Background: Immune checkpoint (CTLA-4, PD-1) inhibitors are increasingly used to treat cancers including advanced melanoma. Although endocrine immune related adverse events (IRAEs) are now well reported, the frequency and type of thyroid and pituitary dysfunction reported varies considerably, with hypophysitis after CTLA-4 inhibitors reported in 216%, and thyroid dysfunction after PD-1 inhibitors in 239%. In addition, recovery rates for endocrinopathies are not well documented.
Methods: Retrospective case note review of all cases of endocrine IRAEs identified at our institution since introduction of ICI therapy, in order to determine the type and recovery rate of endocrinopathy.
Results: Since 2015, 19 patients developed endocrine IRAEs. Mean age 63 years (SD+/−13 years), mean follow-up 17 months (SD+/−8 months). All patients were referred to endocrinology and were investigated for recovery routinely.
Patients (n=5) developed hypophysitis a mean of 3.2 months following Ipilimumab. All had ACTH, TSH, Gonadotropin and Growth hormone deficiency; 2/5 had low prolactin concentrations (not measured in 3). Despite being assessed for recovery at regular intervals, all hormone deficits persisted.
Patients (n=10) developed thyroid dysfunction a mean of 2.9 months following Pembrolizumab (n=8) or Nivolumab (n=2). Primary hypothyroidism occurred in 6/10 cases. One case each of hyperthyroidism, thyroiditis and subclinical hyperthyroidism were identified. Secondary hypothyroidism occurred in 1 case and may not have been treatment related. The majority (n=8) remain on treatment.
Patients (n=4) treated with combination therapy developed thyroid dysfunction (n=3); 2 primary hypothyroidism and 1 thyroiditis; and hypophysitis (n=1).
Conclusions: Panhypophysitis occurred in all patients who developed pituitary disease; none recovered. Primary hypothyroidism was the commonest form of thyroid dysfunction. Despite interval surveillance for endocrine recovery, resolution was infrequent, suggesting that this form of IRAE (in contrast to others) is permanent. Such information is valuable when counselling patients of the risks and benefits of ICI treatment.