Endocrine Abstracts

Introduction: Cancer is the result of genetic and epigenetic alterations generating uncontrolled cell growth. These molecular changes maintain an immunosuppressive microenvironment allowing tumor spread. Immune checkpoint inhibitors (ICI) are novel therapeutic strategies in cancer treatment, promoting anti-tumor response by boosting cytotoxic T lymphocytes. Despite their high effectiveness, they can trigger the activation of diverse autoimmune diseases in genetically predisposed individuals. New-onset autoimmune Diabetes Mellitus type 1 (T1D) is an extremely unusual side effect, described in less than 1% of patients.

Materials and Methods: A case report description conducted with the consent of the patient and with provisions of the Declaration of Helsinki.

Results: Here we present a 44-year-old male with a medical history that includes chronic hepatitis C virus infection, and paranoid schizophrenia. No personal or familial diagnosis of diabetes. He had recently been diagnosed with hepatocarcinoma, presenting retroperitoneal and hepatic hilar adenopathy, making the tumor unresectable. After the onset of ICI, he was diagnosed of two PD-L1 inhibitor-induced autoimmune endocrinopathies, presented as diabetic ketoacidosis (DKA) and thyroiditis. After two cycles of atezolizumab and bevacizumab, he consulted the emergency department with abdominal pain and diabetes cardinal features (polyuria, polydipsia, vomiting). Blood tests demonstrated hyperglycemia superior to 800 mg/dl, capillary ketonemia >3 mmol/l, metabolic acidosis (pH 7.24 with HCO3- 14 mEq/l). Subsequent studies detected a low level of C-peptide level 11 pmol/l, and positive glutamic acid decarboxylase and insulinoma-associated antigen-2 antibodies. Thyroid examination was compatible with thyroiditis, showing a high free thyroxine level (1.91 ng/dl) with low thyrotropin (0.08 mIU/l), negative anti-peroxidase, and anti-TSH receptor, and slight positivity of antithyroglobulin antibodies. After reaching metabolic stabilization, treatment with Atezolizumab was restarted, with no further complications.

Conclusion: Monoclonal antibody targeting has become a breakthrough, generating a shift in the treatment of advanced malignancies. These new drugs promote an anti-tumor immune response. Nevertheless, immune checkpoint blockade is associated with a risk for immune-related adverse events in genetically predisposed individuals. T1M related to ICI is a rare condition that presents as a life-threatening emergency and should be recognized and treated early. Blood glucose and Hb1Ac determinations should be performed at periodic visits for detection. There are genetic factors that predispose susceptible individuals, but there is no evidence of studies to be performed before the onset of ICI or preventive strategies.