Thyrotoxicosis after Denileukin Diftitox Therapy in Patients with Mycosis Fungoides

Abstract

Denileukin diftitox is a recombinant novel fusion protein of diphtheria toxin and the ligand-binding domain of human IL-2. Denileukin diftitox binds to the high-affinity IL-2 receptor on the cell surface, and it is internalized by endocytosis and enzymatically cleaved. The cytotoxic A-fragment of the toxin inhibits protein synthesis and causes cell death. The objective of this study was to recognize thyrotoxicosis in association with denileukin diftitox therapy. This study was a retrospective case series. The setting of this study was a comprehensive cancer center. Eight mycosis fungoides patients who were receiving 9 or 18 microg/kg.d iv denileukin diftitox for 5 d every 3 wk were identified with thyrotoxicosis. Thyroid testing was performed. Hypothyroidism after thyrotoxicosis was treated. In eight mycosis fungoides patients who developed transient thyrotoxicosis during therapy, thyroid function tests were normal before onset of therapy. Clinical thyrotoxicosis developed within days of the first cycle of denileukin diftitox therapy in four patients and after the second cycle in the other four patients. Symptoms included tremors, nervousness, tachycardia, diarrhea, and weight loss. After cessation of denileukin diftitox, thyrotoxicosis resolved in all patients; two became euthyroid, and five became hypothyroid, requiring levothyroxine therapy. One patient was lost to follow-up. Monitoring thyroid function before and during treatment with denileukin diftitox is recommended. Symptomatic thyrotoxicosis may be missed due to other acute reactions to the drug, and subsequent hypothyroidism may develop.