New causes of old diseases. are we ready?.

Abstract

A 67-year-old male with metastatic cholangiocarcinoma presented with dehydration and delirium approximately 6 weeks after participating into a Rare Cancer Trial utilising combination of immune checkpoint inhibitors (ICIs), i.e., ipilimumab and nivolumab. His electrolytes were normal but cortisol was 36 nmol/L (185-625) and ACTH was 2 pmol/L (<10). Sixty-minute post-Synacthen cortisol was 153 nmol/L (>530). Secondary hypoadrenalism was diagnosed on the basis of low ACTH and baseline cortisol with poor response to Synacthen. Thyroid function tests revealed thyrotoxicosis, while TPO, thyroglobulin and TSH receptor antibodies were all negative. ICIs have been increasingly implicated in autoimmune endocrinopathies. Combination of ipilimumab and nivolumab can give rise to hypopituitarism or hypophysitis, and thyroid dysfunction. In healthy individuals, immune checkpoints maintain immunological tolerance to self-antigens. By inhibiting these immune checkpoints, ICIs cause auto-immune like manifestations against multiple organs. Typically, complications develop in susceptible patients 6-15 weeks after introduction of ICIs. The preferred screening test for hypophysitis is morning cortisol and ACTH, followed by Synacthen test.1 In oncology, ICIs are the most rapidly expanding class of drugs alternatives to traditional chemotherapy. Therefore, oncologists, endocrinologists and pathologists need to understand their mechanism of action, side effects, importance of monitoring ICI usage to detect and investigate the associated endocrine disorders. Reference 1. Barroso-Sousa R, Ott PA, Hodi FS, et al. Endocrine dysfunction induced by immune checkpoint inhibitors: practical recommendations for diagnosis and clinical management. Cancer 2018; 124: 1111-21. Copyright © 2020