1、1 -2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and other causes of Thyrotoxicosis *Douglas S. Ross1, *Henry B. Burch2, David S. Cooper3, M. Carol Greenlee4, Peter Laurberg,5 Ana Luiza Maia6, Scott A. Rivkees7, Mary Samuels8, Julie Ann Sosa9, Marius N.
2、 Stan10, and Martin A. Walter11 1Massachusetts General Hospital, Boston, Massachusetts. 2Endocrinology Metabolic Service, Walter Reed National Military Medical Center, Bethesda, Maryland. 3Division of Endocrinology, Diabetes, & Metabolism, The Johns Hopkins University School of Medicine, Baltimore,
3、Maryland. 4Western Slope Endocrinology, Grand Junction, CO. 5Departments of Clinical Medicine and Endocrinology, Aalborg University and Aalborg University Hospital, Aalborg, Denmark. 6Thyroid Section, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
4、. 7Pediatrics Chairmans Office, University of Florida College of Medicine, Gainesville, Florida. 8Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland, Oregon. 9Section of Endocrine Surgery, Duke University School of Medicine, Durham, North Carolin
5、a. 10Division of Endocrinology, Mayo Clinic, Rochester. 11Institute of Nuclear Medicine, University Hospital Bern, Switzerland. _ *Authorship listed in alphabetical order following the Chairperson. *One or more of the authors are military service members (or employees of the U.S. Government). The vi
6、ews expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Army, the Department of Defense or the United States Government. This work was prepared as part of the service members official duties. Thyroid American Thyroid Association Mary
7、Ann Liebert, Inc. DOI: 10.1089/thy.2016.0229 Page 1 of 304 2 -Background: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document des
8、cribes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. Methods: The American Thyroid Association (ATA) previously co-sponsored guidelines for the managem
9、ent of thyrotoxicosis that were published in 2011. Considerable new literature has been published since 2011, the ATA felt updated evidence-based guidelines were needed, and assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a syst
10、ematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting each
11、 was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Results: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves hyperthyroidism using radioactive iodine, antith
12、yroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves orbitopathy; and management of other miscellaneou
13、s causes of thyrotoxicosis. New Page 2 of 304 3 -paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparati
14、on of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. Conclusions: One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rat
15、ional, and optimal medical practice. Introduction Thyrotoxicosis is a condition having multiple etiologies, manifestations, and potential therapies. The term thyrotoxicosis refers to a clinical state that results from inappropriately high thyroid hormone action in tissues generally due to inappropri
16、ately high tissue thyroid hormone levels. The term hyperthyroidism, as used in these guidelines, is a form of thyrotoxicosis due to inappropriately high synthesis and secretion of thyroid hormone(s) by the thyroid. Appropriate treatment of thyrotoxicosis requires an accurate diagnosis. For example,
17、thyroidectomy is an appropriate treatment for some forms of thyrotoxicosis and not for others. Additionally, beta-blockers may be used in almost all forms of thyrotoxicosis, whereas antithyroid drugs (ATDs) are useful in only some. In the United States, the prevalence of hyperthyroidism is approxima
18、tely 1.2% (0.5% overt and 0.7% subclinical); the most common causes include Graves disease Page 3 of 304 4 (GD), toxic multinodular goiter (TMNG), and toxic adenoma (TA) (1). Scientific advances relevant to this topic are reported in a wide range of literature, including subspecialty publications in
19、 endocrinology, pediatrics, nuclear medicine, and surgery, making it challenging for clinicians to keep abreast of new developments. Although guidelines for the diagnosis and management of patients with thyrotoxicosis were published previously by the American Thyroid Association (ATA) and the Americ
20、an Association of Clinical Endocrinologists (AACE) in 2011, the ATA determined that thyrotoxicosis represents a priority area in need of updated evidence-based practice guidelines. The target audience for these guidelines includes general and subspecialty physicians and others providing care for pat
21、ients with thyrotoxicosis. In this document, we outline what we believe is current, rational, and optimal medical practice. It is not the intent of these guidelines to replace clinical judgment, individual decision making, or the wishes of the patient or family. Rather, each recommendation should be
22、 evaluated in light of these elements in order that optimal patient care is delivered. In some circumstances, it may be apparent that the level of care required may be best provided in centers where there is specific expertise, and that referral to such centers should be considered. Methods of Devel
23、opment of Evidence-Based Guidelines Administration Page 4 of 304 5 The ATA Executive Council selected a chairperson to lead the task force and this individual (D.S.R.) identified the other 10 members of the panel in consultation with the ATA board of directors. Membership on the panel was based on c
24、linical expertise, scholarly approach, and representation of adult and pediatric endocrinology, nuclear medicine, and surgery. The task force included individuals from North America, South America, and Europe. Panel members declared whether they had any potential conflict of interest at the initial
25、meeting of the group and periodically during the course of deliberations. Funding for the guidelines was derived solely from the general funds of the ATA and thus the task force functioned without commercial support. The task force reviewed the 2011 guidelines and published editorials regarding thos
26、e guidelines, and developed a revised list of the most common causes of thyrotoxicosis and the most important questions that a practitioner might pose when caring for a patient with a particular form of thyrotoxicosis or special clinical condition. One task force member was assigned as the primary w
27、riter for each topic. One or more task force members were assigned as secondary writers for each topic, providing their specific expertise and critical review for the primary writer. The relevant literature was reviewed using a systematic PubMed search for primary references and reviews published af
28、ter the submission of the 2011 guidelines, supplemented with additional published materials found on focused PubMed searches. Recommendations were based on the literature and expert opinion where appropriate. A preliminary document and a series of recommendations concerning all of the topics were ge
29、nerated by each primary writer and then critically reviewed by the task force at large. The panel agreed recommendations would be based on consensus of the panel and that voting would be Page 5 of 304 6 used if agreement could not be reached. Task force deliberations took place between 2014 and 2016
30、 during several lengthy committee meetings, and through electronic communication. Rating of the recommendations These guidelines were developed to combine the best scientific evidence with the experience of seasoned clinicians and the pragmatic realities inherent in implementation. The task force el
31、ected to rate the recommendations according to the system developed by the Grading of Recommendations, Assessment, Development, and Evaluation Group (3-6). The balance between benefits and risks, quality of evidence, applicability, and certainty of the baseline risk are all considered in judgments a
32、bout the strength of recommendations (7). Grading the quality of the evidence takes into account study design, study quality, consistency of results, and directness of the evidence. The strength of a recommendation is indicated as a strong recommendation (for or against) that applies to most patient
33、s in most circumstances with benefits of action clearly outweighing the risks and burdens (or vice versa), or a weak recommendation or a suggestion that may not be appropriate for every patient, depending on context, patient values, and preferences. The quality of the evidence is indicated as low-qu
34、ality evidence, moderate-quality evidence, or high-quality evidence, based on consistency of results between studies and study design, limitations, and the directness of the evidence. In several instances, the evidence was insufficient to recommend for or against a test or a treatment, and the task
35、force made a statement labeled “no recommendation.” Table 1 describes the criteria to be met for each rating category. Each recommendation is preceded by a description of the Page 6 of 304 7 -evidence and, in some cases, followed by a remarks section including technical suggestions on issues such as
36、 dosing and monitoring. Presentation of recommendations The organization of the task forces recommendations is presented in Table 2. The page numbers and the location key can be used to locate specific topics and recommendations. Specific recommendations are presented within boxes in the main body o
37、f the text. Location keys can be copied into the Find or Search function in a file or Web page to rapidly navigate to a particular section. A listing of the recommendations without text is provided as Appendix A. Results A Background A1 Causes of thyrotoxicosis In general, thyrotoxicosis can occur i
38、f (i) the thyroid is excessively stimulated by trophic factors; (ii) there is constitutive activation of thyroid hormone synthesis and secretion leading to autonomous release of excess thyroid hormone; (iii) thyroid stores of preformed hormone are passively released in excessive amounts owing to aut
39、oimmune, infectious, chemical, or mechanical insult; or (iv) there is exposure to extra-thyroidal sources of thyroid hormone, which may be either endogenous (struma ovarii, metastatic differentiated thyroid cancer) or exogenous (factitious thyrotoxicosis). Page 7 of 304 8 Hyperthyroidism is generall
40、y considered overt or subclinical, depending on the biochemical severity of the hyperthyroidism, although in reality the disease represents a continuum of overactive thyroid function. Overt hyperthyroidism is defined as a subnormal (usually undetectable) serum thyroid-stimulating hormone (TSH) with
41、elevated serum levels of triiodothyronine (T3) and/or free thyroxine estimates (free T4). Subclinical hyperthyroidism is defined as a low or undetectable serum TSH with values within the normal reference range for both T3 and free T4. Both overt and subclinical disease may lead to characteristic sig
42、ns and symptoms, although subclinical hyperthyroidism is usually considered milder. Overzealous or suppressive thyroid hormone administration may cause either type of thyrotoxicosis, particularly subclinical thyrotoxicosis. Endogenous overt or subclinical thyrotoxicosis is caused by excess thyroid h
43、ormone production and release or by inflammation and release of hormone by the gland. Endogenous hyperthyroidism is most commonly due to GD or nodular thyroid disease. GD is an autoimmune disorder in which thyrotropin receptor antibodies (TRAb) stimulate the TSH receptor, increasing thyroid hormone
44、production and release. The development of nodular thyroid disease includes growth of established nodules, new nodule formation, and development of autonomy over time (8). In toxic adenomas (TA), autonomous hormone production can be caused by somatic activating mutations of genes regulating thyroid
45、growth and hormone synthesis. Germline mutations in the gene encoding the TSH receptor can cause sporadic or familial nonautoimmune hyperthyroidism associated with a diffuse enlargement of the thyroid gland (9). Autonomous hormone production may progress from subclinical to overt Page 8 of 304 9 hyp
46、erthyroidism, and the administration of pharmacologic amounts of iodine to such patients may result in iodine-induced hyperthyroidism (10). GD is the most common cause of hyperthyroidism in the United States (11,12). Although toxic nodular goiter is less common than GD, its prevalence increases with
47、 age and in the presence of dietary iodine deficiency. Therefore, toxic nodular goiter may actually be more common than GD in older patients, especially in regions of iodine deficiency (13,14). Unlike toxic nodular goiter, which is progressive (unless triggered by excessive iodine intake), remission
48、 of mild GD has been reported in up to 30% of patients without treatment (15). Less common causes of thyrotoxicosis include the entities of painless and subacute thyroiditis, which occur due to inflammation of thyroid tissue with release of preformed hormone into the circulation. Painless thyroiditi
49、s caused by lymphocytic inflammation appears to occur with a different frequency depending on the population studied: in Denmark it accounted for only 0.5% of thyrotoxic patients, it was 6% of patients in Toronto, and 22% of patients in Wisconsin (16-18). Painless thyroiditis may occur during lithiu
50、m (19), cytokine (e.g., interferon-alpha) (20), or tyrosine kinase inhibitor therapy (21), and in the postpartum period it is referred to as postpartum thyroiditis (22). A painless destructive thyroiditis (not usually lymphocytic) occurs in 510% of amiodarone-treated patients (23). Subacute thyroidi
