Clinical characteristics, management, and prognosis of pembrolizumab-induced hypophysitis: retrospective analysis based on case reports.

BACKGROUND

Pembrolizumab-induced hypophysitis is a rare but clinically important immune-related adverse event. Its clinical features and long-term outcomes are not fully defined. This study aimed to summarize the clinical characteristics, management, and prognosis of pembrolizumab-associated hypophysitis to support early recognition and appropriate treatment.

METHODS

PubMed, EMBASE, Web of Science, WanFang Data, and CNKI were searched for reports of pembrolizumab-induced hypophysitis published up to Jan 31, 2026, using relevant keywords and Boolean operators. Eligible case reports and case series were screened, and patient-level data were extracted using a standardized form. Study quality was assessed with the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports.

RESULTS

A total of 22 patients were included. The median age was 66 years (range 39-85), with equal distribution between males and females. The median time to onset was 15 weeks (range 2-36), most frequently occurring within 11-20 weeks. Fatigue was the predominant symptom (86.4%), followed by nausea/vomiting (54.5%), adrenal insufficiency manifestations (40.9%), hyponatremia (31.8%), and headache (27.3%). Median cortisol and ACTH levels were markedly reduced at 0.9 μg/dL and 5.0 pg/mL, respectively. Among patients with available pituitary MRI data, normal findings were observed in 50.0% of cases, whereas pituitary enlargement was present in 27.8%. Hormone replacement therapy, primarily hydrocortisone, was administered in 81.8% of cases. Clinical improvement occurred in 90.9% of patients; however, persistent endocrine dysfunction remained in 95.5%, with recovery of the hypothalamic-pituitary axis documented in only one case. Rechallenge was performed in seven patients without recurrence in most cases. According to the WHO-UMC system, 86.4% of cases were classified as probable.

CONCLUSION

Pembrolizumab-induced hypophysitis typically presents subacutely with nonspecific symptoms and frequently exhibits normal imaging findings. Although clinical symptoms improve with prompt hormone replacement, permanent endocrine insufficiency is common. Early recognition and long-term endocrine follow-up are essential in affected patients.