Thyrotoxicosis after denileukin diftitox therapy in patients with mycosis fungoides.
BACKGROUND
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.


METHODS
This study was a retrospective case series.


METHODS
The setting of this study was a comprehensive cancer center.


METHODS
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.


METHODS
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.
Ghori
Farah
F
Department of Dermatology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 434, Houston, Texas 77030, USA.
Polder
Kristel D
KD
Pinter-Brown
Lauren C
LC
Hoff
Ana O
AO
Gagel
Robert F
RF
Sherman
Steven I
SI
Duvic
Madeleine
M
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004167:Diphtheria Toxin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects*; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy*; D013971:Thyrotoxicosis / Q000139:chemically induced*
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D007453:Iodide Peroxidase