Endocrine Abstracts

Hypophysitis is one of the immune-related adverse events of immune checkpoint blockade. This complication is potentially dangerous, mainly because of the insidious development of a life-threatening hypocortisolism. Unnecessary morbidity or mortality in an oncological responder may be the result. The number of patients treated with immune checkpoint inhibitors increases rapidly, due to the expansion of indications and trials. Moreover, the introduction of combination schedules leads to more adverse events.PD-1 inhibitors induce hypophysitis in an estimated 1%, the CTLA-4 inhibitor ipilimumab in approx. 5–10% and for the ipilimumab plus PD-1 inhibitor combination percentages up to more than 10% are reported. Caregivers need to be aware of this complication, and should coordinate their protocols accordingly. During the last 5 years we have encountered 26 patients with an immune checkpoint inhibitor-related hypophysitis, of which 11 patients in the last year alone. Ipilimumab is the main cause, but due to the large number of patients treated, monotherapy with PD-1 blockers is represented as well. The time of occurrence of a hypophysitis after starting immunotherapy was 5–18 weeks for Ipilimumab and 13–57 weeks for PD-1 inhibition (Pembrolizumab or Nivolumab). In 2 patients the hypophysitis occurred more than 1 year after the start of immunotherapy, and even after the discontinuation of immunotherapy, illustrating the need for long-term surveillance. The pattern of endocrine dysfunction was typical, failure of especially the adrenal axis (24 out of 26), accompanied by failure of the gonadal and thyroid axis (18 out of 26). The gonadal and thyroid axis showed recovery of function in about half of the cases. MRI abnormalities were minor, mostly in the form of a short-lived infiltrate in the sella without a large mass effect, and especially present in the Ipilimumab group (7 out of 12, as far as a simultaneous MRI is present). In 9 patients the hypophysitis was preceded by a thyroiditis, mostly during treatment with PD-1 inhibitors. Glucocorticoid substitution alone could suffice, without the need for high-dose steroid therapy, which was only applied in the first index patient in 2012, according to the guideline at that time. Based on our current experience the role for high-dose steroid therapy in immune checkpoint inhibitor-related hypophysitis is less prominent than recommended in the recent ESMO Clinical Practice Guidelines.