title: Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.
abstract: The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6thadministration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7thadministration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7thadministration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Okano
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyoda
authors.forename: Aya
authors.initials: A
authors.lastname: Osaki
authors.forename: Shunichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Tomaru
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Sumiyasu
authors.initials: S
authors.lastname: Ishii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ozawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shibusawa
authors.forename: Takehiro
authors.initials: T
authors.lastname: Shimada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higuchi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chikamatsu
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D000072659:Hypophysitis / Q000139:chemically induced*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D000077594:Nivolumab; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000077594:Nivolumab