Introduction: Immune checkpoint inhibitors (IPCI) are part of the therapeutic armamentarium against different types of solid tumors, demonstrating different usefulness in metastatic and stage III melanoma. In Colombia, for this indication, antibodies against antigen 4 of cytotoxic T lymphocytes (anti CTLA-4) and antibodies against programmed cell death receptor 1 (anti PD1) were approved. Immune-mediated adverse events have been described, being endocrinopathies one of the most frequent. Hypophysitis is frequently associated with anti-CTLA-4 therapy, the presentation being rare in patients with anti-PD-1 therapy, presenting, in the latter, more larval and nonspecific clinical pictures, although consequences can be serious.
Purpose: This article reports the case of an 81-year-old male patient with hypophysitis with grade 3 adverse reaction with adrenal insufficiency secondary to the use of Pembrolizumab, part of the treatment of a metastatic pulmonary melanoma.
Case presentation: The patient presented with general symptoms, asthenia, nausea
and hyporexia, normovolemic hypotonic hyponatremia with low cortisol levels and with inappropriately normal ACTH (adrenocorticotropic hormone). He required in-hospital management with glucocorticoids with adequate clinical and paraclinical response to treatment.
Discussion and conclusions: Immunotherapy treatments in patients with neoplastic diseaseare increasingly used and can lead to the development of adverse events. We present, in the clinical case, a pembrolizumab toxicity event causing isolated secondary adrenal insufficiency. This is an uncommon situation and usually presents with a non-specific clinical presentation, so we must have a high level of suspicion to provide adequate management; the delay in initiating corticosteroid treatment has consequences for the patient.
Cukier P, Santini FC, Scaranti M, Hoff AO. Endocrine side effects of cancer immunotherapy. Endocr Relat Cancer. 2017;24(12):T331-47. DOI: https://doi.org/10.1530/ERC-17-0358
Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018;378(2):158-68. DOI: https://doi.org/10.1056/NEJMra1703481
Haanen JB, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(supl. 4):iv119-42. DOI: https://doi.org/10.1093/annonc/mdx225
Castillero F, Castillo-Fern O, Jim G. Cancer immunotherapy-associated hypophysitis. 2019;15:3159-69. DOI: https://doi.org/10.2217/fon-2019-0101
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med 2015; 372:2521-32. DOI: https://doi.org/10.1056/NEJMoa1503093
Elia G, Ferrari SM, Galdiero MR, Ragusa F, Paparo SR, Ruffilli I, et al. New insight in endocrine-related adverse events associated to immune checkpoint blockade. Best Pract Res Clin Endocrinol Metab. 2020;34(1). DOI: https://doi.org/10.1016/j.beem.2019.101370
Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev. 2018;40(1):17-65. DOI: https://doi.org/10.1210/er.2018-00006
Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens a systematic review and meta-analysis. JAMA Oncol. 2018;4(2):173-82. DOI: https://doi.org/10.1001/jamaoncol.2017.3064
Faje A, Reynolds K, Zubiri L, Lawrence D, Cohen JV, Sullivan RJ, et al. Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis. Eur J Endocrinol. 2019;181(3):211-9. DOI: https://doi.org/10.1530/EJE-19-0238
Ariyasu R, Horiike A, Yoshizawa T, Dotsu Y, Koyama J, Saiki M, et al. Adrenal insufficiency related to anti-programmed death-1 therapy. Anticancer Res. 2017;37(8):4229-32. DOI: https://doi.org/10.21873/anticanres.11814
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