ICI-Induced Hypophysitis — RACP Adult Medicine MCQ

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HardEndocrinology & DiabetesICI-Induced HypophysitisRACP Adult Medicine

A 60-year-old man with metastatic melanoma on combined nivolumab + ipilimumab develops acute onset headache, visual disturbance, and fatigue 6 weeks after starting treatment. His morning cortisol is 45 nmol/L, TSH is 0.8 mIU/L, free T4 is 8 pmol/L. What endocrine emergency has occurred?

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Correct answer: C — ICI-induced type 1 diabetes

ICI-induced hypophysitis is an immune-related adverse event most common with anti-CTLA-4 (ipilimumab) – incidence ~10% with combination nivolumab + ipilimumab. It presents with headache, visual disturbance, fatigue, and panhypopituitarism. The low morning cortisol with inappropriately normal/low TSH (secondary hypothyroidism – TSH should be elevated if primary) suggests central adrenal insufficiency and central hypothyroidism from pituitary inflammation. MRI pituitary shows enlargement. Management: stress-dose hydrocortisone IMMEDIATELY (before levothyroxine – starting thyroid hormone without cortisol replacement can precipitate adrenal crisis), then levothyroxine. Gonadotrophin and GH deficiency may also occur. ACTH and gonadotrophin recovery is rare; TSH function sometimes recovers.

Reference: ASCO – 2021 – irAE Management Guidelines; eTG – 2025 – Endocrinology