Thyroid Nodules: Past, Present, and Future.

BACKGROUND: Over the past millennia, the evaluation and management of thyroid nodules has essentially remained the same with thyroidectomy as the only reliable method to identify malignancy. However, in the last 30 years, technological advances have significantly improved diagnostic management of thyroid nodules. Advances in imaging have allowed development of a reliable risk- based stratification system to identify nodules at increased risk of malignancy. At the same time, sensitive imaging has caused collateral damage to the degree that we are now identifying and treating many small, low risk nodules with little to no clinical relevance. OBJECTIVE: To review the history of thyroid nodule evaluation with emphasis on recent changes and future pathways. METHODS: Literature review and discussion. RESULTS: Thyroid ultrasound remains the best initial method to evaluate the thyroid gland for nodules. Different risk-of-malignancy protocols have been developed and introduced by different societies, reporting methods have been developed and improved each, with goals of improving the ability to recognize nodules requiring further intervention and minimizing excessive monitoring of those who do not. Once identified, cytological evaluation of nodules further enhances malignancy identification with molecular markers assisting in ruling out malignancies in indeterminate nodules preventing unneeded intervention. And all societies have urged avoidance of overdiagnosis and overtreatment of low-risk cancers of little to no clinical relevance. CONCLUSION: In this review, we describe advancements in nodule evaluation and management, while emphasizing caution in overdiagnosing and overtreating low-risk lesions without clinical importance.

American Association of Clinical Endocrinology And Associazione Medici Endocrinologi Thyroid Nodule Algorithmic Tool.

OBJECTIVE: The first edition of the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi Guidelines for the Diagnosis and Management of Thyroid Nodules was published in 2006 and updated in 2010 and 2016. The American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi multidisciplinary thyroid nodules task force was charged with developing a novel interactive electronic algorithmic tool to evaluate thyroid nodules. METHODS: The Thyroid Nodule App (termed TNAPP) was based on the updated 2016 clinical practice guideline recommendations while incorporating recent scientific evidence and avoiding unnecessary diagnostic procedures and surgical overtreatment. This manuscript describes the algorithmic tool development, its data requirements, and its basis for decision making. It provides links to the web-based algorithmic tool and a tutorial. RESULTS: TNAPP and TI-RADS were cross-checked on 95 thyroid nodules with histology-proven diagnoses. CONCLUSION: TNAPP is a novel interactive web-based tool that uses clinical, imaging, cytologic, and molecular marker data to guide clinical decision making to evaluate and manage thyroid nodules. It may be used as a heuristic tool for evaluating and managing patients with thyroid nodules. It can be adapted to create registries for solo practices, large multispecialty delivery systems, regional and national databases, and research consortiums. Prospective studies are underway to validate TNAPP to determine how it compares with other ultrasound-based classification systems and whether it can improve the care of patients with clinically significant thyroid nodules while reducing the substantial burden incurred by those who do not benefit from further evaluation and treatment.

THYROID AND AGING.

OBJECTIVE: Review physiologic thyroid function changes with aging and emphasize careful interpretation of tests in the aging population. METHODS: Literature review. RESULTS: Using age-specific thyroid-stimulating hormone (TSH) reference ranges should minimize or avoid the unnecessary diagnosis of thyroid disease in elderly patients. Subclinical thyroid dysfunction and abnormal TSH with normal thyroid levels may improve with time, so careful monitoring of thyroid function is recommended. Overt thyroid disease should always be treated. CONCLUSION: Clinical judgement is always warranted to decide how and when to treat subclinical thyroid disease in the elderly. ABBREVIATIONS: FT4 = free thyroxine; rT3 = reverse triiodothyronine; T3 = triiodothyronine; T4 = thyroxine; TFT = thyroid function test; TSH = thyroid-stimulating hormone.

Clinical outcomes of patients with hypothyroidism undergoing percutaneous coronary intervention.

AIMS: The aim of this study was to investigate the association between hypothyroidism and major adverse cardiovascular and cerebral events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Two thousand four hundred and thirty patients who underwent PCI were included. Subjects were divided into two groups: hypothyroidism (n = 686) defined either as a history of hypothyroidism or thyroid-stimulating hormone (TSH) ≥5.0 mU/mL, and euthyroidism (n = 1744) defined as no history of hypothyroidism and/or 0.3 mU/mL ≤ TSH < 5.0 mU/mL. Patients with hypothyroidism were further categorized as untreated (n = 193), or those taking thyroid replacement therapy (TRT) with adequate replacement (0.3 mU/mL ≤ TSH < 5.0 mU/mL, n = 175) or inadequate replacement (TSH ≥ 5.0 mU/mL, n = 318). Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. Median follow-up was 3.0 years (interquartile range, 0.5-7.0). After adjustment for covariates, the risk of MACCE and its constituent parts was higher in patients with hypothyroidism compared with those with euthyroidism (MACCE: HR: 1.28, P = 0.0001; myocardial infarction (MI): HR: 1.25, P = 0.037; heart failure: HR: 1.46, P = 0.004; revascularization: HR: 1.26, P = 0.0008; stroke: HR: 1.62, P = 0.04). Compared with untreated patients or those with inadequate replacement, adequately treated hypothyroid patients had a lower risk of MACCE (HR: 0.69, P = 0.005; HR: 0.78, P = 0.045), cardiac death (HR: 0.43, P = 0.008), MI (HR: 0.50, P = 0.0004; HR: 0.60, P = 0.02), and heart failure (HR: 0.50, P = 0.02; HR: 0.52, P = 0.017). CONCLUSION: Hypothyroidism is associated with a higher incidence of MACCE compared with euthyroidism in patients undergoing PCI. Maintaining adequate control on TRT is beneficial in preventing MACCE.

ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS STATEMENT-REPLACEMENT THERAPY FOR PRIMARY HYPOTHYROIDISM: A BRIEF GUIDE FOR CLINICAL PRACTICE.

OBJECTIVE: Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled. METHODS: The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed. RESULTS: LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy. CONCLUSION: LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE.

Thyroid nodules are detected in up to 50 to 60% of healthy subjects. Most nodules do not cause clinically significant symptoms, and as a result, the main challenge in their management is to rule out malignancy, with ultrasonography (US) and fine-needle aspiration (FNA) biopsy serving as diagnostic cornerstones. The key issues discussed in these guidelines are as follows: (1) US-based categorization of the malignancy risk and indications for US-guided FNA (henceforth, FNA), (2) cytologic classification of FNA samples, (3) the roles of immunocytochemistry and molecular testing applied to thyroid FNA, (4) therapeutic options, and (5) follow-up strategy. Thyroid nodule management during pregnancy and in children are also addressed. On the basis of US features, thyroid nodules may be categorized into 3 groups: low-, intermediate-and high-malignancy risk. FNA should be considered for nodules ≤10 mm diameter only when suspicious US signs are present, while nodules ≤5 mm should be monitored rather than biopsied. A classification scheme of 5 categories (nondiagnostic, benign, indeterminate, suspicious for malignancy, or malignant) is recommended for the cytologic report. Indeterminate lesions are further subdivided into 2 subclasses to more accurately stratify the risk of malignancy. At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data, US signs, elastographic pattern, or results of other imaging techniques to improve the management of these lesions. Most thyroid nodules do not require any treatment, and levothyroxine (LT4) suppressive therapy is not recommended. Percutaneous ethanol injection (PEI) should be the first-line treatment option for relapsing, benign cystic lesions, while US-guided thermal ablation treatments may be considered for solid or mixed symptomatic benign thyroid nodules. Surgery remains the treatment of choice for malignant or suspicious nodules. The present document updates previous guidelines released in 2006 and 2010 by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Associazione Medici Endocrinologi (AME).

A Computer-Interpretable Version of the AACE, AME, ETA Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules.

OBJECTIVE: Clinical practice guidelines (CPGs) could have a more consistent and meaningful impact on clinician behavior if they were delivered as electronic algorithms that provide patient-specific advice during patient-physician encounters. We developed a computer-interpretable algorithm for U.S. and European users for the purpose of diagnosis and management of thyroid nodules that is based on the "AACE, AME, ETA Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules," a narrative, evidence-based CPG. METHODS: We initially employed the guideline-modeling language GuideLine Interchange Format, version 3, known as GLIF3, which emphasizes the organization of a care algorithm into a flowchart. The flowchart specified the sequence of tasks required to evaluate a patient with a thyroid nodule. PROforma, a second guideline-modeling language, was then employed to work with data that are not necessarily obtained in a rigid flowchart sequence. Tallis-a user-friendly web-based "enactment tool"- was then used as the "execution engine" (computer program). This tool records and displays tasks that are done and prompts users to perform the next indicated steps. The development process was iteratively performed by clinical experts and knowledge engineers. RESULTS: We developed an interactive web-based electronic algorithm that is based on a narrative CPG. This algorithm can be used in a variety of regions, countries, and resource-specific settings. CONCLUSION: Electronic guidelines provide patient-specific decision support that could standardize care and potentially improve the quality of care. The "demonstrator" electronic thyroid nodule guideline that we describe in this report is available at http://demos.deontics.com/trace-review-app (username: reviewer; password: tnodule1). The demonstrator must be more extensively "trialed" before it is recommended for routine use.

Risk of malignancy in thyroid nodules with increased 11C-Choline uptake detected incidentally on PET/CT: A diagnostic accuracy study.

PURPOSE: The purpose was to evaluate the pathological nature of focal thyroid uptake seen in 11C-Choline PET/CT performed for prostate cancer. MATERIAL AND METHODS: The study was IRB-approved. All 11C-Choline PET/CT exam reports for studies performed between January 01, 2018, and July 30, 2021, in male patients with prostate cancer in our institution were retrospectively reviewed. Exams with "focal thyroid uptake" on their final report were selected. Patients with surgery or ablation in the thyroid prior to the PET/CT, proven parathyroid adenomas or absent thyroid ultrasound were excluded. Repeated PET/CT exams of same patient were excluded. PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Available thyroid ultrasound images, cytology and pathology reports were reviewed. Statistical analyses were performed. RESULTS: Out of 10,047 sequential 11C-Choline PET/CT studies, 318 reports included "focal thyroid uptake." About 128 of these studies were repeat exams and were excluded. Additional 87 patients were excluded, because the uptake was determined to be adjacent, rather than confined to the thyroid gland. Out of the remaining 103 patients, 74 patients had focal thyroid uptake and concurrent thyroid sonographic evaluation. Out of the 74 focal uptakes evaluated with ultrasound, 21 were presumed benign thyroid nodules based on the ultrasound and 53 had further evaluation with biopsy. Sixty three nodules were benign (21 presumed benign on ultrasound and 42 cytology or surgical pathology-proven), 9 nodules were malignant and 2 remained indeterminate. There was no significant difference between the SUVs of the benign and malignant groups (P > .3). CONCLUSION: In this retrospective study of patients with prostate cancer who underwent 11C-Choline PET/CT, we identified a group of patients who underwent thyroid ultrasound for incidental finding of focal 11C-Choline thyroid uptake. Incidence of malignancy in this group was 12%. Therefore, further investigation with ultrasound and possibly ultrasound-guided biopsy may be warranted when a choline avid thyroid nodule is found incidentally on choline PET.

Global, regional, and national burden and quality of care index (QCI) of thyroid cancer: A systematic analysis of the Global Burden of Disease Study 1990-2017.

BACKGROUND: Thyroid cancer (TC) is the most prevalent malignancy of the endocrine system. Over the past decades, TC incidence rates have been increasing. TC quality of care (QOC) has yet to be well understood. We aimed to assess the quality of TC care and its disparities. METHODS: We retrieved primary epidemiologic indices from the Global Burden of Disease (GBD) 1990-2017 database. We calculated four secondary indices of mortality to incidence ratio, disability-adjusted life years (DALYs) to prevalence ratio, prevalence to incidence ratio, and years of life lost (YLLs) to years lived with disability (YLD) ratio and summarized them by the principal component analysis (PCA) to produce one unique index presented as the quality of care index (QCI) ranged between 0 and 100, to compare different scales. The gender disparity ratio (GDR), defined as the QCI for females divided by QCI for males, was applied to show gender inequity. RESULTS: In 2017, there were 255,489 new TC incident cases (95% uncertainty interval [UI]: 245,709-272,470) globally, which resulted in 41,235 deaths (39,911-44,139). The estimated global QCI was 84.39. The highest QCI was observed in the European region (93.84), with Italy having the highest score (99.77). Conversely, the lowest QCI was seen in the African region (55.09), where the Central African Republic scored the lowest (13.64). The highest and lowest socio-demographic index (SDI) regions scored 97.27 and 53.85, respectively. Globally, gender disparity was higher after the age of 40 years and in favor of better care in women. CONCLUSION: TC QOC is better among those countries of higher socioeconomic status, possibly due to better healthcare access and early detection in these regions. Overall, the quality of TC care was higher in women and younger adults. Countries could adopt the introduced index of QOC to investigate the quality of provided care for different diseases and conditions.

American Association of Clinical Endocrinology And Associazione Medici Endocrinologi Thyroid Nodule Algorithmic Tool.

OBJECTIVE: The first edition of the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi Guidelines for the Diagnosis and Management of Thyroid Nodules was published in 2006 and updated in 2010 and 2016. The American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi multidisciplinary thyroid nodules task force was charged with developing a novel interactive electronic algorithmic tool to evaluate thyroid nodules. METHODS: The Thyroid Nodule App (termed TNAPP) was based on the updated 2016 clinical practice guideline recommendations while incorporating recent scientific evidence and avoiding unnecessary diagnostic procedures and surgical overtreatment. This manuscript describes the algorithmic tool development, its data requirements, and its basis for decision making. It provides links to the web-based algorithmic tool and a tutorial. RESULTS: TNAPP and TI-RADS were cross-checked on 95 thyroid nodules with histology-proven diagnoses. CONCLUSION: TNAPP is a novel interactive web-based tool that uses clinical, imaging, cytologic, and molecular marker data to guide clinical decision making to evaluate and manage thyroid nodules. It may be used as a heuristic tool for evaluating and managing patients with thyroid nodules. It can be adapted to create registries for solo practices, large multispecialty delivery systems, regional and national databases, and research consortiums. Prospective studies are underway to validate TNAPP to determine how it compares with other ultrasound-based classification systems and whether it can improve the care of patients with clinically significant thyroid nodules while reducing the substantial burden incurred by those who do not benefit from further evaluation and treatment.

Thyroid nodules: clinical importance, assessment, and treatment.

In the general population, thyroid nodules are found in 5% by palpation and in 50% by ultrasonography (US). Initial evaluation of nodules should include serum thyroid-stimulating hormone measurement, fine-needle aspiration (FNA) biopsy, and US. Thyroid micronodules are being detected with increasing frequency and are currently evaluated by US-FNA. Routine measurement of serum calcitonin and thyroglobulin and FNA rebiopsy are not recommended. Cytologically benign thyroid nodules should be followed rather than treated. Novel treatment options including iodine 131, percutaneous ethanol injection, and percutaneous laser thermal ablation have specific indications, advantages, and adverse effects.

A Systematic Review of the Methods of Diagnostic Accuracy Studies of the Afirma Gene Expression Classifier.

BACKGROUND: The Afirma® Gene Expression Classifier (GEC) risk stratifies The Bethesda System for the Reporting of Thyroid Cytopathology class III/IV (indeterminate) thyroid nodules (ITNs) as suspicious for malignancy or benign. Several authors have published studies describing the diagnostic accuracy of the GEC. However, the quality of these methods has not been rigorously examined. SUMMARY: In this study, MEDLINE and EMBASE were searched for studies published between January 1, 2010, and June 30, 2016, examining the sensitivity, specificity, negative predictive value, and positive predictive value of the GEC. The Quality of Diagnostic Accuracy Studies 2 was customized to evaluate the methods of included studies in each of four domains: nodule selection, index test execution, reference standard assignment, and flow and timing. Signaling questions were used to identify sources of potential bias in calculation of diagnostic accuracy, and issues of applicability were assessed. Three panelists applied the Quality of Diagnostic Accuracy Studies 2 tool to each study included, and divergence was resolved in conference. In 12 studies evaluated, the most common methodologic flaw was lack of reference standard diagnosis assignment to un-excised GEC-benign ITNs. Exclusion of these ITNs from the analyses resulted in unreliable estimates of specificity and negative predictive value. Other flaws identified included restriction to ITNs that had already been selected for referral for thyroidectomy or lobectomy. CONCLUSIONS: Future studies should define and assign a "true negative" label to GEC-benign nodules that do not develop malignant signs or symptoms during a pre-specified period of follow-up, and these nodules should be included in calculations of diagnostic accuracy.

Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review.

PURPOSE: Levothyroxine (LT4) is a drug with a narrow therapeutic index, applied in small amounts (micrograms), which makes interactions in the absorption phase clinically significant. The main aim of this article was to review and present the latest information on factors that affect the gastrointestinal absorption of this drug. METHODS: Relevant data were collected by using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words levothyroxine and absorption. Searches were not limited to specific publication types, study designs, dates, or languages. The reports were highly variable in the amount of information provided regarding study design and methods. Because of the heterogeneity of studies, no statistical analysis was performed. FINDINGS: Many gastrointestinal disorders, such as celiac disease, atrophic gastritis, lactose intolerance, and Helicobacter pylori infection, may impede the absorption of levothyroxine. During treatment of these disorders, it is necessary to monitor serum thyroid-stimulating hormone and free T4 values to reduce the risk of developing iatrogenic hyperthyroidism. Soybeans and coffee have the greatest impact on the reduction of absorption, whereas vitamin C has the ability to increase it. Conversely, the effect of dietary fiber on the absorption of LT4 is not yet fully understood; further research is needed on this topic. A decrease in the absorption of LT4 is established and clinically significant when administered concomitantly with cholestyramine, colesevelam, lanthanum, calcium carbonate, calcium citrate, calcium acetate, iron sulfate, ciprofloxacin, aluminum hydroxide, sevelamer, or proton pump inhibitors. This effect should be taken into consideration when prescribing these drugs concomitantly with LT4. The effects of Giardia lamblia infection and the influence of orlistat, polystyrene sulfonate, raloxifene, and simethicone on absorption of LT4 have been poorly documented. For bariatric surgery, sucralfate and H2-antagonist interactions are not well founded or contradictory evidence is available regarding their existence; additional research should be conducted. IMPLICATIONS: The majority of the interactions are clinically significant. They are based on the LT4 adsorption on interfering substances in the digestive tract, as well as a consequently reduced amount of the drug available for absorption. These interactions can be avoided by separating the administration of LT4 and the interfering substance.

Inferior laryngeal paraganglioma mimicking a primary thyroid tumor.

OBJECTIVE: To report an unusual case of inferior laryngeal paraganglioma that manifested as a thyroid neoplasm. METHODS: A case report is presented, including ultra-sonographic, surgical, histologic, and immunohistochemical findings, and diagnostic and therapeutic strategies are discussed. RESULTS: In a 33-year-old man with a mass in the left side of his neck, color Doppler ultrasonography revealed an extremely hypervascular lesion that appeared to arise in the left lobe of the thyroid gland. Fine-needle aspiration was noncontributory because of bloody samples, but core biopsy specimens suggested a nonthyroidal neoplasm. At surgical intervention, a 3.5-cm mass was found immediately posterior to the left thyroid lobe, not involving the thyroid capsule. Because the mass could not be dissected free from the thyroid, performance of a left thyroid lobectomy and isthmectomy was necessary. The pathology specimen was a paraganglioma. CONCLUSION: Paragangliomas may be sonographically similar to thyroid neoplasms and may be included in the differential diagnosis of a hypervascular thyroid mass.

American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules.

Thyroid nodules are common and are frequently benign. Current data suggest that the prevalence of palpable thyroid nodules is 3% to 7% in North America; the prevalence is as high as 50% based on ultrasonography (US) or autopsy data. The introduction of sensitive thyrotropin (thyroid-stimulating hormone or TSH) assays, the widespread application of fine-needle aspiration (FNA) biopsy, and the availability of high-resolution US have substantially improved the management of thyroid nodules. This document was prepared as a collaborative effort between the American Association of Clinical Endocrinologists (AACE) and the Associazione Medici Endocrinologi (AME). Most Task Force members are members of AACE. We have used the AACE protocol for clinical practice guidelines, with rating of available evidence, linking the guidelines to the strength of recommendations. Key observations include the following. Although most patients with thyroid nodules are asymptomatic, occasionally patients complain of dysphagia, dysphonia, pressure, pain, or symptoms of hyperthyroidism or hypothyroidism. Absence of symptoms does not rule out a malignant lesion; thus, it is important to review risk factors for malignant disease. Thyroid US should not be performed as a screening test. All patients with a palpable thyroid nodule, however, should undergo US examination. US-guided FNA (US-FNA) is recommended for nodules > or = 10 mm; US-FNA is suggested for nodules < 10 mm only if clinical information or US features are suspicious. Thyroid FNA is reliable and safe, and smears should be interpreted by an experienced pathologist. Patients with benign thyroid nodules should undergo follow-up, and malignant or suspicious nodules should be treated surgically. A radioisotope scan of the thyroid is useful if the TSH level is low or suppressed. Measurement of serum TSH is the best initial laboratory test of thyroid function and should be followed by measurement of free thyroxine if the TSH value is low and of thyroid peroxidase antibody if the TSH value is high. Percutaneous ethanol injection is useful in the treatment of cystic thyroid lesions; large,symptomatic goiters may be treated surgically or with radioiodine. Routine measurement of serum calcitonin is not recommended. Suggestions for thyroid nodule management during pregnancy are presented. We believe that these guidelines will be useful to clinical endocrinologists, endocrine surgeons, pediatricians, and internists whose practices include management of patients with thyroid disorders. These guidelines are thorough and practical, and they offer reasoned and balanced recommendations based on the best available evidence.

Continuing controversies in the management of thyroid nodules.

Although thyroid nodules are common, few are malignant and require surgical treatment. A systematic approach to their evaluation is important to avoid unnecessary surgery. Fine-needle aspiration biopsy has resulted in substantial improvements in diagnostic accuracy, cost reductions, and higher malignancy yield at time of surgery. The preferred approach when repeated fine-needle aspiration biopsy fails to yield an adequate specimen remains a challenge. Management of patients with nodules "suspicious for follicular neoplasm" is difficult, since only 15% to 20% of such lesions have been shown to be malignant. Immunohistochemical markers, such as galectin-3 and human bone marrow endothelial cell (HBME-1), have shown promise in preliminary studies. Routine calcitonin measurement in patients with thyroid nodules has been advocated for early detection of medullary thyroid cancer. However, the low frequency of this cancer, coupled with the high cost associated with case detection, has resulted in a lack of general acceptance of this recommendation.

Thyroid nodule update on diagnosis and management.

Thyroid nodules are common. The clinical importance of thyroid nodules is related to excluding malignancy (4.0 to 6.5% of all thyroid nodules), evaluate their functional status and assess for the presence of pressure symptoms. Incidental thyroid nodules are being diagnosed with increasing frequency in the recent years with the use of newer and highly sensitive imaging techniques. The high prevalence of thyroid nodules necessitates that the clinicians use evidence-based approaches for their assessment and management. New molecular tests have been developed to help with evaluation of malignancy in thyroid nodules. This review addresses advances in thyroid nodule evaluation, and their management considering the current guidelines and supporting evidence.

Retraction Note: Thyroid nodules update in diagnosis and management.

[This retracts the article DOI: 10.1186/s40842-015-0011-7.].