title: Nivolumab-induced thyroid dysfunction.
abstract: Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki ryota621@hotmail.co.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Saitama.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology, Tokyo Metropolitan Komagome Hospital, Tokyo.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Ohtsuka
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology* / Q000628:therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D000077594:Nivolumab; D011788:Quality of Life; D013972:Thyrotropin / Q000032:analysis; D013974:Thyroxine / Q000032:analysis; D014284:Triiodothyronine / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014284:Triiodothyronine; D000077594:Nivolumab; D013972:Thyrotropin; D013974:Thyroxine
keywords: endocrine-med; immunotherapy; skin