Concomitant Immune Checkpoint Inhibitors Induced Central and Primary Adrenal Insufficiency

Alberto Nascè, Sophie Leboulleux, Simina Chiriac, Petros Tsantoulis, Maria Mavromati
JCEM Case Reports, Volume 3, Issue 10, October 2025, luaf194
https://doi.org/10.1210/jcemcr/luaf194

Abstract

Immune checkpoint inhibitors (ICI) have several endocrine toxicities. Dual sequential pituitary and adrenal toxicities are rare and difficult to diagnose. This case report describes a 63-year-old man with metastatic clear cell renal carcinoma treated with combined nivolumab and ipilimumab. After 3 cycles, he presented with severe headaches. The imaging studies revealed pituitary enlargement consistent with hypophysitis. Hormonal assessment confirmed panhypopituitarism, leading to high-dose hydrocortisone replacement. Four months later, a routine computed tomography scan showed significant bilateral adrenal enlargement. Later symptoms of fatigue and low blood pressure, combined with high potassium, suppressed aldosterone, and high renin, confirmed the diagnosis of immune checkpoint inhibitor-associated adrenalitis, while ACTH remained low due to pituitary function impairment. Fludrocortisone was added, resulting in clinical improvement, and a control scan showed reduced adrenal size compared to previous imaging. This case emphasizes the importance of radiological and laboratory assessments in diagnosing concomitant central and peripheral adrenal insufficiency during ICI therapy.

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