Thyroid nodules ATA guideline 2017

Thyroid nodules ATA guideline 2017

1. Presenter: Dr.Anil Yadav Resident (Phase-B) Department of Endocrinology BSMMU WELCOME TO JOURNAL CLUB

2. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer Source : American Thyroid Association Volume : 26( 1) Published in : 2016,January.

3. Authors Bryan R. Haugen Erik K. Alexander Keith Gerard M. Doherty Susan J. Mandel Yuri E. Nikiforov Furio Pacini Gregory W. Randolph Anna M. Sawka Martin Schlumberger Kathryn G. Schuff Steven I. Sherman Julie Ann Sosa David L. Steward R . Michael Tuttle LeonardWartofsky

4. Introduction Thyroid nodule : A discrete lesion within the thyroid gland Radiologically distinct from the surrounding thyroid parenchyma. May be palpable or non palpable Prevalence of palpable thyroid nodules : 5 % in women and 1 % in men living in iodine-sufficient parts of the world .

5. Introduction Non-palpable nodules detected on USG or other anatomic imaging studies are termed incidentally discovered nodules or ‘‘ incidentalomas .’’

6. Introduction (cont..) High-resolution USG can detect thyroid nodules in 19%–68% of randomly selected individuals, with higher frequencies in women and the elderly. Non-palpable nodules have the same risk of malignancy as do sonographically confirmed palpable nodules of the same size.

7. Introduction (cont..) By 2019, one study predicts that papillary thyroid cancer will become the third most common cancer in women at a cost of 19-21 billion dollars in the U.S. The clinical importance of thyroid nodules rests with the need to exclude thyroid cancer, which occurs in 7%–15% of cases depending on age, sex, radiation exposure history, family history, and other factors.

8. Introduction (cont..) Generally, only nodules >1cm should be evaluated, since they have a greater potential to be clinically significant cancers. Occasionally , there may be nodules <1cm that require further evaluation because of clinical symptoms or associated lymphadenopathy.

9. With the discovery of a thyroid nodule, complete history and physical examination focusing on the thyroid gland and adjacent cervical lymph nodes should be performed. Introduction (cont..)

10. Pertinent historical factors predicting malignancy include: a history of childhood head and neck irradiation, total body irradiation for bone marrow transplantation exposure to ionizing radiation from fallout in childhood or adolescence Introduction (cont..)

11. Introduction (cont..) familial thyroid carcinoma, or thyroid cancer syndrome in a first-degree relative, rapid nodule growth and/or hoarseness .

12. Pertinent physical findings suggesting possible malignancy include vocal cord paralysis, cervical lymphadenopathy , and fixation of the nodule to surrounding tissues. Introduction (cont..)

13. Purpose To inform clinicians, patients, researchers, and health policy makers about the best available evidence (and its limitations), relating to the diagnosis and treatment of adult patients with thyroid nodules.

14. Method A task force chair of specialists with complementary expertise (endocrinology, surgery, nuclear medicine, radiology, pathology, oncology, molecular diagnostics, and epidemiology) was appointed by the ATA President with approval of the Board. Upon discussion among the panel members and the Chair with other Chairs of other ATA guideline committees, the American College of Physicians’ (ACP) Grading System was adopted

15. RECOMMENDATIONS

16. What is the appropriate laboratory and imaging evaluation for patients with clinically or incidentally discovered thyroid nodules ?

17. Serum thyrotropin measurement ( TSH ) Recommendation Serum thyrotropin (TSH) should be measured during the initial evaluation of a patient with a thyroid nodule . If the serum TSH is subnormal, a radionuclide ( preferably 123I thyroid scan should be performed. ( Strong recommendation, Moderate-quality evidence)

18. Serum thyrotropin measurement(TSH) ( CONT..) If the serum TSH is normal or elevated, a radionuclide scan should not be performed as the initial imaging evaluation . (Strong recommendation, Moderate-quality evidence)

19. Serum thyrotropin measurement ( TSH) ( CONT.. ) A higher serum TSH level, even within the upper part of the reference range, is associated with increased risk of malignancy in a thyroid nodule, as well as more advanced stage thyroid cancer

20. Serum thyrotropin measurement ( TSH) ( CONT.. ) If TSH low, risk of malignancy depends on radio uptake scan: Tracer uptake : hyperfunctioning “hot” nodule- rarely harbor malignancy, no cytologic evaluation is necessary. Tracer uptake is equal to the surrounding thyroid isofunctioning “warm” nodule Uptake : nonfunctioning “ cold”nodule

21. Thyroid sonography Recommendation Thyroid sonography with survey of the cervical lymph nodes should be performed in all patients with known or suspected thyroid nodules. (Strong recommendation, High-quality evidence)

22. Thyroid sonography (cont…) Thyroid US can answer the following: Is there truly a nodule? How large is the nodule? What is the nodule’s pattern of ultrasound imaging characteristics?

23. Thyroid sonography (cont…) Is suspicious cervical lymphadenopathy present? Is the nodule greater than 50% cystic? Is the nodule located posteriorly in the thyroid gland?

24. Thyroid sonography (cont…) Sonography features that are associated with thyroid cancer include: microcalcifications , nodule hypoechogenicity compared with the surrounding thyroid or strap muscles, irregular margins (defined as either infiltrative, microlobulated or spiculated ), and A shape taller than wide measured on a transverse view.

25. S onographic patterns, estimated risk of malignancy, and fine-needle aspiration guidance for thyroid nodules Sonographic pattern US features Estimated risk of malignancy % FNA size cutoff (largest dimension) High suspicion Solid hypoechoic nodule or solid hypoechoic component of a partially cystic nodule  with  one or more of the following features: a) Irregular margins (infiltrative, microlobulated ), b ) Microcalcifications , c) Taller than wide shape, > 70–90 Recommend FNA at ≥1 cm

26. d) Rim calcifications with small extrusive soft tissue component, e)Evidence of ETE Intermediate suspicion Hypoechoic solid nodule with smooth margins   without   microcalcifications , ETE, or taller than wide shape 10–20 Recommend FNA at ≥1 cm

27. Low suspicion Isoechoic or hyperechoic solid nodule, or partially cystic nodule with eccentric solid areas,  without   microcalcification , irregular margin or ETE, or taller than wide shape. 5–10 Recommend FNA at ≥1.5 cm

28. Very low suspicion Spongiform or partially cystic nodules  without  any of the sonographic features described in low, intermediate, or high suspicion patterns <3 Consider FNA at ≥2 cm Observation without FNA is also a reasonable option Benign Purely cystic nodules (no solid component) <1 No biopsy b

29. Serum thyroglobulin ( Tg ) Recommendation Routine measurement of serum thyroglobulin ( Tg ) for initial evaluation of thyroid nodules is not recommended. (Strong recommendation, Moderate-quality evidence)

30. Serum calcitonin measurement Recommendation : The panel cannot recommend either for or against routine measurement of serum calcitonin in patients with thyroid nodules. ( No recommendation, Insufficient evidence)

31. FNAC Recommendation FNA is the procedure of choice in the evaluation of thyroid nodules, when clinically indicated. (Strong recommendation, High-quality evidence)

32. Recommendation for Diagnostic FNA of a thyroid nodule based on sonographic pattern Recommendation 1.Thyroid nodule diagnostic FNA is recommended for : (A) Nodules ≥1cm in greatest dimension with high suspicion sonographic pattern. ( Strong recommendation, Moderate quality evidence)

33. Recommendation for Diagnostic FNA of a thyroid nodule based on sonographic pattern B)Nodules ≥1cm in greatest dimension with intermediate suspicion sonographic pattern. ( Strong recommendation, Low-quality evidence) C)Nodules ≥1.5cm in greatest dimension with low suspicion sonographic pattern. (Weak recommendation, Low-quality evidence)

34. Recommendation for Diagnostic FNA of a thyroid nodule based on sonographic pattern 2) Thyroid nodule diagnostic FNA may be considered for: (D) Nodules ≥2cm in greatest dimension with very low suspicion sonographic pattern (e.g., spongiform). Observation without FNA is also a reasonable option. (Weak recommendation, Moderate-quality evidence)

35. Recommendation for Diagnostic FNA of a thyroid nodule based on sonographic pattern 3) Thyroid nodule diagnostic FNA is not required for : (E) Nodules that do not meet the above criteria. (F) Nodules that are purely cystic. (Strong recommendation, Moderate-quality evidence)

36. Thyroid nodule FNA cytology should be reported using diagnostic groups outlined in the: Bethesda System for Reporting Thyroid Cytopathology

37. Nondiagnostic cytology Recommendation ( A) For a nodule with an initial nondiagnostic cytology result , FNA should be repeated with US guidance and, if available , on-site cytologic evaluation ( Strong recommendation, Moderate-quality evidence )

38. Nondiagnostic cytology (B) Repeatedly nondiagnostic nodules without a high suspicion sonographic pattern require close observation or surgical excision for histopathologic diagnosis (Weak recommendation, Low-quality evidence)

39. Nondiagnostic cytology Recommendation (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 (Weak recommendation, Low-quality evidence)

40. Benign cytology Recommendation If the nodule is benign on cytology, further immediate diagnostic studies or treatment are not required ( Strong recommendation, High-quality evidence)

41. Malignant cytology Recommendation If a cytology result is diagnostic for primary thyroid malignancy, surgery is generally recommended. ( Strong recommendation, Moderate-quality evidence

42. An alternative active surveillance management approach can be considered in: patients with very low risk tumors patients at high surgical risk because of co-morbid conditions, patients expected to have a relatively short remaining life span Patients with concurrent medical or surgical issues that need to be addressed prior to thyroid surgery.

43. Indeterminate cytology ( AUS/FLUS, FN, SUSP ) What are the principles of the molecular testing of FNA samples?

44. Recommendation 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 . (Strong recommendation,Low -quality evidence )

45. Recommendation 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. ( Strong recommendation, Low-quality evidence)

46. AUS/FLUS cytology Recommendation For nodules with AUS/FLUS cytology, after consideration of worrisome clinical & sonographic features, investigations such as repeat FNA/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 & feasibility should be considered in clinical decision-making . ( Weak recommendation, Moderate-quality evidence)

47. AUS/FLUS cytology (B) If repeat FNA 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. (Strong recommendation, Low-quality evidence)

48. Follicular neoplasm/suspicious for follicular neoplasm cytology Recommendation ( 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 . ( Weak recommendation, Moderate-quality evidence)

49. Follicular neoplasm/suspicious for follicular neoplasm cytology (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. (Strong recommendation, Low-quality evidence)

50. Suspicious for malignancy cytology Recommendation 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). ( Strong recommendation, Low-quality evidence )

51. What is the utility of 18FDG-PET scanning to predict malignant or benign disease when FNA cytology is indeterminate (AUS/FLUS, FN, SUSP)?

52. 18 FDG-PET scan Recommendation 18FDG-PET imaging is not routinely recommended for the evaluation of thyroid nodules with indeterminate cytology. (Weak recommendation, Moderate-quality evidence)

53. 18 FDG-PET scan Recommendation Focal [18 F] fluorodeoxyglucose positron emission tomography (18FDG-PET) uptake within a sonographically confirmed thyroid nodule conveys an increased risk of thyroid cancer, and FNA is recommended for those nodules ≥ 1cm. (Strong recommendation, Moderate-quality evidence)

54. 18 FDG-PET scan Diffuse 18FDG-PET uptake, in conjunction with sonographic and clinical evidence of chronic lymphocytic thyroiditis , does not require further imaging or FNA. (Strong recommendation, Moderate- qualityevidence )

55. What is the appropriate operation for cytologically indeterminate thyroid nodules?

56. Recommendation 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 ( Strong recommendation, Moderate-quality evidence )

57. Recommendation 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 (>4cm), 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 . ( Strong recommendation, Moderate-quality evidence)

58. How should multinodular thyroid glands (i.e., two or more clinically relevant nodules) be evaluated for malignancy?

59. Recommendation Patients with multiple thyroid nodules˃1cm should be evaluated in the same fashion as patients with a solitary nodule ˃1cm, excepting that each nodule that is >1cm carries an independent risk of malignancy and therefore multiple nodules may require FNA. (Strong recommendation, Moderate-quality evidence)

60. When multiple nodules˃1cm are present, FNA should be performed preferentially based upon nodule sonographic pattern and respective size cutoff (Strong recommendation, Moderate-quality evidence)

61. Recommendation 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 (≥2cm) or continue surveillance without FNA. (Weak recommendation, Low-quality evidence)

62. Recommendation 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 ≥1cm .

63. FNA should then be considered only for those isofunctioning or nonfunctioning nodules, among which those with high suspicion sonographic pattern should be aspirated preferentially. (Weak recommendation, Low-quality evidence)

64. What are the best methods for long term follow-up of patients with thyroid nodules ?

65. Recommendations for initial follow-up of nodules with benign FNA cytology Recommendation Nodules with high suspicion US pattern: repeat US and US-guided FNA within 12 months. (Strong recommendation, Moderate-quality evidence)

66. Nodules with low to intermediate suspicion US pattern: repeat US at 12–24 months . (Weak recommendation, Low-quality evidence)

67. Recommendations for initial follow-up of nodules with benign FNA cytology Nodules with very low suspicion US pattern (including spongiform nodules): repeating FNA to detect a missed malignancy is limited. If US is repeated, it should be done at 24 months. (Weak recommendation, Low-quality evidence)

68. 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. (Strong recommendation, Moderate-quality evidence)

69. Follow-up for nodules that do not meet FNA criteria Recommendation Nodules with high suspicion US pattern: repeat US in 6–12 months. (Weak recommendation, Low-quality evidence) Nodules with low to intermediate suspicion US pattern: consider repeat US at 12–24 months. (Weak recommendation, Low-quality evidence)

70. Follow-up for nodules that do not meet FNA criteria Recommendation: Nodules >1cm with very low suspicion US pattern 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. (No recommendation, Insufficient evidence)

71. Nodules ≤1cm with very low suspicion US pattern (including spongiform nodules) and pure cysts do not require routine sonographic follow-up. (Weak recommendation, Low-quality evidence)

72. What is the role of medical or surgical therapy for benign thyroid nodules?

73. Recommendation 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. (Strong recommendation, High-quality evidence)

74. Recommendation 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 150lg iodine) is recommended. (Strong recommendation, Moderate-quality evidence)

75. Recommendation (A) Surgery may be considered for growing nodules that are benign after repeat FNA if they are large (>4cm), causing compressive or structural symptoms, or based upon clinical concern. ( Weak recommendation, Low-quality evidence)

76. ( 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. (Strong recommendation, Low-quality evidence)

77. Recommendation 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. (Weak recommendation, Low-quality evidence)

78. Recommendation There are no data to guide recommendations on the use of thyroid hormone therapy in patients with growing nodules that are benign on cytology. (No recommendation, Insufficient evidence)

79. How should thyroid nodules In pregnant women be managed ?

80. FNA for thyroid nodules discovered during pregnancy Recommendation FNA of clinically relevant thyroid nodules should be performed in euthyroid and hypothyroid pregnant women . ( Strong recommendation, Moderate-quality evidence )

81. FNA for thyroid nodules discovered during pregnancy 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. (Strong recommendation, Moderate-quality evidence)

82. Approaches to pregnant patients with malignant or indeterminate cytology PTC discovered by cytology in early pregnancy should be monitored sonographically . If it grows progressively before 24-26 weeks gestation, or if US reveals cervical lymph nodes that are suspicious for metastatic disease, surgery should be considered during pregnancy.

83. Approaches to pregnant patients with malignant or indeterminate cytology 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 delivery 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.

84. Take home message The clinical importance to evaluate thyroid nodule is to exclude thyroid carcinoma. High resolution US can detect thyroid nodules upto 19-68% with higher frequencies in women & elderly. Minimize potential harm from overtreatment of patients at low risk and appropriately treat and monitor those patients at higher risk.

85. Take home message Non-palpable nodules have the same risk of malignancy as do sonographically confirmed palpable nodules of the same size. FNA is choice , most accurate & cost effective method of procedure in evaluation of thyroid nodule. FNA should be repeated after 3 month to prevent false-positive interpretation due to biopsy induced reactive/ reparative changes.

86. Take home message Most nodules with non-diagnostic cytology interpretation are benign. Slight enlargement of nodules throughout gestation dose not implies malignant transformation. Avoid radio- nuclied scan in pregnancy.