The medical management of many malignancies has been transformed in recent years by the development of different immunotherapies, either targeting specific growth factors or tumour-specific ligands, or by stimulating endogenous anti-tumour immunity. Immune modulatory therapies that target immune check-points such as CTLA4 and PD-1 reduce tumour immune tolerance, thereby promoting anti-tumour immune activity via inhibition of activated T cells. Whilst such therapies have resulted in significant improvements in cancer outcomes, these have been at the expense of a reduction in self-tolerance, and “immune-related adverse events” including rash, colitis, hepatitis and endocrinopathies, such as hypophysitis and thyroiditis.
The commonest endocrine immune-related adverse event of Ipilimumab, an antibody directed against CTLA4, is hypophysitis, which has been reported to occur in up to 17% of patients. There is some dose-dependency and hypophysitis usually develops 6-12 weeks after initiation of therapy. It occurs more commonly in males and is more likely to present with symptoms of hypopituitarism, rather than symptoms due to a pituitary mass. An enlarged pituitary gland may be visible on MRI scan. Treatment with high doses of glucocorticoids has been advocated by some, but does not appear to alter the course of the disease. Partial recovery of anterior pituitary function may occur, but ACTH deficiency usually persists. A review of local experience with Ipilimumab will be presented and monitoring guidelines proposed.
Clinical experience with antibodies blocking the programmed cell death receptor (PD-1) or its ligand is more limited, but hypophysitis appears to be less common than with Ipilimumab. Thyroid dysfunction and thyroiditis have been reported, but these events have been less-well characterised.
The increasing use of immune check point inhibitors in the treatment of malignancies will require increased awareness of the potential endocrine adverse effects of such therapies and the implementation of routine monitoring systems to facilitate the early detection..