Pembrolizumab-Associated Adrenal Insufficiency Presenting as Adrenal Crisis: A Case Report

Immunotherapy regimens containing the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab are widely utilised in the management of non-small cell lung cancer (NSCLC). However, the administration of pembrolizumab is associated with unique immune-related adverse events. Adrenal insufficiency is a rare, potentially life-threatening endocrinopathy that can manifest even after the cessation of planned treatment. A male in his 50s with metastatic pulmonary adenocarcinoma developed an acute adrenal crisis 12 days after completing a 24-month course of pembrolizumab immunotherapy. Routine outpatient blood tests first identified critical hypocortisolaemia (morning serum cortisol <50 nmol/L), prompting the patient to attend hospital. The patient subsequently developed severe hypotension (58/45 mmHg) and reported malaise, anorexia, and vomiting after oral intake. Septic shock was considered but felt to be less likely given the absence of infective symptoms. The patient was successfully resuscitated in the emergency department with administration of fluids and high-dose intravenous hydrocortisone. Following clinical stabilisation, under the supervision of the endocrinology team, he was transitioned to a long-term oral maintenance regimen consisting of hydrocortisone and fludrocortisone. This case illustrates that pembrolizumab-associated adrenal insufficiency can present as an abrupt, life-threatening crisis in the immediate post-treatment phase. Frontline clinicians must remain vigilant for late-onset endocrinopathies, regardless of the treatment completion date. Proactive patient education and long-term biochemical surveillance are imperative to ensuring early clinical intervention and avoiding catastrophic management delays and poor clinical outcomes.