Two Cases of Atezolizumab-Induced Hypophysitis

Abstract

Cancer immunotherapy has emerged as treatment of multiple advanced cancer types. Immune checkpoint inhibitors, namely anticytotoxic T-lymphocyte antigen-4 (CTLA-4), antiprogrammed cell death-1 (PD-1), and antiprogrammed cell death-1 ligand 1 (PD-L1) antibodies, have been used for treatment of various cancers. Classified as immune-related adverse events, several endocrinopathies, including hypophysitis, are associated with these agents. Although anti-CTLA-4–induced hypophysitis has been frequently observed, hypophysitis upon use of anti-PD-1 and anti-PD-L1 antibodies is rare. Case 1 is a 65-year-old man presented with a stage IV non-small cell lung cancer (NSCLC) treated with atezolizumab (an anti-PD-L1 antibody) following several inefficacious chemotherapies. After 56 weeks of the treatment, he complained of general malaise and appetite loss, and was diagnosed with adrenal insufficiency. Endocrinological examination revealed isolated adrenocorticotropic hormone (ACTH) deficiency; pituitary magnetic resonance imaging (MRI) showed anterior pituitary atrophy. Hydrocortisone replacement therapy rapidly improved his symptoms and enabled him to continue atezolizumab therapy. Case 2 is a 70-year-old man with a stage IV NSCLC treated with atezolizumab. After 52 weeks of treatment, he was diagnosed with isolated ACTH deficiency. Pituitary MRI revealed no obvious abnormalities in the anterior pituitary. Hydrocortisone replacement therapy was also efficacious. We report two cases of atezolizumab-induced hypophysitis. Both showed isolated ACTH deficiency, suggesting similar clinical characteristics of hypophysitis associated with the use of anti-PD-1 antibodies. These results suggest a caution for the late-onset central adrenal insufficiency associated with hypophysitis in patients treated with anti-PD-L1 antibodies.

Hypopituitarism manifesting after invasive dental treatment in a patient with carcinoma of the tongue: a case report

“…Brain injury resulting from traumatic thoracic injury [4], autoimmune disease [5], and Cytotoxic T-lymphocyte antigen (CTLA)-4 is expressed in the pituitary gland; anti-CTLA-4 antibodies were reported to induce hypophysitis [7]. Furthermore, anti-programmed cell death (PD)-1 and anti-PD-ligand 1 antibodies have been reported to induce hypophysitis, leading to pituitary atrophy [8]. Therefore, we must be aware of various signs of hypopituitarism when we perform invasive dental treatment.…”

Management of immune checkpoint inhibitor‐related adverse events: A review of case reports

“…It was reported that hypophysitis occurred mostly in patients treated with anticytotoxic T lymphocyte associated antigen‐4 (CTLA4) inhibitors due to CTLA‐4 expressed on pituitary cells . However, hypophysitis has also been reported in patients treated with atezolizumab or nivolumab . Hypophysitis induced by PD‐1/PD‐L1 inhibitor usually presents as isolated ACTH deficiency.…”

“…The order of hormone deficiency specific to hypophysitis is as follows: ACTH > TSH > luteinizing hormone/follicle‐stimulating hormone > prolactin > growth hormone . Immune‐related hypophysitis may not affect all pituitary cell lines, and isolated ACTH deficiency has been reported …”

“…8 However, hypophysitis has also been reported in patients treated with atezolizumab or nivolumab. 9 Hypophysitis induced by PD-1/PD-L1 inhibitor usually presents as isolated ACTH deficiency. The pituitary gland can be divided into two different parts: the anterior and posterior lobes.…”

“…10 Immune-related hypophysitis may not affect all pituitary cell lines, and isolated ACTH deficiency has been reported. 9,11 ICI-induced bile duct obstruction and cholangitis have been reported, and they should be considered as causes of cholangitis. 12 Patients presented with fever, abdominal discomfort, fatigue, predominant elevation of alkaline phosphatase (ALP) and gamma-glutamyl-transpeptidase (GGT), and moderate elevation of transaminases (ALT/AST) and total bilirubin.…”