Work

Arginine vasopressin deficiency following pembrolizumab-induced hypophysitis: a case report and review of the literature

Year: 2026

Type: article

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized oncologic therapy by substantially improving survival outcomes in various malignancies. These agents-such as ipilimumab, nivolumab, pembrolizumab, atezolizumab, and durvalumab-modulate the immune system by inhibiting key checkpoint receptors, including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PDL-1), thereby facilitating tumor regression. However, immune modulation frequently triggers immune-related adverse events, which can affect any organ system, particularly the skin, liver, gastrointestinal tract, lung, and endocrine glands. Among the most common endocrine disorders induced by ICIs are thyroid, pituitary, adrenal, and beta-cell dysfunctions. Pituitary dysfunction is most commonly associated with combined CTLA-4 and PD-1/PDL-1 inhibitor regimens. This case report discusses a rare instance of presumed arginine vasopressin deficiency (AVP-D) secondary to pembrolizumab-monotherapy-induced hypophysitis, which was unmasked following glucocorticoid therapy. A 59-year-old male with metastatic lung adenocarcinoma treated with pembrolizumab developed gastrointestinal symptoms and was subsequently diagnosed with toxic colitis. Following the initiation of glucocorticoid therapy, he developed hypernatremia, polyuria, and polydipsia. Further evaluation suggested AVP-D, with rapid symptom resolution under desmopressin. This report underscores the complexity of endocrine disturbances associated with ICIs and the diagnostic challenges associated with glucocorticoid therapy in patients with ICI-related hypophysitis. The occurrence of arginine vasopressin deficiency in the context of pembrolizumab-induced hypophysitis is rare and not well investigated, highlighting the need for further research into the underlying mechanisms and optimal clinical management of these immune-mediated endocrine disorders.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1976186

Authors: Annina Rebecca Dold, Raphael Jeker, Michael Mark

Institution: Università della Svizzera italiana

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801