Immune checkpoint inhibitor-associated hypothyroidism, macular rash and adrenal insufficiency: case report and review of the literature

Immune checkpoint inhibitors (ICIs) represent the most significant therapeutic advancement in oncology over the past decade, with sintilimab demonstrating efficacy as a programmed cell death-1 (PD-1) inhibitor. While these agents have markedly improved tumor response rates and overall survival across multiple malignancies, their use is complicated by a growing incidence of immune-related adverse events (irAEs), particularly endocrine toxicities. To our knowledge, this is the first case report of adrenal crisis during levothyroxine supplementation for ICI-induced hypothyroidism and undiagnosed adrenal insufficiency.

A 71-year-old male patient was admitted to our hospital with complaints of anorexia, fatigue, and weight loss. He had a confirmed diagnosis of esophageal squamous cell carcinoma 18 months prior and received systemic therapy, including sintilimab and esophagectomy (with normal thyroid and renal function at baseline). Sintilimab was administered for 10 treatment cycles. 4 months after completion of chemotherapy, the patient developed macular rash on the trunk and extremities and was treated with high-dose topical corticosteroids, and 1 month later, he began to suffer from anorexia and weight loss of 4.0 kg until this admission. At the same time, hypothyroidism and hyponatremia were detected, and levothyroxine (100 µg/day) was commenced. However, he worsened, with two episodes of fever, hypotension, and somnolence, as well as hyponatremia, hypoglycemia, anemia, and elevated serum creatinine. Cortisol and adrenocorticotrophic hormone (ACTH) levels decreased in the morning, and concurrent pericardial effusion and diffuse T-wave inversions were detected via electrocardiogram. He was diagnosed with secondary adrenal insufficiency and took prednisone (5 mg twice a day), and the symptoms improved rapidly. 1 week later, the serum electrolytes were normal, his weight increased by 3.5 kg, his physical activity improved, and the T wave on the electrocardiogram normalized. After taking prednisone for 18 days, his condition improved further. The morning cortisol level still decreased, while ACTH levels normalized, and pericardial effusion disappeared.

This is a typical case of endocrine irAEs caused by ICIs, and the patient’s macular rash may also be related to ICIs. For patients treated with ICIs, preventive monitoring of symptoms of irAEs and related hormones is crucial for timely diagnosis, treatment, and even prevention of endocrine crisis.