Late-onset hypophysitis after discontinuation of nivolumab treatment for advanced skin melanoma: a case report

• Published in: BMC endocrine disorders Vol. 21; no. 1; pp. 191 - 6
• Main Authors: Antoniou, Sofia, Bazazo, Georgios, Röckl, Ludwig, Papadakis, Marios, Berg, Christian
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.09.2021; BioMed Central; BMC
• Subjects: ACTH; Adrenocorticotropic hormone; Age of Onset; Antibodies; Antigens; Antineoplastic Agents, Immunological - adverse effects; Apoptosis; Blood pressure; Cancer immunotherapy; Case Report; Cell death; Complications and side effects; Corticosteroids; Cytotoxicity; Dextrose; Diabetes; Drug therapy; Endocrine system; Glucose; Humans; Hydrocortisone; Hypoglycemia; Hyponatremia; Hypophysitis; Hypophysitis - chemically induced; Hypophysitis - pathology; Immunotherapy; Inflammation; Insulin; Ipilimumab; Lymphatic system; Magnetic resonance imaging; Male; Medical research; Medicine, Experimental; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Melanoma, Cutaneous Malignant; Middle Aged; Monoclonal antibodies; Nivolumab; Nivolumab - adverse effects; Patients; PD-1 protein; Pituitary (anterior); Pituitary gland; Pituitary hormones; Prognosis; Skin; Skin cancer; Skin melanoma; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Thyroid gland; Tumors; Viral antibodies; Withholding Treatment - statistics & numerical data; Cancer immunotherapy; Skin melanoma; Nivolumab; Hypophysitis
• ISSN: 1472-6823; 1472-6823
• DOI: 10.1186/s12902-021-00854-y

Nivolumab is an anti-programmed cell death protein 1 antibody, typically used as cancer immunotherapy agent. Despite multiple clinical benefits it might cause autoimmune-related side-effects, often involving the endocrine system. To our knowledge, this is the first case of nivolumab-induced hypophysitis manifesting several months after treatment discontinuation. We, herein, report a 53-year-old patient with hypophysitis and isolated adrenocorticotropic hormone deficiency, who presented with recurring syncopal episodes and persistent mild hyponatremia. The performed challenged tests were consistent with secondary adrenal insufficiency, while responses of other anterior pituitary hormones were preserved. Magnetic resonance imaging revealed thickened pituitary stalk, consistent with hypophysitis. The patient's condition gradually improved after administration of hydrocortisone, with normalization of sodium and glucose-levels. The related literature is discussed. We conclude that even after discontinuation of nivolumab, isolated adrenal insufficiency can occur. Therefore, in case of administration of such agents, clinical assessment, and routine monitoring of blood pressure, sodium-, glucose-levels, pituitary hormones as well as magnetic resonance imaging are needed to identify such conditions and prevent an adrenal crisis.