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Review

Hypophysitis related to immune checkpoint inhibitors: An intriguing adverse event with many faces

ORCID Icon, & ORCID Icon
Pages 1097-1120 | Received 14 Aug 2020, Accepted 22 Dec 2020, Published online: 01 Apr 2021

References

  • Couzin-Frankel J, Breakthrough of the year 2013 Cancer immunotherapy. Science. 2013;3426165.1432–1433.
  • Pardoll DM, The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer. 2012;124.252–264.
  • Li B, Chan HL, Chen P, Immune Checkpoint Inhibitors: basics and Challenges. Current Medicinal Chemistry. 2019;2617.3009–3025.
  • Sznol M, Postow MA, Davies MJ et al. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management Cancer Treatment Reviews 2017 58 70–76.
  • Topalian SL, Drake CG, Pardoll DM, Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;274.450‐461.
  • Lipson EJ, Drake CG, Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Clinical Cancer Research. 2011;1722.6958–6962.
  • Trinh S, Le A, Gowani S, et al., Management of Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitor Therapy: A Minireview of Current Clinical Guidelines. Asia-Pacific Journal of Oncology Nursing. 2019;62.154–160.
  • Raschi E, Mazzarella A, Antonazzo IC; et al. Toxicities with Immune Checkpoint Inhibitors: emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System. Target Oncol. 2019.142 205–221.
  • Ji -H-H, Tang X-W, Dong Z; et al. Adverse Event Profiles of Anti-CTLA-4 and Anti-PD-1 Monoclonal Antibodies Alone or in Combination: analysis of Spontaneous Reports Submitted to FAERS. Clinical Drug Investigation. 2019.393 319–330.
  • Garon-Czmil J, Petitpain N, Rouby F; et al. Immune check point inhibitors-induced hypophysitis: a retrospective analysis of the French Pharmacovigilance database. Sci Rep. 2019.91 19419.
  • Ali AK, Watson DE, Pharmacovigilance Assessment of Immune-Mediated Reactions Reported for Checkpoint Inhibitor Cancer Immunotherapies. Pharmacotherapy. 2017;3711.1383–1390.
  • Tan MH, Iyengar R, Mizokami-Stout K et al. Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports. Clinical Diabetes and Endocrinology.2019 51 1.
  • Joshi MN, Whitelaw BC, Carroll PV, MECHANISMS IN ENDOCRINOLOGY: hypophysitis: diagnosis and treatment. European Journal of Endocrinology. 2018;1793.R151–R163.
  • Gutenberg A, Landek-Salgado MA, Tzou S-C, et al. Autoimmune hypophysitis: expanding the differential diagnosis to CTLA-4 blockade. Expert Review of Endocrinology & Metabolism. 2009; 4 681–6986.
  • Araujo PB, Coelho MC, Arruda M, et al.Ipilimumab-induced hypophysitis: review of the literature. Journal of Endocrinological Investigation. 2015; 3 3811 1159–1166.
  • Chang LS, Barroso-Sousa R, Tolaney SM, et al. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev.2019;40(1):17–65.
  • Dillard T, Yedinak CG, Alumkal J; et al. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary. 2010.131 29–38.
  • Ryder M, Callahan M, Postow MA; et al. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocrine-Related Cancer. 2014.212 371–381.
  • Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Available from: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm Accessed Mar 2020.
  • Chan KK, Bass AR, Autoimmune complications of immunotherapy: pathophysiology and management.BMJ.2020;369.m736.
  • June CH, Warshauer JT, Bluestone JA,Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat.Med.2017;235.540–547.
  • Young A, Quandt Z, Bluestone JA, The Balancing Act between Cancer Immunity and Autoimmunity in Response to Immunotherapy. Cancer Immunology Research. 2018;612.1445–1452.
  • Heaney AP, Sumerel B, Rajalingam R; et al. HLA Markers DQ8 and DR53 Are Associated With Lymphocytic Hypophysitis and May Aid in Differential Diagnosis. The Journal of Clinical Endocrinology & Metabolism. 2015;100(11):4092–4097.
  • Stamatouli AM, Quandt Z, Perdigoto AL et al., Collateral Damage: insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes.2018;678 1471–1480.
  • Iwama S, De Remigis A, Callahan MK et al., Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Science Translational Medicine.2014;6230 230ra45.
  • Caturegli P, Di Dalmazi G, Lombardi M et al., Hypophysitis Secondary to Cytotoxic T-Lymphocyte–Associated Protein 4 Blockade. The American Journal of Pathology.2016;18612 3225–3235.
  • Javorsky BR, Aron DC, Findling JW, et al. Hypothalamus and Pituitary Gland.Greenspan’s Basic and Clinical Endocrinology. Gardner DG, Shoback D, editors. 9th ed. Mc Graw-Hill Lange; 2011. p. 65–114.
  • Robinson AG The Posterior Pituitary (Neurohypophysis).Greenspan’s Basic and Clinical Endocrinology. Gardner DG, Shoback D, editors. 9th ed. Mc Graw-Hill Lange; 2011. p. 115–128.
  • Mei Y, Bi WL, Greenwald NF; et al. Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors. Oncotarget. 2016.747 76565–76576.
  • Da Gama Duarte J, Parakh S, Andrews MC et al. Autoantibodies May Predict Immune-Related Toxicity: results from a Phase I Study of Intralesional Bacillus Calmette–Guérin followed by Ipilimumab in Patients with Advanced Metastatic Melanoma Frontiers in Immunology 2018;9:411.
  • Gowen MF, Giles KM, Simpson D; et al. Baseline antibody profiles predict toxicity in melanoma patients treated with immune checkpoint inhibitors. Journal of Translational Medicine. 2018;16(1):82.
  • Leiter A, Gnjatic S, Fowkes M; et al. A COMMON PITUITARY AUTOANTIBODY IN TWO PATIENTS WITH IMMUNE CHECKPOINT INHIBITOR-MEDIATED HYPOPHYSITIS: ZCCHC8. AACE Clinical Case Reports. 2020;6(4):e151–e160.
  • Zhai Y, Ye X, Hu F, et al. Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system. Journal for ImmunoTherapy of Cancer. 2019; 7 2861.
  • González-Rodríguez E, Rodríguez-Abreu D,Immune checkpoint inhibitors review and management of endocrine adverse events.Oncologist.2016;217.804–816.
  • Byun DJ, Wolchok JD, Rosenberg LM; et al. Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies. Nature Reviews Endocrinology. 2017.134 195–207.
  • Ferrari SM, Fallahi P, Elia G et al., Autoimmune Endocrine Dysfunctions Associated with Cancer Immunotherapies. International Journal of Molecular Sciences. 2019;20(10):2560.
  • Cukier P, Santini FC, Scaranti M; et al. Endocrine side effects of cancer immunotherapy. Endocrine-Related Cancer. 2017.2412 T331–T347.
  • Corsello SM, Barnabei A, Marchetti P; et al. Endocrine side effects induced by immune checkpoint inhibitors. The Journal of Clinical Endocrinology & Metabolism. 2013.984 1361–1375.
  • Xu H, Tan P, Zheng X et al. Immune-related adverse events following administration of anti-cytotoxic T-lymphocyte-associated protein-4 drugs: a comprehensive systematic review and meta-analysis Drug Des Devel Ther 2019 13 2215–2234.
  • Khoja L, Day D, Wei-Wu Chen T; et al. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Annals of Oncology. 2017.2810 2377–2385.
  • Bertrand A, Kostine M, Barnetche T, et al. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med. 2015; 13 2111.
  • Costa R, Carneiro BA, Agulnik M; et al. Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Oncotarget. 2017.85 8910–8920.
  • Faje A, Reynolds K, Zubiri L et al., Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis. European Journal of Endocrinology.2019;1813 211‐219.
  • de Filette J, Andreescu CE, Cools F et al., A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors. Hormone and Metabolic Research.2019;513 145–156.
  • Barroso-Sousa R, Barry WT, Garrido-Castro AC; et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncology. 2018.42 173–182.
  • Zhang B, Wu Q, Zhou YL et al. Immune-related adverse events from combination immunotherapy in cancer patients: A comprehensive meta-analysis of randomized controlled trials. International Immunopharmacology. 2018;63 292–298.
  • Baxi S, Yang A, Gennarelli RL et al. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis BMJ 2018 360 k793.
  • Bekki T, Takakura Y, Kochi M, et al. A Case of Isolated Adrenocorticotropic Hormone Deficiency Caused by Pembrolizumab. Case Reports in Oncology. 2020; 13 200–2061.
  • Keitaro Kanie K, Genzo Iguchi G, Bando H; et al. Two Cases of Atezolizumab-Induced Hypophysitis. Journal of the Endocrine Society. 2018.21 91–95.
  • Percik R, Shlomai G, Tirosh A; et al. Isolated autoimmune adrenocorticotropic hormone deficiency: from a rare disease to the dominant cause of adrenal insufficiency related to check point inhibitors. Autoimmunity Reviews. 2020.192 102454.
  • Cho KY, Miyoshi H, Nakamura A; et al. Hyponatremia can be a powerful predictor of the development of isolated ACTH deficiency associated with nivolumab treatment [Letter to the Editor]. Endocrine Journal. 2017.642 235–236.
  • Ohara N, Kobayashi M, Ohashi K; et al. Isolated adrenocorticotropic hormone deficiency and thyroiditis associated with nivolumab therapy in a patient with advanced lung adenocarcinoma: a case report and review of the literature. Journal of Medical Case Reports. 2019.131 88.
  • Takeno A, Yamamoto M, Morita M; et al. Late-onset isolated adrenocorticotropic hormone deficiency caused by nivolumab: a case report. BMC Endocrine Disorders. 2019.191 25.
  • Kitajima K, Ashida K, Wada N; et al. Isolated ACTH deficiency probably induced by autoimmune-related mechanism evoked with nivolumab. Japanese Journal of Clinical Oncology. 2017.475 463–466.
  • Seki T, Yasuda A, Oki M, et al. Secondary Adrenal Insufficiency Following Nivolumab Therapy in a Patient with Metastatic Renal Cell Carcinoma. The Tokai Journal of Experimental and Clinical Medicine.2017;423.115–120.
  • Takaya K, Sonoda M, Fuchigami A; et al. Isolated adrenocorticotropic hormone deficiency caused by nivolumab in a patient with metastatic lung cancer. Internal Medicine. 2017.5618 2463–2469.
  • Zhu Y, Wu HH, Wang W, <p>A case of small-cell lung cancer with adrenocorticotropic hormone deficiency induced by nivolumab.OncoTargets and Therapy.2019;12.2181‐2186.
  • Zeng MF, Chen L, Ye HY, et al. Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: case report and review. Medicine (Baltimore). 2017; 96 e842644.
  • Kastrisiou M, Kostadima F-L, Kefas A et al. Nivolumab-induced hypothyroidism and selective pituitary insufficiency in a patient with lung adenocarcinoma: a case report and review of the literature. ESMO Open.2017 24 e000217.
  • Takebayashi K, Ujiie A, Kubo M; et al. Isolated Adrenocorticotropic Hormone Deficiency and Severe Hypercalcemia After Destructive Thyroiditis in a Patient on Nivolumab Therapy With a Malignant Melanoma. Journal of Clinical Medicine Research. 2018;10(4):358–362.
  • Ariyasu H, Inaba H, Ota T; et al. Thyrotoxicosis and Adrenocortical Hormone Deficiency During Immune-checkpoint Inhibitor Treatment for Malignant Melanoma. In Vivo (Athens, Greece). 2018.322 345–351.
  • Okano Y, Satoh T, Horiguchi K; et al. Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma. Endocrine Journal. 2016.6310 905–912.
  • Yamagata S, Kageyama K, Takayasu S; et al. Progression of Hypopituitarism and Hypothyroidism after Treatment with Pembrolizumab in a Patient with Adrenal Metastasis from Non-small-cell Lung Cancer. Internal Medicine. 2019.5824 3557–3562.
  • Okahata S, Sakamoto K, Mitsumatsu T; et al. Fulminant type 1 diabetes associated with Isolated ACTH deficiency induced by anti-programmed cell death 1 antibody—insight into the pathogenesis of autoimmune endocrinopathy. Endocrine Journal. 2019.664 295–300.
  • Lupi I, Brancatella A, Cosottini M. et al. Clinical heterogeneity of hypophysitis secondary to PD-1/PD-L1 blockade: insights from four cases. Endocrinol Diabetes Metab Case Rep. 2019;19–0102. Advance online publication
  • Ascierto PA, Del Vecchio M, Robert C; et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2017;18(5):611–622.
  • Maker AV, Yang JC, Sherry RM; et al. Intrapatient dose escalation of Anti???CTLA-4 antibody in patients with metastatic melanoma. Journal of Immunotherapy. 2006.294 455–463.
  • Albarel F, Gaudy C, Castinetti F; et al. Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma. European Journal of Endocrinology. 2015;172(2):195–204
  • Faje AT, Sullivan R, Lawrence D; et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic Melanoma. The Journal of Clinical Endocrinology & Metabolism. 2014.9911 4078–4085.
  • Min L, Hodi FS, Giobbie-Hurder A; et al. Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study. Clinical Cancer Research. 2015:21(4):749–755.
  • Torino F, Barnabei A, De Vecchis L; et al. Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen 4: challenges from a new cause of a rare disease. The Oncologist. 2012;17(4):525–535.
  • Kumar M, Bowyer S, Lorigan P, et al. Ipilimumab-induced hypophysitis in melanoma patients: a single centre experience. Endocrine Abstracts. 2016 41 GP164.
  • Weber JS, Hodi FS, Wolchok JD; et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. Journal of Clinical Oncology. 2017;35(7):785–792.
  • Scott ES, Long GV, Guminski A; et al. The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma. European Journal of Endocrinology. 2018;178(2):173–180
  • KEYTRUDA® (pembrolizumab) Prescribing Information Available from: http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. Accessed May 2020.
  • Bai X, Lin X, Zheng K; et al. Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: a disproportionality analysis using the WHO adverse drug reaction database, VigiBase. Endocrine. 2020;69(3):670–681.
  • Castinetti F, Albarel F, Archambeaud F; et al. French endocrine society guidance on endocrine side effects of immunotherapy. Endocrine-Related Cancer. 2019;26(2):G1–G18.
  • Sanders LR Water Metabolism McDermott MT endocrine secrets 6th Edition [United States of America] Elsevier, Saunders; 2013. p.  198–218.
  • De Sousa SMC, Sheriff N, Tran CH; et al. Fall in thyroid stimulating hormone (TSH) may be an early marker of ipilimumab-induced hypophysitis. Pituitary. 2018;21(3):274–282.
  • Bellastella G, Maiorino MI, Bizzarro A; et al. Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects. Pituitary. 2016;19(6)625–642.
  • Falorni A, Minarelli V, Bartoloni E; et al. Diagnosis and classification of autoimmune hypophysitis. Autoimmunity Reviews. 2014;13(4–5) 412‐416.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. New England Journal of Medicine. 2015;373(1):23–34.
  • Juszczak A, Gupta A, Karavitaki N; et al. MECHANISMS IN ENDOCRINOLOGY: ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review. European Journal of Endocrinology. 2012;167(1):1–5.
  • Min L, Vaidya A, Becker C, Association of ipilimumab therapy for advanced melanoma with secondary adrenal insufficiency: a case series. Endocrine Practice. 2012;18(3):351–355.
  • Weber JS, Dummer R, de Pril V; et al. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer. 2013;119(9):1675–1682.
  • Weber JS, Kähler KC, Hauschild A, Management of immune-related adverse events and kinetics of response with ipilimumab. Journal of Clinical Oncology. 2012;30(21):2691–2697.
  • Caturegli P, Newschaffer C, Olivi A; et al. Autoimmune hypophysitis. Endocrine Reviews. 2005;26(5):599–614.
  • Mahzari M, Liu D, Arnaout A et al. Immune checkpoint inhibitor therapy associated hypophysitis Clinical Medicine Insights: Endocrinology and Diabetes 2015;8:21‐28.
  • Thapi S, Leiter A, Galsky M; et al. Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis. Journal for ImmunoTherapy of Cancer. 2019;7(1):248.
  • Nallapaneni NN, Mourya R, Bhatt VR; et al. Ipilimumab-induced hypophysitis and uveitis in a patient with metastatic melanoma and a history of ipilimumab-induced skin rash. Journal of the National Comprehensive Cancer Network. 2014;12(8):1077–1081.
  • Zhao C, Tella SH, Del Rivero J; et al. Anti–PD-L1 treatment induced central diabetes insipidus. The Journal of Clinical Endocrinology & Metabolism. 2018;103(2):365–369.
  • Gunawan F, George E, Roberts A, Combination immune checkpoint inhibitor therapy nivolumab and ipilimumab associated with multiple endocrinopathies.Endocrinology, Diabetes & Metabolism Case Reports.2018;2018:17–0146.
  • Deligiorgi MV, Siasos G, Vergadis C et al. Central diabetes insipidus related to anti-programmed cell-death 1 protein active immunotherapy International Immunopharmacology 2020;83:106427.
  • Andrioli M, Giraldi FP, Cavagnini F, Isolated corticotrophin deficiency.Pituitary. 2006;9(4):289–295.
  • Haanen J, Carbonnel F, Robert C; et al. ESMO guidelines committee. management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2017.28suppl_4 iv119–iv142.
  • Brahmer JR, Lacchetti C, Schneider BJ; et al. National comprehensive cancer network. management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: american society of clinical oncology clinical practice guideline. Journal of Clinical Oncology. 2018;36(17):1714–1768.
  • Puzanov I, Diab A, Abdallah K; et al. Society for immunotherapy of cancer toxicity management working group. managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the society for immunotherapy of cancer (sitc) toxicity management working group. Journal for ImmunoTherapy of Cancer. 2017;5(1): 95.
  • Management of immunotherpy-Related Toxicities. National comphrehensive cancer network (NCCN) guidelines. Version 2; 2019. Available from https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Accessed Jul 2019
  • Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab.2016;101(11):3392–3888.
  • Sugihara H, Review on recent topics in hypophysitis. Journal of Nippon Medical School. 2017;84(5):201‐208.
  • Bornstein SR, Allolio B, Arlt W; et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2016.1012 364–389.
  • Min L, Hodi FS, Giobbie-Hurder A, et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. Clin. Cancer Res. 2015;21(4):749–55.
  • Molitch ME, Clemmons DR, Malozowski S, et al. Endocrine Society. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 20112011;96(6):1587–609.
  • https://radiopaedia.org/articles/lymphocytic-hypophysitis. Accessed Jun 2020.
  • Carpenter KJ, Murtagh RD, Lilienfeld H; et al. Ipilimumab-induced hypophysitis: MR imaging findings. American Journal of Neuroradiology. 2009;30(9):1751–1753.
  • Prete A, Salvatori R, Hypophysitis 2018 Aug 15 Endotext Feingold KR, Anawalt B, Boyce A et al. editors www.ncbi.nlm.nih.gov/books/NBK519842/MDText.com Inc, South Dartmouth, MA
  • Girotra M, Hansen A, Farooki A; et al. Investigational drug steering committee (idsc) immunotherapy task force collaboration. the current understanding of the endocrine effects from immune checkpoint inhibitors and recommendations for management. JNCI Cancer Spectrum. 2018.23 pky021.
  • Xu C, Ricciuti A, Caturegli P, et al. Autoimmune lymphocytic hypophysitis in association with autoimmune eye disease and sequential treatment with infliximab and rituximab. Pituitary. 2015; 18 441–4474.
  • Adams NC, Farrell TP, O’Shea A; et al. Neuroimaging of central diabetes insipidus—when, how and findings. Neuroradiology. 2018;60(10):995–1012.
  • Cacciari E, Zucchini S, Carlà G; et al. Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance. Archives of Disease in Childhood. 1990.6511 1199–1202.
  • Turner HE, Wass JAH Hypothyroidism Oxford handbook of endocrinology and diabetes 2nd ed [United States of America] Oxford University Press Inc; 2009. p. 56–65.
  • Meikle AW, Tyler FH, Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function. The American Journal of Medicine. 1977;63(2):200–207.
  • Higham CE, Olsson-Brown A, Carroll P; et al. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: acute management of the endocrine complications of checkpoint inhibitor therapy. Endocr Connect. 2018;7(7): G1–G7.
  • Cooksley T, Girotra M, Ginex P; et al. Multinational association of supportive care in cancer (MASCC) 2020 clinical practice recommendations for the management of immune checkpoint inhibitor endocrinopathies and the role of advanced practice providers in the management of immune-mediated toxicities. Support Care Cancer. 2020;28(12): 6175–6181.
  • Faje AT, Lawrence D, Flahert 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):3706–3714.
  • Johnson DB, Toxicities and outcomes: do steroids matter? Cancer. 2018;12418.3638–3640.
  • Lammert A, Schneider HJ, Bergmann T; et al. Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or immunosuppressive therapy. Experimental and Clinical Endocrinology & Diabetes. 2013.12110 581–587.
  • Park HJ, Ahn ST, Moon DG, Evolution of guidelines for testosterone replacement therapy. J Clin Med. 2019;83.410.
  • Deli T, Orosz M, Jakab A, Hormone replacement therapy in cancer survivors – review of the literature. Pathol Oncol Res. 2020;261.63–78.
  • D’Alonzo M, Bounous VE, Villa M, et al., Current evidence of the oncological benefit-risk profile of hormone replacement therapy. Medicina (Kaunas). 2019;559.573.
  • Fraietta R, Zylberstejn DS, Esteves SC, Hypogonadotropic hypogonadism revisited. Clinics (Sao Paulo). 2013;68Suppl S1.81–88.
  • Stuenkel CA, Davis SR, Gompel A; et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2015;100(11):3975–4011.
  • The 2017 hormone therapy position statement of The North American Menopause Society The 2017 hormone therapy position statement of the North American menopause society. Menopause . 2017. 247. 728–753.
  • Bhasin S, Brito JP, Cunningham GR; et al. Testosterone therapy in men with hypogonadism: an endocrine society* clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2018.1035 1715–1744.
  • Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an endocrine society clinical practice guideline. J Endocrinol Metab.2016;10111.3888–3921.
  • Treatment of central diabetes insipidus. Available from http://www.uptodate.com. Accessed Feb 2019
  • Curtò L, Torre ML, Cotta OR et al. Lymphocytic hypophysitis: differential diagnosis and effects of high-dose pulse steroids, followed by azathioprine, on the pituitary mass and endocrine abnormalities — report of a case and literature review ScientificWorldJournal 2010 10 126–134.
  • Si X, Song P, Ni J, Management of immune checkpoint inhibitor-related adverse events: a review of case reports.Thoracic Cancer.2020;113.498–504.
  • Myers G,Immune-related adverse events of immune checkpoint inhibitors: a brief review.Current Oncology.2018;25(5):342–347.
  • Stelmachowska-Banaś M, Czajka-Oraniec I, Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review. Endocrine Connections. 2020;9(10):R207–R228.
  • El Majzoub I, Qdaisat A, Thein KZ; et al. Adverse effects of immune checkpoint therapy in cancer patients visiting the emergency department of a comprehensive cancer center. Annals of Emergency Medicine. 2019;73(1):79–87.
  • Cooksley T, Gupta A, Al-Sayed T, et al., Emergency presentations in patients treated with immune checkpoint inhibitors.European Journal of Cancer.2020;130.193–197.
  • Cooksley T, Knight T, Gupta A; et al. Emergency ambulatory outpatient management of immune-mediated hypophysitis. Supportive Care in Cancer. 2020;28(9):3995–3999.
  • https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761097s000lbl.pdf. Accessed Jun 2020
  • https://www.ema.europa.eu/en/documents/product-information/libtayo-epar-product-information_en.pdf. Accessed Jun 2020
  • Migden MR, Rischin D, Schmults CD; et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. New England Journal of Medicine. 2018.3794 341–351.
  • Johnson DB, Sullivan RJ, Ott PA; et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncology. 2016.22 234–240.
  • Menzies AM, Johnson DB, Ramanujam S; et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Annals of Oncology. 2017.282 368–376.
  • Abdel-Wahab N, Shah M, Lopez-Olivo MA, et al. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review. Annals of Internal Medicine. 2018; 168(2):121–130.
  • Kuo C-HS, Wang -C-C, Huang Y-C; et al. Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non-small cell lung cancer. Thoracic Cancer. 2019;10(5):1158–1166.
  • Langer CJ, Gadgeel SM, Borghaei H; et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497–1508.
  • Rizvi NA, Hellmann MD, Brahmer JR; et al. Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non–small-cell lung cancer.Journal of Clinical Oncology. 2016.34(25):2969–2979.
  • Ribas A, Dummer R, Puzanov I; et al. Oncolytic virotherapy promotes intratumoral t cell infiltration and improves anti-PD-1 immunotherapy. Cell. 2018;174(4):1031–1032.
  • Amin A, Lawson DH, Salama AKS, et al. Phase II study of vemurafenib followed by ipilimumab in patients with previously untreated BRAF-mutated metastatic melanoma. Journal for ImmunoTherapy of Cancer. 2016; 4(1):44.
  • Weiss GJ, Waypa J, Blaydorn L; et al. A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). British Journal of Cancer. 2017;117(1):33–40.
  • Hodi FS, Lawrence D, Cecilia Lezcano C, Bevacizumab plus ipilimumab in patients with metastatic Melanoma. Cancer Immunology Research. 2014;2(7):632–642.
  • van den Eertwegh AJ, Versluis J, van den Berg HP; et al. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2012;13(5):509–517.
  • Mitsaki S, Flynn M, Gore M, et al. Development of endocrinopathy following treatment of metastatic melanoma with an immune checkpoint inhibitor is associated with better response. Endocrine Abstracts.2017;50:OC2.4.
  • Downey SG, Klapper JA, Smith FO; et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clinical Cancer Research. 2007;13(22):6681–6688.
  • Ricciuti B, Genova C, De Giglio A; et al. 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. Journal of Cancer Research and Clinical Oncology. 2019:145(2):479–485.
  • Indini A, Di Guardo L, Cimminiello C; et al. Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma. Journal of Cancer Research and Clinical Oncology. 2019;145(2) 511–521.
  • Rogado J, Sánchez-Torres JM, Romero-Laorden N et al. Immune-related adverse events predict the therapeutic efficacy of anti–PD-1 antibodies in cancer patients European Journal of Cancer 2019 109 21–27.
  • Hu W, Wang G, Wang Y; et al. Uncoupling therapeutic efficacy from immune-related adverse events in immune checkpoint blockade. iScience. 2020;23(10):101580.
  • Das S, Johnson DB, Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. Journal for ImmunoTherapy of Cancer. 2019;71.306.
  • Krashin E, Piekiełko-Witkowska A, Ellis M et al. Thyroid hormones and cancer: a comprehensive review of preclinical and clinical studies Frontiers in Endocrinology 2019 10 59.
  • Hercbergs A, Johnson RE, Ashur‐Fabian O; et al. Medically induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study. Oncologist. 2015;20(1):72–76.
  • Rodríguez-Molinero A, Hercbergs A, Sarrias M; et al. Plasma 3,3’,5-Triiodo-L-thyronine [T3] level mirrors changes in tumor markers in two cases of metastatic cancer of the breast and pancreas treated with exogenous L-T3. Cancer Biomarkers. 2018.21(2):433–438.
  • Martins F, Sykiotis GP, Maillard M, et al. New therapeutic perspectives to manage refractory immune checkpoint-related toxicities. The Lancet Oncology. 2019; 20(1):e54–e64
  • Köessler T, Olivier T, Fertani S. et al.Ipilimumab-related hypophysitis may precede severe CNS immune attack.Ann Oncol. LETTERS TO THE EDITOR 2016;27(10):P1975–1976.

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