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Thyrotoxicosis after Denileukin Diftitox Therapy in Patients with Mycosis Fungoides

Departments of Endocrine Neoplasia and Hormonal Disorders (F.G., A.O.H., R.F.G., S.I.S.) and Dermatology (K.D.P., M.D.), University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; and Division of Hematology and Oncology (L.C.P.-B.), University of California Los Angeles Medical Center, Los Angeles, California 90095

Address all correspondence and requests for reprints to: Madeleine Duvic, M.D., Department of Dermatology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 434, Houston, Texas 77030. E-mail: mduvic{at}mdanderson.org.

Context: 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.

Objective: The objective of this study was to recognize thyrotoxicosis in association with denileukin diftitox therapy.

Design: This study was a retrospective case series.

Setting: The setting of this study was a comprehensive cancer center.

Patients: Eight mycosis fungoides patients who were receiving 9 or 18 µg/kg·d iv denileukin diftitox for 5 d every 3 wk were identified with thyrotoxicosis.

Intervention(s): Thyroid testing was performed. Hypothyroidism after thyrotoxicosis was treated.

Results: 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.

Conclusions: 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.

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