Adrenal Insufficiency and Thyrotoxicosis Following Combined Immune Checkpoint Inhibitor Use: A Case Report and Literature Review

Abstract

Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the timing at which each event occurs most frequently after drug administration varies, and cases where multiple events occur simultaneously are rare. We encountered a patient who concurrently suffered from thyrotoxicosis and adrenal insufficiency. An 80-year-old woman with a history of type 2 diabetes mellitus (DM) was diagnosed with stage IVA squamous cell carcinoma of the lungs. Treatment with a combination of nivolumab and ipilimumab was initiated. Although she tested positive for thyroglobulin antibody and transient subclinical hyperthyroidism was observed after two courses, treatment with ICIs was continued. Four months later, treatment was discontinued due to drug-induced lung disease. One month after the last administration, the patient became unconscious and was admitted to another hospital, diagnosed with diabetic ketoacidosis, urinary tract infection, and sepsis. After acute-phase treatment, she was transferred to our hospital due to persistent fever and tachycardia. Thyrotoxicosis and adrenal insufficiency were observed, with high levels of free thyroxine, low thyroid-stimulating hormone (TSH), and cortisol levels. Treatment with extracellular fluids, potassium iodide, beta-blockers, and hydrocortisone was initiated, and the patient’s condition improved. No other pituitary hormone deficiencies were observed. She was diagnosed with painless thyroiditis and secondary adrenal insufficiency based on the positive thyroglobulin antibody, negative TSH receptor antibody, decreased Doppler flow in thyroid ultrasonography, low adrenocorticotrophic hormone (ACTH), and low response of ACTH and cortisol to corticotropin-releasing hormone loading test. MRI revealed no abnormalities. We report a case of thyrotoxicosis and secondary adrenal insufficiency five months after the first administration of nivolumab and ipilimumab. Careful follow-up and early detection of endocrine disorders are critical in patients treated with a combination of ICIs.