Ipilimumab, a novel
therapy for metastatic
melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including
autoimmune thyroiditis.
Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of
steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of
ipilimumab-associated
thyroid storm and implicates
iopanoic acid as an alternative
therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic
melanoma presented with
fatigue,
anorexia, decreased functional status, and intermittent
diarrhea for several months, shortly after initiation of
ipilimumab - a recombinant human
monoclonal antibody to the
cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed
supraventricular tachycardia. Blood, urine, and stool cultures were collected, and empiric
antibiotics were started. A computed tomography (CT) angiogram of the chest was negative for
pulmonary embolism or
pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroid function testing. TSH was decreased at 0.16 μIU/ml (normal 0.3-4.7); free tri-iodothyronine (T3) was markedly elevated at 1031 pg/dl (normal 249-405), as was free
thyroxine (T4) at 5.6 ng/dl (normal 0.8-1.6). With
iopanoic acid and
methimazole therapy, she markedly improved within 48 h, which could be attributed to lowering of serum T3 with
iopanoic acid rather than to any effect of the
methimazole.
Ipilimumab is a cause of overt
thyrotoxicosis and its immune-mediated adverse effects can be treated with
iopanoic acid, a potent inhibitor of T4-to-T3 conversion.
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