Thyrotoxicosis and Adrenocortical Hormone Deficiency During Immune-checkpoint Inhibitor Treatment for Malignant Melanoma

Immune-checkpoint inhibitors (ICIs) are novel promising agents for the treatment of malignant tumors. However, critical endocrine immune-related adverse events (irAEs) by ICIs often occur.

A 63-year-old woman with advanced malignant melanoma had received anti-PD-1 antibody (nivolumab, 2 mg/kg every 3 weeks) for 8 cycles (from day 0 to day 147). On day 168, nivolumab was switched to anti-CTLA-4 antibody (ipilimumab, 3mg/kg every 3 weeks). Twenty-eight days later, she was diagnosed with thyrotoxicosis due to painless thyroiditis (day 196). Thirty-five days later (day 231), thyrotoxicosis turned to hypothyroidism. In addition, twenty-five days later (day 256), she was diagnosed with adrenocortical insufficiency due to adrenocortical hormone (ACTH) deficiency. Hormone replacements with levothyroxine and hydrocortisone were administered. She showed eosinophilia, ESR/CRP/LDH elevation, liver dysfunction and hyponatremia before diagnosis of ACTH insufficiency. Eosinophilia, thrombocytopenia, ESR/CRP/LDH elevation, and liver dysfunction might be important for early detection of thyrotoxicosis in our case.

The present report provides the first detailed presentation of combined thyrotoxicosis and isolated ACTH deficiency induced by ICIs. Since rapidly progressive fatal endocrine system failure may be provoked during ICI therapy, precise diagnosis and prompt treatment as well as close follow-up is critical. We propose routine monitoring of endocrine functions and related symptoms (worsened fatigue, hypoglycemia, hypotension or hyponatremia), as well as other laboratory tests during ICI therapy.