AACE-AME 2016 Thyroid Nodule Update

Transcription

1 AACE-AME 2016 Thyroid Nodule Update 26 th Annual AACE Meeting & Clinical Congress Austin May 1-5, 2017 Hossein Gharib, MD, MACP, MACE Professor, Mayo Clinic College of Medicine Past President, American Thyroid Association Past President, American Association of Clinical Endocrinologists 2016 MFMER

2 Disclosure and Thanks Nothing to disclose My sincere thanks for the invitation to speak to you today 2016 MFMER

3 Objectives 1. To review highlights of 2016 AACE-AME Thyroid Nodule Guidelines Endo Pract To compare with 2015 ATA recommendations Thyroid To discuss survey of practice vs GLs JCEM 2016 JCEM 101:2853, MFMER

4 Strength-of-Evidence Scales Reported in the Medical Literature Level of evidence Description 1 Well-controlled, generalizable, randomized trials Adequately powered, well-controlled multicenter trials Large meta-analyses with quality ratings All-or-none evidence 2 Randomized controlled trials with limited body of data Well-conducted prospective cohort studies Well-conducted meta-analyses of cohort studies 3 Methodologically flawed randomized clinical trials Observational studies Case series or case reports Conflicting evidence, with weight of evidence supporting the recommendation 4 Expert consensus Expert opinion based on experience Theory-driven conclusions Unproven claims Gharib et al: Endo Pract, MFMER

5 Grading Recommendations Level of evidence Description Action A >1 Conclusive level 1 publications demonstrating benefit >> risk Action based on strong evidence Action recommended for indications reflected by published reports Action can be used with other conventional therapy or as first-line therapy B No conclusive level 1 publication Action recommended for indications reflected by the published reports 1 Conclusive level 2 publications demonstrating benefit >> risk Use if the patient declines or does not respond to conventional therapy; must monitor for adverse effects Action based on intermediate evidence Can be recommended as second-line therapy C No conclusive level 1 or 2 publications Action recommended for indications reflected by the published reports D 1 Conclusive level 3 publication demonstrating benefit >> risk OR No conclusive risk at all and no benefit at all No conclusive level 1, 2, or 3 publication demonstrating benefit >> risk Conclusive level 1, 2, or 3 publication demonstrating risk >> benefit Use when the patient declines or does not respond to conventional therapy, provided there are no important adverse effects; No objection to recommending their use OR No objection to continuing their use Action based on weak evidence Not recommended Patient is advised to discontinue use Action not based on any evidence Gharib et al: Endo Pract, MFMER

6 AACE-AME Thyroid Nodule 2016 Update Update of 2011 guidelines 9 primary authors (U.S., Denmark, Germany, Italy) 11 Task Force members 60-page document 367 references Published in Endocrine Practice May 2016:22: MFMER

7 A 38-year-old man undergoes an executive health exam. He has no prior h/o thyroid disease or radiation. Thyroid palpation is normal. Order neck US fro routine exam? US exam is not recommended as a screening test for the general population or a patient with normal thyroid palpation & low risk of thyroid disease [BEL 4, Grade C] 2016 MFMER

8 A young woman is discovered to have a thyroid nodule on routine exam. A. TSH B. Thyroglobulin (Tg) C. Calcitonin (Ctn) D. Neck US E. Thyroid scintigraphy (scan) AACE A. Yes (BEL 2, Grade B) B. No (BEL 2, Grade A) C. No recommendation (BEL 3, Grade D) D. YES (BEL 2, Grade A) E. If TSH low (BEL2, Grade A) 2016 MFMER

9 ATA Recommendations Serum TSH should be measured during initial evaluation Screen Tg is not recommended The panel cannot recommend either for or against routine Ctn measurement Thyroid US in all patient with known or suspected thyroid nodules 2016 MFMER

10 Clinical Practice Survey Laboratory Evaluation TSH Free T4 TPO Ab Tg Ab T3/Free T3 Calcitonin Thyroglobulin Routine Laboratory Testing Respondents (no.) 99.4 Burch et al: JCEM, MFMER

11 Clinical Practice Survey International Differences in Calcitonin Testing Routine Calcitonin Measurement Europe 32.1 Asia & Oceania M. East & Africa L. America 6.2 N. America % Burch et al: JCEM, MFMER

12 Risk of Malignancy (ROM) Assessment for Thyroid Nodules 1. Clinical 2. Sonography 3. Cytologic 2016 MFMER

13 Features Suggesting Increased Risk of Malignancy History of head and neck irradiation Family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, or papillary thyroid carcinoma Age <14 or >70 years Male sex Growth of the nodule Firm or hard nodule consistency Cervical adenopathy Fixed nodule Persistent dysphonia, dysphagia, or dyspnea [BEL 2, Grade A] 2016 MFMER

14 Thyroid US AACE US is recommended for patient at risk for thyroid cancer, a palpable nodule or goiter, or neck lymphadenopathy [BEL 4, Grade C] ATA Thyroid sonography with survey of cervical lymph nodes should be performed in all patient with known or suspect thyroid nodules 2016 MFMER

15 Clinical Practice Survey Imaging Requested Imaging Any US 98% LNs included Radiology US Clinic US 68.5 % 57.2 % 52.1% Thyroid scan 4.5% Respondents (no.) Burch et al: JCEM, MFMER

16 AACE Thyroid US Report Focus report on stratification for risk of malignancy Describe nodule(s) characteristics in detail (position, size, shape, margins, echogenic & vascular pattern) Identify & describe suspicious cervical lymph node Select nodule(s) for FNA 2016 MFMER

17 A 30-year-old woman is referred for a recent thyroid nodule. US shows a solid, hypoechogenic lesion with intranodular vascularization & smooth borders. What is the approximate risk of malignancy in this nodule based in US features? A. Low <1% B. Intermediate 5-15% C. High 50-90% 2016 MFMER

18 ROM by Thyroid US US features (ROM) High (50-90%) Intermediate (5-15%) Low (<1%) Mostly cystic >50% Isoechoic Spongiform Hypoechoic Intranodular vascularization Smooth/ill-defined margins Marked hypoechogenicity Spiculated margins Microcalcifications Taller, than wide ETE and/or nodes 2016 MFMER

19 US Features of Benign or Malignant Thyroid Nodule US features indicative of a benign nodule Isoechoic spongiform appearance (microcystic spaces comprising >50% of the nodule) Simple cyst with thin regular margins Mostly cystic (>50%) nodules containing colloid (hyperechoic spots with comet-tail sign) Regular eggshell calcification around the periphery of a nodule US features indicative of a malignant nodule Papillary carcinoma Solid hypoechoic (relative to prethyroid muscles) nodule, which may contain hyperechoic foci without posterior shadowing (i.e., microcalcifications) Solid hypoechoic nodule, with intranodular vascularity and absence of peripheral halo Taller-than-wide nodule (AP>TR diameter when imaged in the transverse plane) Hypoechoic nodule with spiculated or lobulated margin Hypoechoic mass with a broken calcified rim and tissue extension beyond the calcified margin Follicular neoplasm (either follicular adenoma or carcinoma) Isoechoic or mildly hypoechoic homogeneous nodule with intranodular vascularization and well-defined halo Indeterminate US features Isoechoic or hyperechoic nodule with hypoechoic halo Mild hypoechoic (relative to surrounding parenchyma) nodule with smooth margin Peripheral vascularization Intranodular macrocalcification 2016 MFMER

20 Comparison of the 2016 AACE/AME & 2015 ATA Nodule Ultrasound Classification Systems AACE/ACE-AME 1. Low-risk lesion Cysts (fluid component >80%) Mostly cystic nodules with reverberating artifacts and not associated with suspicious US signs Isoechoic spongiform nodules, either confluent or with regular halo. <1% 2. Intermediate-risk thyroid lesion Slightly hypoechoic (vs. thyroid tissue) or isoechoic nodules, with ovoid-to-round shape, smooth or ill-defined margins May be present: Intranodular vascularization Elevated stiffness at elastography, Macro or continuous rim calcifications Indeterminate hyperechoic spots 5-15% 3. High-risk thyroid lesion (50-90%) Nodules with at least 1 of the following features: Marked hypoechogenicity (vs. prethyroid muscles) Spiculated or lobulated margins Microcalcifications Taller-than-wide shape (AP>TR) Extrathyroidal growth Pathologic adenopathy Expected risk of malignancy in accordance with the presence of 1 or more suspicious findings % ATA Benign 1% Purely cystic nodules (no solid component) Very low suspicion 3% Spongiform or partially cystic nodules without any of the US features described in low-, intermediate- or high-suspicion patterns Low suspicion 5-10% Isoechoic or hyperechoic solid nodule, or partially cystic nodule with eccentric solid area without: Microcalcifications Irregular margin Extrathyroidal extension Taller than wide shape Intermediate suspicion Hypoechoic solid nodule with smooth margins without: Microcalcifications Extrathyroidal extension Or taller than wide shape 10-20% High suspicion Solid hypoechoic nodule or solid hypoechoic component of partially cystic nodule with 1 or more of the following features: Irregular margins (infiltrative, microlobulated) Microcalcifications Taller than wide shape Rim calcifications with small extrusive soft tissue component Evidence of extrathyroidal extension >70% 2016 MFMER

21 Thyroid FNA Gold standard separating benign from malignant nodules Improved results using ultrasound guidance Safe, reliable & cost effective Conventional cytologic classification Benign 75% Malignant 5% Suspicious 10% Nondiagnostic 10% 2016 MFMER

22 A 60-year-old woman is referred for FNA of a recent thyroid nodule. She has no pain history of thyroid disease or radiation. Neck US shows a 9 mm, solid, hypoechoic nodule with clear borders. It is not clear if microcalcifications are present. Nodule is subcapsular; no adenopathy is present. You discuss FNA & recent guideline recommendations: A. AACE FNA B. ATA FNA 2016 MFMER

23 AACE How to Select Nodule(s) for FNA? FNA High-risk 5-10 mm Subcapsular Paratracheal Suspicious LN High-risk >10 mm Intermediate risk >20 mm Low-risk >20 mm Recommendations In light of the low clinical risk, nodules with a major diameter <5 mm should be monitored with US rather than biopsied, irrespective of their sonographic appearance [BEL 3, GRADE B]. In nodules with a major diameter 5-10 mm that are associated with suspicious US signs (high US risk thyroid lesions), consider either FNA sampling or watchful waiting on the basis of the clinical setting and patient preference [BEL 3, GRADE B]. Specifically, US-guided FNA is recommended for the following nodules: Subcapsular or paratracheal lesions Suspicious lymph nodes or extrathyroid spread Positive personal or family history of thyroid cancer Coexistent suspicious clinical findings (e.g., dysphonia) [BEL 2, GRADE A] FNA is recommended for the following: High US risk thyroid lesions 10 mm Intermediate US risk thyroid lesions >20 mm Low US risk thyroid lesions only when >20 mm and increasing in size or associated with a risk history and before thyroid surgery or minimally invasive ablation therapy [BEL 2, GRADE A] FNA is not recommended for nodules that are functional on scintigraphy (see difference in recommendations for children; Section 8.4.) [BEL 2, GRADE B] MFMER

24 ATA: Sonographic Patterns Estimated Risk of Malignancy, and Fine-Needle Aspiration Guidance for Thyroid Nodules Sonographic pattern High suspicion Intermediate suspicion Low suspicion Very low suspicion US features Solid hypoechoic nodule or solid hypoechoic component of a partially cystic nodule with one or more of the following features: Irregular margins (infiltrative, microlobulated), microcalcifications, taller than wide shape, rim calcifications with small extrusive soft tissue component, evidence of ETE Hypoechoic solid nodule with smooth margins without microcalcifications, ETE, or taller than wide shape Isoechoic or hyperchoic solid nodule, or partially cystic nodule with eccentric solid areas, without microcalcification, irregular margin or ETE, or taller than wide shape Spongiform or partially cystic nodules without any of the sonographic features described in low, intermediate, or high suspicion patterns Estimated risk of malignancy (%) FNA size cutoff (largest dimension) >70-90 Recommend FNA at 1 cm Recommend FNA at 1 cm 5-10 Recommend FNA at 1.5 cm <3 Consider FNA at 2 cm Observation without FNA is also a reasonable option Benign Purely cystic nodules (no solid component) <1 No biopsy 2016 MFMER

25 % Young (<40 years) Middle age (40-59 years) Older ( 60 years) 5.9 Outcomes after 10 years of observation Increase in size Novel LN mets Progression to clinical disease Ito et al: Thyroid, MFMER

26 AACE 5 cytologic classes with subdivision of indeterminate samples in 3 subclasses are recommended for cytologic reports [BEL 2, Grade A] ATA Thyroid FNA cytology should be reported using the Bethesda System for Reporting Thyroid Cytopathology 2016 MFMER

27 Bethesda System for Reporting Thyroid Cytopathology Diagnostic category Risk of malignancy (%) Usual management I Nondiagnostic 1-4 Repeat FNA II Benign 0-3 Clinical F-U III AUS or FLUS* 5-15 Repeat FNA IV FN** Lobectomy, TTx V Suspicious for malignancy VI Malignant TTx or lobectomy Total thyroidectomy *Atypical of undetermined significance or follicular lesion of undetermined significance **Follicular neoplasm; Cibas & Ali: Thyroid, MFMER

28 Management after Benign FNA AACE Recommendations Clinical follow-up of FNA benign nodule unless symptomatic [BEL 2, Grade A] Repeat clinical, US & TSH in 12 months [BEL 2, Grade B] If nodule stable, repeat US in 24 months [BEL 3, Grade C] LT4 suppressive Rx is not recommended [BEL 1, Grad A] 2016 MFMER

29 Clinical Practice Survey Management after a Benign FNA Index patient has a benign FNA. How are most patients with this finding managed at your institution? Exam only Repeat FNA Return to PCP Repeat US once 19.7 Repeat US serially % Burch et al: JCEM, MFMER

30 Clinical Practice Survey Management after a Benign FNA When would you next repeat a thyroid ultrasound after a benign FNA result? 3 months months months months Never Unless growth or symptoms % Burch et al: JCEM, MFMER

31 Selection of Nodules for FNA: Guidelines vs Practice US features Nodule size ATA AACE FNA ordered? Solid, hypoechoic 1.5 Yes Yes 98% Solid, hypoechoic microcalcifications 0.7 No Yes 67% 2016 MFMER

32 Medical Rx of Benign Thyroid Nodule AACE ATA LT4 suppressive Rx is not recommended [BEL 2, Grade B] In I-deficiency, TSH nonsuppressive Rx in young pt with small goiter [BEL 2, Grade B] Routine TSH suppressive Rx for benign thyroid nodules in I-sufficient populations is not recommended 2016 MFMER

33 A 43-year-old woman was discovered to have a right thyroid during evaluation for dizziness. She has no h/o radiation. TSH is 2.8 IU/L Thyroid US showed a solid hypoechoic nodule, with increased vascularity FNA was indeterminate, suspicious for follicular lesion (FLUS) 2016 MFMER

34 AACE: Management Options after Low-risk Indeterminate FNA A. Conservative management for nodule with favorable clinical criteria (BEL 3, Grade C] B. Repeat FNA & review with expert cytopathologist [BEL 3, Grade B] C. Core needle biopsy (CNB), but routine use not recommended (BEL 3, Grade C] D. No recommendation for or against molecular markers [BEL 2, Grade B] 2016 MFMER

35 Compare 2 Tests Afirma Thyroseq 10, ,500 8,000 % ,000 6,000 4, ,000 0 NPV PPV NPV PPV Cost, $ 0 AUS/FLUS FN/SFN 2016 MFMER

36 When to Order Molecular Markers? AACE Markers BRAF, RET, etc testing if available No recommendations for or against use of GECs In GEC neg nodules careful follow-up is recommended Recommended To complement rather than replace cytologic evaluation [BEL 2, GRADE A]. The results are expected to influence clinical management [BEL 2, GRADE A]. As a general rule, testing is not recommended in nodules with established benign or malignant cytologic characteristics [BEL 2, GRADE A] Molecular testing for cytologically indeterminate nodules Cytopathology expertise, patient characteristics, and prevalence of malignancy within the population being tested impact the negative predictive values (NPVs) and positive predictive values (PPVs) for molecular testing [BEL 3, GRADE B]. Consider the detection of BRAF and RET/PTC and, possibly, PAX8/PPARG and RAS mutations if such tests are available [BEL 2, GRADE B]. Because of the insufficient evidence and the limited follow-up, we do not recommend either in favor of or against the use of gene expression classifiers (GECs) for cytologically indeterminate nodules [BEL 2, GRADE B]. Role of molecular testing for deciding the extent of surgery Currently, with the exception of mutations such as BRAFV600E that have a PPV approaching 100% for papillary thyroid carcinoma, evidence is insufficient to recommend in favor of or against the use of mutation testing as a guide to determine the extent of surgery [BEL 2, GRADE A]. How should patients with nodules that are negative at mutation testing be monitored? Since the false-negative rate for indeterminate nodules is 5 to 6%, and the experience and follow-up for mutation-negative nodules or nodules classified as benign by a GEC are still insufficient, close follow-up is recommended [BEL 3, GRADE B] MFMER

37 Management after Low-risk Indeterminate FNA ATA Recommendation (A) For nodules with AUS/FLUS cytology, investigations such as repeat FNA or molecular testing may be used to supplement malignancy risk assessment. (Weak recommendation, Moderate-quality evidence) (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) 2016 MFMER

38 A. AUS/FLUS n= % 4.4% 2.7% Clinical Practice Survey 2.7% 31.5% B. Follicular neoplasm n= % 14.6% 2.1% 4.9% 2.9% 38.8% C. Suspicious for malignancy n= % 0.2% 3.9% 9.5% Observe Thyroid scan Repeat FNA Molecular profile Lobectomy Total thyroidectomy D. Malignant n=827 <1.0% 7.6% 29.0% 43.1% 43.0% 91.8% Burch et al: JCEM, MFMER

39 Management After High-risk Indeterminate FNA AACE Surgery is recommended for most thyroid nodules in this category [BE 2, Grade A] Thyroid lobectomy is preferred [BEL 2, Grade A] 2016 MFMER

40 Multinodular Goiter (MNG) Is risk of malignancy similar in single vs MNG? How do you select nodule(s) for FNA in MNG? How many nodules to FNA? 2016 MFMER

41 Multinodular Goiter Nodule risk The risk of cancer in any given nodule is lower in a MNG Patient risk A multinodular pt has the same cancer risk as a solitary nodule pt 2016 MFMER

42 Patient Risk of Cancer also Lower in a Multinodular Gland? Meta-analysis 14 studies (44,288 pt) 4 in US (2,442 pt) 10 outside US 23,565 MNG pt 20,723 solitary nodule pt Overall lower risk of cancer in multinodular pt US subset: No difference % Cancer Prevalence MNG vs Solitary Nodule ALL studies 1.4 MGN Solitary 1.4 U.S. studies Brito JP et al: Thyroid 23:449, MFMER

43 AACE Recommendations No more than 2 nodules, selected per criteria for single lesion, need FNA [BEL3, Grade C] Do not FNA hot nodules if scan available [BEL 2, Grade B] With suspicious cervical adenopathy, FNA both nodule & node [BEL 2, Grade A] 2016 MFMER

44 ATA Recommendations for MNG Recommendation (A) In patients with multiple thyroid nodules 1 cm 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 (Strong recommendation, Moderate-quality evidence) 2016 MFMER

45 Clinical Practice Survey Multinodular Thyroid Approach Survey question: 52-year-old woman with multinodular gland, 5 nodules >1 cm, and no suspicious clinical or US features, TSH 1.5 mu/l 2-3 largest nodules 46.4 Single largest nodule All nodules >1 cm No FNA Cold nodules % Burch HB et al: JCEM, MFMER

46 A 56-year-old woman presents with recent neck pain and a right thyroid mass. On US this is a primarily cystic lesion 4x4 cm. US-FNA was benign; 22 ml fluid was aspirated with near-complete cyst collapse. Two months later she returns with right neck pain and on exam cyst has recurred. What is recommendation for Rx? 2016 MFMER

47 Percutaneous Ethanol Injection (PEI) AACE A safe & effective out pt Rx for thyroid cysts & complex nodules with a large fluid component [BEL 1, Grade A] Recommend as first line Rx for relapsing benign cystic lesions [BEL1, Grade A] Not recommended for solid nodules, whether hot or not, or for MNG [BEL 2, Grade A] 2016 MFMER

48 Summary Pearls Use clinical, sonographic & cytologic information to assess ROM in thyroid nodules AACE US risk classification is a practical, 3-tier system Use of BSRTC is recommended No recommendation is made for use of molecular markers for indeterminate FNA Follow benign nodule with US & TSH in 12 mos 2016 MFMER

49 Acknowledgements Guidelines Committee Task Force Hossein Gharib, MD, MACE, U.S.A., Co-Chair Sofia Tseleni Balafouta, MD Enrico Papini, MD, FACE, Italy, Co-Chair Zubair Baloch, MD Anna Crescenzi, MD Jeffrey Garber, MD, FACP, FACE, U.S.A. Henning Dralle, MD Daniel Quick, MD, FACP, FACE, U.S.A. Andrea Frasoldati, MD R. Mack Harrell, MD, FACP, FACE, U.S.A. Roland Gartner, MD Laszlo Hegedus, MD, Denmark Rinaldo Guglielmi, MD Ralf Paschke, MD, Germany Jeffrey I. Mechanick, MD, FACP, FACN, FACE Christoph Reiners, MD Roberto Valcavi, MD, Italy Isvan Szabolcs, MD, PhD, DSc Paolo Vitti, MD, Italy Martha A. Zeiger, MD, FACS Michele Zini, MD 2016 MFMER

50 Thank you 2016 MFMER

51 Questions & Discussion 2016 MFMER

52 AACE-AME 2016 Thyroid Nodule Update 2 nd Italian AACE Chapter Meeting Roma November 9-10, 2016 Hossein Gharib, MD, MACP, MACE Professor, Mayo Clinic College of Medicine Past President, American Thyroid Association Past President, American Association of Clinical Endocrinologists 2016 MFMER