Abstract:
Immune checkpoint inhibitors (ICIs), particularly PD-1 inhibitors such as pembrolizumab, have transformed the management of advanced melanoma. However, ICIs are associated with immune-related adverse events (irAEs), which can affect various organs, including the endocrine system. One such rare but serious irAE is hypophysitis resulting in secondary adrenal insufficiency. This case report presents a 62-year-old female with stage 3 BRAF- negative cutaneous superficial spreading melanoma who developed pembrolizumab- induced adrenal insufficiency.
Following wide local excision of recurrent in-transit metastases, the patient commenced adjuvant pembrolizumab therapy in October 2024. After three cycles, she presented in February 2025 with fatigue, nausea, and hypotension. Biochemical investigations revealed a cortisol level of 16 nmol/L, consistent with adrenal insufficiency. Pembrolizumab was discontinued, and she was initiated on hydrocortisone replacement therapy (10+5+5 mg). The patient remains clinically stable with no evidence of disease recurrence. She is under ongoing endocrinology and oncology follow-up, with plans for pituitary imaging and adrenal axis reassessment.
This case highlights the importance of recognising rare endocrine complications associated with ICIs. Clinicians should maintain a high index of suspicion for irAEs, especially in patients presenting with vague systemic symptoms. Early diagnosis, prompt hormone replacement, and patient education on steroid use and sick day rules are essential in preventing adrenal crises. Multidisciplinary collaboration is critical to ensure safe and effective management of immunotherapy-related toxicities.
