THYROID Volume 16, Number 2, 2006 © American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Taskforce* Members: David S. Cooper,1 (Chair), Gerard M. Doherty,2 Bryan R. Haugen,3 Richard T. Kloos,4 Stephanie L. Lee,5 Susan J. Mandel,6 Ernest L. Mazzaferri,7 Bryan McIver,8 Steven I. Sherman,9 and R. Michael Tuttle10 Contents 1. Introduction . 4 2. Methods . 4 a. Literature search strategy b. Evaluation of the evidence 3. Thyroid Nodules . 5 a. Thyroid nodule evaluation iii. Laboratory studies iii. Fine needle aspiration biopsy iii. Multinodular goiter b. Thyroid nodule follow up and treatment ii. Long-term follow-up iii. Role of medical therapy iii. Thyroid nodules and pregnancy 4. Differentiated Thyroid Cancer . 8 a. Goals of therapy b. Role of preoperative staging with diagnostic testing c. Surgery for differentiated thyroid cancer iii. Extent of initial surgery iii. Completion thyroidectomy d. Pathological and clinical staging systems e. Postoperative radioiodine remnant ablation iii. Modes of thyroid hormone withdrawal iii. Role of diagnostic scanning before ablation iii. Radioiodine ablation dosage iv. Use of recombinant human thyrotropin for remnant ablation iv. Role of low iodine diets vi. Performance of post therapy scans f. Thyroxine suppression therapy g. Role of adjunctive external beam radiation or chemotherapy 5. Differentiated Thyroid Cancer: Long-Term Management . 13 a. Risk stratification for follow-up intensity b. Utility of serum thyroglobulin measurements c. Role of diagnostic radioiodine scans, ultrasound, and other imaging techniques d. Long-term thyroxine suppression therapy e. Management of patients with metastatic disease iii. Locoregional recurrence 1. Surgery 2. Radioiodine therapy iii. Distant metastatic disease 1. Pulmonary metastases 2. Bone metastases 3. Brain metastases iii. Complications of radioactive iodine treatment f. Management of thyroglobulin positive patients g. Role of external beam radiotherapy h. Role of chemotherapy 6. Directions for Future Research . 22 1Sinai Hospital of Baltimore and Johns Hopkins University School of Medicine, Baltimore, Maryland. 2University of Michigan Medical Center, Ann Arbor, Michigan. 3University of Colorado Health Sciences Center, Denver, Colorado. 4Ohio State University School of Medicine and Public Health, Columbus, Ohio. 5Boston University Medical Center, Boston, Massachusetts. 6University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 7University of Florida College of Medicine, Gainesville, Florida. 8The Mayo Clinic, Rochester, Minnesota. 9University of Texas, M.D. Anderson Cancer Center, Houston, Texas. 10Memorial Sloan-Kettering Cancer Center, New York, New York. *Taskforce members are listed in alphabetical order. 1 2 Thyroid Cancer Guidelines Task Force Disclosure Information David S. Cooper, MD 1 Gerard M. Doherty, MD 1 Bryan Haugen, MD 2, 3 Richard T. Kloos, MD 3, 4 Stephanie Lee, MD, PhD 5 Susan Mandel, MD, MPH 5, 6 Ernest L. Mazzaferri, MD 7 Bryan McIver, MD, PhD 1 Steven I. Sherman, MD 8, 9, 10 R. Michael Tuttle, MD 11, 12 1 No financial interests, arrangements, or affiliations with the manufacturer of any products or devices to be discussed in these guidelines. 2 Speakers Bureau and CME Faculty: Genzyme Corp. 3 Consultant, Speakers Bureau and CME Faculty: Abbott Laboratories 4 Grant/Research Support, Consultant, Speakers Bureau and CME Faculty: Genzyme Corp. 5 CME Faculty: Abbott Laboratories 6 Paid Consultant: King Pharmaceuticals, Inc. 7 Paid Consultant and Speakers Bureau: Genzyme Corp. 8 CME Faculty: Abbott Laboratories, Genzyme Corp. 9 Grant or Research Support: Genzyme Corp. 10 Paid Consultant: Abbott Laboratories 11 Grant/Research Support, Consultant and CME Faculty: Genzyme Corp. 12 Speakers Bureau and CME Faculty: Abbott Laboratories The American Thyroid Association Disclosure Policy Standards and guidelines are to insure that individuals participating in professional activities are aware of author relationships with commercial companies that could potentially affect the information presented. The American Thyroid Association has endorsed the requirement that authors disclose any significant financial interest or affiliations they may have with the manufacturers of products or devices that may be discussed in the development of guidelines. In compliance with this policy, a superscript number placed by the name of an author denotes an author who has indicated an affiliation with organizations which have interests related to the content of these guidelines. The intent of this policy is to openly identify potential conflicts of interest so that physicians may form their own judgments about the guidelines with full disclosure of the facts; it remains for the audience to determine whether an author’s outside interest may reflect a possible bias in either the exposition or the conclusions presented. 4 COOPER ET AL. Introduction • What is the best method of long-term follow-up of patients with thyroid nodules? HYROID NODULES are a common clinical problem. Epi- • What is the role of medical therapy of patients with be- demiologic studies have shown the prevalence of palpa- T nign thyroid nodules? ble thyroid nodules to be approximately 5% in women and • How should thyroid nodules in children and pregnant 1% in men living in iodine-sufficient parts of the world (1,2). women be managed? In contrast, high-resolution ultrasound can detect thyroid nodules in 19%–67% of randomly selected individuals with Differentiated Thyroid Cancer: Initial Management higher frequencies in women and the elderly (3). The clinical importance of thyroid nodules rests with the need to exclude • What is the role of preoperative staging with diagnostic thyroid cancer that occurs in 5%–10% depending on age, gen- imaging and laboratory tests? der, radiation exposure history, family history, and other fac- • What is the appropriate operation for differentiated thy- tors (4, 5). Differentiated thyroid cancer, which includes pap- roid cancer? illary and follicular cancer, comprises the vast majority (90%) • What is the role of postoperative staging systems and of all thyroid cancers (6). In the United States, approximately which should be used? 23,500 cases of differentiated thyroid cancer are diagnosed • What is the role of postoperative radioiodine remnant ab- each year (7), and the yearly incidence may be increasing (8). lation? In 1996, the American Thyroid Association (ATA) pub- • What is the role of thyrotropin suppression therapy? lished treatment guidelines for patients with thyroid nod- • Is there a role for adjunctive external beam irradiation or ules and thyroid cancer (9). Over the last decade, there have chemotherapy? been many advances in the diagnosis and therapy of both thyroid nodules and differentiated thyroid cancer. Contro- Differentiated Thyroid Cancer: Long-Term versy exists in many areas, including the most cost-effective Management approach in the diagnostic evaluation of a thyroid nodule, • What are the appropriate features of long-term manage- the extent of surgery for small thyroid cancers, the use of ra- ment? dioactive iodine to ablate remnant tissue after thyroidec- • What is the role of serum thyroglobulin assays? tomy, the appropriate use of thyroxine suppression therapy, • What is the role of ultrasound and other imaging tech- and the role of human recombinant thyrotropin. In recogni- niques during follow-up? tion of the changes that have taken place in the overall man- • What is the role of thyrotropin suppression in long-term agement of these clinically important problems, the ATA ap- follow-up? pointed a task force to reexamine the current strategies that • What is the most appropriate management of patients are used to diagnose and treat thyroid nodules and differ- with metastatic disease? entiated thyroid cancer, and to develop clinical guidelines • How should thyroglobulin positive, scan negative patients using principles of evidence-based medicine. Members of the be managed? taskforce included experts in thyroid nodule and thyroid • What is the role of external radiation therapy cancer management with representation by endocrinology, • What is the role of chemotherapy? surgery, and nuclear medicine. Other groups have previ- • What are directions for future research? ously developed guidelines, including the American Asso- ciation of Clinical Endocrinologists and the American Asso- A 2-day meeting of the taskforce was held on January ciation of Endocrine Surgeons (10), the British Thyroid 21–23, 2005. Prior to the meeting, the taskforce members un- Association and The Royal College of Physicians (11), and dertook a complete literature review. Relevant articles were the National Comprehensive Cancer Network (12), which identified by searching MEDLINE using the following search have provided somewhat conflicting recommendations be- terms: {THRYOID NODULE/diagnosis, drug therapy, sur- cause of the lack of high-quality evidence from randomized gery, therapy, ultrasonography} or {CANCER} or {CARCI- controlled trials. NOMA} and {THYROID} and {FOLLICULAR CARCI- NOMA} or {PAPILLARY CACINOMA} and {FOLLOW-UP} Materials and Methods and {TREATMENT} and {RECURRENCE}. All English- The ATA guidelines taskforce used a strategy similar to language papers published between 1995 and December that used by the National Institutes of Health for its Con- 2004 were reviewed and categorized in tabular form by date, sensus Development