ArticleFrontiers in endocrinology2026
Systematic monitoring identified a high incidence of hypopituitarism following combined ipilimumab plus nivolumab therapy for metastatic melanoma.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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3 authors.
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Abstract
Introduction: Combination immunotherapy with ipilimumab and nivolumab has improved long-term progression-free and overall survival in patients with metastatic melanoma. Unfortunately, a high percentage of patients develop immune-related side effects, including endocrinopathy. The incidence and timing of hypopituitarism remains poorly characterized. Methods: We routinely performed laboratory screening for hypopituitarism and hypothyroidism every 3-4 weeks on each treatment visit for patients receiving first-line ipilimumab plus nivolumab therapy for metastatic melanoma. A retrospective analysis of patient treatment records was performed to determine the incidence and timing of biochemical evidence for endocrinopathy. Results: Records from 59 sequential patients treated with first-line combination immunotherapy were reviewed. Endocrinopathy was detected in 44.1%, including 18.7% with hypopituitarism and 25.4% with primary hypothyroidism. The median time to onset of was 72.5 ± 107.3 and 58 ± 48.7 days, respectively. Only one patient developed delayed onset of hypothyroidism, 3 months after elective treatment discontinuation. Development of endocrinopathy trended with improved clinical outcomes. All patients underwent prompt endocrine replacement therapy, and only one patient required hospitalization for symptomatic hypopituitarism. Conclusions: Both the standard and alternate regimens of ipilimumab plus nivolumab treatment resulted in biochemical evidence for endocrinopathy in 54.6% and 38.9% of treated patients, respectively. Endocrinopathy always presented during or shortly following active treatment. Delayed onset of endocrinopathy was uncommon. Prompt replacement therapy allowed continuation of immune checkpoint inhibitors and minimized the risk for hospitalizations. Due to the high incidence of hypopituitarism, routine monitoring of both pituitary and thyroid and function of patients is strongly recommended receiving combination immunotherapy.
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