Diabetes insipidus: A rare endocrine complication of immune check point inhibitors: A case report and literature review

Abstract

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are novel therapeutic agents widely used in numerous malignancies. They are known to cause multiple immune-related endocrine adverse events (irAEs); however, anterior pituitary hypophysitis with secondary hypopituitarism is the most frequently reported irAE, especially in patients receiving anti-CTLA-4 treatment. By contrast, posterior pituitary involvement, such as central diabetes insipidus (CDI), is relatively rare and only few case reports have been published. The present report describes the case of a 53-year-old woman with metastatic melanoma treated with nivolumab an anti-PD-L1 monoclonal antibody. At 6 months after the initiation of nivolumab treatment, the patient was diagnosed with deficiency of the corticotrope and thyreotrope axes and in the following 2 months the patient was diagnosed with progressive development of polyuria-polydipsia syndrome. The diagnosis of partial CDI was retained based on plasma and urinary osmolalities, the water deprivation test and baseline copeptin levels as well as on the absence of the bright spot in the posterior pituitary in magnetic resonance imaging. Systematic research of the literature revealed a total of 13 cases reports (including 14 patients) presenting with CDI treated with monotherapy with CTLA-4 (n=5) or PD-1/PD-L1 Abs (n=6) or combined treatments (n=3). The improved understanding of the mechanisms of ICI action along with their extensive use should contribute to the early recognition of irAE symptoms. We hypothesized that clinicians should be aware of this clinical entity and its symptoms and treat it appropriately.

Keywords: diabetes insipidus; hypothalamus; immune check point inhibitors; immunotherapy; posterior pituitary.

Figure 1

MRI of our patient's pituitary gland. (A) Non-contrast T1 sagittal sequence showing the absence of the bright spot of the posterior pituitary gland (white arrow). (B) Post-contrast T1 sagittal sequence showing a normal posterior pituitary gland (white arrow). (C) Pre-contrast T1 coronal sequence showing a normal posterior pituitary gland (white arrow).

Figure 2

Flow diagram of the research strategy for the identification of cases reporting immunotherapy-induced DI. COVID-19, coronavirus disease 2019; DI, diabetes insipidus; ICI, immune checkpoint inhibitor; PICOT, population, intervention, comparison, outcomes, time.