A novel melanoma therapy stirs up a storm: ipilimumab-induced thyrotoxicosis

[摘要] Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumoractivity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment ofimmune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumorresponse exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoicacid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanomapresented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly afterinitiation 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. Shehad diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, andstool cultures were collected, and empiric antibiotics were started. A computed tomography (CT) angiogram of the chest wasnegative for pulmonary embolism or pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroidfunction testing. TSH was decreased at 0.16 mIU/ml (normal 0.3–4.7); free tri-iodothyronine (T3) was markedly elevated at1031 pg/dl (normal 249–405), as was free thyroxine (T4) at 5.6 ng/dl (normal 0.8–1.6). With iopanoic acid and methimazoletherapy, she markedly improved within 48 h, which could be attributed to lowering of serum T3 with iopanoic acid ratherthan to any effect of the methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune-mediated adverse effectscan be treated with iopanoic acid, a potent inhibitor of T4-to-T3 conversion.

[学科分类] 血液学

[关键词] Geriatric;Female;White;United States;Thyroid;Thyroid;Thyroxine (T4);Triiodothyronine (T3);Metastatic melanoma;Thyroid storm;Thyrotoxicosis;Fatigue;Anorexia;Diarrhoea;Pyrexia;Hypertension;Hyperthyroidism;Goitre;Tachycardia;Atrial fibrillation;Weight loss;Anxiety;Abdominal pain;Chest pain;Electrocardiogram;CT scan;Angiography;TSH;Total T3;Total T4;Thyroid function;FT3;FT4;Calcium (serum);Ultrasound scan;Ipilimumab;Methimazole;Metoprolol;Beta-blockers;Digoxin;Iopanoic acid;Geriatrics;Oncology;Unusual effects of medical treatment;February;2015