A Systematic Review of Ipilimumab-Induced Hypophysitis

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.

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.

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.

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.