Nivolumab-induced hypophysitis followed by acute-onset type 1 diabetes with renal cell carcinoma: a case report

Abstract

Background Immune checkpoint inhibitors have recently become widely used for the management of advanced cancer patients. During the development of immune checkpoint inhibitors (ICPIs), it was quickly recognized that they are associated with autoimmune or autoinflammatory side effects. These toxicities are known as immune-related adverse events (irAEs): common endocrine irAEs include hypophysitis and thyroid dysfunction, and uncommon irAEs include type 1 diabetes mellitus (T1DM). Case presentation A 62-year-old Japanese man with metastatic renal cell carcinoma was treated with sunitinib followed by the 10th cycle of treatment with the ICPI nivolumab. He had already had thyroiditis and hypophysitis due to these anti-cancer drugs. On admission, he showed an extremely elevated plasma glucose level (601 mg/dl) and a low C-peptide level, and was diagnosed with acute T1DM. The patient was treated with intravenous fluid infusion and continuous insulin infusion. On the second day, he was switched to multiple daily injections of insulin therapy. Since these treatments, his blood glucose levels have been stable and he has been treated with an additional 10 ICPI treatments for renal cell carcinoma for over a year. Conclusions Treatment with ICPIs is expected to increase in the future. There may be cases in which their use for cancer treatment is inevitable despite the side effects. As long as treatment with ICPI continues, multiple side effects can be expected in some cases. It is important to carefully observe the side effects that occur during ICPI treatment and to provide appropriate treatment for each side effect.

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

“…Baseline characteristics are presented in Table 2 . In addition to our patients, 171 cases were identified [ 7 , 8 , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [...…”

Fulminant ACTH decrease following diabetic ketoacidosis induced by immune checkpoint inhibitor combination therapy with nivolumab and ipilimumab: A case report

“…The involvement of activated T cells in irAEs such as T1D [ 34 ] and hypophysitis [ 16 ] has been suggested as a mechanism, and HLA polymorphisms would play an important role in the development. [ 30 , 33 ]…”

“…Table 5 shows cases reporting hypophysitis and T1D. [3,[21][22][23][24][25][26][27][28][29][30][31][32] ICIs are anti-PD-1 monotherapy, anti-PD-L1 monotherapy, and combination therapy of anti-PD-1/anti-PD-L1 and anti-CTLA-4. No cases with hypophysitis and T1D due to ipilimumab monotherapy were reported.…”

“…The involvement of activated T cells in irAEs such as T1D [34] and hypophysitis [16] has been suggested as a mechanism, and HLA polymorphisms would play an important role in the development. [30,33] Because adrenal insufficiency due to ICI therapy could be fatal, this condition should be more widely recognized by physicians with appropriate ACTH/cortisol monitoring as well as associated clinical manifestations. The present report provides a detailed course of hypophysitis, which will contribute to better care for patients receiving ICI therapy.…”

Autoimmune Polyendocrinopathy Induced by an Antibody (KN046) That Simultaneously Inhibits PD-L1 and CTLA-4: A Case Report and Literature Review

“… 23 Malik Asif Humayun also reported a case of T1DM secondary to hypophysitis during treatment with nivolumab, a PD-1 inhibitor, in combination with ipilimumab, a CTLA-4 inhibitor. 24 Laura Boswell reported a case of hypophysitis in the course of immunotherapy with ipilimumab, a CTLA-4 inhibitor, and then explosive T1DM after the cessation of combined immunotherapy. 25 Therefore, patients undergoing immunotherapy need to pay close attention to changes in endocrine and glandular functions during treatment, and even after the treatment ends.…”