[Checkpoint inhibitors-induced hypophysitis].

Area of Science:

• Endocrinology
• Oncology
• Immunology

Background:

• Checkpoint inhibitors (e.g., anti-CTLA4, anti-PD1/PDL1) are increasingly used in cancer treatment.
• These therapies can lead to immune-related endocrine adverse events, including hypophysitis.

Purpose of the Study:

• To describe the clinical presentation, diagnosis, and management of hypophysitis induced by checkpoint inhibitors.
• To differentiate hypophysitis related to anti-CTLA4 from that related to anti-PD1/PDL1.

Main Methods:

• Review of clinical cases and literature on hypophysitis in patients treated with checkpoint inhibitors.
• Analysis of hormonal deficiencies, onset, symptoms, and treatment responses.

Main Results:

• Anti-CTLA4-induced hypophysitis occurs ~2-3 months after treatment initiation, presenting with headache, asthenia, and hyponatremia, often involving ACTH, gonadotropic, and thyrotropic deficiencies.
• Anti-PD1/PDL1-induced hypophysitis has a later onset and is less symptomatic, with ACTH deficiency being constant and often isolated.
• ACTH deficiency can be life-threatening, requiring urgent supplementation; MRI is used to rule out other causes.

Conclusions:

• Hypophysitis is a significant, potentially life-threatening complication of checkpoint inhibitor therapy.
• Systematic biological screening is essential for early detection.
• Lifelong hormone supplementation is typically required for pituitary deficits, with immunotherapy potentially continuing if oncologically beneficial.