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Clin Diabetes Endocrinol. 2019 Jan 22;5:1. doi: 10.1186/s40842-018-0073-4. eCollection 2019.

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports.

Author information

1
1Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan, 24 Frank Lloyd Wright Drive, Ann Arbor, MI 48106 USA.
2
2Present address: Endocrinology, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612 USA.
3
3Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 USA.
4
4Taubman Health Sciences Library, University of Michigan, 1135 Catherine Street, Ann Arbor, MI 48109 USA.
5
5Affiliated Hospital of QingDao University, QingDao, 16 Jiangsu Road, Sinan Qu, Qingdao, Shi, Shandong Sheng China.

Abstract

Background:

Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug's AEs (which may change during a drug's life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O'Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed.

Methods:

In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles' references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized.

Results:

One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing's syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis.

Conclusions:

The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.

KEYWORDS:

Cancer immunotherapy; Endocrine immune-related AEs; ICI-induced endocrinopathies; Immune checkpoint inhibitors (ICI)

Conflict of interest statement

Not applicable.No patient consent needed.None.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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