Pembrolizumab (anti-PD-1 monoclonal antibody) causes immune-related adverse events (irAEs). Which mechanism is responsible for pembrolizumab-induced hypophysitis?
- A PD-1 blockade releases autoreactive T-cells that were previously suppressed by PD-1 signaling; these attack pituitary antigens (including TSH-secreting cells) in a manner similar to autoimmune hypophysitis ✓
- B Direct antibody binding to PD-1 expressed on pituitary cells causing cell death
- C Pembrolizumab activates NK cells that selectively destroy pituitary gonadotrophs
- D Anti-PD-1 therapy increases ACTH secretion, causing Cushing's syndrome rather than hypopituitarism
Explanation
PD-1 (programmed death-1) on T-cells normally receives inhibitory signals from PD-L1/PD-L2 on tumor cells and normal tissues (including pituitary), preventing immune attack on self-antigens. Pembrolizumab blocks PD-1, releasing previously suppressed autoreactive T-cells. In susceptible individuals, these T-cells attack pituitary cells expressing self-antigens, causing autoimmune hypophysitis — presenting as headaches, visual field defects, and anterior pituitary hormone deficiencies (ACTH, TSH, LH/FSH deficiency). This is an irAE distinct from tumor response and requires immunosuppression with glucocorticoids.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.