MANAGEMENT OF THYROID NODULES Tracy S. Wang, MD, MPH Associate Professor of Surgery Chief, Section of Endocrine Surgery Medical College of Wisconsin DEPARTMENT OF SURGERY DIVISION OF SURGICAL ONCOLOGY

Objectives •  Review initial management of thyroid nodules –  Initial evaluation –  Indications for biopsy

•  Discuss treatment options –  Role and extent of surgery –  Long-term surveillance

DEPARTMENT OF SURGERY DIVISION OF SURGICAL ONCOLOGY

American Thyroid Association Guidelines (2015) •  Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer’ •  American College of Physicians’ Guidelines Grading System Recommendation

Clarity of Risk / Benefit

Strong

Benefits clearly outweigh harms and burdens (or vice versa)

Weak

Benefits closely balanced with harms and burdens

None

Balance of benefits and risks cannot be determined

Evidence Quality

Description of supporting evidence

High-quality

Randomized controlled trial without important limitations or overwhelming evidence from observational studies

Moderate-quality

RCT with important limitations or strong evidence from observational studies

Low-quality

Observational studies / case studies Haugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133.

4

HAUGEN ET AL.

Table 3. Interpretation of the American Thyroid Association Guideline Grading System for Diagnostic Tests

Recommendation

Accuracy of diagnostic information versus risks and burden of testinga

Implications

Strong recommendation

Knowledge of the diagnostic test result clearly outweighs risks and burden of testing or vice versa.

Weak recommendation

Knowledge of the diagnostic test result is closely balanced with risks and burden of testing.

No recommendation

Balance of knowledge of the diagnostic test result cannot be determined.

Patients: In the case of an accurate test for which benefits outweigh risks/burden, most would want the diagnostic to be offered (with appropriate counseling). A patient should request discussion of the test if it is not offered. In contrast, for a test in which risks and burden outweigh the benefits, most patients should not expect the test to be offered. Clinicians: In the case of an accurate test for which benefits outweigh risks/burden, most patients should be offered the diagnostic test (and provided relevant counseling). Counseling about the test should include a discussion of the risks, benefits, and uncertainties related to testing (as applicable), as well as the implications of the test result. In contrast, for a test in which risks and burden outweigh the perceived benefits, most patients should not be offered the test, or if the test is discussed, the rationale against the test should, for the particular clinical situation, be explained. Policymakers: In the case of an accurate test for which benefits outweigh risks/burden, availability of the diagnostic test should be adopted in health policy. In contrast, for a test in which risks and burden outweigh the perceived benefits, some restrictions on circumstances for test use may need to be considered. Patients: Most would want to be informed about the diagnostic test, but some would not want to seriously consider undergoing the test; a decision may depend on the individual circumstances (e.g., risk of disease, comorbidities, or other), the practice environment, feasibility of optimal execution of the test, and consideration of other available options. Clinicians: Different choices will be appropriate for different patients, and counseling about the test (if being considered) should include a discussion of the risks, benefits, and uncertainties related to testing (as applicable), as well as the implications of the test result. The decision to perform the test should include consideration of the patients’ values, preferences, feasibility, and the specific circumstances. Counseling the patient on why the test may be helpful or not, in her/his specific circumstance, may be very valuable in the decision-making process. Policymakers: Policymaking decisions on the availability of the test will require discussion and stakeholder involvement. Decisions on the use of the test based on evidence from scientific studies cannot be made.

a Frequently in these guidelines, the accuracy of the diagnosis of thyroid cancer (relative to a histologic gold standard) was the diagnostic outcome unless otherwise specified. However, prognostic, disease staging, or risk stratification studies were also included in the grading scheme of diagnostic studies. For disease staging systems, the implication for use would be on the part of the clinician, in reporting results in the medical record and communicating them to the patient (at the applicable time point in disease or follow-up trajectory), as opposed to offering a specific choice of staging/risk stratification system to the patient.

Haugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133.

Thyroid Nodules •  A discrete lesion within the thyroid gland that is radiologically distinct from the surrounding parenchyma –  Nodules are often NOT palpable –  Palpable lesions may not correspond to distinct radiographic findings •  Palpable thyroid nodules are present in 4-7% of the population •  Can be detected with high-frequency ultrasound in 19-68% of individuals (higher in women and the elderly)

•  Most common endocrine problem in the U.S. –  Up to 50% of the population will have thyroid nodules by age 50

Incidence of Thyroid Cancer

Siegel RL, Miller KD, Hemal A. Ca Cancer J Clin 2015;65:5-29.

Incidence of Thyroid Cancer •  Thyroid cancer may be present in up to 15% of nodules –  Incidence: 63,000 new cases in 2014 (37,000 in 2009)

•  MAJORITY OF THYROID NODULES ARE BENIGN

Surveillance, Epidemiology and End Results (SEER) data, 2014

Patient OM •  63-year-old woman referred by her primary care physician for an incidental nodule palpated on physical examination

History and Physical Exam •  History – key questions re: nodule –  Rapid growth –  Compressive symptoms •  Globus sensation / feeling of fullness •  Dysphagia •  Respiratory compromise •  Changes in voice quality –  Family history •  History of thyroid cancers •  Other cancers (breast, colon) suggestive of other syndromes –  History of radiation to the head/neck area •  Previous malignancy •  Treatment for benign processes •  Environmental or occupational exposures

History and Physical Exam •  Physical Examination –  Thyroid •  Size, firmness, mobility •  Tracheal deviation –  Central and lateral neck to examine for lymphadenopathy

edle aspiration biopsy (FNAB), and the ated. Thyroglobulin washings of FNAB helpful in this situation and can be resence of circulating thyroglobulin antie or nodule is not amenable to biopsy or nosis by cytologic evaluation or Tg aswaiting for growth on serial USs may

by the body of the mandible superiorly, stylohyoid muscle posteriorly, and the anterior belly of the digastric muscle on the contralateral side anteriorly. This level may be subdivided into a single midline level Ia, the submental triangle (bounded by the anterior bellies of

Central  and  Lateral  Neck  Lymph  Nodes  

yroid surgery for cancer and an elevated el, a thorough search for persistent and/ disease should include assessment of lly using high resolution US examinane scanning may also be a part of the n of recurrence. Disease burden is the Tg level in relation to the serum ormone (TSH) level; TSH provocation of elicited by direct TSH injection, or by hdrawal and secondary TSH elevation. ents measured in a state of a suppressed ning for recurrent/residual/bulky disTg assay and the presence of interfering tibodies are important considerations lute Tg levels or trends.

al neck anatomy

developing classifications for neck dismly define the clinical and surgical the lymph node groups removed in a develop a classification that correlates cervical metastases thus meeting the on standards following basic oncologic This classification was used to describe tatic dissemination observed in more ell carcinoma patients who were treated s from a surgeon’s perspective (28). ateral neck are grouped into levels I–V, e submandibular and submental nodes e, and lower jugular nodes (levels II, III,

FIG. 1.

Nodal levels with corresponding anatomic Haugen BR et al. 2015landATA Guidelines. Thyroid 2016;26(1):1-133.

Laboratory evaluation •  Thyroid function –  Serum TSH (thyroid stimulating hormone) should be measured during the initial evaluation of a patient with a thyroid nodule –  Most sensitive predictor of thyroid function –  Strong recommendation, Moderate-quality evidence

•  Serum thyroglobulin (Tg): NOT recommended –  Strong recommendation, Moderate-quality evidence

•  Serum calcitonin – marker for medullary thyroid cancer –  May detect C-cell hyperplasia and medullary thyroid cancer earlier –  Dependent on pentagastrin stimulation, not available in U.S. –  Cannot recommend for or against routine measurement •  No recommendation, Insufficient evidence Haugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133.

Patient OM •  63-year-old woman referred by her primary care physician for an incidental nodule palpated on physical examination •  Has not noticed any compressive symptoms •  No symptoms of hypo- or hyperthyroidism •  No family history of endocrinopathies •  No personal history of head/neck irradiation •  Palpable left thyroid nodule, visible with deglutition. No tracheal deviation, no palpable lymphadenopathy •  TSH: 0.866 (normal range: 0.45 – 4.5 uIU/mL)

Imaging •  Radionuclide thyroid scan with 123I should be performed if the serum TSH is below normal (suggestive of hyperthyroidism) –  Should NOT be the initial imaging study for normal / elevated serum TSH levels –  Strong recommendation, Moderate-quality evidence

•  Ultrasonography [US] of the thyroid and cervical lymph nodes should be performed in all patients with known or suspected thyroid nodules –  Should assess thyroid parenchyma, gland size, nodule size, and presence/absence of suspicious cervical lymph nodes –  Nodules: size in three dimensions and sonographic features –  Strong recommendation, High-quality evidence Haugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133.

Sonographic features of malignancy

16

Table 7. Ultrasound Features of Lymph Nodes Predictive of Malignant Involvementa

overl patie ules, Reported Reported not c Sign sensitivity, % specificity, % wide FIG. 2. ATA nodule sonographic patterns and risk of malignancy. grayMicrocalcifications 5–69 93–100 there Cystic aspect 10–34 91–100 Peripheral vascularity 40–86 57–93 helpf Table 6. Sonographic Patterns, Estimated Risk of Malignancy, and Fine-Needle Aspiration Hyperechogenicity 30–87 43–95 in wh Guidance for Thyroid Nodules Round shape 37 70 comm Estimated risk FNAasize cutoff wide with permission from the European Thyroid AssociaSonographic pattern US features of malignancy, % (largestAdapted dimension) not p tion guidelines for cervical ultrasound (20). tradit aHaugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133. >70–90 High suspicion Solid hypoechoic nodule or solid hypoechoic Recommend FNA at ‡1 cm

Patient OM • 

• 

• 

The right thyroid lobe measures 1.4 x 1.7 x 4.2 cm. 5 mm colloid cyst is noted within the right mid thyroid lobe. A benign-appearing 4 mm spongiform nodule is seen within the inferior pole. Right thyroid lobe otherwise demonstrates normal echotexture. The left thyroid lobe measures 2.0 x 1.4 x 5.3 cm. 3 nodules are seen on the left. 1.3 cm benign-appearing spongiform nodule is seen superiorly within the left hemithyroid. The dominant nodule within the left lobe measures 1.5 x 1.1 x 1.9 cm and contains a central shadowing coarse calcification within the mid left thyroid. A 1 cm benign-appearing nodule is seen inferiorly within left hemithyroid. No abnormal cervical lymph nodes.

Trachea

Carotid artery

Biopsy with FNA •  Fine needle aspiration (FNA) is the procedure of choice (when clinically indicated) –  Accurate and cost-effective –  Should be performed WITH ultrasound – lower rates of nondiagnostic and false-negative cytology results –  Strong recommendation, high-quality evidence

Haugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133.

Recommendations for FNA Suspicion based on sonographic pattern High

Risk of malignancy (%)

FNA size cutoff (largest dimension)

Strength of Recommendation

Level of evidence

>70-90 %

≥1 cm

Strong

Moderate

Intermediate

10-20%

≥1 cm

Strong

Low

Low

5-10%

≥1.5 cm

Weak

Low

Very low

4 cm •  Previous studies have suggested that nodules >3-4 cm in size may have higher rates of false-negative FNA [‘sampling error’]

–  –  –  – 

Symptomatic Recurrent cystic nodules causing compression or cosmetic concerns ‘Clinical concern’ Weak Recommendation, Low-quality evidence

•  Routine TSH suppression therapy for benign nodules is not recommended –  Strong recommendation, High-quality evidence Haugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133.

Bethesda II: Benign •  What is the optimal follow-up for benign nodules? Suspicion based on US pattern

Recommendation

Strength of recommendation

Level of evidence

High

Repeat US and US-guided FNA within 12 months

Strong

Moderate

Low-Intermediate

Consider repeat FNA if there is: (1) evidence of growth (20% in at least 2 dimensions with minimal increase of 2 mm) or (2) development of new suspicious features

Weak

Low

Very low

Utility of repeat US is limited. If repeated, should be at ≥24 months

Weak

Low

•  Nodules with TWO benign FNA results and no evidence of growth do not need additional US surveillance –  Strong recommendation, Moderate-quality evidence Haugen BR et al. 2015 ATA Guidelines. Thyroid 2016;26(1):1-133.

Bethesda VI: Malignant •  Surgery is generally recommended –  Strong recommendation, Moderate-quality evidence

•  Exceptions: –  Very low-risk thyroid cancers (