Isolated ACTH deficiency probably induced by autoimmune-related mechanism evoked with nivolumab.
Nivolumab, an anti-programmed death-1 antibody, is a breakthrough treatment for several malignancies. Its specific adverse effects caused by autoimmunity are termed immune-related adverse events, which involve several endocrine dysfunctions. Herein, we report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency induced by nivolumab for the treatment of metastatic malignant melanoma. Case 1 was a 39-year-old man and Case 2 was a 50-year-old woman, both of whom presented with progressive melanoma. After 13 courses of nivolumab administration, both cases were diagnosed with adrenal insufficiency. Despite their basal serum ACTH and cortisol levels being low with little response to corticotropin-releasing hormone loading, other anterior pituitary hormone levels were preserved. Based on these endocrinological data, isolated ACTH deficiency was diagnosed. Magnetic resonance imaging showed normal pituitary glands, excluding hypophysitis. Finally, hydrocortisone replacement enabled the patients to continue nivolumab treatment. Therefore, it is important to consider isolated ACTH syndrome as a possible and potentially severe immune-related adverse event of nivolumab, even when head magnetic resonance imaging of affected cases does not show enlargement. We should not misdiagnose hidden immune-related adverse events behind general complaints of malignancies such as general malaise and appetite loss, to allow successful treatment using this beneficial immune checkpoint inhibitor.
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.|Department of Metabolism and Endocrinology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka.
Keiko
K
Kitajima
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Kenji
K
Ashida
Department of Dermatology, Kyushu University Hospital, Fukuoka.
Naoko
N
Wada
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.|Department of Metabolism and Endocrinology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka.
Ryoko
R
Suetsugu
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Yukina
Y
Takeichi
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Shohei
S
Sakamoto
Department of Dermatology, Kyushu University Hospital, Fukuoka.
Hiroshi
H
Uchi
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Takamitsu
T
Matsushima
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Motoaki
M
Shiratsuchi
Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Keizo
K
Ohnaka
Department of Dermatology, Kyushu University Hospital, Fukuoka.
Masutaka
M
Furue
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Masatoshi
M
Nomura
D000324:Adrenocorticotropic Hormone / Q000172:deficiency* / Q000276:immunology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D015551:Autoimmunity / Q000187:drug effects; D004700:Endocrine System Diseases / Q000139:chemically induced* / Q000276:immunology*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000139:chemically induced* / Q000276:immunology*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077594:Nivolumab
D000911:Antibodies, Monoclonal; D000077594:Nivolumab; D000324:Adrenocorticotropic Hormone
dermatology; endocrine-med; immunotherapy