Autoimmune Addison's disease after treatment with interleukin-2 and tumor-infiltrating lymphocytes

Autoimmune thyroiditis with hypothyroidism is a well-known complication of immunotherapy with interleukin-2 (IL-2) with or without lymphokine-activated killer (LAK) cells. To date, however, no cases of IL-2/LAK-induced autoimmune adrenalitis with adrenal insufficiency have been reported. We describe a patient who developed primary adrenal insufficiency following IL-2/tumor-infiltrating lymphocytes (TIL) immunotherapy for renal cell carcinoma. A 64-year-old male with renal cell carcinoma metastatic to bone, skin, lung, and the central nervous system presented for IL-2/TIL treatment. Nine months earlier, he had undergone a right nephrectomy and adrenalectomy. He had already received two courses of IL-2 and one course of IL-4 following surgery. Dynamic studies of adrenal function performed prior to IL-2/TIL immunotherapy demonstrated intact cortisol and aldosterone responses to ACTH as well as negative adrenal antibodies. One week after IL-2/TIL therapy, the patient developed a nonanion gap metabolic acidosis, hypotension and hypoglycemia. Adrenocortical function was re-evaluated demonstrating blunted cortisol and aldosterone responses to ACTH with an elevated plasma ACTH confirming the presence of primary adrenal insufficiency. Adrenal antibodies were now positive. Hydrocortisone and fludrocortisone were given with a good clinical response. We suggest immunotherapy with IL-2/TIL may cause adrenal insufficiency by activating autoimmune adrenalitis.