Article type: Review
Article title: A systematic review of ipilimumab-induced hypophysitis
Journal: Endocrine Connections
Year: 2026
Authors: Sarah Kim, Sudhakar Narayana Yadav Teerupati, Jamir Pitton Rissardo, Pranav Patel, Emily Lai, Vishnu Vardhan Byroju, Ana LetÃcia Fornari Caprara
E-mail: jamirrissardo@gmail.com
ABSTRACT
Background: Ipilimumab, a CTLA-4 targeting monoclonal antibody, enhances T-cell activation and improves outcomes in various malignancies. However, it is associated with Immune Related Adverse Events (IRAEs), including hypophysitis- a rare but potentially life-threatening condition. This review characterizes the clinical features, diagnostic approaches, and therapeutic strategies for ipilimumab-induced hypophysitis, and explores its underlying pathophysiology through a case report and literature synthesis. Methodology: We conducted a systematic review of published cases of ipilimumab-induced hypophysitis, extracting data on demographics, comorbidities, cancer types, treatment regimens, imaging findings, endocrine dysfunctions, and therapeutic outcomes. Additionally, we present a detailed case report of a 60-year-old male with renal cell carcinoma who developed hypophysitis following ipilimumab-nivolumab combination immunotherapy. Results: The literature review included 92 patients (mean age 57, 68% male), most commonly treated for melanoma. MRI revealed pituitary abnormalities in 46 patients. The most frequent symptoms were headache and fatigue, with panhypopituitarism and secondary adrenal insufficiency being the most common endocrine manifestations. Glucocorticoids were administered in 86 patients, and 62 required hormone replacement. Only 15/92 patients had full pituitary function recovery. Our case report mirrored these findings, with symptom onset after the third immunotherapy cycle and partial hormonal recovery following steroids. Conclusions: Ipilimumab-induced hypophysitis is a significant IRAE with a variable clinical course and often irreversible endocrine dysfunction. Early recognition and management with glucocorticoids are critical, though long-term hormone replacement is frequently required. The autoimmune pathogenesis, linked to CTLA-4 expression in pituitary cells, underscores the need for further research into predictive markers and preventive strategies.
Keywords: Autoimmune hypophysitis; immune checkpoint inhibitors; immunotherapy; ipilimumab.
Full text available at:
https://ec.bioscientifica.com/view/journals/ec/15/1/EC-25-0697.xml
DOI
https://doi.org/10.1530/EC-25-0697
Citation
Kim S, Yadav Teerupati SN, Rissardo JP, Patel P, Lai E, Byroju VV, Fornari Caprara AL. A Systematic Review of Ipilimumab-Induced Hypophysitis. Endocr Connect 2026;15: e250697. doi: 10.1530/EC-25-0697.
Graphical abstract. Ipilimumab-induced hypophysitis.
Figure 1. Ipilimumab mechanism of action. (A) T-cell activation necessitating two signals: first between MHC and TCR, and second between B7 and CD28. (B) T-cell inactivation due to CTLA-4 binding to B7. (C) T-cell activation due to ipilimumab binding to CTLA-4.
Figure 2. Flowchart of the screening process.
Figure 3. Dedicated pituitary magnetic resonance imaging. Pituitary enlargement with heterogeneous enhancement. The pituitary stalk is midline. There is no evidence of optic chiasm compression. Craniocaudal diameter measures approximately 12 mm, significantly increased from prior neuroimaging when it measured approximately 5 mm.
Figure 4. Forest plot showing the incidence of endocrine dysfunction in patients with ipilimumab-induced hypophysitis. The points represent the proportion of patients experiencing each hormonal deficiency, and the horizontal lines indicate 95% confidence intervals calculated using the Wilson method. Among 92 patients, panhypopituitarism was the most common manifestation, followed by central adrenal insufficiency, central hypothyroidism, and central hypogonadism.