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

2015 ◽  
Vol 2015 ◽  
Author(s):  
Christine Yu ◽  
Inder J Chopra ◽  
Edward Ha
Keyword(s):  
Adverse Effects ◽  
T Lymphocyte ◽  
Autoimmune Thyroiditis ◽  
Cytotoxic T Lymphocyte ◽  
Alternative Therapy ◽  
Thyroid Storm ◽  
Iopanoic Acid ◽  
Immune Mediated ◽  
Thyroid Function Testing ◽  
Function Testing

Summary 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. Learning points While ipilimumab more commonly causes autoimmune thyroiditis, it can also cause thyroid storm and clinicians should include thyroid storm in their differential diagnosis for patients who present with systemic inflammatory response syndrome. Immune-related adverse reactions usually occur after 1–3 months of ipilimumab and baseline thyroid function testing should be completed before initiation with ipilimumab. Conflicting data exist on the use of prednisone for treatment of CTLA4 adverse effects and its attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as an alternative therapy in this setting.

scholarly journals Amiodarone-Induced Thyrotoxic Thyroiditis: A Diagnostic and Therapeutic Challenge

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Umang Barvalia ◽  
Barkha Amlani ◽  
Ram Pathak
Keyword(s):  
Adverse Effects ◽  
Best Practices ◽  
Thyroid Tissue ◽  
Overt Hypothyroidism ◽  
Structural Resemblance ◽  
Thyroid Function Testing ◽  
Function Testing ◽  
Thyroid Abnormalities

Amiodarone is an iodine-based, potent antiarrhythmic drug bearing a structural resemblance to thyroxine (T4). It is known to produce thyroid abnormalities ranging from abnormal thyroid function testing to overt hypothyroidism or hyperthyroidism. These adverse effects may occur in patients with or without preexisting thyroid disease. Amiodarone-induced thyrotoxicosis (AIT) is a clinically recognized condition commonly due to iodine-induced excessive synthesis of thyroid, also known as type 1 AIT. In rare instances, AIT is caused by amiodarone-induced inflammation of thyroid tissue, resulting in release of preformed thyroid hormones and a hyperthyroid state, known as type 2 AIT. Distinguishing between the two states is important, as both conditions have different treatment implications; however, a mixed presentation is not uncommon, posing diagnostic and treatment challenges. We describe a case of a patient with amiodarone-induced type 2 hyperthyroidism and review the current literature on the best practices for diagnostic and treatment approaches.

scholarly journals Enterocolitis in Patients With Cancer After Antibody Blockade of Cytotoxic T-Lymphocyte–Associated Antigen 4

2006 ◽  
Vol 24 (15) ◽  
pp. 2283-2289 ◽  
Author(s):  
Kimberly E. Beck ◽  
Joseph A. Blansfield ◽  
Khoi Q. Tran ◽  
Andrew L. Feldman ◽  
Marybeth S. Hughes ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Tumor Response ◽  
Cytotoxic T Lymphocyte ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Objective Tumor Response ◽  
Systemic Corticosteroids ◽  
Immune Mediated ◽  
Alpha Blockade ◽  
Grade 3

Purpose Cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. Patients and Methods We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. Results The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). Conclusion CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.

scholarly journals Anti-PD-1 Therapy-Associated Perforating Colitis

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Romulo Celli ◽  
Harriet M. Kluger ◽  
Xuchen Zhang
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Adverse Effects ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Colonic Perforation ◽  
Advanced Malignancies ◽  
Cell Death Protein

Inhibition of immune checkpoint T cell regulatory molecules by using programmed cell death protein 1 (PD-1), or its ligand (PDL-1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has been increasingly used to treat advanced malignancies. The immune-related adverse effects associated with these treatments such as diarrhea, colitis, and CTLA-4 treatment-associated perforating colitis have been reported. However, anti-PD-1/PD-L1-associated perforating colitis has rarely been reported. We report a case of colonic perforation in a patient recently treated with pembrolizumab, a PD-1 inhibitor for metastatic melanoma. Awareness of anti-PD-1/PD-L1-associated colitis and perforation will facilitate a timely diagnosis and management as they are increasingly used in oncology.

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