How to Investigate Thyroid Nodules like A Pro

Chris Sadler, MA, PA‐C, CDE, DFAAPAMedical Science Outcomes Liaison – Intarcia Diabetes and Endocrine AssociatesLa Jolla, CAPast President ‐ ASEPA

DisclosuresEmployee of Intarcia Therapeutics Inc, I am speaking on my own behalf and do not represent Intarcia on this subject matter. 

PA Sadler does not intend to discuss the use of any off‐label use/unapproved drugs or devices 

Objectives

• Summarize the current data on thyroid cancer occurrence and trends in mortality

• List ultrasound characteristics that increase the risk for thyroid malignancy

• Identify the appropriate work-up and follow-up of thyroid nodules based on initial presentation and findings

A 35 yo asymptomatic female is found to have a solitary solid hypoechoic 2.0 cm nodule which was found to be benign on FNA x2.  It has not grown on yearly US exams x 2 yrs. You recommend: 

1. Reassure, repeat US in 3 yrs

2. Repeat FNA just to be sure

3. Continue yearly US exams for life

4. This nodule no longer needs follow‐up 

A 35 yo asymptomatic female is found to have a solitary 2.0 cm solid, markedly hypoechoic nodule with microcalcifications on thyroid ultrasound. The TSH is normal. The most appropriate next step would be to: 

1. Reassure, repeat US 6‐12 months

2. Order an FNA

3. Refer for surgery

4. Order thyroid uptake and scan

Thyroid cancer diagnosis rates have increased dramatically over the last decade along with thyroid cancer mortality rates

1. True

2. False 

3. I don’t know, ask me another question

4. I’ll answer after the lecture 

Thyroid Nodules

Principles of Anatomy and Physiology,, Seventh Edition, 1993, Biological Sciences Textbooks, Inc.

Thyroid Nodule/CA Overview Using US 19 – 68% of randomly selected adults have thyroid nodules1

More common in women and elderly1

2009 ‐ 37,200 cases of thyroid cancer diagnosed2

2014 ‐ 63,000 cases of thyroid cancer diagnosed2

Mortality rates unchanged despite the increase in thyroid cancer incidence2

1) Guth, S, et al. Very high prevalence of thyroid nodules detected by high frequency ultrasound examination. Eur J Clin Invest 2009;39:699-706.2) Siegel, R et al. Cancer Statistics, 2014 Cancer J Clin 2014;64:9-29.

Causes of Thyroid Nodules

Benign nodular goiterChronic lymphocytic thyroiditis (Hashimoto’s)Simple or hemorrhagic cystsToxic autonomous noduleFollicular neoplasmSubacute thyroiditisPapillary carcinoma – most commonFollicular carcinomaMedullary carcinomaAnaplastic carcinomaPrimary thyroid lymphomaMetastatic tumors

Laboratory Testing – TSH/Other A low TSH = low risk for malignancy (indicates need for thyroid scan) Also check FT4 

An elevated or ULN TSH = increased risk for malignancy in nodular thyroid disease.  Check FT4 and TPO antibodies 

A single, non‐stimulated serum calcitonin measurement if medullary thyroid carcinoma is suspected due to FNA results or history. 

AACE Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules –2016 Update

Thyroid Nodule Work‐up (ATA Guidelines)

Evaluation: Do you need a I123 scan?

• If TSH is low – Yes

• If TSH normal or high - No

• Cold nodule = non-functioning (no iodine uptake)• Most cancers are cold nodules

• most nodules are cold and most are not cancers

Low TSH: ? Toxic “Hot” Nodule or Toxic MNG

Hyper-functioning nodules almost never cancer

CLINICAL FACTORS SUGGESTING INCREASED RISK OF MALIGNANT POTENTIAL

Hx of head and neck irradiation (<25 yrs ago)

Family Hx of MTC, MEN 2, PTC, Familial Polyposis coli, Cowden dz, Gardner syndrome

Age <14, >70

Male sex

Firm or hard consistency

Fixed nodule

Palpable cervical adenopathy

Persistent dysphonia, dysphagia, or dyspnea

History & Exam: Nodular Thyroid

• How long has it been there? Is it changing? Any symptoms (pressure, voice, etc.).

• Lymphadenopathy present or absent

• Fingers assess size poorly; ultrasound required

• Assess for mobility and consistency (fixed and firm/hard on palpation more suspicious)

ULTRASOUND FACTORS SUGGESTING MALIGNANCY

THESE ARE ADDITIVE

Microcalcifications

Irregular margins

Solid – marked hypoechogenicity

Suspicious cervical lymphadenopathy

Taller than wide in transverse view

Extra‐capsular extension

Interrupted rim calcification 

QUALITY of the Ultrasound Experience varies widely: What to look for?

Documented details of nodule characteristics Size, location, solid, cystic, mixed

Hypo/iso/hyperechoic

Margins, calcifications, vascularity

Taller than wide, extra‐thyroidal extension

Mention of presence or absence of adenopathy

Clear report with guidance regarding next steps –(FNA, repeat US, no further f/u needed)

Follow‐up – a rapidly growing or changing nodule is more suspicious (change in US characteristics is more prognostic than change in size) 

Fine Needle Aspiration

•Best means of evaluating a thyroid nodule.

•For solitary nodule the diagnostic procedure of choice

•If multiple nodules, choose high risk nodules for sampling based on suspicious characteristics, not size

•ACR – recommends sampling not more than 2 nodules with the most suspicious findings based on point totals

•Dependent on an experienced cytopathologist

(Ultrasound guided FNA is standard of care)

Fine Needle Aspiration(Ultrasound guided FNA is standard of care)

Who needs an FNA? Depends on the risk category based on suspicious US characteristics. 

Single Feature Approach

Pattern Approach

ACR – TI‐RADS

NODULE CHARACTERISTICS• Normal

• Transverse

NODULE CHARACTERISTICS• Normal

• Long axis

Superior Inferior

NODULE CHARACTERISTICS

• Pure CysticBenign, < 1 % Risk 

No FNA (but may 

aspirate fluid if

symptomatic)

TI‐RADS = 0 pts (no FNA) 

NODULE CHARACTERISTICS

• Spongiform

Very Low

Suspicion

< 3% Risk

Consider FNA

If > 2.0 cm

TI-RADS = 3 pts

(FNA if over 2.5 cm)

NODULE CHARACTERISTICS

• Partially CysticVery low

Suspicion

< 3 % Risk

Consider FNA

If > 2.0 cm

TI-RADS = 3 pts

(FNA if over 2.5 cm)

NODULE CHARACTERISTICS

• Solid hypoechoic, regular margins• Intermediate suspicion

• 10-20%

• FNA > 1 cm

• TI-RADS = 4 pts

• (FNA if >1.5 cm)

NODULE CHARACTERISTICS

• Lumpy Bumpy Thyroid• No need for FNA

Nodule Characteristics• Solid hypoechoic w/Microcalcifications

High suspicion

> 70-90%

FNA if > 1 cm

(punctate echogenic

Foci)

TI-RADS = 7 pts

(FNA if >1 cm)

NODULE CHARACTERISTICS• Solid iso/hyperechoic

• Regular Margins –

• Low suspicion

• 5-10%

• FNA if > 1.5 cm

• TI-RADS = 3 pts

• (FNA > 2.5 cm)

NODULE CHARACTERISTICS• Solid Hypoechoic

• Lobulated Margins

• Calcifications

• High suspicion

• 70-90% Risk

• FNA if > 1 cm

• TI-RADS = 9 pts

• (FNA > 1 cm

NODULE CHARACTERISTICS

• Solid Hypoechoic-Taller than Wide (transverse view)

• High suspicion

• > 70-90% Risk

• FNA > 1 cm

• TI-RADS = 7 pts

• FNA > 1 cm

Nodule Characteristics• Extra-capsular invasion

• High suspicion

• > 70-90% Risk

• FNA > 1 cm

• TI-RADS = 7 pts

• (FNA > 1 cm)

LYMPH NODE CHARACTERISTICS

• Normal Abnormal• Transverse view

• A/T ratio > 2 A/T ratio < 2

A/T ratio = 1.1

The Onion

Case: Joe A.

• 36 yo male with incidental finding of a 6 mm solid thyroid mass on MRI during w/u for cervical disc dz., no family history or risk factors for thyroid cancer.

• What test do you order?• TSH

• Ultrasound

Case: Joe A.• TSH is normal

• Ultrasound Results: 5.6x4x5.5 mm (L x AP x W) solid hypoechoic nodule in the right lower pole, no microcalcifications, irregular borders or abnormal lymph nodes

• What next?

The most appropriate next step would be to: 

1. Reassure, repeat US in  1 year

2. Order an FNA

3. Refer for surgery

4. Order thyroid uptake and scan

FNA for Low Risk Patients w/o Abnormal LNs Solid Hypoechoic nodule = intermediate risk 10‐20% 

But given < 1 cm can reassure and repeat US in 12 months, if > 1 cm and/or more importantly, develops new suspicious features –> FNA. 

If repeat US are stable for several years, then may no longer need to follow this nodule

TI‐RADS = 4 pts moderately suspicious (FNA if > 1.5 cm) Follow‐up. Repeat US at 1, 3 and 5 yrs. 

Case: Keri M.

• 22 yo female presents with left sided nodule on routine exam 

•Ultrasound order by PCP: 1.8 cm solid hypoechoic nodule in the left lower pole with irreg. margins

•On exam, the left sided nodule is firm, non‐tender

•TSH and TPO antibodies are normal

•Here in my office with very anxious mother

How would you proceed?

• 1) refer immediately to surgeon 

• 2) US guided FNA of left thyroid nodule

• 3) Observe and repeat US in 6 months

• 4) Give thyroid hormone to suppress the nodule and repeat US in 6 months 

FNA for Low Risk Patients w/o Abnormal LNsHypoechoic solid  > 1.0 cm + irreg. margins

High suspicion pattern (70‐90% risk) 

Iso or Hyperechoic and solid > 1.5 cm

Complex, non‐calcified > 1.5‐2.0 cm

Spongiform nodules > 2.0‐2.5 cm

Multiple nodules

Prioritize based on above criteria

If multiple similar appearing, coalescent nodules, FNA the largest

TI‐RADS = 6 pts – moderately suspicious (FNA if > 1.5 cm)

Case: Keri M.

JV

CATR

Case: Keri M.

TRCA

JV

Case: Keri M. 

Case: Keri M.

Case: Keri M.

Case: Keri M.

• FNA:  Suspicious for Papillary Thyroid Carcinoma

• Suspected metastatic lymph nodes throughout left neck

• Plan: Total Thyroidectomy with left neck dissection, postoperative RAI and total body scan

Thyroid Cancer

• Rare ~ 5-10% of all palpable thyroid nodules

• Female/male ratio = 4:1

Thyroid CancerFive typesPapillary: 60-80% of all cases; slow growingFollicular: 15-30%. More aggressive than

papillaryMedullary: 2-10%. Familial, associated with

MEN IIAnaplastic: (rare) Most aggressive of all; 20%

five year survival. Differentiates into small and giant cell. Death within 6 months if giant cellThyroid Lymphoma: 4-10% usually women

over 50 with Hashimoto’s thyroiditis. Rapid growing neck mass

Thyroid Cancer

• Generally found as a thyroid nodule

• Diagnosis is histological

• Treatment

•Surgical excision

•RAI ablation (none for low risk, lower doses)

•Radiotherapy?

•Chemotherapy?

Thyroid Cancer

•Prognosis depends on:

•Type

•Patient’s age at diagnosis

•Extrathyrodal extension or distant metastases

•In patient with metastatic disease, the right initial surgery improves prognosis

Case: Rick •42 yo male 2.5 cm nodule in left thyroid lobe

•Solid hyperechoic, well defined borders, no other suspicious features

•Visible, firm, moves well 

•FNA 4 years ago = benign cytology

•Yearly US exams stable

•Pt. with young children, continues to worry 

•Last US one year ago ‐ no change 

ACR ‐ TIRADS

Case: Rick

TSH: 1.110 (0.35 - 4.00) , Free T4: 1.25 (0.89 - 1.80) , TPO antibodies: negative

What would you do next?

1. Repeat US

2. Repeat US guided FNA

3. Refer for surgery

4. Reassure – repeat US in one year

Benign cytology has low risk for malignancy

Follow‐up of cytologically benign nodules

Growth = > 50% increase in volume or > 20% increase in 2 of 3

dimensions (min 2 mm) However growth not related to malignancy

Case: Rick

• Repeat US guided FNA reveals cytology c/w papillary thyroid carcinoma

• Referred for surgical removal

• If 2 US guided FNA’s are benign the risk of malignancy is virtually zero.

• Always listen to the patient

Follow-up of benign nodules

• Prospective, multicenter, observational study of 992 patients with 1,567 asymptomatic thyroid nodules

•The majority of nodules benign at 5 yrs

•Cancer in only 0.3% of nodules in 5 years 

• Of the 5 cancers only 2 had grown, the others had changes in US characteristics

• Repeat US in 6-18 months in sonographically and cytologically benign nodules and then ever 3-5 yrs as long as no significant growth

JAMA 2015;313:926-35

TI‐RADS – Follow up of Nodules too small to meet FNA criteria Mildly to Moderately suspicious – repeat US at 1,3 and 5 yrs 

Highly suspicious – US yearly for 5 yrs

Caveats – Abnormal cervical lymph nodes in the presence of a thyroid nodule dramatically increases risk of malignancy regardless of size

ATA – Recommends repeat of FNA within a year for highly suspicious nodules with benign cytology on initial FNA. 

Future for Indolent “Cancers”

“Encapsulated follicular variant of papillary thyroid carcinoma”  

proposed name change to: 

“Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features” (NIFTP)

(This diagnosis only made after surgery but has implications for treatment and follow‐up)  

Summary•Thyroid nodules are common and most are

benign

•TSH to determine if scan necessary

•US to identify suspicious nodules based on single characteristics, patterns or TI-RADS

•USG-FNA should be performed on suspicious nodules

•Follow-up determined by risk category of nodule

•Good clinical judgement trumps guidelines

A 35 yo asymptomatic female is found to have a solitary solid hypoechoic 2.0 cm nodule which was found to be benign on FNA x2.  It has not grown on yearly US exams x 2 yrs. You recommend: 

1. Reassure, repeat US in 3 yrs

2. Repeat FNA just to be sure

3. Continue yearly US exams for life

4. This nodule no longer needs follow‐up 

A 35 yo asymptomatic female is found to have a solitary 2.0 cm solid, markedly hypoechoic nodule with microcalcifications on thyroid ultrasound. The TSH is normal.  The most appropriate next step would be to: 

1. Reassure, repeat US 6‐12 months

2. Order an FNA

3. Refer for surgery

4. Order thyroid uptake and scan

Thyroid cancer diagnosis rates have increased dramatically over the last decade along with thyroid cancer mortality rates

1. True

2. False 

3. I still don’t know, quit pestering me

4. Ask me again tomorrow 

Resources•www.thyroid.org - American Thyroid Association

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

•www.aace.com – American Association of Clinical Endocrinologists

•Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules –2016 Update

• ACR Thyroid Imaging, Reporting and Data System (TI-RADS) J Am Coll Radiol. 2017;14:587-595