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Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation
Tomonori Sekizaki1, Hiraku Kameda1, Chiho Oba1
1Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Endocrine Journal
|June 21, 2019
Summary
Elevated ACTH and cortisol during nivolumab treatment may signal early hypophysitis. Close monitoring for adrenal insufficiency is crucial when ACTH levels rise during immune checkpoint inhibitor therapy.
Area of Science:
- Endocrinology
- Oncology
- Immunology
Background:
- Nivolumab, an immune checkpoint inhibitor (ICI), is used for renal cell carcinoma.
- Hypophysitis is a known side effect of ICIs, often presenting with adrenal insufficiency.
- Typical hypophysitis diagnosis involves low ACTH and cortisol levels.
Observation:
- A 62-year-old man on nivolumab developed elevated ACTH and cortisol without symptoms.
- Hormone levels normalized then sharply decreased, indicating potential pituitary dysfunction.
- Brain MRI was normal; ACTH response to CRH was normal, but cortisol response to ACTH was blunted.
Findings:
- The patient's presentation suggested secondary adrenal insufficiency due to nivolumab-induced hypophysitis.
- Unlike typical cases, this patient initially showed elevated ACTH and cortisol.
- Cortisol response to ACTH stimulation was reduced, confirming adrenal insufficiency.
Implications:
- Elevated ACTH during ICI therapy might be an early indicator of hypophysitis.
- This finding necessitates careful monitoring for subsequent adrenal insufficiency.
- Early detection through monitoring ACTH can improve management of ICI-induced hypophysitis.
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