R. D. Schreiber, L. J. Old, and M. J. Smyth, Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion, Science. 25 mars, vol.331, issue.6024, p.156570, 2011.

G. P. Dunn, A. T. Bruce, H. Ikeda, L. J. Old, and R. D. Schreiber, Cancer immunoediting: from immunosurveillance to tumor escape, Nat Immunol, vol.3, issue.11, p.9918, 2002.
DOI : 10.1038/ni1102-991

A. S. , Cancer after transplantation

D. Sur,

I. P. , Malignant melanoma in organ allograft recipients. -PubMed -NCBI

D. Sur,

T. N. Schumacher and R. D. Schreiber, Neoantigens in cancer immunotherapy, Science. 3 avr, vol.348, issue.6230, p.6974, 2015.
DOI : 10.1126/science.aaa4971

M. Desbois, S. Champiat, and N. Chaput, Lever la tolérance immunitaire en cancérologie
DOI : 10.1016/j.bulcan.2014.12.002

D. Sur,

. Wh-f, Historique de l'immunothérapie. Changement de paradigme!?

C. Granier, S. Karaki, H. Roussel, C. Badoual, T. Tran et al.,

, Rev Med Interne, vol.37, issue.10, p.694700, 2016.

L. Bris, Y. Béné, and M. C. , Le point sur les CAR T-cells, Rev Oncol Hématologie Pédiatrique. 1 déc, vol.4, issue.4, p.2029, 2016.

O. J. Finn, Cancer immunology, N Engl J Med. 19 juin, vol.358, issue.25, p.270415, 2008.

V. A. Boussiotis, Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway

, N Engl J Med, vol.375, issue.18, p.176778, 2016.

D. M. Pardoll, The blockade of immune checkpoints in cancer immunotherapy, Nat Rev Cancer. 22 mars, vol.12, issue.4, p.25264, 2012.

Y. Xia, L. J. Medeiros, and K. H. Young, Immune checkpoint blockade: Releasing the brake towards hematological malignancies, Blood Rev. mai, vol.30, issue.3, p.189200, 2016.
DOI : 10.1016/j.blre.2015.11.003

A. Ribas, Tumor immunotherapy directed at PD-1, N Engl J Med. 28 juin, vol.366, issue.26, p.25179, 2012.
DOI : 10.1056/nejme1205943

F. S. Hodi, S. J. O'day, D. F. Mcdermott, R. W. Weber, J. A. Sosman et al.,

, Improved Survival with Ipilimumab in Patients with Metastatic Melanoma, N Engl J Med. 19 août, vol.363, issue.8, p.71123, 2010.

C. Robert, L. Thomas, I. Bondarenko, S. O'day, J. Weber et al., Ipilimumab plus dacarbazine for previously untreated metastatic melanoma, N Engl J Med. 30 juin, vol.364, issue.26, p.251726, 2011.

J. S. Weber, S. P. Angelo, D. Minor, F. S. Hodi, R. Gutzmer et al., Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, Lancet Oncol. avr, vol.16, issue.4, p.37584, 2015.

C. Robert, G. V. Long, B. Brady, C. Dutriaux, M. Maio et al., Nivolumab in previously untreated melanoma without BRAF mutation, N Engl J Med. 22 janv, vol.372, issue.4, p.32030, 2015.

A. Ribas, I. Puzanov, R. Dummer, D. Schadendorf, O. Hamid et al.,

, Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial, Lancet Oncol. août, vol.16, issue.8, p.90818, 2015.

C. Robert, J. Schachter, G. V. Long, A. Arance, J. J. Grob et al., Pembrolizumab 78# # versus Ipilimumab in Advanced Melanoma, N Engl J Med. 25 juin, vol.372, issue.26, p.252132, 2015.

J. Schachter, A. Ribas, G. V. Long, A. Arance, J. Grob et al., Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006), Lancet Lond Engl. 16 août, 2017.

J. Larkin, V. Chiarion-sileni, R. Gonzalez, J. J. Grob, C. L. Cowey et al., Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma, N Engl J Med. 2 juill, vol.373, issue.1, p.2334, 2015.

A. Eggermont, V. Chiarion-sileni, J. Grob, R. Dummer, J. D. Wolchok et al., Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy, N Engl J Med, vol.10, p.184555, 2016.

J. Weber, M. Mandala, D. Vecchio, M. Gogas, H. J. Arance et al.,

, Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma, N Engl J Med, vol.09, p.182435, 2017.

H. Borghaei, L. Paz-ares, L. Horn, D. R. Spigel, M. Steins et al., Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer, N Engl J Med, vol.373, issue.17, p.162739, 2015.

J. Brahmer, K. L. Reckamp, P. Baas, L. Crinò, W. Eberhardt et al., Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer, N Engl J Med. 9 juill, vol.373, issue.2, p.12335, 2015.

P. N. Aguiar, D. Mello, R. A. Hall, P. Tadokoro, H. et al., PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data, Immunotherapy. mai, vol.9, issue.6, p.499506, 2017.

M. Reck, D. Rodríguez-abreu, A. G. Robinson, R. Hui, T. Cs?szi et al., Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer, N Engl J Med, vol.10, p.182333, 2016.

D. P. Carbone, M. Reck, L. Paz-ares, B. Creelan, L. Horn et al., First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer, N Engl J Med, vol.22, issue.25, p.241526, 2017.

M. D. Hellmann, T. Ciuleanu, A. Pluzanski, J. S. Lee, G. A. Otterson et al., Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden, N Engl J Med. 16 avr, 2018.

L. Fehrenbacher, A. Spira, M. Ballinger, M. Kowanetz, J. Vansteenkiste et al., Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial, Lancet Lond Engl. 30 avr, vol.387, p.183746, 2016.

A. Rittmeyer, F. Barlesi, D. Waterkamp, K. Park, F. Ciardiello et al.,

, Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial, Lancet Lond Engl, vol.21, p.25565, 2017.

R. J. Motzer, B. Escudier, D. F. Mcdermott, S. George, H. J. Hammers et al., Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma, N Engl J Med, vol.373, p.180313, 2015.

R. J. Motzer, N. M. Tannir, D. F. Mcdermott, A. Frontera, O. Melichar et al., Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma, N Engl J Med. 05, vol.378, issue.14, p.127790, 2018.

J. Bellmunt, R. De-wit, D. J. Vaughn, Y. Fradet, J. Lee et al., Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma, N Engl J Med, vol.16, issue.11, p.101526, 2017.

R. L. Ferris, G. Blumenschein, F. J. Guigay, J. Colevas, A. D. Licitra et al., Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck, N Engl J Med. 10 79# #, vol.375, p.185667, 2016.

R. Chen, P. L. Zinzani, M. A. Fanale, A. P. Johnson, N. A. Brice et al., Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma, J Clin Oncol Off J Am Soc Clin Oncol. 1 juill, vol.35, p.212532, 2017.

H. L. Kaufman, J. Russell, O. Hamid, S. Bhatia, P. Terheyden et al.,

, KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer, Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial, vol.17, 2016.

M. J. Overman, R. Mcdermott, J. L. Leach, S. Lonardi, H. Lenz et al.,

, Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study, Lancet Oncol. sept, vol.18, issue.9, p.118291, 2017.

A. B. El-khoueiry, B. Sangro, T. Yau, T. S. Crocenzi, M. Kudo et al., Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, noncomparative, phase 1/2 dose escalation and expansion trial, Lancet Lond Engl. 24 juin, vol.389, p.2492502, 2017.

D. T. Le, J. N. Uram, H. Wang, B. R. Bartlett, H. Kemberling et al.,

G. , C. F. Robert, C. Kerr, K. M. Peters, S. Larkin et al., Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Blockade in Tumors with Mismatch-Repair Deficiency, vol.372, p.11942, 2015.

J. Gong, A. Chehrazi-raffle, S. Reddi, and R. Salgia, Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations, J Immunother Cancer. 23 janv, vol.6, issue.1, p.8, 2018.

S. Andrews and R. Holden, Characteristics and management of immunerelated adverse effects associated with ipilimumab, a new immunotherapy for metastatic melanoma, Cancer Manag Res. 12 sept, vol.4, p.299307, 2012.

L. Spain, S. Diem, and J. Larkin, Management of toxicities of immune checkpoint inhibitors, Cancer Treat Rev. mars, vol.44, p.5160, 2016.

J. S. Weber, K. C. Kähler, and A. Hauschild, Management of immune-related adverse events and kinetics of response with ipilimumab, J Clin Oncol Off J Am Soc Clin Oncol. 20 juill, vol.30, issue.21, p.26917, 2012.

A. Bertrand, M. Kostine, T. Barnetche, M. Truchetet, and T. Schaeverbeke, Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis, BMC Med. 4 sept, vol.13, p.211, 2015.

S. Champiat, O. Lambotte, E. Barreau, R. Belkhir, A. Berdelou et al., Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper, Ann Oncol Off J Eur Soc Med Oncol. avr, vol.27, issue.4, p.55974, 2016.

R. Pillai, M. Behera, T. Owonikoko, A. Kamphorst, S. Pakkala et al., , p.6

, Evaluation of Toxicity Profile of PD-1 versus PD-L1 Inhibitors in Non-Small Cell Lung Cancer (NSCLC), Congrès français de rhumatologie!: gérer les effets secondaires rhumatologiques des inhibiteurs du check-point, vol.12, 2017.

D. Sur,

F. Torino, A. Barnabei, R. M. Paragliola, P. Marchetti, R. Salvatori et al., Endocrine side-effects of anti-cancer drugs: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses, Eur J Endocrinol. déc, vol.169, issue.6, pp.153-164, 2013.

G. Borodic, D. M. Hinkle, and Y. Cia, Drug-induced graves disease from CTLA-4 receptor suppression, Ophthal Plast Reconstr Surg. août, vol.27, issue.4, pp.87-88, 2011.

C. Yu, I. J. Chopra, and E. Ha, A novel melanoma therapy stirs up a storm: ipilimumabinduced thyrotoxicosis, Endocrinol Diabetes Metab Case Rep, p.140092, 2015.

P. Cukier, F. C. Santini, M. Scaranti, and A. O. Hoff, Endocrine side effects of cancer immunotherapy, Endocr Relat Cancer. déc, vol.24, issue.12, p.33147, 2017.

D. A. Delivanis, M. P. Gustafson, S. Bornschlegl, M. M. Merten, L. Kottschade et al., Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms, J Clin Endocrinol Metab. 1 août, vol.102, issue.8, p.277080, 2017.

J. De-filette, Y. Jansen, M. Schreuer, H. Everaert, B. Velkeniers et al., Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab, J Clin Endocrinol Metab, vol.101, issue.11, p.44319, 2016.

S. Bacanovic, I. A. Burger, P. Stolzmann, J. Hafner, and M. W. Huellner, Ipilimumab-Induced Adrenalitis: A Possible Pitfall in 18F-FDG-PET/CT, Clin Nucl Med. nov, vol.40, issue.11, pp.518-519, 2015.

A. T. Faje, R. Sullivan, D. Lawrence, N. A. Tritos, R. Fadden et al.,

, Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma, J Clin Endocrinol Metab, vol.99, issue.11, p.407885, 2014.

E. Mcelnea, N. Mhéalóid, A. Moran, S. Kelly, R. Fulcher et al., Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab, Orbit Amst Neth. déc, vol.33, issue.6, p.4247, 2014.

C. A. Sheldon, J. Kharlip, and M. A. Tamhankar, Inflammatory Orbitopathy Associated With Ipilimumab, Ophthal Plast Reconstr Surg. juin, vol.33, issue.3S, p.1558, 2017.

L. B. Jørgensen and K. Yderstraede, Acutely induced diabetes mellitus in a 63-year-old female after treatment with ipilimumab for metastatic melanoma

, Ugeskr Laeger. 11 sept, vol.179, 2017.

D. J. Byun, J. D. Wolchok, L. M. Rosenberg, and M. Girotra, Cancer immunotherapy -immune checkpoint blockade and associated endocrinopathies, Nat Rev Endocrinol. avr, vol.13, issue.4, p.195207, 2017.

B. Mcmillen, M. S. Dhillon, Y. , and S. , A rare case of thyroid storm, BMJ Case Rep. 18 avr, 2016.

M. A. Win, K. Z. Thein, A. Qdaisat, and S. Yeung, Acute symptomatic hypocalcemia from immune checkpoint therapy-induced hypoparathyroidism, Am J Emerg Med. juill, vol.35, issue.7, pp.1039-1044, 2017.

M. N. Joshi, B. C. Whitelaw, M. Palomar, Y. Wu, and P. V. Carroll, Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review, Clin Endocrinol (Oxf). sept, vol.85, issue.3, p.3319, 2016.

S. M. Corsello, A. Barnabei, P. Marchetti, D. Vecchis, L. Salvatori et al., Endocrine Side Effects Induced by Immune Checkpoint Inhibitors, J Clin Endocrinol Metab. 1 avr, vol.98, issue.4, p.136175, 2013.

M. Ryder, M. Callahan, M. A. Postow, J. Wolchok, and J. A. Fagin, Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution, Endocr Relat Cancer. avr, vol.21, issue.2, p.37181, 2014.

L. Min, F. S. Hodi, A. Giobbie-hurder, P. A. Ott, J. J. Luke et al., Systemic high dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study, Clin Cancer Res Off J Am Assoc Cancer Res. 15 févr, vol.21, issue.4, p.74955, 2015.

S. Iwama, A. De-remigis, M. K. Callahan, S. F. Slovin, J. D. Wolchok et al., Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody, Sci Transl Med. 2 avr, vol.6, issue.230, pp.230-275, 2014.

P. Caturegli, D. Dalmazi, G. Lombardi, M. Grosso, F. Larman et al.,

, Hypophysitis Secondary to Cytotoxic T-Lymphocyte-Associated Protein 4 Blockade: Insights into Pathogenesis from an Autopsy Series, Am J Pathol. déc, vol.186, issue.12, p.322535, 2016.

S. Orlov, F. Salari, L. Kashat, and P. G. Walfish, Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies, J Clin Endocrinol Metab. mai, vol.100, issue.5, p.173841, 2015.

M. Alhusseini and J. Samantray, Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms, Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc. avr, vol.125, issue.4, p.2679, 2017.

T. E. Angell, L. Min, T. J. Wieczorek, and F. S. Hodi, Unique Cytologic Features of Thyroiditis Caused by Immune Checkpoint Inhibitor Therapy for Malignant Melanoma, Genes Dis. mars, vol.5, issue.1, p.468, 2018.

I. Yamauchi, Y. Sakane, Y. Fukuda, T. Fujii, D. Taura et al., Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study, Thyroid Off J Am Thyroid Assoc. juill, vol.27, issue.7, p.894901, 2017.

T. Narita, N. Oiso, Y. Taketomo, K. Okahashi, K. Yamauchi et al., Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab, J Dermatol. févr, vol.43, issue.2, p.2104, 2016.

N. M. Villa, A. Farahmand, L. Du, M. W. Yeh, S. Smooke-praw et al., Endocrinopathies with use of cancer immunotherapies, Clin Endocrinol (Oxf). févr, vol.88, issue.2, p.32732, 2018.

J. C. Osorio, A. Ni, J. E. Chaft, R. Pollina, M. K. Kasler et al., Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer, Ann Oncol Off J Eur Soc Med Oncol, vol.01, issue.3, p.5839, 2017.

K. Haratani, H. Hayashi, Y. Chiba, K. Kudo, K. Yonesaka et al., Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non-Small-Cell Lung Cancer, JAMA Oncol. 1 mars, vol.4, issue.3, p.3748, 2018.

U. Azmat, D. Liebner, A. Joehlin-price, A. Agrawal, and F. Nabhan, Treatment of Ipilimumab Induced Graves' Disease in a Patient with Metastatic Melanoma, Case Rep Endocrinol, p.2087525, 2016.

U. Khan, H. Rizvi, D. Sano, J. Chiu, and T. Hadid, Nivolumab induced myxedema crisis, J Immunother Cancer, vol.5, p.13, 2017.

L. Min, A. Vaidya, and C. Becker, Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy, Eur J Endocrinol. févr, vol.164, issue.2, p.3037, 2011.

M. Shiba, H. Inaba, H. Ariyasu, S. Kawai, Y. Inagaki et al., A Case of Fulminant Type 1 Diabetes Mellitus Accompanied by Positive Conversion of Anti-insulin Antibody after the Administration of Anti-CTLA-4 Antibody Following the Discontinuation of Anti-PD-1 Antibody, Intern Med Tokyo Jpn. 28 févr, 2018.

P. N. Changizzadeh, S. Mukkamalla, and V. A. Armenio, Combined checkpoint inhibitor therapy causing diabetic ketoacidosis in metastatic melanoma, J Immunother Cancer. 19 déc, vol.5, issue.1, p.97, 2017.

L. Min and N. Ibrahim, Ipilimumab immunotherapy for advanced melanoma induced autoimmune adrenalitis, Lancet Diabetes Endocrinol. nov, vol.1, issue.3, p.15, 2013.

H. Trainer, P. Hulse, C. E. Higham, P. Trainer, P. Lorigan et al., Hyponatraemia secondary to nivolumab-induced primary adrenal failure. Endocrinol Diabetes Metab Case Rep, J Clin, vol.88, p.82, 2016.

, Epidémiologie des cancers -Les chiffres du cancer en France | Institut National Du Cancer, # Oncol Off J Am Soc Clin Oncol. 10 juin, vol.36, issue.17, 2018.

T. Kobayashi, S. Iwama, Y. Yasuda, N. Okada, T. Tsunekawa et al., Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study, J Endocr Soc. 1 mars, vol.2, issue.3, p.24151, 2018.

K. D. Burman, L. Wartofsky, . Clinical, and . Practice, Thyroid Nodules, N Engl J Med. 10 déc, vol.373, issue.24, p.234756, 2015.

J. R. Garber, R. H. Cobin, H. Gharib, J. V. Hennessey, I. Klein et al., Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association, Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. déc, vol.18, issue.6, p.9881028, 2012.

C. Robert, G. V. Long, B. Brady, C. Dutriaux, M. Maio et al., Nivolumab in Previously Untreated Melanoma without BRAF Mutation, N Engl J Med. 22 janv, vol.372, issue.4, p.32030, 2015.

A. Eggermont, C. U. Blank, M. Mandala, G. V. Long, V. Atkinson et al.,

, Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma, N Engl J Med. 15 avr, 2018.

P. Chanson, L. Guignat, B. Goichot, O. Chabre, D. S. Boustani et al., Adrenal insufficiency: screening methods and confirmation of diagnosis, Ann Endocrinol. déc, vol.2, issue.6, p.495511, 2017.

M. Gauci, P. Laly, T. Vidal-trecan, B. Baroudjian, J. Gottlieb et al., Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: a case report and literature review, Cancer Immunol Immunother CII, vol.66, issue.11, p.1399410, 2017.

M. Ansari, A. D. Salama, T. Chitnis, R. N. Smith, H. Yagita et al., The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice, J Exp Med. 7 juill, vol.198, issue.1, p.639, 2003.

N. M. Kochupurakkal, A. J. Kruger, S. Tripathi, B. Zhu, L. T. Adams et al., Blockade of the programmed death-1 (PD1) pathway undermines potent genetic protection from type 1 diabetes, PloS One, vol.9, issue.2, p.89561, 2014.

R. Fujisawa, F. Haseda, C. Tsutsumi, Y. Hiromine, S. Noso et al., Low programmed cell death-1 (PD-1) expression in peripheral CD4(+) T cells in Japanese patients with autoimmune type 1 diabetes, Clin Exp Immunol. juin, vol.180, issue.3, p.4527, 2015.

L. M. Francisco, P. T. Sage, and A. H. Sharpe, The PD-1 pathway in tolerance and autoimmunity, Immunol Rev. juill, vol.236, p.21942, 2010.

M. J. Redondo, P. R. Fain, and G. S. Eisenbarth, Genetics of type 1A diabetes, Recent Prog Horm Res, vol.56, 2001.

, Non"faite" Hydrocortisone"30"mg/j

, !"pas"de"récupération"à"2"ans" Normale" Hydrocortisone"20"mg/j" Levothyrox®"150"µg/j" "! Thyroïdectomie" Stabilité"8"mois" Suivi"total"36"mois" Patient"8" Asymptomatique" 2" Insuffisance"corticotrope," thyréotrope,"gonadotrope"et" somatotrope"" !"récupération"complète"à"6"mois, Normale" Hydrocortisone"30"mg/j" Levothyrox®"100"µg/j" Pas"de"réponse" Suivi"total"23"mois" Patient"7" AEG" Céphalée" 3" Insuffisance"corticotrope

. Cortisol, #La#glycémie#était#à#6,39#g/L#avec# une# croix# de# cétone# dans# les# urines.# Les# anticorps# anti?GAD# et# IA2# étaient# négatifs# et# les# anticorps# anti?insuline# se# sont# positivés# à# 1,8%# (négatif# si# inférieur# à# 0,4%).# Le# scanner# pancréatique#était#normal.#Un#traitement#par#insuline#a#été#instauré#(84).## # Notre#patiente#est#donc#le#troisième#cas#décrit#de#diabète#induit#par#anticorps#anti?CTLA?4.# Contrairement#aux#deux#cas#précédents,#elle#n'avait#pas#été#traitée#par#anticorps#anti?PD1#au# préalable.#Elle#a#présenté#un#tableau#d'acidocétose#un#mois#après#le#début#de#l'ipilimumab#et# avait#des#anticorps#anti?GAD#très#fortement#positifs#à#23933#U/ml#associés#à#des#anticorps# anti?insuline#faiblement#positifs.#L'HbA1c#et#le#C?peptide#initiaux#n'étaient#pas#disponibles.#La# lipasémie#initiale#était#très#élevée.## # L'histoire# clinico?biologique# de# ces# diabètes# s'apparente# à# celle# des# diabètes# fulminants# décrite# dans# les# pays# d'Asie.# En# effet,# les# patients# présentent# des# tableaux# brutaux# d'acidocétose# avec# des# HbA1c# modérément# élevées# témoignant# de# l'installation# rapide# du# diabète.#Les#auto?anticorps#sont#positifs#chez#la#moitié#des#patients,#le#C?peptide#effondré#et# la#lipasémie#initialement#élevée.## Le# délai# de# survenue# des# diabètes# induits# par# ICPi# varie# de# 3# semaines# à# 12# mois# après# l'instauration#de#l'ICPi.#Il#s'installerait#plus#rapidement#en#présence#d'auto?anticorps#(96), Testostérone"Totale"(TestoT)":"1,44b6,92"ng/mL" IgF1"51b60"ans":"99b254"ng/mL

, ## # En#tous#les#cas,#la#survenue#d'un#diabète#induit#par#un#ICPi#est#très#rare.#Il#faut#savoir#y#penser# devant#la#gravité#du#tableau#initial#d'acidocétose.## Il#semblerait#que#ce#diabète#soit#définitif#puisque#tous#les#patients#décrits#dans#la#littérature# ont#ensuite#été#traités#par#insuline#au#long#cours.#Une#fois#l'insulinothérapie#mise#en#place,#la# poursuite#de#l'ICPi#n'est#pas#contre?indiquée.#### Il#est#difficile#d'établir#un#arbre#décisionnel#devant#le#peu#de#cas#décrits, L'implication#de#CTLA?4#dans#la#survenue#d'un#diabète#de#type#1#est#moins#étudiée.# Il#a#cependant#été#mis#en#évidence#que#le#polymorphisme#dans#la#région#du#gène#codant#pour# CTLA?4#est#associé#à#un#surrisque#de#diabète#de#type#1#chez#certains#individus#(101)