhibitors have revolutionized the treatment of cancer patients, increasing disease-free survival; These are therapies with endorsement for the management of solid neoplasms. Among the adverse events are those at the level of the endocrine system. We report the case of a patient treated with anti CTLA-4 and anti PD-1 who developed hypophysitis and adrenalitis.
Objective: To describe the case of a patient who presented endocrinopathies (hypophysitis and adrenalitis) associated with the use of immunotherapy, in a clinic in the city of Medellin, Colombia.
Case presentation: 74-year-old woman with a history of renal cell carcinoma, treated with ipilimumab and nivolumab, that were suspended due to pneumonitis. Three months later, she presented to the emergency department due to decreased functional class and drowsiness. On physical examination with hypotension. Hypotonic hyponatremia, and low basal cortisol were evidenced. A pituitary profile was requested, finding low somatomedin, low Follicle-stimulating hormone (FSH) and high adrenocorticotropic hormone (ACTH). MRI of the sella turcica showed absence of structural alterations. Hypophysitis with a normal image and primary adrenal insufficiency secondary to adrenalitis was concluded.
Discussion and conclusions: Immune checkpoint inhibitors are drugs currently used for different types of neoplasms, these drugs are associated in a significant percentage with endocrinopathies, however, finding the simultaneous involvement of two endocrine glands is unusual, being this the second reported case in the literature with hypophysitis and adrenalitis.
The clinical manifestations of endocrinopathies associated with immunotherapy should be recognized, considering the increasing use of these therapies for different neoplasms. The involvement of more than one endocrine gland is uncommon, however it should be suspected and recognized. It is important to establish in each center a protocol for the approach and follow-up of these patients.
Oiseth SJ, Aziz M. Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead. J. Cancer Metastasis Treat. 2017;3:250-61. https://doi.org/10.20517/2394-4722.2017.41
Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020 nov.;20(11):651-68. https://doi.org/10.1038/s41577-020-0306-5
Smith JL, Stehlin JS. Spontaneous regression of primary malignant melanomas with regional metastases. Cancer. 1965 nov.;18(11):1399-415. https://doi.org/10.1002/1097-0142(196511)18:11%3C1399::AID-CNCR2820181104%3E3.0.CO;2-R
Chow MT, Möller A, Smyth MJ. Inflammation and immune surveillance in cancer. Semin Cancer Biol. 2012 febr.;22(1):23-32. https://doi.org/10.1016/j.semcancer.2011.12.004
Fernandes S, Varlamov EV, McCartney S, Fleseriu M. A Novel Etiology of Hypophysitis: Immune Checkpoint Inhibitors. Endocrinol Metab Clin North Am. 2020 sept.;49(3):387-99. https://doi.org/10.1016/j.ecl.2020.05.002
Caturegli P, Di Dalmazi G, Lombardi M, Grosso F, Larman HB, Larman T, et al. Hypophysitis Secondary to Cytotoxic T-Lymphocyte-Associated Protein 4 Blockade: Insights into Pathogenesis from an Autopsy Series. Am J Pathol. 2016 dic.;186(12):3225-35. https://doi.org/10.1016/j.ajpath.2016.08.020
Sum M, Vallejo-García F. Immunotherapy-induced autoimmune diabetes and concomitant hypophysitis. Pituitary. 2018 oct.;21(5):556-7. https://doi.org/10.1007/s11102-018-0880-8
Castinetti F, Albarel F, Archambeaud F, Bertherat J, Bouillet B, Buffier P, et al. French Endocrine Society Guidance on endocrine side effects of immunotherapy. Endocr Relat Cancer. 2019 febr.;26(2):G1-18. https://doi.org/10.1530/ERC-18-0320
Sznol M, Postow MA, Davies MJ, Pavlick AC, Plimack ER, Shaheen M, et al. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. Cancer Treat Rev. 2017 jul.;58:70-6. https://doi.org/10.1016/j.ctrv.2017.06.002
Min L, Ibrahim N. Ipilimumab-induced autoimmune adrenalitis. Lancet Diabetes Endocrinol 2013;1:e15. https://doi.org/10.1016/S2213-8587(13)70031-7
Haissaguerre M, Hescot S, Bertherat J, Chabre O. Expert opinions on adrenal complications in immunotherapy. Ann Endocrinol (París). 2018 oct.;79(5):539-44. https://doi.org/10.1016/j.ando.2018.07.002
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Copyright (c) 2022 Revista Colombiana de Endocrinología, Diabetes & Metabolismo