Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Case Report

A Case of Cancer-Associated Hyponatraemia: Primary Adrenal Insufficiency Secondary to Nivolumab

Author(s): Silvia Galliazzo*, Filippo Morando, Paola Sartorato, Michela Bortolin and Ernesto De Menis

Volume 22, Issue 3, 2022

Published on: 12 January, 2022

Page: [363 - 366] Pages: 4

DOI: 10.2174/1871530321666210708142815

Price: $65

Abstract

Background: Immunotherapy with immune checkpoint inhibitors is a new frontier for cancer treatment. On the safety profile, this drugs class is associated with a new spectrum of side effects, the so-called immune-related adverse events that can potentially affect any organs, mainly endocrine glands. Scant data are available to inform the appropriate strategy of their management and treatment.

Case Presentation: A 74-years old man with a squamous non-small cell lung cancer on nivolumab was hospitalized for fatigue, nausea, vomiting and severe hyponatremia. Biochemical tests were significant for hypotonic hyponatremia with a high urine sodium concentration. Endocrine tests showed overt primary hypothyroidism and low serum cortisol and aldosterone levels associated with an elevated circulating level of adrenocorticotrophic hormone. Adrenal antibody screening and the search of adrenal lesion on CT abdomen were negative. Thus, a nivolumab-induced primary adrenal insufficiency was diagnosed. Nivolumab withdrawal and replacement treatment with glucocorticoid and mineralocorticoid allowed clinical and biochemical recovery.

Conclusion: Physicians need to be aware of potential immune-related adverse events in all patients treated with an immune checkpoint inhibitor. Their timely recognition is essential to carry out the proper treatment.

Keywords: Checkpoint inhibitors, nivolumab, adrenal insufficiency, hyponatraemia, cancer, immunotherapy.

« Previous
[1]
Mantovani, A. The inflammation - cancer connection. FEBS J., 2018, 285(4), 638-640.
[http://dx.doi.org/10.1111/febs.14395] [PMID: 29479848]
[2]
Hegde, P.S.; Chen, D.S. Top 10 challenges in cancer immunotherapy. Immunity, 2020, 52(1), 17-35.
[http://dx.doi.org/10.1016/j.immuni.2019.12.011] [PMID: 31940268]
[3]
Hoos, A. Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations. Nat. Rev. Drug Discov., 2016, 15(4), 235-247.
[http://dx.doi.org/10.1038/nrd.2015.35] [PMID: 26965203]
[4]
Sharma, P.; Allison, J.P. The future of immune checkpoint therapy. Science, 2015, 348(6230), 56-61.
[http://dx.doi.org/10.1126/science.aaa8172] [PMID: 25838373]
[5]
He, J.; Hu, Y.; Hu, M.; Li, B. Development of pd-1/pd-l1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci. Rep., 2015, 5, 13110.
[http://dx.doi.org/10.1038/srep13110] [PMID: 26279307]
[6]
Francisco, L.M.; Sage, P.T.; Sharpe, A.H. The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev., 2010, 236, 219-242.
[http://dx.doi.org/10.1111/j.1600-065X.2010.00923.x] [PMID: 20636820]
[7]
Elia, G.; Ferrari, S.M.; Galdiero, M.R.; Ragusa, F.; Paparo, S.R.; Ruffilli, I.; Varricchi, G.; Fallahi, P.; Antonelli, A. New insight in endocrine-related adverse events associated to immune checkpoint blockade. Best Pract. Res. Clin. Endocrinol. Metab., 2020, 34(1), 101370.
[http://dx.doi.org/10.1016/j.beem.2019.101370] [PMID: 31983543]
[8]
Topalian, SL; Taube, JM; Pardoll, DM Neoadjuvant checkpoint blockade for cancer immunotherapy. Science, 2020, 31(367(6477)), eaax0182.
[http://dx.doi.org/10.1126/science.aax0182]
[9]
Nagai, H.; Muto, M. Optimal management of immune-related adverse events resulting from treatment with immune checkpoint inhibitors: A review and update. Int. J. Clin. Oncol., 2018, 23(3), 410-420.
[http://dx.doi.org/10.1007/s10147-018-1259-6] [PMID: 29516216]
[10]
Calabrese, L.; Mariette, X. The evolving role of the rheumatologist in the management of immune-related adverse events (irAEs) caused by cancer immunotherapy. Ann. Rheum. Dis., 2018, 77(2), 162-164.
[http://dx.doi.org/10.1136/annrheumdis-2017-212061] [PMID: 28928270]
[11]
Brahmer, J.R.; Drake, C.G.; Wollner, I.; Powderly, J.D.; Picus, J.; Sharfman, W.H.; Stankevich, E.; Pons, A.; Salay, T.M.; McMiller, T.L.; Gilson, M.M.; Wang, C.; Selby, M.; Taube, J.M.; Anders, R.; Chen, L.; Korman, A.J.; Pardoll, D.M.; Lowy, I.; Topalian, S.L. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol., 2010, 28(19), 3167-3175.
[http://dx.doi.org/10.1200/JCO.2009.26.7609] [PMID: 20516446]
[12]
Borghaei, H.; Paz-Ares, L.; Horn, L.; Spigel, D.R.; Steins, M.; Ready, N.E.; Chow, L.Q.; Vokes, E.E.; Felip, E.; Holgado, E.; Barlesi, F.; Kohlhäufl, M.; Arrieta, O.; Burgio, M.A.; Fayette, J.; Lena, H.; Poddubskaya, E.; Gerber, D.E.; Gettinger, S.N.; Rudin, C.M.; Rizvi, N.; Crinò, L.; Blumenschein, G.R. Jr.; Antonia, S.J.; Crinò, L.; Dorange, C.; Harbison, C.T.; Graf Finckenstein, F.; Brahmer, J.R. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N. Engl. J. Med., 2015, 373(17), 1627-1639.
[13]
Wang, Y.; Zhou, S.; Yang, F.; Qi, X.; Wang, X.; Guan, X.; Shen, C.; Duma, N.; Vera Aguilera, J.; Chintakuntlawar, A.; Price, K.A.; Molina, J.R.; Pagliaro, L.C.; Halfdanarson, T.R.; Grothey, A.; Markovic, S.N.; Nowakowski, G.S.; Ansell, S.M.; Wang, M.L. Treatment-related adverse events of pd-1 and pd-l1 inhibitors in clinical trials: A systematic review and meta-analysis. JAMA Oncol., 2019, 5(7), 1008-1019.
[http://dx.doi.org/10.1001/jamaoncol.2019.0393] [PMID: 31021376]
[14]
Bleicken, B.; Hahner, S.; Ventz, M.; Quinkler, M. Delayed diagnosis of adrenal insufficiency is common: A cross-sectional study in 216 patients. Am. J. Med. Sci., 2010, 339(6), 525-531.
[http://dx.doi.org/10.1097/MAJ.0b013e3181db6b7a] [PMID: 20400889]
[15]
Grouthier, V.; Lebrun-Vignes, B.; Moey, M.; Johnson, D.B.; Moslehi, J.J.; Salem, J.E.; Bachelot, A. Immune checkpoint inhibitor-associated primary adrenal insufficiency: WHO vigibase report analysis. Oncologist, 2020, 25(8), 696-701.
[http://dx.doi.org/10.1634/theoncologist.2019-0555] [PMID: 32390168]
[16]
Baker, S.; Kenward, D.; White, K.G. Addison’s disease: After 40 years much remains the same. BMJ, 2001, 322(7284), 494.
[http://dx.doi.org/10.1136/bmj.322.7284.494] [PMID: 11256368]
[17]
Løvås, K.; Husebye, E.S. Addison’s disease. Lancet, 2005, 365(9476), 2058-2061.
[http://dx.doi.org/10.1016/S0140-6736(05)66700-1] [PMID: 15950720]
[18]
Bancos, I.; Hahner, S.; Tomlinson, J.; Arlt, W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol., 2015, 3(3), 216-226.
[http://dx.doi.org/10.1016/S2213-8587(14)70142-1] [PMID: 25098712]
[19]
Trainer, H.; Hulse, P.; Higham, C.E.; Trainer, P.; Lorigan, P. Hyponatraemia secondary to nivolumab-induced primary adrenal failure. Endocrinol. Diabetes Metab. Case Rep., 2016, 2016, 16-0108.
[http://dx.doi.org/10.1530/EDM-16-0108] [PMID: 27857838]
[20]
Deligiorgi, M.V.; Trafalis, D.T. Reversible primary adrenal insufficiency related to anti-programmed cell-death 1 protein active immunotherapy: Insight into an unforeseen outcome of a rare immune-related adverse event. Int. Immunopharmacol., 2020, 89(Pt B), 107050.
[http://dx.doi.org/10.1016/j.intimp.2020.107050]
[21]
Ellison, D.H.; Berl, T. Clinical practice. The syndrome of inappropriate antidiuresis. N. Engl. J. Med., 2007, 356(20), 2064-2072.
[http://dx.doi.org/10.1056/NEJMcp066837] [PMID: 17507705]
[22]
Spasovski, G.; Vanholder, R.; Allolio, B.; Annane, D.; Ball, S.; Bichet, D.; Decaux, G.; Fenske, W.; Hoorn, E.J.; Ichai, C.; Joannidis, M.; Soupart, A.; Zietse, R.; Haller, M.; van der Veer, S.; Van Biesen, W.; Nagler, E. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur. J. Endocrinol., 2014, 170(3), G1-G47.
[http://dx.doi.org/10.1530/EJE-13-1020] [PMID: 24569125]
[23]
Brahmer, J.R.; Lacchetti, C.; Schneider, B.J.; Atkins, M.B.; Brassil, K.J.; Caterino, J.M.; Chau, I.; Ernstoff, M.S.; Gardner, J.M.; Ginex, P.; Hallmeyer, S.; Holter Chakrabarty, J.; Leighl, N.B.; Mammen, J.S.; McDermott, D.F.; Naing, A.; Nastoupil, L.J.; Phillips, T.; Porter, L.D.; Puzanov, I.; Reichner, C.A.; Santomasso, B.D.; Seigel, C.; Spira, A.; Suarez-Almazor, M.E.; Wang, Y.; Weber, J.S.; Wolchok, J.D.; Thompson, J.A. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J. Clin. Oncol., 2018, 36(17), 1714-1768.
[http://dx.doi.org/10.1200/JCO.2017.77.6385] [PMID: 29442540]
[24]
Sonehara, K.; Tateishi, K.; Araki, T.; Komatsu, M.; Yamamoto, H.; Koizumi, T.; Hanaoka, M. The role of immune-related adverse events in prognosis and efficacy prediction for patients with non-small cell lung cancer treated with immunotherapy: A retrospective clinical analysis. Oncology, 2021, 99(5), 271-279.
[http://dx.doi.org/10.1159/000511999] [PMID: 33631764]
[25]
Bouhlel, L.; Doyen, J.; Chamorey, E.; Poudenx, M.; Ilie, M.; Gal, J.; Guigay, J.; Benzaquen, J.; Marquette, C.H.; Berthet, J.P.; Mouroux, J.; Schiappa, R.; Padovani, B.; Hofman, P.; Otto, J. Occurrence and number of immune-related adverse events are independently associated with survival in advanced non-small-cell lung cancer treated by nivolumab. Bull. Cancer, 2020, 107(9), 946-958.
[http://dx.doi.org/10.1016/j.bulcan.2020.04.019] [PMID: 32646604]
[26]
Teraoka, S.; Fujimoto, D.; Morimoto, T.; Kawachi, H.; Ito, M.; Sato, Y.; Nagata, K.; Nakagawa, A.; Otsuka, K.; Uehara, K.; Imai, Y.; Ishida, K.; Fukuoka, J.; Tomii, K. Early immune-related adverse events and association with outcome in advanced non-small cell lung cancer patients treated with nivolumab: A prospective cohort study. J. Thorac. Oncol., 2017, 12(12), 1798-1805.
[http://dx.doi.org/10.1016/j.jtho.2017.08.022] [PMID: 28939128]
[27]
Ricciuti, B.; Genova, C.; De Giglio, A.; Bassanelli, M.; Dal Bello, M.G.; Metro, G.; Brambilla, M.; Baglivo, S.; Grossi, F.; Chiari, R. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: Long-term outcomes from a multi-institutional analysis. J. Cancer Res. Clin. Oncol., 2019, 145(2), 479-485.
[http://dx.doi.org/10.1007/s00432-018-2805-3] [PMID: 30506406]
[28]
Postow, M.A.; Sidlow, R.; Hellmann, M.D. Immune-related adverse events associated with immune checkpoint blockade. N. Engl. J. Med., 2018, 378(2), 158-168.
[http://dx.doi.org/10.1056/NEJMra1703481]

Rights & Permissions Print Cite
Article Metrics
31
1
© 2024 Bentham Science Publishers | Privacy Policy