Medicine (St Vincent's) - Theses
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ItemClinical, Immunological and Radiological Features of Endocrine Immune Related Adverse Events( 2020)Immune checkpoint blockade is a cancer treatment aimed at restoring and enhancing the ability of the immune system to combat a tumour. A recognised side effect is “collateral” immune damage to healthy tissue, or immune related adverse events (irAEs). Immune toxicity to endocrine glands can be rapid and irreversible and may result in the need for lifelong hormone replacement. A major challenge is identifying which patients will develop endocrine irAEs when treated with checkpoint inhibitors. The role of predictive biomarkers such as HLA type or autoantibodies has not been prospectively evaluated. The possibility of detecting pre-clinical endocrine dysfunction using MRI and PET imaging is described in small case series only. This project aims to 1. Define the clinical and immunological features of checkpoint inhibitor related diabetes, hypophysitis and thyroiditis in contrast to spontaneously occuring endocrine autoimminuty and 2. Explore ways to predict and detect endocrine toxicity early with biomarkers and imaging. First, I define the phenotype and immune mechanisms underlying checkpoint inhibitor related autoimmune diabetes. It was then relevant to discuss atypical or alternate phenotypes of diabetes and pancreatitis which have emerged over the past 2 years. This chapter concludes with a discussion of potential treatments aiming to reverse islet cell destruction, with a letter to the editor published in response to a case report. The next focus is the diagnostic evaluation of checkpoint inhibitor related hypophysitis. After hypothesising that the true incidence may be underappreciated, this chapter reviews the clinical, biochemical and radiological features in a cohort of patients monitored closely for this irAE. The third component of the thesis reviews the incidence and natural history of checkpoint inhibitor related thyroiditis. Defining the natural history provided important information guiding management of the hyperthyroid and hypothyroid phases respectively. This chapter includes a diagnostic accuracy study evaluating the role of FDG-PET/CT as a novel tool in the diagnosis of this irAE. In defining the natural history and diagnostic features of these three endocrine immune related adverse events, important recommendations about biochemical screening and the complementary role of routine cancer immaging are made. Importantly, treatment considerations relevant to oncologists and endocrinologists alike are outlined.