Abstract
OBJECTIVE: One of the most severe endocrine side effects of immune checkpoint inhibitors (ICI) is hypophysitis leading to adrenal insufficiency. Recovery is rare, although it has been reported after high-dose glucocorticoid treatment. This is the first randomised study to evaluate whether hormonal recovery differs in patients treated with high-dose glucocorticoids versus glucocorticoid replacement therapy. DESIGN/METHODS: In this single-centre, open, randomised controlled study, patients with ICI associated hypophysitis were randomised 1:1 to high-dose glucocorticoid treatment (1 mg/kg of prednisolone for two weeks, followed by tapering until week 7 and a switch to hydrocortisone 20 mg total daily dose in week 8) or glucocorticoid replacement therapy (hydrocortisone 20 mg total daily dose) over 8 weeks. The primary outcome was the frequency of hormonal axes recovery. RESULTS: Between 17th April 2019 and 16th September 2022, 18 out of the 20 randomised patients finished the trial; eight completed high-dose, 10 glucocorticoid replacement. Nine patients presented with hyponatraemia, two had typical changes on MRI, 12 had isolated adrenal insufficiency, and six had an additional hormone deficiency. None of the patients in neither group experienced a recovery in adrenal function. One patient in each group showed amelioration of hypogonadism. There was a significant, unfavourable treatment effect of high-dose treatment on HbA1c (mean treatment effect 5.16, 95% confidence interval 0.31 to 10.02, p = 0.039). CONCLUSIONS: High-dose glucocorticoid treatment was not effective in restoring adrenal function and leads to adverse effects on glucose metabolism. We therefore do not recommend its use for the treatment of ICI associated hypophysitis, except for compressive symptoms.