Immune-related endocrine disorders in novel Immune checkpoint inhibition therapy

Area of Science:

• Oncology
• Endocrinology
• Immunotherapy

Background:

• Immune checkpoint inhibitors (ICIs) targeting CTLA4, PD1, and PDL1 have revolutionized advanced malignancy treatment.
• Adverse events from ICIs are often autoimmune-related, with endocrine disorders being common.
• Hypophysitis and thyroiditis are significant endocrine toxicities associated with ICI therapy.

Purpose of the Study:

• To review the incidence and clinical presentation of hypophysitis and thyroiditis in patients treated with ICIs.
• To highlight the timing of onset and potential reversibility of these endocrine disorders.
• To emphasize the importance of early diagnosis and management for improving patient outcomes.

Main Methods:

• Review of clinical studies on ICI therapy for advanced malignancies.
• Analysis of reported adverse events, focusing on endocrine disorders (hypophysitis, thyroiditis).
• Evaluation of incidence, onset timing, clinical manifestations, and management strategies.

Main Results:

• Hypophysitis occurs in ~10% of anti-CTLA4 treated patients; thyroiditis is more common with anti-PD1 therapy.
• Both conditions are frequent with combination anti-CTLA4 and anti-PD1 treatment, typically manifesting within 12 weeks.
• Hypophysitis can cause pituitary hormone deficiencies (TSH, gonadotropin, ACTH); thyroiditis presents as hypo- or hyperthyroidism.

Conclusions:

• Hypophysitis and thyroiditis are common, early-onset autoimmune side effects of immune checkpoint inhibition.
• While TSH and gonadotropin deficiencies may be reversible, ACTH deficiency and hypothyroidism appear permanent.
• Prompt identification and management of ICI-induced hypophysitis and thyroiditis are essential for optimizing patient quality of life and treatment efficacy.