2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer

The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Thyroid: official journal of the American Thyroid Association (Impact Factor: 4.49). 11/2009; 19(11):1167-214. DOI: 10.1089/thy.2009.0110
Source: PubMed


Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines.
Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force.
The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, and suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using ultrasound and serum thyroglobulin as well as those related to management of recurrent and metastatic disease.
We created evidence-based recommendations in response to our appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

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Available from: David S Cooper,
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    • "Currently, commercial RNA-based gene expression classifiers are available for molecular marker testing of thyroid nodules with indeterminate cytology [[20],[21]]. The American Thyroid Association recommends use of molecular marker testing for nodules with indeterminate cytology with a specific focus on expression of BRAF, RAS, RET/PTC, PAX8-PPARγ, and galectin-3 [[22]]. One commercially available array Afirma™, lists a total 167 genes in its classifier, however, TGF- β1 is not included [[20]]. "
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    ABSTRACT: Thyroid nodules are common, but only 5% of nodules are found to be malignant. In North America, the incidence of thyroid cancer is increasing. Fine needle aspirate (FNA) biopsy is the diagnostic test of choice. Unfortunately, up to 20% of FNAs are non-diagnostic. A specific molecular marker for thyroid cancer is desirable. Evidence suggests that cell signaling through transforming growth factor beta (TGF- β) is important in the development of thyroid cancer. We sought to compare the expression of TGF- β in malignant and benign thyroid nodules. From 2008-present, thyroid nodule tissue from thyroidectomy specimens was prospectively collected and stored at -80°C. RNA extraction and reverse transcription was performed on 47 samples (24 papillary thyroid cancer and 23 benign nodules). Quantitative PCR using SYBR green was performed to detect TGF-β-1 and -2. Resulting CT values were normalized against β-actin. Gene expression was calculated using the 2(-ΔC) T method. A significantly greater expression of TGF- β1 (p < 0.0001) was detected in the group of malignant thyroid nodules compared to benign nodules. There was no difference in the expression of TGF- β2 (p = 0.4735) between the two groups. In this study, we demonstrated that expression of TGF- β1 but not TGF- β2 is significantly increased in papillary thyroid cancer compared to benign thyroid nodules. This may serve as a potential diagnostic marker for papillary thyroid cancer.
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    • "Recent ATA guidelines (2009) to assess the risk of DTC recurrence Low-risk patient: i) no local or distant metastases; ii) all macroscopic tumor resected; iii) no locoregional tumor invasion; iv) tumor lacks aggressive histology (e.g. tall cell, insular, and columnar cell carcinoma) or vascular invasion; and v) no 131 I uptake outside the thyroid bed on initial post-treatment whole-body RAI scan (RxWBS), if performed (Cooper et al. 2009). "
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    ABSTRACT: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the 5th most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post thyroidectomy patient has included radioactive iodine (RAI) ablation and/or therapy. Prior to 2000, a typical RAI post-operative dose recommendation was 100 mCi for remnant ablation, 150 mCi for locoregional nodal disease and 175-200 mCi for distant metastases (Thyroid 2013;23(6):683-694). Recent recommendations have been made to decrease the dose in order to limit the perceived adverse effects of RAI including salivary gland dysfunction and inducing secondary primary malignancies (SPM). Significant controversy has thus arisen surrounding the use of RAI, particularly in the management of the low risk DTC patient. This debate includes the definition of the low risk patient, RAI dose selection and whether or not RAI is needed in all patients. To allow the reader to form an opinion regarding post-operative RAI therapy in DTC, a literature review of the risks and benefits is presented.
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    • "Such indeterminate FNACs occur in about 20% of FNACs and are due to the fact that the diagnostic criteria of follicular thyroid cancer (FTC), which depend on capsular or vascular invasion, cannot be detected by cytology. Therefore, such patients have to undergo diagnostic thyroid surgery not to overlook malignancy in about 20% of indeterminate cases (Cooper et al., 2009; Gharib et al., 2010; Paschke et al., 2011) or 5–10% or 20–30% of AUS or FLUS cases, respectively (Baloch et al., 2008). The most important differential diagnoses in this FNAC category are: distinction between FTC and follicular variant of papillary thyroid cancer (fvPTC) and follicular adenoma (FA) and adenomatous nodules (Gharib et al., 2010; Paschke et al., 2011), whereas the less frequent differential diagnosis of PTC is often possible by cytology criteria alone. "
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    ABSTRACT: The inherent diagnostic limitations of thyroid fine needle aspiration (FNA), especially in the "indeterminate" category, can be partially overcome by molecular analyses. We aimed at the identification of miRNAs that could be used to improve the discrimination of indeterminate FNAs. miRNA expression profiling was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). The microarray results underwent cross-comparison using three additional microarray data sets. Candidate miRNAs were validated by qPCR in an independent set of 32 FTCs and 46 FAs. 68 differentially expressed miRNAs were identified.13 miRNAs could be confirmed by cross comparison. A two-miRNA-classifier was established improving the diagnostic applicability and resulted in a sensitivity of 82% and a specificity of 49%. We present a classifier that has the potential to be successfully evaluated in cytology material for its capability to discriminate (mutation negative) indeterminate cytologies and thereby improving the pre-surgical diagnostics of thyroid nodules.
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