Case Report: Tislelizumab-associated secondary adrenal insufficiency in a patient with lung squamous cell carcinoma

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but immune-related adverse events remain clinically challenging. Tislelizumab is a humanized anti-PD-1 monoclonal antibody widely used in China, and tislelizumab-associated secondary adrenal insufficiency (SAI) remains insufficiently characterized, particularly with regard to how and when it is recognized.

A 66-year-old man underwent video-assisted thoracoscopic surgery for right lower lobe squamous cell carcinoma (pT1cN1M0, stage IIB), followed by four cycles of carboplatin, paclitaxel liposome and tislelizumab, then 13 cycles of tislelizumab maintenance. His last tislelizumab dose was administered on December 11, 2023. Poor appetite and fatigue first developed in November 2023, accompanied by a blood pressure of 92/57 mmHg. His symptoms improved after supportive treatment, but adrenocorticotropic hormone (ACTH) and cortisol were not measured. He subsequently developed headache, nausea, vomiting, and progressive weight loss of 19 kg. In November 2024, he was admitted with hypotension (75/56 mmHg) and severe hyponatremia (108.9 mmol/L); chest CT and bronchoscopy excluded tumor recurrence, and he improved with supportive care. Symptoms recurred within a week of discharge, and he was readmitted in December 2024 with hypotension (52/37 mmHg) and recurrent hyponatremia. On December 11, 2024, approximately 13 months after the initial symptoms, morning cortisol was <1.00 µg/dL and ACTH was inappropriately low at <5.00 pg/mL, supporting SAI (Naranjo score 6, probable). Pituitary MRI, cosyntropin stimulation testing and comprehensive pituitary hormonal assessment were unavailable; hypophysitis was therefore not confirmed, and the site of hypothalamic-pituitary-adrenal (HPA) axis injury could not be determined. He improved with intravenous hydrocortisone and fluids and was transitioned to oral prednisone. ACTH and cortisol remained low through July 2025 during replacement, although endogenous HPA-axis recovery could not be reliably assessed. At telephone follow-up in June 2026 no recurrent adrenal crisis was reported.

Tislelizumab-associated SAI may present with nonspecific symptoms and remain unrecognized until adrenal crisis develops, including months after the last dose. Unexplained fatigue, gastrointestinal symptoms, weight loss, hyponatremia, hypoglycemia, or hypotension should prompt early measurement of paired morning ACTH and cortisol levels. Prompt glucocorticoid replacement and structured endocrine follow-up are essential for patient safety and assessment of potential HPA-axis recovery.