1. Levothyroxine Suppressive Therapy in Thyroid Cancer R Michael Tuttle, MD Attending Endocrinologist Assistant Professor of Medicine Memorial Sloan Kettering Cancer Center Sanford Weill Medical College of Cornell University New York, NY

2. Estimated New Cases United States, 2003 50 k 100k 150k 200k 250k 22,000 new cases 1,400 deaths American Cancer Society

3. Standard Initial Treatment Usual Pathway Total Thyroidectomy Remove the thyroid with all cancerous tissue Radioactive Iodine Treatment Destroy any microscopic residual thyroid tissue Completely dependent on exogenous levothyroxine Without any functional thyroid tissue

4. Levothyroxine Therapy Thyroid Cancer Normalize TSH Prevent Symptoms of Hypothyroidism Suppress TSH Decreased Risk of Recurrence of Thyroid Cancer Without any functional thyroid tissue

5. Levothyroxine Suppression Free T4 Normal Range (ng/dL) TSH Normal Range (mcU/mL) 0.8 2.0 0.4 4.4 <0.01 0.1 Primary Hypothyroidism Thyroid Cancer Hyperthyroid Symptoms Increased Recurrence TSH Suppression

6. Levothyroxine Suppression Free T4 Normal Range (ng/dL) TSH Normal Range (mcU/mL) 0.8 2.0 0.4 4.4 <0.01 0.1 TSH Suppression 12-15% increase 12-15% decrease Thyroid Cancer Hyperthyroid Symptoms Increased Recurrence Thyroid Cancer

7. Levothyroxine Suppression Therapy Thyroid cancer Very narrow therapeutic window Small changes in administered dose Symptomatic hyperthyroidism Recurrence of disease Product substitution with alternatives that vary by more than 5-10% from the brand name product would be unacceptable in the treatment of thyroid cancer.

8. Treatment Guidelines Thyroid Cancer  Singer PA, Cooper DS, Daniels GH et al. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association. Arch Intern Med. 1996 Oct 28;156(19):2165-72.  AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma. American Association of Clinical Endocrinologists. American College of Endocrinology. Endocr Pract. 2001 May-Jun;7(3):202-20.  British Thyroid Association. Guidelines for the management of thyroid cancer. London: Royal College of Physician, 2002.