Thyroid disorder and isolated adrenocorticotropic hormone insufficiency possess frequently been reported as nivolumab-induced immune-related adverse occasions. insulin secretion. A month later, she developed diabetic ketoacidosis. Her insulin secretion decreased and finally was exhausted. She was diagnosed with acute-onset rather than fulminant t1dm because of a rapidly progressive course to diabetic ketoacidosis during just more than 1 week. She is currently Rabbit Polyclonal to ELAV2/4 receiving insulin replacement. There has been no recurrence of the melanoma. Thus, nivolumab might induce autoimmune diabetes mellitus, with patients having t1dm-sensitive human leucocyte antigen being more susceptible even when receiving glucocorticoids. Physicians should be aware that nivolumab could potentially induce t1dm as a critical immune-related adverse event. strong class=”kwd-title” Keywords: Melanoma, nivolumab, autoimmunity, adverse drug events, diabetes mellitus, type 1 diabetes INTRODUCTION AntiCPD-1 antibodies activate an antitumour immunologic response by abrogating PD-1Crelated T cell inhibition. They reportedly improve the prognosis of patients with several advanced malignancies1. Although nivolumab, an antiCPD-1 antibody, has improved prognosis and become a popular agent in several advanced malignancies, various immune-related adverse events (iraes)2, including endocrinopathies3, have been reported. Several cases of nivolumab-induced type 1 diabetes mellitus (t1dm) have been reported as endocrinologic iraes. The patients in most of those cases had a genetically susceptible background for t1dm4 and experienced rapidly progressive fulminant t1dm5C7. However, the clinical course of their disrupted insulin secretion was not studied. We describe a case of acute-onset t1dm, probably induced by nivolumab, in which the patients insulin secretion was monitored throughout the clinical course. A progressive decline of insulin secretion that exhausted within a month was observed in this patient, indicating that t1dm with a slower clinical course rather than fulminant t1dm can develop as an irae. Thus, in the case of a hyperglycemic event, physicians should consider t1dm, a critical irae, even when insulin secretion is initially reported to be in the normal range. The patients written informed consent was obtained for the publication of this case report. The Institutional Review Board of Kyushu University Hospital waived the need for ethics approval. CASE DESCRIPTION A 68-year-old woman presented to our endocrine department complaining of general fatigue. She had been diagnosed 3 years earlier with vaginal malignant melanoma and had undergone total abdominal hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node resection. Although interferon therapy was given after the surgical procedure, the melanoma progressed 1 year later, with relapse in intra-abdominal lymph nodes. The patient was then started on nivolumab 3 mg/kg every 3 weeks. She had a 10-year history of Graves disease treated with potassium iodide 100 mg daily. She did not have any other past or family history of diabetes mellitus, endocrine, or autoimmune disease. After administration of the 13th course of nivolumab, prednisolone 10 mg daily was prescribed to treat thrombophlebitis in her left lower thigh and was tapered to 5 mg daily after 1 week. At approximately the 27th course of nivolumab, the patients plasma glucose increased to 11.3 mmol/L and 18.2 mmol/L (before dinner), 27 Balaglitazone and 13 days respectively before a ketoacidosis episode. At the Balaglitazone time, endogenous insulin secretion and HbA1c were within the normal range (Figure 1). Fasting plasma glucose, C-peptide, and anti-glutamic acid decarboxylase antibody 26 days before the ketoacidosis episode were 5.1 mmol/L, 0.5 nmol/L, and less than 0.5 U/mL respectively (Table I, Figure 1). Open in a separate window FIGURE 1 Patients clinical course in the present case. On day 26, before diabetic ketoacidosis, insulin secretion is preserved, based on serum C-peptide (CPR) 0.5 nmol/L and fasting plasma glucose (FPG) 5.1 mmol/L. At the time of admission, FPG was highly elevated, and insulin secretion had declined, but not become exhausted (day 1 CPR Balaglitazone 0.1 nmol/L and FPG 13.0 mmol/L). Continuous insulin replacement was required to manage plasma glucose. The patients insulin secretion declined steadily, leading to exhaustion 9 days Balaglitazone after the ketoacidosis event. Her insulin.
Thyroid disorder and isolated adrenocorticotropic hormone insufficiency possess frequently been reported as nivolumab-induced immune-related adverse occasions