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American Association of Clinical Endocrinology Disease State Clinical Review: Evaluation and Management of Immune Checkpoint Inhibitor-Mediated Endocrinopathies: A Practical Case-Based Clinical Approach
Authors:Kevin CJ Yuen  Susan L Samson  Irina Bancos  Aidar R Gosmanov  Sina Jasim  Leslie A Fecher  Jeffrey S Weber
Institution:1. Co-Chair of Task Force, Barrow Neurological Institute, Department of Medicine, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona;2. Co-Chair of Task Force, Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Jacksonville, Florida;3. Division of Endocrinology, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota;4. Division of Endocrinology, Albany Medical College, Albany, New York;5. Endocrinology Section, Stratton VAMC, Albany, New York;6. Division of Endocrinology, Metabolism and Lipid Research, School of Medicine, Washington University in St. Louis, St. Louis, Missouri;7. ASCO Representative, Rogel Cancer Center, Ann Arbor, Michigan;8. ASCO Representative, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York
Abstract:ObjectiveThe aim of this case-based clinical review was to provide a practical approach for clinicians regarding the management of patients with immune checkpoint inhibitor (ICI)-mediated endocrinopathies.MethodsA literature search of PubMed, Embase, and Scopus was conducted using appropriate keywords. The discussions and strategies for the diagnosis and management of ICI-mediated endocrinopathies are based on evidence available from prospective, randomized clinical studies; cohort studies; cross-sectional studies; case-based studies; and an expert consensus.ResultsImmunotherapy with ICIs has transformed the treatment landscape of diverse types of cancers but frequently results in immune-mediated endocrinopathies that can cause acute and persistent morbidity and, rarely, death. The patterns of endocrinopathies differ between the inhibitors of the cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 or programmed cell death protein 1 ligand pathways but most often involve the thyroid and pituitary glands. The less common but important presentations include insulin-deficient diabetes mellitus, primary adrenal insufficiency, primary hypoparathyroidism, central diabetes insipidus, primary hypogonadism, and pancreatitis, with or without subsequent progression to diabetes mellitus or exocrine insufficiency.ConclusionIn recent years, with increasing numbers of patients with cancer being treated with ICIs, more clinicians in a variety of specialties have been called upon to diagnose and treat ICI-mediated endocrinopathies. Herein, we reviewed case scenarios of various clinical manifestations and emphasized the need for a high index of clinical suspicion by all clinicians caring for these patients, including endocrinologists, oncologists, primary care providers, and emergency department physicians. We also provided diagnostic and therapeutic approaches for ICI-induced endocrinopathies and proposed that patients on ICI therapy be evaluated and treated by a multidisciplinary team in collaboration with endocrinologists.
Keywords:immune checkpoint inhibitor  endocrinopathy  hypophysitis  thyroiditis  adrenalitis  diabetes mellitus  ACTH"}  {"#name":"keyword"  "$":{"id":"kwrd0065"}  "$$":[{"#name":"text"  "_":"adrenocorticotropic hormone  AE"}  {"#name":"keyword"  "$":{"id":"kwrd0075"}  "$$":[{"#name":"text"  "_":"adverse event  AI"}  {"#name":"keyword"  "$":{"id":"kwrd0085"}  "$$":[{"#name":"text"  "_":"adrenal insufficiency  CT"}  {"#name":"keyword"  "$":{"id":"kwrd0095"}  "$$":[{"#name":"text"  "_":"computed tomography  CTLA-4"}  {"#name":"keyword"  "$":{"id":"kwrd0105"}  "$$":[{"#name":"text"  "_":"cytotoxic T-lymphocyte antigen 4  DI"}  {"#name":"keyword"  "$":{"id":"kwrd0115"}  "$$":[{"#name":"text"  "_":"diabetes insipidus  DKA"}  {"#name":"keyword"  "$":{"id":"kwrd0125"}  "$$":[{"#name":"text"  "_":"diabetes ketoacidosis  DM"}  {"#name":"keyword"  "$":{"id":"kwrd0135"}  "$$":[{"#name":"text"  "_":"diabetes mellitus  FDG"}  {"#name":"keyword"  "$":{"id":"kwrd0145"}  "$$":[{"#name":"text"  "_":"fluorodeoxyglucose  GAD"}  {"#name":"keyword"  "$":{"id":"kwrd0155"}  "$$":[{"#name":"text"  "_":"glutamic acid decarboxylase  GH"}  {"#name":"keyword"  "$":{"id":"kwrd0165"}  "$$":[{"#name":"text"  "_":"growth hormone  HbA1C"}  {"#name":"keyword"  "$":{"id":"kwrd0175"}  "$$":[{"#name":"text"  "_":"hemoglobin A1C  HC"}  {"#name":"keyword"  "$":{"id":"kwrd0185"}  "$$":[{"#name":"text"  "_":"hydrocortisone  ICI"}  {"#name":"keyword"  "$":{"id":"kwrd0195"}  "$$":[{"#name":"text"  "_":"immune checkpoint inhibitor  Ipi"}  {"#name":"keyword"  "$":{"id":"kwrd0205"}  "$$":[{"#name":"text"  "_":"ipilimumab  IrAE"}  {"#name":"keyword"  "$":{"id":"kwrd0215"}  "$$":[{"#name":"text"  "_":"immune-related adverse event  MRI"}  {"#name":"keyword"  "$":{"id":"kwrd0225"}  "$$":[{"#name":"text"  "_":"magnetic resonance imaging  Nivo"}  {"#name":"keyword"  "$":{"id":"kwrd0235"}  "$$":[{"#name":"text"  "_":"nivolumab  PD-1"}  {"#name":"keyword"  "$":{"id":"kwrd0245"}  "$$":[{"#name":"text"  "_":"programmed cell death protein 1  PD-L1"}  {"#name":"keyword"  "$":{"id":"kwrd0255"}  "$$":[{"#name":"text"  "_":"programmed cell death protein 1 ligand  Pembro"}  {"#name":"keyword"  "$":{"id":"kwrd0265"}  "$$":[{"#name":"text"  "_":"pembrolizumab  PET"}  {"#name":"keyword"  "$":{"id":"kwrd0275"}  "$$":[{"#name":"text"  "_":"positron emission tomography  TSH"}  {"#name":"keyword"  "$":{"id":"kwrd0285"}  "$$":[{"#name":"text"  "_":"thyroid-stimulating hormone  T4"}  {"#name":"keyword"  "$":{"id":"kwrd0295"}  "$$":[{"#name":"text"  "_":"thyroxine
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