Immunotherapy-induced autoimmune hypophysitis

Abstract

Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.

Autoimmune hypophysitis secondary to therapy with immune checkpoint inhibitors: Four cases describing the clinical heterogeneity of central endocrine dysfunction

“…1,7 While this adverse effect is more common under the treatment with CTLA-4 antibodies, it has been rarely described under anti-PD-1/PD-L1, with a reported incidence of 1% or less for Nivolumab. 1,3,4,6,7,9,10 According to recent studies, no significant increase in incidence was noticed between patients treated with anti-PD-1 or anti-PD-L1 compared to placebo controls. 5 This difference in incidence between CTLA-4 antibodies and anti-PD-1/anti-PD-L1 can be explained by the presence of CTLA-4 in healthy pituitary cells with CTLA-4 being a negative regulator of T-cell activation.…”

“…ICIs use the host immune system as a mediator, in order to eliminate tumor cells and prevent tumor growth. 3 They are classified into monoclonal antibodies against cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and to programmed cell death 1 receptor (PD-1) or programmed cell death-ligand 1 (PDL-1). 3…”

“…The autoimmune nature of this mechanism can, however, cause a unique spectrum of immune-related adverse effects (IRAEs) due to unrestrained T-cell activation. 3 The side-effect profile of ICIs is characterized by autoimmune-like manifestations, which can affect the skin, lung, liver, colon, kidney, eyes, nervous system, and endocrine organs. 2,3,8…”

“…It has been shown that the likelihood of developing hypophysitis is significantly increased if two ICIs are used in combination with an incidence of up to 7.8% under combination therapy. 2,3,9 However, there are studies reporting no increase in incidence of hypophysitis under combined therapy. 6…”

“…Unlike sporadic hypophysitis, which is a rare inflammatory condition mostly affecting females, ICI- related hypophysitis is more common in males. 1,3,5 Other risk factors for developing ICI-related hypophysitis are the patient’s age and the presence of pituitary reactive effector T-cells before the treatment, which can get activated under the ICIs. 5,6…”