Guideline Grading System

Diagnosis

1. Screening people with familial follicular cell-derived differentiated thyroid cancer may lead to an earlier diagnosis of thyroid cancer, but the panel cannot recommend for or against ultrasound screening since there is no evidence that this would lead to reduced morbidity or mortality. (NR-I)
2. A) Serum TSH should be measured during the initial evaluation of a patient with a thyroid nodule. (SR-M)
   B) If the serum TSH is subnormal, a radionuclide (preferably ¹²³I) thyroid scan should be performed. (SR-M)
   C) If the serum TSH is normal or elevated, a radionuclide scan should NOT be performed as the initial imaging evaluation (SR-M)
3. Routine measurement of serum Tg for initial evaluation of thyroid nodules is NOT recommended. (SR-M)
4. The panel cannot recommend either for or against routine measurement of serum calcitonin in patients with thyroid nodules. (NR-I)
5. A) Focal ¹⁸FDG-PET uptake within a sonographically confirmed thyroid nodule conveys an increased risk of thyroid cancer, and fine needle aspiration is recommended for those nodules >1 cm. (SR-M)
   B) Diffuse ¹⁸FDG-PET uptake, in conjunction with sonographic and clinical evidence of chronic lymphocytic thyroiditis, does not require further imaging or fine needle aspiration. (SR-M)
6. Thyroid sonography with survey of the cervical lymph nodes should be performed in all patients with known or suspected thyroid nodules. (SR-H)
7. FNA is the procedure of choice in the evaluation of thyroid nodules, when clinically indicated. (SR-H)
8. Thyroid nodule diagnostic FNA is recommended for (Figure 2, Table 1):
   
   A) Nodules >1 cm in greatest dimension with high suspicion sonographic pattern. (SR-M)
   B) Nodules >1 cm in greatest dimension with intermediate suspicion sonographic. (SR-L)
   C) Nodules >1.5 cm in greatest dimension with low suspicion sonographic pattern. (WR-L)
   Thyroid nodule diagnostic FNA may be considered for (Figure 2, Table 1):
   
   D) Nodules >2 cm in greatest dimension with very low suspicion sonographic pattern (e.g., – spongiform). Observation without FNA is also a reasonable option. (WR-M)
   Thyroid nodule diagnostic FNA is not required for (Figure 2, Table 1):
   
   E) Nodules that do not meet the above criteria. (SR-M)
   F) Nodules that are purely cystic. (SR-M)
9. Thyroid nodule FNA cytology should be reported using diagnostic groups outlined in the Bethesda System for Reporting Thyroid Cytopathology (http://ajcp.ascpjournals.org/cgi/pmidlookup?view=long&pmid=20660341). (SR-M)
10. A) For a nodule with an initial nondiagnostic cytology result, FNA should be repeated with US guidance and, if available, on-site cytologic evaluation. (SR-M)
    B) Repeatedly nondiagnostic nodules without a high suspicion sonographic pattern require close observation or surgical excision for histopathologic diagnosis. (WR-L)
    C) Surgery should be considered for histopathologic diagnosis if the cytologically nondiagnostic nodule has a high suspicion sonographic pattern, growth of the nodule (greater than 20% in two dimensions) is detected during ultrasound surveillance, or clinical risk factors for malignancy are present. (WR-L)
11. If the nodule is benign on cytology, further immediate diagnostic studies or treatment are not required. (SR-H)
12. If a cytology result is diagnostic for primary thyroid malignancy, surgery is generally recommended. (SR-M)
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. (SR-L)
14. If intended for clinical use, molecular testing should be performed in CLIA/CAP (Clinical Laboratory Improvement Amendments/College of American Pathologists) certified molecular laboratories, or international equivalent, as reported quality assurance practices may be superior compared to other settings. (SR-L)
15. A) For nodules with AUS/FLUS cytology, after consideration of worrisome clinical and sonographic features, investigations such as repeat FNA 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. (WR-M)
    B) If repeat FNA cytology and/or molecular testing 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. (SR-L)
16. A) Diagnostic surgical excision is the long-established standard of care for the management of follicular neoplasm/suspicious for follicular neoplasm (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. (WR-M)
    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. (SR-L)
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). (SR-L)
    B) After consideration of clinical and sonographic features, mutational testing for BRAF or the 7-gene mutation marker panel (BRAF, RAS, RET/PTC, PAX8/PPAR γ) may be considered in nodules with SUSP cytology if such data would be expected to alter surgical decision-making. (WR-M)
18. ¹⁸FDG-PET imaging is not routinely recommended for the evaluation of thyroid nodules with indeterminate cytology. (WR-M)

Figure 1. Evaluation and Management of Patients With Thyroid Nodules Based on US Pattern and FNA Cytology

Figure 2. ATA Nodule Sonographic Patterns and Risk of Malignancy

Figure 3. Lymph Node Compartments Separated into Levels and Sublevels

Table 1. Sonographic Patterns, Estimated Risk of Malignancy and FNA Guidance for Thyroid Nodules

Note: US-guided FNA is recommended for cervical lymph nodes that are sonographically suspicious for thyroid cancer.
^a The estimate is derived from high volume centers, the overall risk of malignancy may be lower given the interobserver variability in sonography.
^b Aspiration of the cyst may be considered for symptomatic or cosmetic drainage.

Treatment

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. (SR-M)
20. A) Because of increased risk for malignancy, total thyroidectomy may be preferred in patients with indeterminate nodules which are cytologically suspicious for malignancy, positive for known mutations specific for carcinoma, sonographically suspicious, 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. (SR-M)
    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. (WR-L)
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 >1 cm carries an independent risk of malignancy and therefore multiple nodules may require FNA. (SR-M)
    B) When multiple nodules >1 cm are present, those with a suspicious sonographic pattern (Table 1, Figure 2) should be aspirated preferentially. FNA should be performed preferentially based upon nodule sonographic pattern and respective size cut-off (Table 1, Figure 2). (SR-M)
    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 only the largest nodules (>2 cm) or continue surveillance without FNA while observing the others with serial US examinations. (WR-L)
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. (WR-L)
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 ultrasound pattern.
    
    A) Nodules with high suspicion US pattern: repeat US and US-guided FNA within 12 months. (SR-M)
    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 (WR-L).
    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. (WR-L)
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 (WR-L)
    B) Nodules with sonographic features of low to intermediate suspicion US pattern: consider repeat US at 12–24 months. (WR-L).
    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 (NR-I).
    D) Nodules <1 cm with very low suspicion US pattern (including spongiform nodules) and pure cysts do not require routine sonographic follow-up (WR-L).
    E) Nodules <5 mm without high suspicion US pattern do not require routine sonographic FU and if repeated, the US should be performed at ≥24 months (WR-L).
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. (SR-H)
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 mcg iodine) is recommended. (SR-M)
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. (WR-L)
    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. (SR-L)
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. (WR-L)
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 (NR-I)
30. A) FNA of clinically relevant thyroid nodules should be performed in euthyroid and hypothyroid pregnant women. (SR-M)
    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. (SR-M)
31. A) 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 midgestation, or if it is diagnosed in the second half of pregnancy, surgery may be deferred until after delivery. (WR-L).
    B) In pregnant women with FNA that is suspicious for or diagnostic of PTC, thyroid hormone therapy to keep the serum TSH 0.1–1.0mU/L is recommended. (WR-L).