Hypophysitis with adrenal insufficiency secondary to immune checkpoint inhibitors therapy
Cover of our Vol. 11, Issue 2, 2024
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Keywords

Hypophysitis
Immunotherapy
Adrenal
Nivolumab
Immune Checkpoint Inhibitors
Endocrine Side Effects

How to Cite

Barbosa Arana, J., & Torres Grajales, J. L. . (2024). Hypophysitis with adrenal insufficiency secondary to immune checkpoint inhibitors therapy . Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 11(2). https://doi.org/10.53853/encr.11.2.817

Abstract

Background: Checkpoint inhibitors are monoclonal antibodies with action against solid and hematologic neoplasia with increasing use, which is why there have been reports of adverse events including endocrine system compromise. We report the case of a patient treated with anti PD-1 who developed an endocrinopathy.

Purpose: To present the case of a patient with an endocrinopathy (hypophysitis) with secondary adrenal compromise associated with the use of checkpoint inhibitor therapy in a clinic in the city of Medellín, Colombia.

Case presentation: 75-year-old male patient with a history of poorly differentiated squamocellular carcinoma of the lung, without lymphovascular invasion, treated with nivolumab, who after 6 months of treatment seeks consultation due to abdominal pain and several emetic episodes. On physical examination, the patient was hypotensive, and hypotonic hyponatremia was documented with decreased morning and afternoon cortisol. A pituitary profile was requested, showing decreased ACTH, prolactin, and luteinizing hormone with a normal TSH. Additionally, a sella turcica MRI was performed without evidence of structural damage, which is why it was concluded to be hypophysitis with a secondary adrenal insufficiency.

Discussion and conclusion: Checkpoint inhibitor therapy offers a great advance in cancer treatment, and its increasing use allows us to watch and describe its adverse effects, making it possible to understand its mechanisms and possible risk factors. This is the first case of hypophystis secondary to anti PD-1 alone without CTLA-4 reported in the country.

It is important to consider the possible adverse effects that patients undergoing immunotherapy treatment may experience, and to have a high index of clinical suspicion to perform appropriate tests for early identification.

https://doi.org/10.53853/encr.11.2.817
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References

Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol. 2022;19(4):254-67. https://doi.org/10.1038/s41571-022-00600-w

Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management, and surveillance. Nat Rev Clin Oncol. 2019;16(9):563-80. https://doi.org/10.1038/s41571-019-0218-0

Chang J, Tran J, Kamel D, Basu A. Nivolumab-induced hypophysitis leading to hypopituitarism and secondary empty sella syndrome in a patient with non-small cell lung cancer. BMJ Case Rep. 2019;12(3):e228135. https://doi.org/10.1136/bcr-2018-228135

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 sept. 1;181(3):211-9. https://doi.org/10.1530/EJE-19-0238

Prete A, Salvatori R. Hypophysitis [Internet]. En: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editores. Endotext. South Dartmouth, Massachusetts: MDText.com, Inc.; 2021 [citado: 2023 abr. 17]. https://www.ncbi.nlm.nih.gov/books/NBK519842/

García-Ramos A, Saldarriaga-Betancur S, González-Arango J, Estupiñán V, Monsalve C, Aguilar-Londoño C, et al. Hipofisitis y adrenalitis asociada al uso de inhibidores del punto de control inmunitario. Rev Colomb Endocrinol Diabetes Metab. 2022;9(3):e744. https://doi.org/10.53853/encr.9.3.744

U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Estados Unidos: National Cancer Institute; 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf

Lu J, Li L, Lan Y, Liang Y, Meng H. Immune checkpoint inhibitor-associated pituitary-adrenal dysfunction: a systematic review and meta-analysis. Cancer Med. 2019;8(18):7503-15. https://doi.org/10.1002/cam4.2661

Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012 abr. 1;24(2):207-12. https://doi.org/10.1016/j.coi.2011.12.009

Zhai Y, Ye X, Hu F, Xu J, Guo X, Zhuang Y, et al. Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system. J Immunother Cancer. 2019 nov. 6;7(1):286. https://doi.org/10.1186/s40425-019-0754-2

Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 jun. 28;366(26):2455-65. https://doi.org/10.1056/NEJMoa1200694

Mortensen MJ, Oatman O, Azadi A, Fonkem E, Yuen KC. An update on immune checkpoint inhibitor-related hypophysitis. US Endocrinol. 2020;16(2):117-24. https://doi.org/10.17925/USE.2020.16.2.117

Fernandes S, Varlamov EV, McCartney S, Fleseriu M. A novel etiology of hypophysitis: immune checkpoint inhibitors. Endocrinol Metab Clin North Am. 2020 sept. 1;49(3):387-99. https://doi.org/10.1016/j.ecl.2020.05.002

Dillard T, Yedinak CG, Alumkal J, Fleseriu M. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary. 2010 mzo. 1;13(1):29-38. https://doi.org/10.1007/s11102-009-0193-z

Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev. 2019 febr. 1;40(1):17-65. https://doi.org/10.1210/er.2018-00006

Min L, Hodi FS, Giobbie-Hurder A, Ott PA, Luke JJ, Donahue H, et al. Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study. Clin Cancer Res. 2015 febr. 16;21(4):749-55. https://doi.org/10.1158/1078-0432.CCR-14-2353

Guaraldi F, Giordano R, Grottoli S, Ghizzoni L, Arvat E, Ghigo E. Pituitary autoimmunity. En: Savino W, Guaraldi F, editores. Endocrine Immunology. Karger; 2017. p. 48-68. https://karger.com/books/book/113/chapter/5054982/Pituitary-Autoimmunity

Faje AT, Lawrence D, Flaherty K, Freedman C, Fadden R, Rubin K, et al. High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer. 2018;124(18):3706-14. https://doi.org/10.1002/cncr.31629

Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 nov. 1;101(11):3888-921. https://doi.org/10.1210/jc.2016-2118

Rojas Melo LJ, Ojeda Rodríguez KH, Kerguelen Villadiego AL, Parra Prieto DA. Hipofisitis e insuficiencia suprarrenal secundaria asociada a pembrolizumab. Rev Colomb Endocrinol Diabet Metab. 2021;8(4):e726. https://doi.org/10.53853/encr.8.4.726

Prudêncio Jacques J, Pinto Valadares L, Castelo Moura A, Fernandes Oliveira MR, Naves LA. Frequency and clinical characteristics of hypophysitis and hypopituitarism in patients undergoing immunotherapy - A systematic review. Front. Endocrinol. 2023;14:1091185. https://doi.org/10.3389/fendo.2023.1091185

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