I am a General Physician and Endocrinologist at Christchurch Hospital. I trained in the UK, which included a period studying pancreatic islet transplantation in Edinburgh, although my main interests have been clinical. I came to New Zealand to take an SMO position at Ashburton Hospital, subsequently moving to Christchurch. I am a past Chair of the New Zealand Society for the Study of Diabetes and have been Clinical Director for General Medicine here in Christchurch.
Hijacking Checkpoints: How Cancer Treatment Is Triggering An Avalanche Of Endocrine Disease And Why You Need To Know About It
Increasing use of checkpoint inhibitors to treat cancer has found patients succumbing to various endocrine disorders, often presenting with nonspecific symptoms, making recognition difficult. This presentation will cover pathogenesis, diagnosis and management, as well as insights to possible future treatments for autoimmune diseases.
Checkpoint inhibitors have revolutionised the treatment of many cancers. These inhibitors comprise monoclonal antibodies specifically targeting immune checkpoints, key regulators of the immune system along pathways which are critical for self-tolerance and prevent the immune system from attacking cells indiscriminately. Stimulation of inhibitory checkpoints is one mechanism by which cancers avoid detection, dampening down immune responses and permitting uncontrolled tumour growth. Adverse effects of checkpoint inhibitor chemotherapy mimic the phenotype of autoimmune disorders. About 10% of patients treated with these drugs develop clinically significant autoimmune endocrinopathies, a direct result of removing the physiologic inhibition that normally prevents autoreactivity. Symptoms may be nonspecific, such as headache, nausea and fatigue, difficult to recognise in patients unwell from malignancy and from other side-effects. Thyroid dysfunction (both hypo and hyper) and hypophysitis, affecting pituitary function, appear particularly common. Manifestations of hypophysitis include pituitary enlargement and secondary organ failure, including adrenal insufficiency. Failure to recognise these conditions can be of serious consequence and prompt identification and treatment important to optimise outcomes.
Those with pre-existing autoimmune diseases have usually been excluded from clinical trials. Although they may be at increased risk, there is some evidence that in those who do develop autoimmune disease overall survival may be prolonged.
The triggering of autoimmunity by checkpoint inhibitors supports a role for checkpoints in autoimmune disease and could offer novel approaches to prevention and treatment of conditions such as insulin dependent diabetes.