2015 American Thyroid Association Management Guidelines ... ATA Thyroid Nodules and Differentiated Thyroid

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    2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules

    and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Task Force

    on Thyroid Nodules and Differentiated Thyroid Cancer

    Bryan R. Haugen,1,* Erik K. Alexander,2 Keith C. Bible,3 Gerard M. Doherty,4 Susan J. Mandel,5

    Yuri E. Nikiforov,6 Furio Pacini,7 Gregory W. Randolph,8 Anna M. Sawka,9 Martin Schlumberger,10

    Kathryn G. Schuff,11 Steven I. Sherman,12 Julie Ann Sosa,13 David L. Steward,14

    R. Michael Tuttle,15 and Leonard Wartofsky16

    Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association’s (ATA’s) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant cita- tions, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Re- commendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management

    1University of Colorado School of Medicine, Aurora, Colorado. 2Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. 3The Mayo Clinic, Rochester, Minnesota. 4Boston Medical Center, Boston, Massachusetts. 5Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 6University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 7The University of Siena, Siena, Italy. 8Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 9University Health Network, University of Toronto, Toronto, Ontario, Canada.

    10Institute Gustave Roussy and University Paris Sud, Villejuif, France. 11Oregon Health and Science University, Portland, Oregon. 12University of Texas M.D. Anderson Cancer Center, Houston, Texas. 13Duke University School of Medicine, Durham, North Carolina. 14University of Cincinnati Medical Center, Cincinnati, Ohio. 15Memorial Sloan Kettering Cancer Center, New York, New York. 16MedStar Washington Hospital Center, Washington, DC. *Chair. Authors are listed in alphabetical order and were appointed by ATA to independently formulate the content of this manuscript. None of

    the scientific or medical content of the manuscript was dictated by the ATA.

    THYROID Volume 26, Number 1, 2016 ª American Thyroid Association ª Mary Ann Liebert, Inc. DOI: 10.1089/thy.2015.0020


  • of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.


    Thyroid nodules are a common clinical problem.Epidemiologic studies have shown the prevalence of palpable thyroid nodules to be approximately 5% in women and 1% in men living in iodine-sufficient parts of the world (1,2). In contrast, high-resolution ultrasound (US) can detect thyroid nodules in 19%–68% of randomly selected individ- uals, with higher frequencies in women and the elderly (3,4). The clinical importance of thyroid nodules rests with the need to exclude thyroid cancer, which occurs in 7%–15% of cases depending on age, sex, radiation exposure history, family history, and other factors (5,6). Differentiated thyroid cancer (DTC), which includes papillary and follicular cancer, com- prises the vast majority (>90%) of all thyroid cancers (7). In the United States, approximately 63,000 new cases of thyroid cancer were predicted to be diagnosed in 2014 (8) compared with 37,200 in 2009 when the last ATA guidelines were published. The yearly incidence has nearly tripled from 4.9 per 100,000 in 1975 to 14.3 per 100,000 in 2009 (9). Almost the entire change has been attributed to an increase in the inci- dence of papillary thyroid cancer (PTC). Moreover, 25% of the new thyroid cancers diagnosed in 1988–1989 were £1 cm compared with 39% of the new thyroid cancer diagnoses in 2008–2009 (9). This tumor shift may be due to the increasing use of neck ultrasonography or other imaging and early diag- nosis and treatment (10), trends that are changing the initial treatment and follow-up for many patients with thyroid cancer. A recent population-based study from Olmsted County re- ported the doubling of thyroid cancer incidence from 2000 to 2012 compared to the prior decade as entirely attributable to clinically occult cancers detected incidentally on imaging or pathology (11). By 2019, one study predicts that PTC will become the third most common cancer in women at a cost of $19–21 billion in the United States (12). Optimization of long- term health outcomes and education about potential prognosis for individuals with thyroid neoplasms is critically important.

    In 1996, the American Thyroid Association (ATA) pub- lished treatment guidelines for patients with thyroid nodules and DTC (13). Over the last 15–20 years, there have been many advances in the diagnosis and therapy of both thyroid nodules and DTC, but clinical controversy exists in many areas. A long history of insufficient peer-reviewed research funding for high-quality clinical trials in the field of thyroid neoplasia may be an important contributing factor to existing clinical uncertainties (12). Methodologic limitations or con- flicting findings of older studies present a significant chal- lenge to modern-day medical decision-making in many aspects of thyroid neoplasia. Although they are not a specific focus of these guidelines, we recognize that feasibility and cost considerations of various diagnostic and therapeutic options

    also present important clinical challenges in many clinical practice settings.


    Our objective in these guidelines is to inform clinicians, patients, researchers, and health policy makers about the best available evidence (and its limitations), relating to the dia- gnosis and treatment of adult patients with thyroid nodules and DTC. These guidelines should not be applied to children (

  • have recently revised guidelines on treatment of patients with thyroid tumors (23). Given the existing controversies in the field, differences in critical appraisal approaches for existing evidence, and differences in clinical practice patterns across geographic regions and physician specialties, it should not be surprising that the organizational guidelines are not in com- plete agreement for all issues. Such differences highlight the importance of clarifying evidence uncertainties with future high quality clinical research.


    ATA Thyroid Nodules and Differentiated Thyroid Cancer guidelines were published in 2006 (24) and revised in 2009

    (25). Because of the rapid growth of the literature on this topic, plans for revising the guidelines within approximately 4 years of publication were made at the inception of the project. A task force chair was appointed by the ATA Pre- sident with approval of the Board. A task force of specialists with complementary expertise (endocrinology, surgery, nu- clear medicine, radiology, pathology, oncology, molecular diagnostics, and epidemiology) was appointed. In order to have broad specialty and geographic representation, as well as fresh perspectives, one-third of the task force is replaced for each iteration of the guidelines, per ATA policy. Upon discussion among the panel members and the Chair with other Chairs of other ATA guideline committees, the American College of Physicians’ (ACP) Grading System was adopted

    Table 1. Interpretation of the American College of Physicians’ Guideline Grading System (for Therapeutic Interventions)

    Recommendation Clarity of risk/benefit Implications

    Strong recommendation Benefits clearly outweigh harms and burdens, or vice