4.3 Review

Endocrine Dysfunction From Immune Checkpoint Inhibitors: Pearls and Pitfalls in Evaluation and Management

Related references

Note: Only part of the references are listed.
Review Endocrinology & Metabolism

Approach to the Patient With Immune Checkpoint Inhibitor-Associated Endocrine Dysfunction

Jordan J. Wright et al.

Summary: Immune checkpoint inhibitors (ICI) are approved for use in various cancers and can stimulate immune cell responses against cancer. However, they can also cause toxicities in any organ system, with endocrine toxicities being common. These toxicities can range from mild cases of subclinical hypothyroidism to severe cases of adrenal crisis, thyroid dysfunction, or diabetic ketoacidosis. Timely recognition and treatment are crucial for managing ICI-associated endocrine dysfunction.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2023)

Review Oncology

Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis

Yee-Ming Melody Cheung et al.

Summary: The development of immune-related thyroid dysfunction during immune checkpoint inhibitor therapy is associated with improved overall survival and progression free survival for cancer patients. This suggests that thyroid immune-related adverse events can be used as a surrogate marker for clinical response to ICIs.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2022)

Article Endocrinology & Metabolism

Association of Antithyroid Antibodies in Checkpoint Inhibitor-Associated Thyroid Immune-Related Adverse Events

Christopher A. Muir et al.

Summary: This study found that positivity for TPOAb and TgAb at baseline was more prevalent in patients who developed thyroid irAEs, particularly overt thyrotoxicosis. During ICI treatment, significant increases in TgAb and TPOAb titers were associated with overt thyrotoxicosis. TPOAb and TgAb positivity or increases during ICI treatment may be a useful biomarker to identify patients at increased risk of thyroid irAEs.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2022)

Article Medicine, General & Internal

Immune checkpoint inhibitor-induced hypophysitis: lessons learnt from a large cancer cohort

Anupam Kotwal et al.

Summary: This study found that immune checkpoint inhibitors (ICIs) can lead to pituitary dysfunction and hypophysitis, mainly occurring after treatment with ipilimumab. Patients with hypophysitis often develop secondary adrenal insufficiency, and ipilimumab is more likely to cause pituitary enlargement and mass effects compared to pembrolizumab.

JOURNAL OF INVESTIGATIVE MEDICINE (2022)

Article Endocrinology & Metabolism

Immune Checkpoint Inhibitors and Risk of Type 1 Diabetes

Xuan Chen et al.

Summary: This study found that the risk of developing ICI-T1DM is associated with the type of ICI therapy, patient age, and preexisting non-T1DM diabetes. The development of ICI-T1DM does not seem to significantly impact patient survival.

DIABETES CARE (2022)

Article Endocrinology & Metabolism

Thyroid Dysfunction from Treatments for Solid Organ Cancers

Anupam Kotwal et al.

ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA (2022)

Article Oncology

Management of Immunotherapy-Related Toxicities, Version 1.2022

John A. Thompson et al.

Summary: The NCCN Guidelines for Management of Immunotherapy-Related Toxicities aim to provide guidance on managing adverse events resulting from cancer immunotherapy. The guidelines are developed by an interdisciplinary panel of experts from various fields. This article presents excerpts and reviews of recommendations for managing toxicities related to CAR T-cell therapies.

JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK (2022)

Review Endocrinology & Metabolism

Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions

Jia-Xu Li et al.

Summary: Glucocorticoid therapies are effective in treating inflammatory diseases but can lead to adverse metabolic effects such as diabetes mellitus. Activating glucocorticoid receptors in multiple tissues increases hepatic glucose production and inhibits peripheral glucose uptake. Effective management strategies for the metabolic effects are currently lacking.

NATURE REVIEWS ENDOCRINOLOGY (2022)

Article Endocrinology & Metabolism

Optimal Thyroid Hormone Replacement Dose in Immune Checkpoint Inhibitor-Associated Hypothyroidism Is Distinct from Hashimoto's Thyroiditis

Tina Mosaferi et al.

Summary: Patients with ICI-associated hypothyroidism have different thyroid hormone dosing requirements than patients with HT. Based on our findings and prior reports, we recommend that in patients with ICI-associated thyroiditis LT4 therapy be started at an initial weight-based dose of 1.45 mcg/[kg center dot day] once serum free thyroxine levels fall below the reference range.

THYROID (2022)

Review Endocrinology & Metabolism

Diabetes mellitus induced by immune checkpoint inhibitors: type 1 diabetes variant or new clinical entity? Review of the literature

V. Lo Preiato et al.

Summary: The study identified CPI-DM as a relatively frequent side effect of CPI treatment, with distinct characteristics from classical diabetes. CPI-DM often presents early with acute onset, with diabetic ketoacidosis occurring in a majority of cases. Persistent compromised C-peptide levels and the need for lifelong insulin therapy are common features, while autoimmunity and genetic profile may not always be helpful. Close monitoring of glucose levels and early signs of diabetes in cancer patients under CPI treatment is recommended.

REVIEWS IN ENDOCRINE & METABOLIC DISORDERS (2021)

Article Endocrinology & Metabolism

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes

David Tak Wai Lui et al.

Summary: Thyroid immune-related adverse events (irAEs) are common among advanced cancer patients receiving combination anti-PD1/anti-CTLA4 therapy and may have potential prognostic significance. Regular monitoring of thyroid function tests (TFTs) and prompt treatment of thyroid irAEs are recommended to prevent potential morbidities.

ENDOCRINE PRACTICE (2021)

Article Endocrinology & Metabolism

Higher baseline TSH levels predict early hypothyroidism during cancer immunotherapy

C. Luongo et al.

Summary: ICIs are monoclonal antibodies that boost the immune response against cancer cells, but they can also lead to endocrine immune-related adverse events (irAEs). This study found that baseline TSH levels above 1.67 mIU/L and positive anti-thyroid antibodies are risk factors for thyroid irAEs. Patients with thyroid irAEs had better survival outcomes than those who remained euthyroid.

JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION (2021)

Article Oncology

Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns

Ha Nguyen et al.

Summary: Data is limited on immune checkpoint inhibitor-related hypophysitis (irH), so a study was conducted to validate diagnostic criteria and investigate factors associated with irH, finding that ipilimumab has a strong association with irH occurrence. Most irH patients presented with headache, fatigue, central hypothyroidism, central adrenal insufficiency and MRI changes, with recovery rates varying among different hormonal axes.

ENDOCRINE-RELATED CANCER (2021)

Article Endocrinology & Metabolism

Thyroid Immune-related Adverse Events Following Immune Checkpoint Inhibitor Treatment

Christopher A. Muir et al.

Summary: Thyroid dysfunction is common following immune checkpoint inhibition, with different subtypes of thyroid immune-related adverse events having unique clinical and biochemical associations. Overt thyrotoxicosis was associated with longer progression free survival and overall survival, while hypothyroidism showed no association with cancer outcomes. Multiple distinct phenotypes of thyroid irAEs suggest potentially different etiologies for thyrotoxicosis and hypothyroidism.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

Article Endocrinology & Metabolism

Coexistence of Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes and Pancreatitis

Amy L. Zhang et al.

Summary: Autoimmune diabetes is a rare but severe endocrine toxicity induced by immune checkpoint inhibitor treatment. It is unclear whether ICI causes selective islet toxicity or non-selective pancreas toxicity. The onset of autoimmune diabetes with ICI treatment may be associated with pancreatitis in some patients, but the majority of cases suggest selective islet toxicity as the main mechanism of ICI-induced toxicity.

FRONTIERS IN ENDOCRINOLOGY (2021)

Review Oncology

Graves' Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review)

Mathilde Peiffert et al.

Summary: Immune checkpoint inhibitor (ICPi)-induced immune-related thyroid dysfunction is a common adverse event, mainly presenting as a biphasic thyroiditis with secondary hypothyroidism. ICPi-induced Graves' disease (GD) is rare, typically following a quick course with varying outcomes. The study shows that the evolution of GD during ICPi therapy can differ among patients, with some transitioning to classical GD and others to thyroiditis, while pre-existing GD tends to progress towards hypothyroidism without exacerbation. Observing the spontaneous evolution and performing biochemical surveillance are important for managing ICPi-induced thyroid dysfunction.

CANCERS (2021)

Review Endocrinology & Metabolism

Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers

Anupam Kotwal et al.

Summary: Studies have shown a link between immune-related adverse events induced by ICIs and improved survival in cancer patients, with thyroid irAEs being most strongly associated with improved outcomes.

CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY (2021)

Article Endocrinology & Metabolism

Thyroid Immune-related Adverse Events Following Immune Checkpoint Inhibitor Treatment

Christopher A. Muir et al.

Summary: Thyroid dysfunction is common following immune checkpoint inhibition, with distinct phenotypes of thyroid irAEs showing unique clinical and biochemical associations. Overt thyrotoxicosis was associated with longer survival outcomes, while no association was found between hypothyroidism and cancer outcomes.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

Article Endocrinology & Metabolism

Hypophysitis (Including IgG4 and Immunotherapy)

Anna Angelousi et al.

NEUROENDOCRINOLOGY (2020)

Article Endocrinology & Metabolism

Immune Checkpoint Inhibitor-Associated Diabetes: A Single-Institution Experience

David J. Byun et al.

DIABETES CARE (2020)

Review Endocrinology & Metabolism

Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints

Lee-Shing Chang et al.

ENDOCRINE REVIEWS (2019)

Review Endocrinology & Metabolism

Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review

Jeroen M. K. de Filette et al.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2019)

Article Endocrinology & Metabolism

Checkpoint Inhibitor-Associated Autoimmune Diabetes Is Distinct From Type 1 Diabetes

Venessa H. M. Tsang et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2019)

Article Endocrinology & Metabolism

Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis

Alexander Faje et al.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2019)

Review Endocrinology & Metabolism

Immune check point inhibitors-induced hypophysitis

Frederique Albarel et al.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2019)

Article Endocrinology & Metabolism

Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes

Anupam Kotwal et al.

BMJ OPEN DIABETES RESEARCH & CARE (2019)

Article Endocrinology & Metabolism

Anti-PD-L1 Treatment Induced Central Diabetes Insipidus

Chen Zhao et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2018)

Article Endocrinology & Metabolism

Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors

Angeliki Stamatouli et al.

DIABETES (2018)

Review Endocrinology & Metabolism

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus

Katrien Clotman et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2018)

Article Endocrinology & Metabolism

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

Tomoko Kobayashi et al.

JOURNAL OF THE ENDOCRINE SOCIETY (2018)

Article Endocrinology & Metabolism

Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study

Ichiro Yamauchi et al.

THYROID (2017)

Article Primary Health Care

Steroid-induced hyperglycaemia in primary care

Edouard Mills et al.

LONDON JOURNAL OF PRIMARY CARE (2015)

Article Endocrinology & Metabolism

Ipilimumab-Induced Hypophysitis: A Detailed Longitudinal Analysis in a Large Cohort of Patients With Metastatic Melanoma

Alexander T. Faje et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2014)

Review Endocrinology & Metabolism

Glucocorticoid-induced hyperglycemia

Antonio Perez et al.

JOURNAL OF DIABETES (2014)

Article Endocrinology & Metabolism

Hyperglycemic Crises in Adult Patients with Diabetes

Abbas E. Kitabchi et al.

DIABETES CARE (2009)

Article Immunology

Mechanisms of PDL-1 mediated regulation of autoimmune diabetes

Indira Guleria et al.

CLINICAL IMMUNOLOGY (2007)

Review Endocrinology & Metabolism

Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners

Toshiaki Hanafusa et al.

NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM (2007)

Article Endocrinology & Metabolism

Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases

F Santini et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2005)