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THYROID CANCER Jassin M. Jouria, MD Dr. Jassin M. Jouria is a medical doctor, professor of academic medicine, and medical author. He graduated from Ross University School of Medicine and has completed his clinical clerkship training in various teaching hospitals throughout New York, including King’s County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep tutor and instructor for Kaplan. He has developed several medical courses and curricula for a variety of educational institutions. Dr. Jouria has also served on multiple levels in the academic field including faculty member and Department Chair. Dr. Jouria continues to serves as a Subject Matter Expert for several continuing education organizations covering multiple basic medical sciences. He has also developed several continuing medical education courses covering various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-module training series for trauma patient management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy & Physiology. Abstract The thyroid gland has been called the “Master Gland” because it is active in virtually every cell of the body, regulating cellular respiration, energy expenditure, overall metabolism, growth and development of cells and tissues. Because the thyroid gland’s role is so pervasive in the body, it is important for clinicians to understand the symptoms of various thyroid diseases. The management and treatment of thyroid conditions are discussed. 1 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities. Continuing Education Credit Designation This educational activity is credited for 3 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Statement of Learning Need The thyroid gland is active in virtually every cell of the body, regulating cellular respiration, energy expenditure, overall metabolism, growth and development of cells and tissues. It is important to understand the symptoms of thyroid diseases, and to know the management and treatment of these conditions. Course Purpose To provide advanced learning for clinicians interested in the diagnosis, treatment and prevention of thyroid disease. 2 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Target Audience Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion) Course Author & Planning Team Conflict of Interest Disclosures Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures Acknowledgement of Commercial Support There is no commercial support for this course. Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. 3 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. Most thyroid tumors are a. b. c. d. malignant and usually found on routine examination. painful, multinodular growths. benign and usually found on self-examination. benign and only found on autopsy. 2. True or False: Approximately 1% of new cancers diagnosed in the U.S., are of the thyroid. a. True b. False 3. The sudden onset of pain associated with a thyroid tumor is associated with a. b. c. d. benign disease. Hürtle cell carcinoma. incidentalomas. papillary carcinomas. 4. Some experts consider the Hürtle cell carcinoma as a variant of a. b. c. d. follicular carcinoma. primary thyroid sarcoma. anaplastic carcinoma. medullary carcinoma. 5. __________________ are the most common thyroid cancer constituting approximately 80% of all thyroid malignancies. a. b. c. d. Primary thyroid sarcomas Follicular carcinomas Papillary carcinomas Anaplastic carcinomas 4 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Introduction In the United States, thyroid cancer has been called an epidemic, though this may represent an “epidemic of diagnosis.” Most thyroid tumors are benign and only found on autopsy. In addition, a majority of thyroid cancers are found as a palpable and painless thyroid nodule on routine examination. When a thyroid nodule is diagnosed, it is important to first understand basic definition and guidelines to treat a thyroid nodule. Overview Of Thyroid Cancer Approximately 1% of new cancers diagnosed in the U.S., are cancers of the thyroid. Papillary carcinomas are the most common thyroid cancer constituting approximately 80% of all thyroid malignancies. Since the mid 1970’s, the incidence of thyroid cancer has nearly tripled, with most of the increase due to papillary carcinomas. Follicular carcinomas constitute approximately 10% of thyroid tumors while medullary thyroid carcinomas comprise from 5-10% of all thyroid tumors. Anaplastic carcinomas are found in 1-2% of cases while primary thyroid sarcomas and Hürtle cell carcinomas are the rarest forms, though some experts consider the Hürtle cell carcinoma as a variant of follicular carcinoma. Anaplastic carcinomas and metastatic medullary carcinomas are highly malignant but most thyroid cancers are not considered highly malignant.74 Solitary nodules are of greatest concern for malignancy in those patients over the age of 60 or in patients younger than 30 years. Thyroid tumors have a higher rate of malignancy in males. Other characteristics include: 1) Most thyroid tumors are painless to palpation. The sudden onset of pain associated with the tumor is 5 nursece4less.com nursece4less.com nursece4less.com nursece4less.com associated with benign disease. 2) Rapid growth is a worrying sign. 3) Nodules are hard and fixed. Fine needle aspiration biopsies (FNAB) are a primary diagnostic tool. There are no significant differences in results between conventional smears and liquid-based preparations — the choice should be based on lab experience, cost and preferences.77 Thyroid nodule ultrasound is increasingly being used to aid in the diagnosis of thyroid cancer. However, a recent review concluded that Low- to moderate-quality evidence suggests that individual ultrasound features are not accurate predictors of thyroid cancer. Two features, cystic content and spongiform appearance, however, might predict benign nodules, but this has limited applicability to clinical practice due to their infrequent occurrence. The authors further concluded that according to guidelines, a suspicious nodule should undergo a fineneedle aspiration biopsy with cytology (FNAB), which, depending on the results, could lead to thyroid surgery.77 Within this diagnostic algorithm, the use of ultrasound (US) evaluation has become widely accepted as a key diagnostic step in stratifying patients' risk of malignancy. Nevertheless, there is significant uncertainty surrounding the diagnostic accuracy of several of the features analyzed during the sonographic evaluation of thyroid nodules. Guidelines For The Treatment Of Thyroid Cancer The American Thyroid Association (ATA) has published guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Recommendations for thyroid nodules are identified in the table below. The ATA provides the following definition of a thyroid nodule as a: 6 nursece4less.com nursece4less.com nursece4less.com nursece4less.com discrete lesion within the thyroid gland that is radiologically distinct from the surrounding thyroid parenchyma. Some palpable lesions may not correspond to distinct radiologic abnormalities. Such abnormalities do not meet the strict definition for thyroid nodules. Nonpalpable nodules detected on US or other anatomic imaging studies are termed incidentally discovered nodules or ‘incidentalomas.’ Nonpalpable nodules have the same risk of malignancy as do sonographically confirmed palpable nodules of the same size. Generally, only nodules >1 cm should be evaluated, since they have a greater potential to be clinically significant cancers. Occasionally, there may be nodules <1 cm that require further evaluation because of clinical symptoms or associated lymphadenopathy. In very rare cases, some nodules <1 cm lack these sonographic and clinical warning signs yet may nonetheless cause future morbidity and mortality. This remains highly unlikely, and given the unfavorable cost/benefit considerations, attempts to diagnose and treat all such small thyroid cancers in an effort to prevent exceedingly rare outcomes is deemed to cause more harm than good. In general, the guiding clinical strategy acknowledges that most thyroid nodules are low risk, and many thyroid cancers pose minimal risk to human health and can be effectively treated.78 In general, thyroid cancer presents as a painless, palpable thyroid nodule which may be solitary or multiple. The critical issue is to determine if the nodule(s) is or are benign, which can be managed by watchful waiting and treatment as necessary, or malignant, in which case more aggressive treatment as per the recommendations should 7 nursece4less.com nursece4less.com nursece4less.com nursece4less.com be considered. The physical examination should include the head, neck, cervical soft tissues and indirect laryngoscopy, particularly if there is hoarseness in the patient’s voice suggesting the involvement of the recurrent laryngeal nerve or vocal fold paralysis. Well-differentiated thyroid carcinomas include both papillary carcinomas and follicular carcinomas. Women have a threefold higher risk of papillary carcinoma, with a mean age of 35-40 years. Radiation is associated with an increased risk of papillary carcinomas. Hashimoto’s thyroiditis may be associated with a greater risk of papillary carcinomas, but the association is not yet proven. Follicular carcinoma is the second most common well-differentiated thyroid carcinoma. Follicular carcinomas are associated with low iodine intake and are three times more common in women than in men. Age of diagnosis is usually between the ages of 40-60. ATA Recommendations For Thyroid Nodules This section captures the basic recommendations by the American Thyroid Association (ATA) to screen for and diagnose thyroid nodules. The first recommendation is on the role of thyroid cancer screening in people with familial follicular cell–derived differentiated thyroid cancer (DTC). This first ATA recommendation establishes the mainstay of all of the other recommendations that follow: screening people with familial follicular cell–derived DTC may lead to an earlier diagnosis of thyroid cancer, however, clinicians are informed that the ATA is unable to recommend for or against the value of ultrasound (US) screening because it has not been established through research that such thyroid testing leads to less morbidity or mortality.78 8 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Appropriate laboratory and imaging evaluation for patients with clinically or incidentally discovered thyroid nodules are highlighted in the table below, beginning with Recommendation 2 (the first ATA recommendation for thyroid nodule screening is explained above).78 Serum thyrotropin measurement RECOMMENDATION 2 (A) Serum thyrotropin (TSH) should be measured during the initial evaluation of a patient with a thyroid nodule. (B) If the serum TSH is subnormal, a radionuclide (preferably 123I) thyroid scan should be performed. (C) If the serum TSH is normal or elevated, a radionuclide scan should not be performed as the initial imaging evaluation. Serum thyroglobulin measurement RECOMMENDATION 3 Serum calcitonin measurement RECOMMENDATION 4 Routine measurement of serum thyroglobulin (Tg) for initial evaluation of thyroid nodules is not recommended. The panel cannot recommend either for or against routine measurement of serum calcitonin in patients with thyroid nodules. Fluorodeoxyglucose positron emission tomography scan RECOMMENDATION 5 (A) Focal fluorodeoxyglucose positron emission tomography (FDG-PET) uptake within a sonographically confirmed thyroid nodule conveys an increased risk of thyroid cancer, and FNA is recommended for those nodules >1 cm. (B) Diffuse FDG-PET uptake, in conjunction with sonographic and clinical evidence of chronic lymphocytic thyroiditis, does not require further imaging or FNA. 9 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Thyroid sonography RECOMMENDATION 6 Thyroid sonography with survey of the cervical lymph nodes should be performed in all patients with known or suspected thyroid nodules. US for FNA decision-making RECOMMENDATION 7 FNA(B) is the procedure of choice in the evaluation of thyroid nodules, when clinically indicated. Recommendations for diagnostic FNA of a thyroid nodule based on sonographic pattern RECOMMENDATION 8 I. Thyroid nodule diagnostic FNA(B) is recommended for: (A) Nodules ≥1 cm in greatest dimension with high suspicion sonographic pattern. (B) Nodules ≥1 cm in greatest dimension with intermediate suspicion sonographic pattern. (C) Nodules ≥1.5 cm in greatest dimension with low suspicion sonographic pattern. II. Thyroid nodule diagnostic FNA(B) may be considered for: (D) Nodules ≥2 cm in greatest dimension with very low suspicion sonographic pattern (i.e., spongiform). Observation without FNA is also a reasonable option. III. Thyroid nodule diagnostic FNA(B) is not required for: (E) Nodules that do not meet the above criteria. (F) Nodules purely cystic. What is the role of FNA, cytology interpretation, and molecular testing in patients with thyroid nodules? RECOMMENDATION 9 Nondiagnostic cytology RECOMMENDATION 10 Thyroid nodule FNA cytology should be reported using diagnostic groups outlined in the Bethesda System for Reporting Thyroid Cytopathology. (A) For a nodule with an initial nondiagnostic cytology result, FNA(B) should be repeated with US guidance and, if available, on-site cytologic evaluation. (B) Repeatedly nondiagnostic nodules without a high suspicion sonographic pattern require close observation or surgical excision for histopathologic diagnosis. 10 nursece4less.com nursece4less.com nursece4less.com nursece4less.com (C) Surgery should be considered for histopathologic diagnosis if the cytologically nondiagnostic nodule has a high suspicion sonographic pattern, growth of the nodule (>20% in two dimensions) is detected during US surveillance, or clinical risk factors for malignancy are present. Benign cytology RECOMMENDATION 11 If the nodule is benign on cytology, further immediate diagnostic studies or treatment are not required. Malignant cytology RECOMMENDATION 12 If a cytology result is diagnostic for primary thyroid malignancy, surgery is generally recommended. Indeterminate cytology (AUS/FLUS, FN, SUSP) What are the principles of the molecular testing of FNA samples? RECOMMENDATION 13 If molecular testing is being considered, patients should be counseled regarding the potential benefits and limitations of testing and about the possible uncertainties in the therapeutic and long-term clinical implications of results. RECOMMENDATION 14 If intended for clinical use, molecular testing should be performed in Clinical Laboratory Improvement Amendments/College of American Pathologists (CLIA/CAP)certified molecular laboratories, or the international equivalent, because reported quality assurance practices may be superior compared to other settings. AUS/FLUS cytology AUS/FLUS= atypia of undetermined significance or follicular lesion of undetermined significance RECOMMENDATION 15 (A) For nodules with AUS/FLUS cytology, after consideration of worrisome clinical and sonographic features, investigations such as repeat FNA(B) or molecular testing may be used to supplement malignancy risk assessment in lieu of proceeding directly with a strategy of either surveillance or diagnostic surgery. Informed patient preference and feasibility should be considered in clinical decision-making. 11 nursece4less.com nursece4less.com nursece4less.com nursece4less.com (B) If repeat FNA(B) cytology, molecular testing, or both are not performed or inconclusive, either surveillance or diagnostic surgical excision may be performed for an AUS/FLUS thyroid nodule, depending on clinical risk factors, sonographic pattern, and patient preference. Follicular neoplasm or suspicious for follicular neoplasm cytology RECOMMENDATION 16 (A) Diagnostic surgical excision is the long-established standard of care for the management of FN/SFN cytology nodules. However, after consideration of clinical and sonographic features, molecular testing may be used to supplement malignancy risk assessment data in lieu of proceeding directly with surgery. Informed patient preference and feasibility should be considered in clinical decision-making. (B) If molecular testing is either not performed or inconclusive, surgical excision may be considered for removal and definitive diagnosis of an FN/SFN thyroid nodule. Suspicious for malignancy cytology RECOMMENDATION 17 (A) If the cytology is reported as suspicious for papillary carcinoma (SUSP), surgical management should be similar to that of malignant cytology, depending on clinical risk factors, sonographic features, patient preference, and possibly results of mutational testing (if performed). (B) After consideration of clinical and sonographic features, mutational testing for BRAF or the sevengene mutation marker panel (BRAF, RAS, RET/PTC, PAX8/PPARc) may be considered in nodules with SUSP cytology if such data would be expected to alter surgical decision-making. What is the utility of 18FDG-PET scanning to predict malignant or benign disease when FNA cytology is indeterminate (AUS/FLUS, FN, SUSP)? RECOMMENDATION 18 FDG-PET imaging is not routinely recommended for the evaluation of thyroid nodules with indeterminate cytology. 18 12 nursece4less.com nursece4less.com nursece4less.com nursece4less.com What is the appropriate operation for cytologically indeterminate thyroid nodules? RECOMMENDATION 19 When surgery is considered for patients with a solitary, cytologically indeterminate nodule, thyroid lobectomy is the recommended initial surgical approach. This approach may be modified based on clinical or sonographic characteristics, patient preference, and/or molecular testing when performed. RECOMMENDATION 20 (A) Because of increased risk for malignancy, total thyroidectomy may be preferred in patients with indeterminate nodules that are cytologically suspicious for malignancy, positive for known mutations specific for carcinoma, sonographically suspicious, or large (>4 cm), or in patients with familial thyroid carcinoma or history of radiation exposure, if completion thyroidectomy would be recommended based on the indeterminate nodule being malignant following lobectomy. (B) Patients with indeterminate nodules who have bilateral nodular disease, those with significant medical comorbidities, or those who prefer to undergo bilateral thyroidectomy to avoid the possibility of requiring a future surgery on the contralateral lobe, may undergo total or near-total thyroidectomy, assuming completion thyroidectomy would be recommended if the indeterminate nodule proved malignant following lobectomy. How should multinodular thyroid glands (i.e., two or more clinically relevant nodules) be evaluated for malignancy? RECOMMENDATION 21 (A) Patients with multiple thyroid nodules ≥1 cm should be evaluated in the same fashion as patients with a solitary nodule ≥1 cm, excepting that each nodule that is >1 cm carries an independent risk of malignancy and therefore multiple nodules may require FNA. (B) When multiple nodules ≥1 cm are present, FNA should be performed preferentially based upon nodule sonographic pattern and respective size cutoff. (C) If none of the nodules has a high or moderate suspicion sonographic pattern, and multiple sonographically (very low or low suspicion pattern nodules) coalesce with no intervening normal parenchyma, the likelihood of malignancy is low and it is reasonable to aspirate the largest nodules (≥2 cm) or continue surveillance without FNA. 13 nursece4less.com nursece4less.com nursece4less.com nursece4less.com RECOMMENDATION 22 A low or low-normal serum TSH concentration in patients with multiple nodules may suggest that some nodule(s) may be autonomous. In such cases, a radionuclide (preferably 123I) thyroid scan should be considered and directly compared to the US images to determine functionality of each nodule ≥1 cm. FNA should then be considered only for those isofunctioning or nonfunctioning nodules, among which those with high suspicion sonographic pattern should be aspirated preferentially. RECOMMENDATION 23 Given the low false-negative rate of US-guided FNA cytology and the higher yield of missed malignancies based upon nodule sonographic pattern rather than growth, the follow-up of thyroid nodules with benign cytology diagnoses should be determined by risk stratification based upon US pattern. (A) Nodules with high suspicion US pattern: repeat US and US-guided FNA within 12 months. (B) Nodules with low to intermediate suspicion US pattern: repeat US at 12–24 months. If sonographic evidence of growth (20% increase in at least two nodule dimensions with a minimal increase of 2 mm or more than a 50% change in volume) or development of new suspicious sonographic features, the FNA could be repeated or observation continued with repeat US, with repeat FNA in case of continued growth. (C) Nodules with very low suspicion US pattern (including spongiform nodules): the utility of surveillance US and assessment of nodule growth as an indicator for repeat FNA to detect a missed malignancy is limited. If US is repeated, it should be done at ≥24 months. Recommendation for follow-up of nodules with two benign FNA cytology results If a nodule has undergone repeat US-guided FNA with a second benign cytology result, US surveillance for this nodule for continued risk of malignancy is no longer indicated. Follow-up for nodules that do not meet FNA criteria RECOMMENDATION 24 Nodules may be detected on US that do not meet criteria for FNA at initial imaging (Recommendation 8). The strategy for sonographic follow-up of these nodules should be based upon the nodule’s sonographic pattern. 14 nursece4less.com nursece4less.com nursece4less.com nursece4less.com (A) Nodules with high suspicion US pattern: repeat US in 6–12 months. (B) Nodules with low to intermediate suspicion US pattern: consider repeat US at 12–24 months. (C) Nodules >1 cm with very low suspicion US pattern (including spongiform nodules) and pure cyst: the utility and time interval of surveillance US for risk of malignancy is not known. If US is repeated, it should be at ≥24 months. (D) Nodules ≥1 cm with very low suspicion US pattern (including spongiform nodules) and pure cysts do not require routine sonographic follow-up. What is the role of medical or surgical therapy for benign thyroid nodules? RECOMMENDATION 25 Routine TSH suppression therapy for benign thyroid nodules in iodine sufficient populations is not recommended. Though modest responses to therapy can be detected, the potential harm outweighs benefit for most patients. RECOMMENDATION 26 Individual patients with benign, solid, or mostly solid nodules should have adequate iodine intake. If inadequate dietary intake is found or suspected, a daily supplement (containing 150 μg iodine) is recommended. RECOMMENDATION 27 (A) Surgery may be considered for growing nodules that are benign after repeat FNA if they are large (>4 cm), causing compressive or structural symptoms, or based upon clinical concern. (B) Patients with growing nodules that are benign after FNA should be regularly monitored. Most asymptomatic nodules demonstrating modest growth should be followed without intervention. RECOMMENDATION 28 Recurrent cystic thyroid nodules with benign cytology should be considered for surgical removal or percutaneous ethanol injection (PEI) based on compressive symptoms and cosmetic concerns. Asymptomatic cystic nodules may be followed conservatively. 15 nursece4less.com nursece4less.com nursece4less.com nursece4less.com RECOMMENDATION 29 There are no data to guide recommendations on the use of thyroid hormone therapy in patients with growing nodules that are benign on cytology. How should thyroid nodules in pregnant women be managed? FNA for thyroid nodules discovered during pregnancy RECOMMENDATION 30 (A) FNA of clinically relevant thyroid nodules should be performed in euthyroid and hypothyroid pregnant women. (B) For women with suppressed serum TSH levels that persist beyond 16 weeks gestation, FNA may be deferred until after pregnancy and cessation of lactation. At that time, a radionuclide scan can be performed to evaluate nodule function if the serum TSH remains suppressed. Approaches to pregnant patients with malignant or indeterminate cytology RECOMMENDATION 31 PTC discovered by cytology in early pregnancy should be monitored sonographically. If it grows substantially before 24–26 weeks gestation, or if US reveals cervical lymph nodes that are suspicious for metastatic disease, surgery should be considered during pregnancy. However, if the disease remains stable by mid-gestation, or if it is diagnosed in the second half of pregnancy, surgery may be deferred until after delivery. Initial And Long-Term Management Of Thyroid Cancer The ATA Recommendations guide clinicians in the differentiation of thyroid cancer, including the initial as well as the long-term management of the disease. These recommendations are listed in the table below. 16 nursece4less.com nursece4less.com nursece4less.com nursece4less.com ATA Recommendations for Differentiated Thyroid Cancer DIFFERENTIATED THYROID CANCER: INITIAL MANAGEMENT GUIDELINES Goals of initial therapy of DTC The basic goals of initial therapy for patients with DTC are to improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and associated morbidity, and permit accurate disease staging and risk stratification, while minimizing treatment-related morbidity and unnecessary therapy. The specific goals of initial therapy are to: 1) Remove the primary tumor, disease that has extended beyond the thyroid capsule, and clinically significant lymph node metastases. Completeness of surgical resection is an important determinant of outcome, while residual metastatic lymph nodes represent the most common site of disease persistence/recurrence. 2) Minimize the risk of disease recurrence and metastatic spread. Adequate surgery is the most important treatment variable influencing prognosis, while RAI treatment, TSH suppression, and other treatments each play adjunctive roles in at least some patients. 3) Facilitate postoperative treatment with RAI, where appropriate. For patients undergoing RAI remnant ablation, or RAI treatment of presumed (adjuvant therapy) or known (therapy) residual or metastatic disease, removal of all normal thyroid tissue is an important element of initial surgery. 4) Permit accurate staging and risk stratification of the disease. Because disease staging and risk stratification should be used to guide initial prognostication, disease management, and follow-up strategies, accurate postoperative risk assessment is a crucial element in the management of patients with DTC. 5) Permit accurate long-term surveillance for disease recurrence. 17 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6) Minimize treatment-related morbidity. The extent of surgery and the experience of the surgeon both play important roles in determining the risk of surgical complications. What is the role of preoperative staging with diagnostic imaging and laboratory tests? RECOMMENDATION 32 (A) Preoperative neck US for cervical (central and especially lateral neck compartments) lymph nodes is recommended for all patients undergoing thyroidectomy for malignant or suspicious for malignancy cytologic or molecular findings. (B) US-guided FNA of sonographically suspicious lymph nodes ≥8–10 mm in the smallest diameter should be performed to confirm malignancy if this would change management. (C) The addition of FNA-Tg washout in the evaluation of suspicious cervical lymph nodes is appropriate in select patients, but interpretation may be difficult in patients with an intact thyroid gland. Neck imaging— CT/MRI/PET RECOMMENDATION 33 (A) Preoperative use of cross-sectional imaging studies (CT, MRI) with intravenous (IV) contrast is recommended as an adjunct to US for patients with clinical suspicion for advanced disease, including invasive primary tumor, or clinically apparent multiple or bulky lymph node involvement. (B) Routine preoperative 18FDG-PET scanning is not recommended. Measurement of serum Tg and anti-Tg antibodies RECOMMENDATION 34 Routine preoperative measurement of serum Tg or anti-Tg antibodies is not recommended. Operative approach for a biopsy diagnostic for follicular cell–derived malignancy RECOMMENDATION 35 (A) For patients with thyroid cancer >4 cm, or with gross extrathyroidal extension (clinical T4), or clinically apparent metastatic disease to nodes (clinical N1) or distant sites (clinical M1), the initial surgical procedure should include a near-total or total thyroidectomy 18 nursece4less.com nursece4less.com nursece4less.com nursece4less.com and gross removal of all primary tumor unless there are contraindications to this procedure. (B) For patients with thyroid cancer >1 cm and <4 cm without extrathyroidal extension, and without clinical evidence of any lymph node metastases (cN0), the initial surgical procedure can be either a bilateral procedure (near-total or total thyroidectomy) or a unilateral procedure (lobectomy). Thyroid lobectomy alone may be sufficient initial treatment for low-risk papillary and follicular carcinomas; however, the treatment team may choose total thyroidectomy to enable RAI therapy or to enhance follow-up based upon disease features and/or patient preferences. (C) If surgery is chosen for patients with thyroid cancer <1 cm without extrathyroidal extension and cN0, the initial surgical procedure should be a thyroid lobectomy unless there are clear indications to remove the contralateral lobe. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas in the absence of prior head and neck radiation, familial thyroid carcinoma, or clinically detectable cervical nodal metastases. Lymph node dissection RECOMMENDATION 36 (A) Therapeutic central-compartment (level VI) neck dissection for patients with clinically involved central nodes should accompany total thyroidectomy to provide clearance of disease from the central neck. (B) Prophylactic central-compartment neck dissection (ipsilateral or bilateral) should be considered in patients with papillary thyroid carcinoma with clinically uninvolved central neck lymph nodes (cN0) who have advanced primary tumors (T3 or T4) or clinically involved lateral neck nodes (cN1b), or if the information will be used to plan further steps in therapy. 19 nursece4less.com nursece4less.com nursece4less.com nursece4less.com (C) Thyroidectomy without prophylactic central neck dissection is appropriate for small (T1 or T2), noninvasive, clinically node-negative PTC (cN0) and for most follicular cancers. RECOMMENDATION 37 Therapeutic lateral neck compartmental lymph node dissection should be performed for patients with biopsy-proven metastatic lateral cervical lymphadenopathy. Completion thyroidectomy RECOMMENDATION 38 (A) Completion thyroidectomy should be offered to patients for whom a bilateral thyroidectomy would have been recommended had the diagnosis been available before the initial surgery. Therapeutic central neck lymph node dissection should be included if the lymph nodes are clinically involved. Thyroid lobectomy alone may be sufficient treatment for low-risk papillary and follicular carcinomas. (B) RAI ablation in lieu of completion thyroidectomy is not recommended routinely; however, it may be used to ablate the remnant lobe in selected cases. What is the appropriate perioperative approach to voice and parathyroid issues? Preoperative care communication RECOMMENDATION 39 Prior to surgery, the surgeon should communicate with the patient regarding surgical risks, including nerve and parathyroid injury, through the informed consent process and communicate with associated physicians, including anesthesia personnel, regarding important findings elicited during the preoperative workup. 20 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Preoperative voice assessment RECOMMENDATION 40 All patients undergoing thyroid surgery should have preoperative voice assessment as part of their preoperative physical examination. This should include the patient’s description of vocal changes, as well as the physician’s assessment of voice. RECOMMENDATION 41 Preoperative laryngeal exam should be performed in all patients with: (A) Preoperative voice abnormalities; (B) History of cervical or upper chest surgery, which places the RLN or vagus nerve at risk; (C) Known thyroid cancer with posterior extrathyroidal extension or extensive central nodal metastases. Intraoperative voice and parathyroid management RECOMMENDATION 42 (A) Visual identification of the RLN during dissection is required in all cases. Steps should also be taken to preserve the external branch of the superior laryngeal nerve (EBSLN) during dissection of the superior pole of the thyroid gland. (B) Intraoperative neural stimulation (with or without monitoring) may be considered to facilitate nerve identification and confirm neural function. RECOMMENDATION 43 The parathyroid glands and their blood supply should be preserved during thyroid surgery. Postoperative care RECOMMENDATION 44 Patients should have their voice assessed in the postoperative period. Formal laryngeal exam should be performed if the voice is abnormal. RECOMMENDATION 45 Important intraoperative findings and details of postoperative care should be communicated by the surgeon to the patient and other physicians who are important in the patient’s postoperative care. 21 nursece4less.com nursece4less.com nursece4less.com nursece4less.com What are the basic principles of histopathologic evaluation of thyroidectomy samples? RECOMMENDATION 46 (A) In addition to the basic tumor features required for AJCC/UICC thyroid cancer staging including status of resection margins, pathology reports should contain additional information helpful for risk assessment, such as the presence of vascular invasion and the number of invaded vessels, number of lymph nodes examined and involved with tumor, size of the largest metastatic focus to the lymph node, and presence or absence of extranodal extension of the metastatic tumor. (B) Histopathologic variants of thyroid carcinoma associated with more unfavorable outcomes (i.e., tall cell, columnar cell, and hobnail variants of PTC; widely invasive FTC; poorly differentiated carcinoma) or more favorable outcomes (i.e., encapsulated follicular variant of PTC without invasion, minimally invasive FTC) should be identified during histopathologic examination and reported. (C) Histopathologic variants associated with familial syndromes (cribriform-morular variant of papillary carcinoma often associated with FAP, follicular or papillary carcinoma associated with PTEN-hamartoma tumor syndrome) should be identified during histopathologic examination and reported. What is the role of postoperative staging systems and risk stratification in the management of DTC? Postoperative staging RECOMMENDATION 47 AJCC/UICC staging is recommended for all patients with DTC, based on its utility in predicting disease mortality, and its requirement for cancer registries. AJCC/UICC TNM staging T0 No evidence of primary tumor 22 nursece4less.com nursece4less.com nursece4less.com nursece4less.com T1a Tumor ≤1 cm, without extrathyroidal extension T1b Tumor >1 cm but ≤2 cm in greatest dimension, without extrathyroidal extension T2 Tumor >2 cm but ≤4 cm in greatest dimension, without extrathyroidal extension. T3 Tumor >4 cm in greatest dimension limited to the thyroid or any size tumor with minimal extrathyroidal extension (i.e., extension into sternothyroid muscle or perithyroidal soft tissues). T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve. T4b Tumor of any size invading prevertebral fascia or encasing carotid artery or mediastinal vessels N0 No metastatic nodes N1a Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes). N1b Metastases to unilateral, bilateral, or contralateral cervical (levels I, II III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (level VII) M0 No distant metastases M1 Distant metastases Patient age <45 years old at diagnosis: I: Any T Any N M0 II: Any T Any N M1 Patient age ≥45 years old at diagnosis I T1a N0 M0 T1b N0 M0 II T2 N0 M0 III T1a N1a M0 T1b N1a M0 T2 N1a M0 T3 N0 M0 T3 N1a M0 IVa T1a N1b M0 T1b N1b M0 T2 N1b M0 T3 N1b M0 T4a N0 M0 T4a N1a M0 T4a N1b M0 IVb T4b Any N M0 IVc Any T Any N M1 What initial stratification RECOMMENDATION 48 23 nursece4less.com nursece4less.com nursece4less.com nursece4less.com system should be used to estimate the risk of persistent/recurrent disease? (A) The 2009 ATA Initial Risk Stratification System is recommended for DTC patients treated with thyroidectomy, based on its utility in predicting risk of disease recurrence and/or persistence. (B) Additional prognostic variables (such as the extent of lymph node involvement, mutational status, and/or the degree of vascular invasion in FTC), not included in the 2009 ATA Initial Risk Stratification system may be used to further refine risk stratification for DTC as described in the following text in the Modified Initial Risk Stratification system. However, the incremental benefit of adding these specific prognostic variables to the 2009 Initial Risk Stratification system has not been established. (C) While not routinely recommended for initial postoperative risk stratification in DTC, the mutational status of BRAF, and potentially other mutations such as TERT, have the potential to refine risk estimates when interpreted in the context of other clinico-pathologic risk factors. How should initial risk estimates be modified over time? RECOMMENDATION 49 Should postoperative disease status be considered in decisionmaking for RAI therapy for patients with DTC? RECOMMENDATION 50 Initial recurrence risk estimates should be continually modified during follow-up, because the risk of recurrence and disease-specific mortality can change over time as a function of the clinical course of the disease and the response to therapy. (A) Postoperative disease status (i.e., the presence or absence of persistent disease) should be considered in deciding whether additional treatment (i.e., RAI, surgery, or other treatment) may be needed. (B) Postoperative serum Tg (on thyroid hormone therapy or after TSH stimulation) can help in assessing the persistence of disease or thyroid remnant and predicting potential future disease recurrence. The Tg should reach its nadir by 3–4 weeks postoperatively in most patients. (C) The optimal cutoff value for postoperative 24 nursece4less.com nursece4less.com nursece4less.com nursece4less.com serum Tg or state in which it is measured (on thyroid hormone therapy or after TSH stimulation) to guide decision-making regarding RAI administration is not known. (D) Postoperative diagnostic RAI WBSs may be useful when the extent of the thyroid remnant or residual disease cannot be accurately ascertained from the surgical report or neck ultrasonography, and when the results may alter the decision to treat or the activity of RAI that is to be administered. Identification and localization of uptake foci may be enhanced by concomitant single photon emission computed tomography– computed tomography (SPECT/CT). When performed, pretherapy diagnostic scans should utilize 123I (1.5–3 mCi) or a low activity of 131I (1–3 mCi), with the therapeutic activity optimally administered within 72 hours of the diagnostic activity. What is the role of RAI (including remnant ablation, adjuvant therapy, or therapy for persistent disease) after thyroidectomy in the primary management of DTC? RECOMMENDATION 51 (A) RAI remnant ablation is not routinely recommended after thyroidectomy for ATA low-risk DTC patients. Consideration of specific features of the individual patient that could modulate recurrence risk, disease follow-up implications, and patient preferences are relevant to RAI decisionmaking. (B) RAI remnant ablation is not routinely recommended after lobectomy or total thyroidectomy for patients with unifocal papillary microcarcinoma, in the absence of other adverse features. (C) RAI remnant ablation is not routinely recommended after thyroidectomy for patients with multifocal papillary microcarcinoma in absence of other adverse features. Consideration of specific features of the individual patient that could modulate recurrence risk, disease follow-up implications, and patient preferences are relevant to RAI decision-making. (D) RAI adjuvant therapy should be considered 25 nursece4less.com nursece4less.com nursece4less.com nursece4less.com after total thyroidectomy in ATA intermediate-risk level DTC patients. (E) RAI adjuvant therapy is routinely recommended after total thyroidectomy for ATA high-risk DTC patients. What is the role of molecular marker status in therapeutic RAI decision-making? RECOMMENDATION 52 How long does thyroid hormone need to be withdrawn in preparation for RAI remnant ablation/treatment or diagnostic scanning? RECOMMENDATION 53 The role of molecular testing in guiding postoperative RAI use has yet to be established; therefore, no molecular testing to guide postoperative RAI use can be recommended at this time. (A) If thyroid hormone withdrawal is planned prior to RAI therapy or diagnostic testing, LT4 should be withdrawn for 3–4 weeks. Liothyronine (LT3) may be substituted for LT4 in the initial weeks if LT4 is withdrawn for 4 or more weeks, and in such circumstances, LT3 should be withdrawn for at least 2 weeks. Serum TSH should be measured prior to radioisotope administration to evaluate the degree of TSH elevation. (B) A goal TSH of >30 mIU/L has been generally adopted in preparation for RAI therapy or diagnostic testing, but there is uncertainty relating to the optimum TSH level associated with improvement in long-term outcomes. Can rhTSH (Thyrogen) be used as an alternative to thyroxine withdrawal for remnant ablation or adjuvant therapy in patients who have undergone near-total or total thyroidectomy? RECOMMENDATION 54 (A) In patients with ATA low-risk and ATA intermediate risk DTC without extensive lymph node involvement (i.e.,T1–T3, N0/Nx/N1a, M0), in whom RAI remnant ablation or adjuvant therapy is planned, preparation with rhTSH stimulation is an acceptable alternative to thyroid hormone withdrawal for achieving remnant ablation, based on evidence of superior short-term quality of life, noninferiority of remnant ablation efficacy, and multiple consistent observations suggesting no significant difference in long-term outcomes. (B) In patients with ATA intermediate-risk DTC 26 nursece4less.com nursece4less.com nursece4less.com nursece4less.com who have extensive lymph node disease (multiple clinically involved LN) in the absence of distant metastases, preparation with rhTSH stimulation may be considered as an alternative to thyroid hormone withdrawal prior to adjuvant RAI treatment. (C) In patients with ATA high-risk DTC with attendant higher risks of disease-related mortality and morbidity, more controlled data from long-term outcome studies are needed before rhTSH preparation for RAI adjuvant treatment can be recommended. (D) In patients with DTC of any risk level with significant comorbidity that may preclude thyroid hormone withdrawal prior to iodine RAI administration, rhTSH preparation should be considered. Significant comorbidity may include: (a) a significant medical or psychiatric condition that could be acutely exacerbated with hypothyroidism, leading to a serious adverse event, or (b) inability to mount an adequate endogenous TSH response with thyroid hormone withdrawal. What activity of 131I should be used for remnant ablation or adjuvant therapy? RECOMMENDATION 55 (A) If RAI remnant ablation is performed after total thyroidectomy for ATA low-risk thyroid cancer or intermediate-risk disease with lower risk features (i.e., low-volume central neck nodal metastases with no other known gross residual disease or any other adverse features), a low administered activity of approximately of 30 mCi is generally favored over higher administered activities. (B) Higher administered activities may need to be considered for patients receiving less than a total or near-total thyroidectomy in which a larger remnant is suspected or in which adjuvant therapy is intended. RECOMMENDATION 56 27 nursece4less.com nursece4less.com nursece4less.com nursece4less.com When RAI is intended for initial adjuvant therapy to treat suspected microscopic residual disease, administered activities above those used for remnant ablation up to 150 mCi are generally recommended (in absence of known distant metastases). It is uncertain whether routine use of higher administered activities (>150 mCi) in this setting will reduce structural disease recurrence for T3 and N1 disease. Is a low-iodine diet necessary before remnant ablation? RECOMMENDATION 57 Should a posttherapy scan be performed following remnant ablation or adjuvant therapy? RECOMMENDATION 58 A low iodine diet (LID) for approximately 1–2 weeks should be considered for patients undergoing RAI remnant ablation or treatment. A posttherapy WBS (with or without SPECT/CT) is recommended after RAI remnant ablation or treatment, to inform disease staging and document the RAI avidity of any structural disease. Early management of DTC after initial therapy What is the appropriate degree of initial TSH suppression? RECOMMENDATION 59 (A) For high-risk thyroid cancer patients, initial TSH suppression to below 0.1 mU/L is recommended. (B) For intermediate-risk thyroid cancer patients, initial TSH suppression to 0.1– 0.5 mU/L is recommended. (C) For low-risk patients who have undergone remnant ablation and have undetectable serum Tg levels, TSH may be maintained at the lower end of the reference range (0.5–2 mU/L) while continuing surveillance for recurrence. Similar recommendations hold for low-risk patients who have not undergone remnant ablation and have undetectable serum Tg levels. (D) For low-risk patients who have undergone 28 nursece4less.com nursece4less.com nursece4less.com nursece4less.com remnant ablation and have low-level serum Tg levels, TSH may be maintained at or slightly below the lower limit of normal (0.1– 0.5 mU/L) while surveillance for recurrence is continued. Similar recommendations hold for low-risk patients who have not undergone remnant ablation, although serum Tg levels may be measurably higher and continued surveillance for recurrence applies. (E) For low-risk patients who have undergone lobectomy, TSH may be maintained in the mid to lower reference range (0.5–2 mU/L) while surveillance for recurrence is continued. Thyroid hormone therapy may not be needed if patients can maintain their serum TSH in this target range. Is there a role for adjunctive external beam radiation therapy or chemotherapy? External beam radiation therapy (EBRT) RECOMMENDATION 60 There is no role for routine adjuvant EBRT to the neck in patients with DTC after initial complete surgical removal of the tumor. Systemic adjuvant therapy RECOMMENDATION 61 There is no role for routine systemic adjuvant therapy in patients with DTC (beyond RAI and/or TSH suppressive therapy using LT4). DTC: LONG-TERM MANAGEMENT AND ADVANCED CANCER MANAGEMENT GUIDELINES What are the appropriate RECOMMENDATION 62 29 nursece4less.com nursece4less.com nursece4less.com nursece4less.com methods for following patients after initial therapy? What is the role of serum Tg measurement in the follow-up of DTC? (A) Serum Tg should be measured by an assay that is calibrated against the CRM457 standard. Thyroglobulin antibodies should be quantitatively assessed with every measurement of serum Tg. Ideally, serum Tg and anti-Tg antibodies should be assessed longitudinally in the same laboratory and using the same assay for a given patient. (B) During initial follow-up, serum Tg on thyroxine therapy should be measured every 6–12 months. More frequent Tg measurements may be appropriate for ATA high-risk patients. (C) In ATA low- and intermediate-risk patients that achieve an excellent response to therapy, the utility of subsequent Tg testing is not established. The time interval between serum Tg measurements can be lengthened to at least 12–24 months. (D) Serum TSH should be measured at least every 12 months in all patients on thyroid hormone therapy. (E) ATA high-risk patients (regardless of response to therapy) and all patients with biochemical incomplete, structural incomplete, or indeterminate response should continue to have Tg measured at least every 6–12 months for several years. RECOMMENDATION 63 (A) In ATA low-risk and intermediate-risk patients who have had remnant ablation or adjuvant therapy and negative cervical US, serum Tg should be measured at 6–18 months on thyroxine therapy with a sensitive Tg assay (<0.2 ng/mL) or after TSH stimulation to verify absence of disease (excellent response). (B) Repeat TSH-stimulated Tg testing is not recommended for low- and intermediate-risk patients with an excellent response to therapy. (C) Subsequent TSH-stimulated Tg testing may 30 nursece4less.com nursece4less.com nursece4less.com nursece4less.com be considered in patients with an indeterminate, biochemical incomplete, or structural incomplete response following either additional therapies or a spontaneous decline in Tg values on thyroid hormone therapy over time in order to reassess response to therapy. What is the role of serum Tg measurement in patients who have not undergone RAI remnant ablation? RECOMMENDATION 64 Periodic serum Tg measurements on thyroid hormone therapy should be considered during follow-up of patients with DTC who have undergone less than total thyroidectomy and in patients who have had a total thyroidectomy but not RAI ablation. While specific cutoff levels of Tg that optimally distinguish normal residual thyroid tissue from persistent thyroid cancer are unknown, rising Tg values over time are suspicious for growing thyroid tissue or cancer. What is the role of US and other imaging techniques (RAI SPECT/CT, CT, MRI, PET-CT) during follow-up? Cervical ultrasonography RECOMMENDATION 65 (A) Following surgery, cervical US to evaluate the thyroid bed and central and lateral cervical nodal compartments should be performed at 6–12 months and then periodically, depending on the patient’s risk for recurrent disease and Tg status. (B) If a positive result would change management, ultrasonographically suspicious lymph nodes ≥8–10 mm in the smallest diameter should be biopsied for cytology with Tg measurement in the needle washout fluid. (C) Suspicious lymph nodes less than 8–10 mm in smallest diameter may be followed without biopsy with consideration for FNA or intervention if there is growth or if the node threatens vital structures. (D) Low-risk patients who have had remnant 31 nursece4less.com nursece4less.com nursece4less.com nursece4less.com ablation, negative cervical US, and a low serum Tg on thyroid hormone therapy in a sensitive assay (<0.2 ng/mL) or after TSH stimulation (Tg <1 ng/mL) can be followed primarily with clinical examination and Tg measurements on thyroid hormone replacement. Diagnostic whole-body RAI scans RECOMMENDATION 66 After the first posttreatment WBS performed following RAI remnant ablation or adjuvant therapy, low-risk and intermediate-risk patients (lower risk features) with an undetectable Tg on thyroid hormone with negative antiTg antibodies and a negative US (excellent response to therapy) do not require routine diagnostic WBS during follow-up. RECOMMENDATION 67 (A) Diagnostic WBS, either following thyroid hormone withdrawal or rhTSH, 6–12 months after adjuvant RAI therapy can be useful in the follow-up of patients with high or intermediate risk (higher risk features) of persistent disease (see risk stratification system, section [B19]) and should be done with 123I or low activity 131I. (B) SPECT/CT RAI imaging is preferred over planar imaging in patients with uptake on planar imaging to better anatomically localize the RAI uptake and distinguish between likely tumors and nonspecific uptake. FDG-PET scanning 18 RECOMMENDATION 68 (A) 18FDG-PET scanning should be considered in highrisk DTC patients with elevated serum Tg (generally >10 ng/mL) with negative RAI imaging. (B) 18FDG-PET scanning may also be considered as: (i) (ii) a part of initial staging in poorly differentiated thyroid cancers and invasive Hürthle cell carcinomas, especially those with other evidence of disease on imaging or because of elevated serum Tg levels; a prognostic tool in patients with 32 nursece4less.com nursece4less.com nursece4less.com nursece4less.com (iii) CT and MRI metastatic disease to identify lesions and patients at highest risk for rapid disease progression and diseasespecific mortality; and, an evaluation of posttreatment response following systemic or local therapy of metastatic or locally invasive disease. RECOMMENDATION 69 (A) Cross-sectional imaging of the neck and upper chest (CT, MRI) with IV contrast should be considered (i) in the setting of bulky and widely distributed recurrent nodal disease where US may not completely delineate disease, (ii) in the assessment of possible invasive recurrent disease where potential aero-digestive tract invasion requires complete assessment, or (iii) when neck US is felt to be inadequately visualizing possible neck nodal disease (high Tg, negative neck US). (B) CT imaging of the chest without IV contrast (imaging pulmonary parenchyma) or with IV contrast (to include the mediastinum) should be considered in high risk DTC patients with elevated serum Tg (generally >10 ng/mL) or rising Tg antibodies with or without negative RAI imaging. (C) Imaging of other organs including MRI brain, MR skeletal survey, and/or CT or MRI of the abdomen should be considered in high-risk DTC patients with elevated serum Tg (generally >10 ng/mL) and negative neck and chest imaging who have symptoms referable to those organs or who are being prepared for TSH-stimulated RAI therapy (withdrawal or rhTSH) and may be at risk for complications of tumor swelling. What is the role of TSH suppression during thyroid hormone therapy in the long-term follow-up of DTC? RECOMMENDATION 70 (A) In patients with a structural incomplete response to therapy, the serum TSH should be maintained below 0.1 mU/L indefinitely in the absence of specific contraindications. (B) In patients with a biochemical incomplete 33 nursece4less.com nursece4less.com nursece4less.com nursece4less.com response to therapy, the serum TSH should be maintained between 0.1and 0.5 mU/L, taking into account the initial ATA risk classification, Tg level, Tg trend over time, and risk of TSH suppression. (C) In patients who presented with high-risk disease but have an excellent (clinically and biochemically free of disease) or indeterminate response to therapy, consideration should be given to maintaining thyroid hormone therapy to achieve serum TSH levels of 0.1–0.5 mU/L for up to 5 years after which the degree of TSH suppression can by reduced with continued surveillance for recurrence. (D) In patients with an excellent (clinically and biochemically free of disease) or indeterminate response to therapy, especially those at low risk for recurrence, the serum TSH may be kept within the low reference range (0.5–2 mU/L). (E) In patients who have not undergone remnant ablation or adjuvant therapy who demonstrate an excellent or indeterminate response to therapy with a normal neck US, and low or undetectable suppressed serum Tg, and Tg or anti-Tg antibodies that are not rising, the serum TSH can be allowed to rise to the low reference range (0.5–2 mU/L). What is the optimal directed approach to patients with suspected structural neck recurrence? RECOMMENDATION 71 What is the surgical management of aerodigestive invasion? RECOMMENDATION 72 Administered activity of RECOMMENDATION 73 Therapeutic compartmental central and/or lateral neck dissection in a previously operated compartment, sparing uninvolved vital structures, should be performed for patients with biopsyproven persistent or recurrent disease for central neck nodes ‡8 mm and lateral neck nodes ≥10 mm in the smallest dimension that can be localized on anatomic imaging. When technically feasible, surgery for aerodigestive invasive disease is recommended in combination with RAI and/or EBRT. 34 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 131I for loco-regional or metastatic disease (A) Although there are theoretical advantages to dosimetric approaches to the treatment of loco-regional or metastatic disease, no recommendation can be made about the superiority of one method of RAI administration over another (empiric high activity versus blood and/or body dosimetry versus lesional dosimetry). (B) Empirically administered amounts of 131I exceeding 150 mCi that often potentially exceed the maximum tolerable tissue dose should be avoided in patients over age 70 years. Use of rhTSH (Thyrogen) to prepare patients for I therapy for loco-regional or metastatic disease RECOMMENDATION 74 There are currently insufficient outcome data to recommend rhTSH-mediated therapy for all patients with distant metastatic disease being treated with I. RECOMMENDATION 75 Recombinant human TSH–mediated therapy may be indicated in selected patients with underlying comorbidities making iatrogenic hypothyroidism potentially risky, in patients with pituitary disease whose serum TSH cannot be raised, or in patients in whom a delay in therapy might be deleterious. Such patients should be given the same or higher activity that would have been given had they been prepared with hypothyroidism or a dosimetrically determined activity Use of lithium in therapy I 131 RECOMMENDATION 76 Since there are no data that demonstrate a better outcome of patients treated with lithium as an adjunct to I therapies, the data are insufficient to recommend lithium therapy. Summary 35 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Thyroid cancer has been called an epidemic in the U.S., although this may represent an epidemic of diagnosis. A majority of thyroid cancers are found as a palpable and painless thyroid nodule on routine examination. When a thyroid nodule is diagnosed, it is important to first understand basic definition and guidelines to treat a thyroid nodule. The American Thyroid Association (ATA) has published guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. The above review of these guidelines provided the necessary information for a clinician involved in the diagnosis, management and treatment of thyroid diseases. Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation. Completing the study questions is optional and is NOT a course requirement. 1. Most thyroid tumors are 36 nursece4less.com nursece4less.com nursece4less.com nursece4less.com a. b. c. d. malignant and usually found on routine examination. painful, multinodular growths. benign and usually found on self-examination. benign and only found on autopsy. 2. True or False: Approximately 1% of new cancers diagnosed in the U.S., are cancers of the thyroid. a. True b. False 3. The sudden onset of pain associated with a thyroid tumor is associated with a. b. c. d. benign disease. Hürtle cell carcinoma. incidentalomas. papillary carcinomas. 4. Some experts consider the Hürtle cell carcinoma as a variant of a. b. c. d. follicular carcinoma. primary thyroid sarcoma. anaplastic carcinoma. medullary carcinoma. 5. __________________ are the most common thyroid cancer constituting approximately 80% of all thyroid malignancies. a. b. c. d. Primary thyroid sarcomas Follicular carcinomas Papillary carcinomas Anaplastic carcinomas 6. It is theorized that ___________________ may be associated with a greater risk of papillary carcinomas. a. b. c. d. toxic diffuse goiter Graves’ disease Hashimoto’s thyroiditis Plummer’s disease 37 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7. True or False: The incidence of thyroid cancer has increased significantly since the mid-1970s, with most of the increase due to incidents of papillary carcinomas. a. True b. False 8. ___________________ are associated with low iodine intake and are three times more common in women than in men. a. b. c. d. Spongiform sonographic patterns Anaplastic carcinomas Nodules that are purely cystic Follicular carcinomas 9. The _______________ is of greatest concern for malignancy in those patients over the age of 60 or in patients younger than 30 years. a. b. c. d. sudden onset of pain presence of solitary nodules presence of a discreet lesion presence of an incidentaloma 10. Since the mid-1970s, the incidence of thyroid cancer has a. b. c. d. doubled. actually declined. remained level. nearly tripled. 11. A radionuclide thyroid scan (preferably 123I) should be performed if a. b. c. d. the serum TSH is normal. the serum TSH is elevated. the serum TSH is subnormal. a patient presents with a thyroid nodule. 38 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12. True or False: The American Thyroid Association (ATA) recommends ultrasound screening since there is evidence that this could lead to reduced morbidity or mortality. a. True b. False 13. __________________ should be measured during the initial evaluation of a patient with a thyroid nodule. a. b. c. d. Serum thyroglobulin (Tg) Serum calcitonin Serum thyrotropin (TSH) None of the above 14. The American Thyroid Association (ATA) cannot recommend either for or against routine measurement of _____________ in patients with thyroid nodules. a. b. c. d. serum thyrotropin (TSH) serum thyroglobulin (Tg) anti-Tg antibodies serum calcitonin 15. The American Thyroid Association (ATA) recommends a fine needle aspiration with biopsy FNA(B) for a thyroid nodule ____________ with a high suspicion sonographic pattern. a. b. c. d. ≥1 cm in greatest dimension ≥0.5 cm in greatest dimension ≥1.5 cm in greatest dimension ≥1.75 cm in greatest dimension 16. Which of the following should be performed to survey the cervical lymph nodes in patients with known or suspected thyroid nodules? a. b. c. d. Radionuclide thyroid scan (preferably 123I) Thyroid sonography A serum TSH measurement Exploratory surgery 39 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17. True or False: Surgery should be considered for histopathologic diagnosis if the cytologically nondiagnostic nodule has a high suspicion sonographic pattern. a. True b. False 18. Thyroid nodule diagnostic fine needle aspiration with biopsy FNA(B) may be considered for nodules with sonographic pattern of a. ≥2 cm in greatest dimension with spongiform pattern. b. ≥1 cm in greatest dimension with high suspicion sonographic pattern. c. ≥1 cm in greatest dimension with intermediate suspicion sonographic pattern. d. ≥1.5 cm in greatest dimension with low suspicion sonographic pattern. 19. If a cytology result is diagnostic for primary thyroid malignancy, a. b. c. d. FNA(B) should be repeated with US guidance. a radionuclide thyroid scan (preferably 123I) is recommended. surgery is generally recommended. a serum thyrotropin (TSH) test is recommended. 20. How should multinodular thyroid glands (i.e., two or more clinically relevant nodules) be evaluated for malignancy? a. Patients should be evaluated only if ≥2 cm b. It is reasonable to aspirate the largest nodules (≥2 cm) c. Nodule sonographic patterns are not relevant with multinodular thyroid glands d. Multiple nodules do not require FNA 21. With nodules with high suspicion ultrasound pattern, ultrasound and US-guided FNA should be repeated a. b. c. d. within 24 months. within 12 months. on a case-by-case basis. every six months. 40 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22. True or False: If the nodule is benign on cytology, further immediate diagnostic studies or treatment are not required. a. True b. False 23. Patients with nodules with high suspicion ultrasound patterns should repeat ultrasound a. b. c. d. in 6–12 months. at 12–24 months. do not require routine sonographic follow-up. on a case-by-case basis. 24. What is the role of medical or surgical therapy for benign thyroid nodules in iodine sufficient populations? a. Benefits of routine TSH suppression therapy outweighs any harm. b. Surgery is recommended in all cases. c. Thyroid hormone therapy in patients with growing nodules that are benign on cytology is always recommended. d. Routine TSH suppression therapy is not recommended. 25. The role of molecular testing in guiding postoperative RAI use a. b. c. d. is recommended after total thyroidectomy. is recommended with low-risk level DTC patients. has yet to be established. is recommended with multifocal papillary microcarcinoma. 41 nursece4less.com nursece4less.com nursece4less.com nursece4less.com CORRECT ANSWERS: 1. Most thyroid tumors are d. benign and only found on autopsy. “Most thyroid tumors are benign and only found on autopsy.” 2. True or False: Approximately 1% of new cancers diagnosed in the U.S., are cancers of the thyroid. a. True “Approximately 1% of new cancers diagnosed in the U.S., are cancers of the thyroid.” 3. The sudden onset of pain associated with a thyroid tumor is associated with a. benign disease. “The sudden onset of pain associated with the tumor is associated with benign disease.” 4. Some experts consider the Hürtle cell carcinoma as a variant of a. follicular carcinoma. “Anaplastic carcinomas are found in 1-2% of cases while primary thyroid sarcomas and Hürtle cell carcinomas are the rarest forms, though some experts consider the Hürtle cell carcinoma as a variant of follicular carcinoma.” 5. __________________ are the most common thyroid cancer constituting approximately 80% of all thyroid malignancies. c. Papillary carcinomas “Papillary carcinomas are the most common thyroid cancer constituting approximately 80% of all thyroid malignancies.” 42 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6. It is theorized that ___________________ may be associated with a greater risk of papillary carcinomas. c. Hashimoto’s thyroiditis “Hashimoto’s thyroiditis may be associated with a greater risk of papillary carcinomas, but the association is not yet proven.” 7. True or False: The incidence of thyroid cancer has increased significantly since the mid-1970s, with most of the increase due to incidents of papillary carcinomas. a. True “Since the mid 1970’s, the incidence of thyroid cancer has nearly tripled, with most of the increase due to papillary carcinomas.” 8. ___________________ are associated with low iodine intake and are three times more common in women than in men. d. Follicular carcinomas “Follicular carcinomas are associated with low iodine intake and are three times more common in women than in men.” 9. The _______________ is of greatest concern for malignancy in those patients over the age of 60 or in patients younger than 30 years. b. presence of solitary nodules “Solitary nodules are of greatest concern for malignancy in those patients over the age of 60 or in patients younger than 30 years.” 10. Since the mid-1970s, the incidence of thyroid cancer has d. nearly tripled. “Since the mid 1970’s, the incidence of thyroid cancer has nearly tripled, with most of the increase due to papillary carcinomas.” 43 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11. A radionuclide thyroid scan (preferably 123I) should be performed if c. the serum TSH is subnormal. “Serum thyrotropin measurement: RECOMMENDATION 2 - (A) Serum thyrotropin (TSH) should be measured during the initial evaluation of a patient with a thyroid nodule. (B) If the serum TSH is subnormal, a radionuclide (preferably 123I) thyroid scan should be performed. (C) If the serum TSH is normal or elevated, a radionuclidescan should not be performed as the initial imaging evaluation.” 12. True or False: The American Thyroid Association (ATA) recommends ultrasound screening since there is evidence that this could lead to reduced morbidity or mortality. b. False “Screening people with familial follicular cell–derived DTC may lead to an earlier diagnosis of thyroid cancer, but the panel cannot recommend for or against US screening since there is no evidence that this would lead to reduced morbidity or mortality.” 13. __________________ should be measured during the initial evaluation of a patient with a thyroid nodule. c. Serum thyrotropin (TSH) “Serum thyrotropin measurement: RECOMMENDATION 2 - (A) Serum thyrotropin (TSH) should be measured during the initial evaluation of a patient with a thyroid nodule.” 14. The American Thyroid Association (ATA) cannot recommend either for or against routine measurement of _____________ in patients with thyroid nodules. d. serum calcitonin “Serum calcitonin measurement: RECOMMENDATION 4 - The panel cannot recommend either for or against routine measurement of serum calcitonin in patients with thyroid nodules.” 44 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15. The American Thyroid Association (ATA) recommends a fine needle aspiration with biopsy FNA(B) for a thyroid nodule ____________ with a high suspicion sonographic pattern. a. ≥1 cm in greatest dimension “Recommendations for diagnostic FNA of a thyroid nodule based on sonographic pattern: RECOMMENDATION 8 - I. Thyroid nodule diagnostic FNA(B) is recommended for: (A) Nodules ≥1 cm in greatest dimension with high suspicion sonographic pattern. (B) Nodules ≥1 cm in greatest dimension with intermediate suspicion sonographic pattern. (C) Nodules ≥1.5 cm in greatest dimension with low suspicion sonographic pattern. II. Thyroid nodule diagnostic FNA(B) may be considered for: (D) Nodules ≥2 cm in greatest dimension with very low suspicion sonographic pattern (i.e., spongiform). Observation without FNA is also a reasonable option. III. Thyroid nodule diagnostic FNA(B) is not required for: (E) Nodules that do not meet the above criteria. (F) Nodules that are purely cystic.” 16. Which of the following should be performed to survey the cervical lymph nodes in patients with known or suspected thyroid nodules? b. Thyroid sonography “Thyroid sonography: RECOMMENDATION 6 - Thyroid sonography with survey of the cervical lymph nodes should be performed in all patients with known or suspected thyroid nodules.” 17. True or False: Surgery should be considered for histopathologic diagnosis if the cytologically nondiagnostic nodule has a high suspicion sonographic pattern. a. True “Surgery should be considered for histopathologic diagnosis if the cytologically nondiagnostic nodule has a high suspicion sonographic pattern, growth of the nodule (>20% in two dimensions) is detected during US surveillance, or clinical risk factors for malignancy are present.” 45 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18. Thyroid nodule diagnostic fine needle aspiration with biopsy FNA(B) may be considered for nodules with sonographic pattern of a. ≥2 cm in greatest dimension with spongiform pattern. “Recommendations for diagnostic FNA of a thyroid nodule based on sonographic pattern: RECOMMENDATION 8 - … II. Thyroid nodule diagnostic FNA(B) may be considered for: (D) Nodules ≥2 cm in greatest dimension with very low suspicion sonographic pattern (i.e., spongiform). Observation without FNA is also a reasonable option.” 19. If a cytology result is diagnostic for primary thyroid malignancy, c. surgery is generally recommended. “Malignant cytology: RECOMMENDATION 12 - If a cytology result is diagnostic for primary thyroid malignancy, surgery is generally recommended.” 20. How should multinodular thyroid glands (i.e., two or more clinically relevant nodules) be evaluated for malignancy? b. It is reasonable to aspirate the largest nodules (≥2 cm) “How should multinodular thyroid glands (i.e., two or more clinically relevant nodules) be evaluated for malignancy?: RECOMMENDATION 21 - (A) Patients with multiple thyroid nodules ≥1 cm should be evaluated in the same fashion as patients with a solitary nodule ≥1 cm, excepting that each nodule that is >1 cm carries an independent risk of malignancy and therefore multiple nodules may require FNA. (B) When multiple nodules ≥1 cm are present, FNA should be performed preferentially based upon nodule sonographic pattern and respective size cutoff. (C) If none of the nodules has a high or moderate suspicion sonographic pattern, and multiple sonographically similar very low or low suspicion pattern nodules coalesce with no intervening normal parenchyma, the likelihood of malignancy is low and it is reasonable to aspirate the largest nodules (≥2 cm) or continue surveillance without FNA.” 46 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21. With nodules with high suspicion ultrasound pattern, ultrasound and US-guided FNA should be repeated b. within 12 months. “How should multinodular thyroid glands (i.e., two or more clinically relevant nodules) be evaluated for malignancy? … RECOMMENDATION 23 - Given the low false-negative rate of US-guided FNA cytology and the higher yield of missed malignancies based upon nodule sonographic pattern rather than growth, the follow-up of thyroid nodules with benign cytology diagnoses should be determined by risk stratification based upon US pattern. (A) Nodules with high suspicion US pattern: repeat US and US-guided FNA within 12 months. (B) Nodules with low to intermediate suspicion US pattern: repeat US at 12–24 months. If sonographic evidence of growth (20% increase in at least two nodule dimensions with a minimal increase of 2 mm or more than a 50% change in volume) or development of new suspicious sonographic features, the FNA could be repeated or observation continued with repeat US, with repeat FNA in case of continued growth. (C) Nodules with very low suspicion US pattern (including spongiform nodules): the utility of surveillance US and assessment of nodule growth as an indicator for repeat FNA to detect a missed malignancy is limited. If US is repeated, it should be done at ≥24 months.” 22. True or False: If the nodule is benign on cytology, further immediate diagnostic studies or treatment are not required. a. True “Benign cytology: RECOMMENDATION 11 - If the nodule is benign on cytology, further immediate diagnostic studies or treatment are not required.” 47 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23. Patients with nodules with high suspicion ultrasound patterns should repeat ultrasound a. in 6–12 months. “Follow-up for nodules that do not meet FNA criteria: RECOMMENDATION 24 - Nodules may be detected on US that do not meet criteria for FNA at initial imaging (Recommendation 8). The strategy for sonographic follow-up of these nodules should be based upon the nodule’s sonographic pattern. (A) Nodules with high suspicion US pattern: repeat US in 6–12 months….” 24. What is the role of medical or surgical therapy for benign thyroid nodules in iodine sufficient populations? d. Routine TSH suppression therapy is not recommended. “What is the role of medical or surgical therapy for benign thyroid nodules? RECOMMENDATION 25 - Routine TSH suppression therapy for benign thyroid nodules in iodine sufficient populations is not recommended. Though modest responses to therapy can be detected, the potential harm outweighs benefit for most patients.” 25. The role of molecular testing in guiding postoperative RAI use c. has yet to be established. “What is the role of molecular marker status in therapeutic RAI decision-making? The role of molecular testing in guiding postoperative RAI use has yet to be established; therefore, no molecular testing to guide postoperative RAI use can be recommended at this time.” 48 nursece4less.com nursece4less.com nursece4less.com nursece4less.com References Section The References below include published works and in-text citations of published works that are intended as helpful material for your further reading. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Zander, DA. (2014). Smoker, WR. Imaging of ectopic thyroid tissue and thyroglossal cysts. Radiographics, 34(1):37-50, 2014. Muller,R., Liu, Y-Y, Brent, G. (2014). Thyroid Hormone Regulation of Metabolism. Physiol Rev. Apr; 94(2): 355–382, 2014. Liu YY, Brent GA. (2010). Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends Endocrinol Metab. Mar; 21(3):166-73.2010. Bochukova E, et al. (2012). A mutation in the thyroid hormone receptor alpha gene. N Engl J Med. 2012 Jan 19; 366(3):243-9. Moran C, Chatterjee K. (2015). Resistance to thyroid hormone due to defective thyroid receptor alpha. Best Pract Res Clin Endocrinol Metab. Aug;29(4):647-57, 2015. Beaven, SW et al. (2013). Reciprocal regulation of hepatic and adipose lipogenesis by liver X receptors in obesity and insulin resistance. Cell Metab. Jul 2; 18(1):106-17, 2013. Senese R, Cioffi F, de Lange P, Goglia F, Lanni A. (2014). Thyroid: biological actions of 'nonclassical' thyroid hormones. J Endocrinol. Apr 22;221(2):R1-12, 2014. Hoang TD, Olsen CH, Mai VQ, Clyde PW, Shakir MK. (2013). Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab. 2013 May;98(5):198290. Wartofsky L. (2013). Combination L-T3 and L-T4 therapy for hypothyroidism. Curr Opin Endocrinol Diabetes Obes. 2013 Oct;20(5):460-6. Visser WE, Friesema EC, Visser TJ. (2011). Minireview: thyroid hormone transporters: the knowns and the unknowns. Mol Endocrinol. 2011 Jan; 25(1):1-14. Verge CF, et al. (2012). Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. J Clin Endocrinol Metab. 2012 Dec; 97(12):4515-23. Drigo, Rafael Arrojo, et al. (2013). Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone 49 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. signaling. Biochimica et Biophysica Acta (BBA)-General Subjects 1830.7 (2013): 3956-3964. Jansen, Peter LM, and Frank G. Schaap. (2015). Pituitary TSH controls bile salt synthesis. Journal of hepatology 62.5 (2015): 1005-1007. Song, Yongfeng, et al. (2015). Thyroid-stimulating hormone regulates hepatic bile acid homeostasis via SREBP-2/HNF4α/CYP7A1 axis. Journal of hepatology 62.5 (2015): 1171-1179. Pierre, Joseph F., et al. (2016). Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice. American Journal of Physiology-Gastrointestinal and Liver Physiology 311.2 (2016): G286-G304. Dentice, Monica, et al. (2013). The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochimica et Biophysica Acta (BBA)-General Subjects 1830.7 (2013): 3937-3945. Annerbo, Sylvia, and Johan Lökk. (2013). A clinical review of the association of thyroid stimulating hormone and cognitive impairment. ISRN endocrinology. Le, Trang N., Francesco S. Celi, and Edmond P. Wickham. (2014). SAT-0153: Thyroid Stimulating Hormone Levels Are Associated with Cardiometabolic Risk Factors in Euthyroid Adolescents. Kluge, Michael, et al. (2013). Ghrelin suppresses nocturnal secretion of luteinizing hormone (LH) and thyroid stimulating hormone (TSH) in patients with major depression. Journal of psychiatric research 47.9 (2013): 1236-1239. Roelfsema, Ferdinand, and Johannes D. Veldhuis (2013). Thyrotropin secretion patterns in health and disease. Endocrine reviews 34.5 (2013): 619-657. Lopez M, Alvarez CV, Nogueiras R, Dieguez C. (2013). Energy balance regulation by thyroid hormones at central level. Trends Mol Med 19: 418–427. Lopez, M. et al. (2010) Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat. Med. 16, 1001–1008. Cannon, B. and Nedergaard, J. (2010) Thyroid hormones: igniting brown fat via the brain. Nat. Med. 16, 965–967 Astapova, I., & Hollenberg, A. N. (2013). The In Vivo Role of Nuclear Receptor Corepressors in Thyroid Hormone Action. Biochimica et Biophysica Acta, 1830(7), 3876–3881. Lopes, M. et al, (2010) Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med., 12, 1001-1008. 50 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. Duntas, Leonidas H., and Bernadette Biondi (2013). The interconnections between obesity, thyroid function, and autoimmunity: the multifold role of leptin. Thyroid 23.6 (2013): 646-653. Perello M, et al (2010). Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level. Am J Physiol Endocrinol Metab 299: E976–E989. Rosenbaum, M., Leibel, RK. (2010). Adaptive thermogenesis in humans. Int J Obes (Lond). 2010 Oct; 34(0 1): S47–S55. Castillo M, Hall JA, Correa-Medina M, Ueta C, Kang HW, Cohen DE, Bianco AC. (2011). Disruption of thyroid hormone activation in type 2 deiodinase knockout mice causes obesity with glucose intolerance and liver steatosis only at thermoneutrality. Diabetes 60: 1082–1089. Karmisholt J, Andersen S, Laurberg P. (2011). Weight loss after therapy of hypothyroidism is mainly caused by excretion of excess body water associated with myxoedema. J Clin Endocrinol Metab 96: E99–103. Celi FS, Zemskova M, Linderman JD, Smith S, Drinkard B, Sachdev V, Skarulis MC, Kozlosky M, Csako G, Costello R, Pucino F. (2011). Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine. J Clin Endocrinol Metab 96: 3466–3474. Santiago LA, Santiago DA, Faustino LC, Cordeiro A, Lisboa PC, Wondisford FE, Pazos-Moura CC, Ortiga-Carvalho TM. (2011). The Delta337T mutation on the TRbeta causes alterations in growth, adiposity, and hepatic glucose homeostasis in mice. J Endocrinol 211: 39–46. Chakar, L. et al. (2016). Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Medicine, 14:150. Sinha, Rohit A., Brijesh K. Singh, and Paul M. Yen. (2014). Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism." Trends in Endocrinology & Metabolism 25.10: 538545. Booms S, Hill E, Kulhanek L, Vredeveld J, Gregg B. (2016). Iodine Deficiency and Hypothyroidism From Voluntary Diet Restrictions in the US: Case Reports. Pediatrics. Jun;137(6). Lee KW, Shin D, Cho MS, Song WO. (2016). Food Group Intakes as Determinants of Iodine Status among US Adult Population. Nutrients. 8(6). pii: E325. Pearce EN, Andersson M, Zimmermann MB. (2013). Global iodine nutrition: Where do we stand in 2013? Thyroid. 23(5):523-8. 51 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. Ershow, AG., Goodman, G., Coates, PM., Swanson, CA. (2016). Assessing iodine intake, iodine status, and the effects of maternal iodine supplementation: introduction to articles arising from 3 workshops held by the NIH Office of Dietary Supplements. Am J Clin Nutr. 104 (Supplement 3) 859S-863S. Wiltshire JJ; Drake TM; Uttley L; Balasubramanian SP. (2016). Systematic Review of Trends in the Incidence Rates of Thyroid Cancer. Thyroid. 26(11):1541-1552. Grant EG, et al (2015). Thyroid Ultrasound Reporting Lexicon: White Paper of the ACR Thyroid Imaging, Reporting and Data System (TIRADS) Committee. J Am Coll Radiol. Dec;12 (12 Pt A):1272-9 Yu D, Han Y, Chen T. (2014). Contrast-enhanced ultrasound for differentiation of benign and malignant thyroid lesions: metaanalysis. Otolaryngol Head Neck Surg. Dec; 151(6):909-15. De Leo, Simone, Sun Y Lee, and Lewis E Braverman. (2016). “Hyperthyroidism.” Lancet (London, England) 388.10047 (2016): 906–918. Tomer, Y. (2014). MECHANISMS OF AUTOIMMUNE THYROID DISEASES: FROM GENETICS TO EPIGENETICS. Annu Rev Pathol. 9: 147–156. Stefan M, et al. (2011). Novel variant of thyroglobulin promoter triggers thyroid autoimmunity through an epigenetic interferon alpha-modulated mechanism. J Biol Chem. 286(36):31168-79. Tomer Y, Hasham A, Davies TF, Stefan M, Concepcion E, Keddache M, Greenberg DA. (2013). Fine mapping of loci linked to autoimmune thyroid disease identifies novel susceptibility genes. J Clin Endocrinol Metab. 98(1):E144-52. Kanherkar, Riya R., Naina Bhatia-Dey, and Antonei B. Csoka. (2014). “Epigenetics across the Human Lifespan.” Frontiers in Cell and Developmental Biology 2:49. Hargreaves, CE., et al. (2013). Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves' disease. J Immunol. Vondra, K., Starka, L., Hampl, R. (2015). Vitamin D and thyroid diseases. Physiol Res. 64 Suppl 2:S95-S100. Duntas, LH. (2015). The Role of Iodine and Selenium in Autoimmune Thyroiditis. Horm Metab Res. 47(10):721-6. Khong JJ, McNab AA, Ebeling PR, Craig JE, Selva D. (2016). Pathogenesis of thyroid eye disease: review and update on molecular mechanisms. Br J Ophthalmol. 100(1):142-50 Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS. (2010). Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev. 2010 Jan 20; (1):CD003420. 52 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. Mohlin E, Filipsson Nyström H, Eliasson M. (2014). Long-term prognosis after medical treatment of Graves' disease in a northern Swedish population 2000-2010. Eur J Endocrinol. 170(3):419-27. Vaidya, Bijay, and S. H. Pearce. (2014). Diagnosis and management of thyrotoxicosis. BMJ 349: g5128. Genovese BM, Noureldine SI, Gleeson EM, Tufano RP, Kandil E. (2013). What is the best definitive treatment for Graves' disease? A systematic review of the existing literature. Ann Surg Oncol. 20(2):660-7. Bogazzi, F., et al. (2012). Amiodarone and the thyroid: a 2012 update. Journal of endocrinological investigation 35.3: 340-348. Hasham, Alia, et al. (2013). Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways." Journal of autoimmunity 44: 61-70. Douglas, RS., et al (2016). American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 26(10): 1343-1421 Rajagopalan, V. et al. (2016). Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects. PLoS One. 11(3): e0151413 Liu, J. et al (2016). Low T3 syndrome is a strong predictor of poor outcomes in patients with community-acquired pneumonia. Sci Rep. 6: 22271. Hayashi, T. et al (2016). Subclinical hypothyroidism is an independent predictor of adverse cardiovascular outcomes in patients with acute decompensated heart failure. ESC Heart Fail. 3(3): 168–176. Van den Berghe, G. (2014). Non-Thyroidal Illness in the ICU: A Syndrome with Different Faces. Thyroid. 2014 Oct 1; 24(10): 1456–1465. DeGroot, L, et al (2010). Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline. Accessed at: http://press.endocrine.org/doi/full/10.1210/jc.2011-2803 Stott, DJ. et al (2014). The Dilemma of Treating Subclinical Hypothyroidism: Risk that Current Guidelines Do More Harm than Good. European Thyroid J., 3:137-138. Garber, JR., et al (2012). Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid, 22 (12. 53 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. Chiong, YV., Bammerlin, E., Mariash, CN. (2015). Development of an objective tool for the diagnosis of myxedema coma. Translational Research 166.3: 233-243. Sarker, Imran, et al. (2016). AUTOIMMUNE POLYENDOCRINE SYNDROME TYPE 1: A RARE CASE REPORT AND REVIEW OF THE LITERATURE." AACE Clinical Case Reports. Cutolo, Maurizio. (2014). Autoimmune polyendocrine syndromes. Autoimmunity reviews 13.2: 85-89. Maturu, Amita, Aaron Michels, and Boris Draznin. (2014). Multiple Disease Associations in Autoimmune Polyglandular Syndrome Type II. Endocrine Practice 20.12: e250-e255. Sathananthan, Matheni, et al. (2013). Sellar meningiomas: an endocrinologic perspective. Pituitary 16.2: 182-188. Guitelman, M., et al. (2013). Primary empty sella (PES): a review of 175 cases. Pituitary 16.2: 270-274. Davies, Louise, and H. Gilbert Welch. (2014). Current thyroid cancer trends in the United States." JAMA Otolaryngology–Head & Neck Surgery 140.4: 317-322. Witt, Benjamin L., and Robert L. Schmidt. (2013). Rapid onsite evaluation improves the adequacy of fine-needle aspiration for thyroid lesions: a systematic review and meta-analysis. Thyroid 23.4: 428-435. Nagarajan, Neeraja, et al. (2015). Conventional smears versus liquid-based preparations for thyroid fine-needle aspirates: a systematic review and meta-analysis." Journal of the American Society of Cytopathology 4.5: 253-260. Brito, Juan P., et al. (2013). The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic review and meta-analysis. The Journal of Clinical Endocrinology & Metabolism 99.4: 1253-1263. Haugen, Bryan R., et al. (2016) 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. Thyroid 26.1: 1-133. Büyükgebiz A. (2013). Newborn Screening for Congenital Hypothyroidism. Journal of Clinical Research in Pediatric Endocrinology; 5(Suppl 1):8-12. DeGroot, LJ., Jameson, JL. (2013). Endocrinology Adult and Pediatric: The Thyroid Gland, Elsevier Health Sciences. Kosiak W, Piskunowicz M, Świętoń D, Batko T, Kaszubowski M. (2015). An additional ultrasonographic sign of Hashimoto’s lymphocytic thyroiditis in children. Journal of Ultrasonography. 15(63):349-357. doi:10.15557/JoU.2015.0032. 54 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. Kim, DW., et al. (2010). Sonographic Differentiation of Asymptomatic Diffuse Thyroid Disease from Normal Thyroid: A Prospective Study. AJNR. 31: 1956-1960. Seningen JL; Nassar A; Henry MR. (2012). Correlation of thyroid nodule fine-needle aspiration cytology with corresponding histology at Mayo Clinic, 2001-2007: an institutional experience of 1,945 cases. Diagn Cytopathol. 40 Suppl 1:E27-32. Albuja-Cruz MB; Goldfarb M; Gondek SS; Allan BJ; Lew JI. (2013). Reliability of fine-needle aspiration for thyroid nodules greater than or equal to 4 cm. J Surg Res.; 181(1):6-10. Lee DH; Baek HJ; Kook H; Yoon TM; Lee JK; Lim SC. (2014). Clinical value of fine needle aspiration cytology in pediatric cervical lymphadenopathy patients under 12-years-of-age. Int J Pediatr Otorhinolaryngol. 78(1):79-81. Nikiforov, YE., Yip, L., Nikiforova, MN. (2013). New Strategies in Diagnosing Cancer in Thyroid Nodules: Impact of Molecular Markers. Clin Can Res, 19(9), 2283-2288. Moura MM, Cavaco BM, Pinto AE, Leite V. (2011). High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab;96:E863–8. Devdhar M, Drooger R, Pehlivanova M, Singh G, Jonklaas J. (2011). Levothyroxine replacement doses are affected by gender and weight, but not age. Thyroid;21:821-827. Wartofsky, Leonard. (2013). Combination L-T3 and L-T4 therapy for hypothyroidism. Current Opinion in Endocrinology, Diabetes and Obesity 20.5: 460-466. Celi FS, Zemskova M, Linderman JD, Smith S, Drinkard B, Sachdev V, Skarulis MC, Kozlosky M, Csako G, Costello R, Pucino F (2011). Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine. J Clin Endocrinol Metab 96:3466 –3474. Kraut, Eyal, and Pendar Farahani. (2015). A Systematic Review of Clinical Practice Guidelines’ Recommendations on Levothyroxine Therapy Alone versus Combination Therapy (LT4 plus LT3) for Hypothyroidism." Clinical & Investigative Medicine 38.6: 305-313. Pepper GM, Casanova-Romero PY (2014) Conversion to Armour Thyroid from Levothyroxine Improved Patient Satisfaction in the Treatment of Hypothyroidism. J Endocrinol Diabetes Obes 2(3): 1055. Hoang, Thanh D., et al. (2013). Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. 55 nursece4less.com nursece4less.com nursece4less.com nursece4less.com The Journal of Clinical Endocrinology & Metabolism 98.5: 19821990. 91. Wang, Junqi, and Lan Qin (2016). Radioiodine therapy versus antithyroid drugs in Graves’ disease: a meta-analysis of randomized controlled trials." The British journal of radiology: 20160418. 92. Sisson, The American Thyroid Association Taskforce on Radioiodine Safety; James C., et al. (2011). Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I: practice recommendations of the American Thyroid Association." Thyroid 21.4: 335-346. 93. Drutel, Anne, Françoise Archambeaud, and Philippe Caron. (2013). Selenium and the thyroid gland: more good news for clinicians. Clinical endocrinology 78.2 (2013): 155-164. 94. Marcocci, C., Kahaly, G.J., Krassas, G.E. et al. (2011) Selenium and the course of mild Graves’ orbitopathy. The New England Journal of Medicine, 364, 1920–1931. 95. Pludowski, Pawel, et al. (2013). Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence." Autoimmunity reviews 12.10: 976989. 96. Zhang, Hong, Lingyun Liang, and Zhongjian Xie. (2014). Low Vitamin D status is associated with increased thyrotropinreceptor antibody titer in graves disease." Endocrine Practice 21.3: 258-263. 97. D'Aurizio, Federica, et al. (2015). Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases?." Autoimmunity reviews 14.5: 363-369. 98. Tripkovic L, Lambert H, Hart K, et al. (2012). Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25hydroxyvitamin D status: a systematic review and metaanalysis. Am J Clin Nutr;95(6):1357-1364 99. Manzel A, Muller DN, Hafler DA, Erdman SE, Linker RA, Kleinewietfeld M. (2014). Role of “Western Diet” in Inflammatory Autoimmune Diseases. Current allergy and asthma reports;14(1):404. doi:10.1007/s11882-013-0404-6. 100. Procaccini C, Carbone F, Galgani M, La Rocca C, De Rosa V, Cassano S, Matarese G. (2011). Obesity and susceptibility to autoimmune diseases. Expert Rev Clin Immunol. 7(3):287-94. 101. Ezzati, Majid, and Elio Riboli (2013). Behavioral and dietary risk factors for noncommunicable diseases." New England Journal of Medicine 369.10: 954-964. 56 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 102. Ruiz-Núñez, Begoña, et al. (2013). Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context. The Journal of nutritional biochemistry 24.7: 1183-1201. 103. LaFranchi, Stephen (2016). Thyroid physiology and screening in preterm infants. UpToDate. Retrieved online at https://www.uptodate.com/contents/thyroid-physiology-andscreening-in-preterminfants?source=search_result&search=thyroid%20testing%20in %20neonates&selectedTitle=1~150 104. Powers, C.N. (1998). Diagnosis of Infectious Diseases: a Cytopathologist’s Perspective. Clinical Microbiology Perspective. American Society For Microbiology. Retrieved online at http://cmr.asm.org/content/11/2/341.full. 105. Wang, T.S., et al (2016). Initial thyroidectomy. UpToDate. Retrieved online at https://www.uptodate.com/contents/initialthyroidectomy?source=search_result&search=thyroid%20surger y&selectedTitle=1~150. 106. Davies, T. (2016). Treatment of Graves' orbitopathy (ophthalmopathy). UpToDate. Retrieved online at https://www.uptodate.com/contents/treatment-of-gravesorbitopathyophthalmopathy?source=search_result&search=eye%20surgery %20graves&selectedTitle=1~150. 107. Brent, G.A. (2016). Thyroid hormone action. UpToDate. https://www.uptodate.com/contents/thyroid-hormoneaction?source=search_result&search=skin%20and%20thyroid&s electedTitle=1~150. 57 nursece4less.com nursece4less.com nursece4less.com nursece4less.com The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NurseCe4Less.com. The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare. The information provided in this course is general in nature, and is not designed to address any specific situation. This publication in no way absolves facilities of their responsibility for the appropriate orientation of healthcare professionals. Hospitals or other organizations using this publication as a part of their own orientation processes should review the contents of this publication to ensure accuracy and compliance before using this publication. 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