Adrenal insufficiency resulting from immunotherapy: a rare but life-threatening side effect
Keywords:Immunotherapy, Adrenal insufficiency, Immune-checkpoint inhibitor, Pembrolizumab
A 73-year-old male whom suffers from stage 4 adeno-squamous lung carcinoma with high programmed death-ligand 1 (PD-L1 immunohistochemistry-tumor proportion score (TPS)>50 began his treatment with a type of immune checkpoint inhibitors (ICI) therapy. After 8th cycle of treatment, patient experiences vague symptoms of fever, lethargy and drowsy. Initial working diagnosis was infection and empirical treatment was initiated. Subsequently as patient’s condition did not improve despite appropriate antibiotics, other diagnosis was considered which include adrenal insufficiency and this confirms after checking cortisol level. Hydrocortisone was started promptly and patient clinical condition improved. Decision was to stop ICI treatment interim. Consideration to re-challenge again with ICI may be considered once patient is more fit in the future. Adrenal insufficiency following ICI treatments are rare and misdiagnosed due to its non-specific symptoms. Nonetheless, it comes with high morbidity and mortality. Hence, we wanted to emphasize more on this condition as more elderly patients whom suffers from various type of cancers will be exposed towards ICI treatment.
Motzer RJ, Tannir NM, Mc Dermott. Check Mate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma. N Eng J Med. 2018;378(14):1277-90.
Hellmann MD, Rizvi NA. Nivolumab plus ipilimumab as first line treatment for advanced non-small cell lung cancer (CheckMate 012); results of and open label phase 1; multicohort study. Lancet Oncol. 2017;18(1);31-41.
Larkin J, Chiarion- Sileni V. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Eng J Med. 2015;373(1):23-4.
Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM, 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.
Brahmer JR, Lacchetti. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy. American Society of Clinical Oncology Clinical Practice Guideline Summary. J Oncol Pract. 2018;14(4)247-9.
Grouthier V, Lebrun- Vignes B. Immune Checkpoint Inhibitor Associated Primary Adrenal Insufficiency; WHO VigiBase Report Analysis. Oncologist. 2020;25:696-701.
Syn Nicholas L, Teng Michele WL, Mok Tony SK, Soo Ross A. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18(12):e731-41.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer. 2014;12(4):252-64.
Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol. 2016;27(4):559-74.
Sharon DeMorrow, Role of the Hypothalamic-Pituitary-Adrenal Axis in Health and Disease, Int J Mol Sci. 2018;19(4):986.
Hagg E, Asplund K, Lithner. Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency. Clin Endocrinology (Oxf) .1987;26(2):221.
Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GDm et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-89.