Differences between immunotherapy-induced and primary hypophysitis\u2014a multicenter retrospective study

Sylvère Störmann,Mamta Joshi,Felix Amereller,Jochen Schopohl,Leo Duffy,Mario Detomas,Katharina Schilbach,Timo Deutschbein,Sophie Papa,Paul Carroll

doi:10.1007/s11102-021-01182-z

Abstract

ObjectiveImmune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH)DesignRetrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH.MethodsAll patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected.ResultsMedian time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002).ConclusionsClinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.

Highlights

Ten years ago, the immune-modulating monoclonal antibody ipilimumab was approved for the treatment of metastatic melanoma, heralding the introduction of immune checkpoint inhibition as solid tumor treatment [1]
The basic mechanism of action relies on the inhibition of signals that physiologically downregulate immune responses, namely cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1), effectively dis-inhibiting T cells [2, 3]
We present first-time data on the prevalence of autoimmune disease in immunotherapy-induced hypophysitis (IIH) patients before Immune checkpoint inhibitors (ICPI) treatment initiation

Summary

Introduction

The immune-modulating monoclonal antibody ipilimumab was approved for the treatment of metastatic melanoma, heralding the introduction of immune checkpoint inhibition as solid tumor treatment [1]. This sustainably stimulated the field of immuno-oncology and marked a turning point in cancer therapy. Immune checkpoint inhibitors (ICPI) may lead to a multitude of endocrinopathies, such as thyroiditis, primary adrenal insufficiency, diabetes mellitus, and hypophysitis [4, 5]. Hypophysitis is a frequent irAE [6,7,8], occurring in 5% of ICPI-treated patients according to a recent big data analysis [9]

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Discussion

Conclusion