Clinical characteristics, management, and outcomes of nivolumab-associated pituitary toxicity: a pooled analysis of published case reports and case series
- 1Clinical pharmacy, The Central Hospital of Xiangtan (The Affiliated Hospital of Hunan University)
Abstract
Objective: To summarize the clinical features, diagnosis, management, and outcomes of nivolumab-associated pituitary toxicity.
Methods: We conducted a pooled analysis of published case reports and case series describing nivolumab-associated pituitary toxicity. PubMed, Embase, Web of Science Core Collection, CNKI, and Wanfang Data were searched from inception to June 8, 2026, supplemented by reference-list screening. Reports with extractable individual patient data describing nivolumab-associated hypophysitis, isolated adrenocorticotropic hormone (ACTH) deficiency, or central/secondary adrenal insufficiency were included. Combination immune checkpoint inhibitor therapy, insufficient data, and duplicate reports were excluded. Data were extracted per patient. Continuous and categorical variables are presented as median (range) and n/N (%), respectively.
Results: Forty-five independent patients from 43 reports were included; 33 (73.3%) were male, and median age was 68 years (39–85). Toxicity occurred after a median of 9 nivolumab cycles (n=40; range, 1–33); 8 patients (17.8%) developed symptoms after discontinuation, with a median delay of 24 weeks (4–56). Fatigue (41/44, 93.2%), anorexia (32/45, 71.1%), and nausea/vomiting (23/44, 52.3%) predominated. Hyponatremia occurred in 24/33 patients (72.7%). ACTH was low in 38/44 patients (86.4%) and inappropriately normal in 6/44 (13.6%) despite low cortisol; basal cortisol was reduced in 43/44 (97.7%). Pituitary MRI abnormalities were reported in 11/41 patients (26.8%). Hydrocortisone was the most frequently used replacement therapy, and symptoms improved in 44/45 patients (97.8%). Among 29 patients with hormonal follow-up, 2 (6.9%) had partial ACTH–cortisol axis recovery; none had complete recovery. No recurrence was reported among six patients rechallenged with nivolumab.
Conclusion: Nivolumab-associated pituitary toxicity mainly affects the ACTH–cortisol axis and may present without MRI abnormalities. Prompt assessment of cortisol, ACTH, and electrolytes is warranted in symptomatic patients.
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BibTeX
@article{liu2026clinical,
title = {{Clinical characteristics, management, and outcomes of nivolumab-associated pituitary toxicity: a pooled analysis of published case reports and case series}},
author = {Zheng Liu and Nan Huang and Ronghui Li and Haibo Lei and Xiang Liu},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1929591},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1929591/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical characteristics, management, and outcomes of nivolumab-associated pituitary toxicity: a pooled analysis of published case reports and case series
AU - Zheng Liu
AU - Nan Huang
AU - Ronghui Li
AU - Haibo Lei
AU - Xiang Liu
PY - 2026
DA - 2026/10/21
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1929591
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1929591/full
AB - Objective: To summarize the clinical features, diagnosis, management, and outcomes of nivolumab-associated pituitary toxicity. Methods: We conducted a pooled analysis of published case reports and case series describing nivolumab-associated pituitary toxicity. PubMed, Embase, Web of Science Core Collection, CNKI, and Wanfang Data were searched from inception to June 8, 2026, supplemented by reference-list screening. Reports with extractable individual patient data describing nivolumab-associated hypophysitis, isolated adrenocorticotropic hormone (ACTH) deficiency, or central/secondary adrenal insufficiency were included. Combination immune checkpoint inhibitor therapy, insufficient data, and duplicate reports were excluded. Data were extracted per patient. Continuous and categorical variables are presented as median (range) and n/N (%), respectively. Results: Forty-five independent patients from 43 reports were included; 33 (73.3%) were male, and median age was 68 years (39–85). Toxicity occurred after a median of 9 nivolumab cycles (n=40; range, 1–33); 8 patients (17.8%) developed symptoms after discontinuation, with a median delay of 24 weeks (4–56). Fatigue (41/44, 93.2%), anorexia (32/45, 71.1%), and nausea/vomiting (23/44, 52.3%) predominated. Hyponatremia occurred in 24/33 patients (72.7%). ACTH was low in 38/44 patients (86.4%) and inappropriately normal in 6/44 (13.6%) despite low cortisol; basal cortisol was reduced in 43/44 (97.7%). Pituitary MRI abnormalities were reported in 11/41 patients (26.8%). Hydrocortisone was the most frequently used replacement therapy, and symptoms improved in 44/45 patients (97.8%). Among 29 patients with hormonal follow-up, 2 (6.9%) had partial ACTH–cortisol axis recovery; none had complete recovery. No recurrence was reported among six patients rechallenged with nivolumab. Conclusion: Nivolumab-associated pituitary toxicity mainly affects the ACTH–cortisol axis and may present without MRI abnormalities. Prompt assessment of cortisol, ACTH, and electrolytes is warranted in symptomatic patients.
SN - 1664-2392
ER -