The purpose of this study is to find out if the drug AZD6244 can improve the radioactive iodine uptake by the patient's metastatic thyroid cancer. The investigator will also be testing the tumor specimen taken at the time of your surgery for specific genetic changes to see if one of them in particular (the BRAF oncogene) makes your cancer more likely to become sensitive to radioactive iodine after treatment with the drug.

The investigators want to find out if AZD6244 helps to increase the entry of radioactive iodine into thyroid cancer cells that have spread and are resistant to radioactive iodine therapy, especially if they have the BRAF mutation. To measure how much iodine can enter your cancer, the investigators will use iodine-124, a different form of radioactive iodine. Iodine-124 allows the investigators to measure precisely how much radioactivity can enter the cancer cells, whereas iodine-131 does not. The process of scanning with iodine-124 is called "lesional dosimetry". Iodine-124 is an investigational agent approved by the FDA (Food and Drug Administration) for use in this research study.

Inclusion Criteria:

• Patients > or = to 18 years-old

• Patients must have histopathologically confirmed at MSKCC differentiated thyroid carcinoma of follicular cell origin (D-TC-FCO), which includes papillary, follicular, or Hürthle cell histology, along with their respective variants.

• Pathology specimen from the original tumor (thyroid) and/or metastases must be available for genotyping.

• RAI-refractory metastatic disease on structural imaging, defined as any one of the following (as described in MSKCC protocol 08-066):

  • index metastatic lesion non-RAI avid on a diagnostic RAI scan performed up to 2 years prior to enrolment in the current study, OR
  • RAI-avid metastatic lesion which remained stable in size or progressed despite RAI treatment 6 months or more prior to entry in the study. Lesions will be assessed by 2 independent observers in nuclear medicine and in endocrinology. There is no minimal size limit for the index lesion.

• Patients with FDG avid lesions

• Evaluable disease by RECIST

• Preliminary reproductive toxicology data indicate that AZD6244 can have adverse effects on embryofetal development and survival at dose levels that do not induce maternal toxicity in mice. For this reason, female patients will need to be post-menopausal or with negative serum pregnancy test if pre-menopausal. Patients of childbearing potential must agree to employ adequate contraception throughout the study.

• ANC > 1500 per mm3, platelets > 100,000 per mm3, and hemoglobin > 9 g/dL

• ALT/SGOT and AST/SGPT ≤ 2.5 X upper limit of normal (ULN)

• Bilirubin ≤ 1.5 X ULN

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients may not be receiving any other investigational agents.

• Patient with chronic renal insufficiency, as defined initially by an estimated creatinine clearance of < 30 ml/minute calculated using the Cockcroft and Gault equation: (140 - age in years) X (weight in kg) X (0.85 if female)/72 X serum Cr. If estimated creatinine clearance is < 30 ml/min, a 24 hour urine creatinine clearance may be collected and a patient would be eligible if the creatinine clearance is >30 ml/min.

• Patients unable to follow a low iodine diet, patients requiring medication with high content in iodide (amiodarone), or patients receiving IV iodine containing contrast as part of radiographic procedure.

• Patients with clinically significant cardiovascular disease as defined by the following:

  • LVEF < institutional LLN
  • New York Heart Association grade III or greater congestive heart failure
  • uncontrolled hypertension, defined as systolic blood pressure > 180 mmHg OR diastolic blood pressure > 105 mmHg, on at least 2 repeated determinations on separate days within past 3 months
  • Uncontrolled coronary artery disease, angina, congestive heart failure, or ventricular arrhythmia requiring acute medical management.

• Patient with known hypersensitivity to Thyrogen (human recombinant thyrotropin).

• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women will be ineligible; breast feeding should be discontinued if the mother is treated with AZD6244.

• Brain metastases or spinal cord compression unless treated and stable (for at least 3 months) off steroids.

• Mean QTc interval >450 ms