Sipos 1

Update on Thyroid NodulesNew Imaging Techniques

Jennifer A. Sipos, MDAssociate Professor

Division of EndocrinologyThe Ohio State University

Prevalence of Endocrine Disorders in U.S. Adults

Endocrine Condition Prevalence

Metabolic syndrome 35-40%

Obesity 25-50%

Diabetes 5-25%

Hyperlipidemia 15-20%

Osteoporosis 7%

Thyroid nodules 30-70%

Golden SH., et al. J Clin Endo Metab 2009; 94:1853-78Mazzaferri M. New England Journal Medicine 1993; 328:553-558Guth S., et al. Eur J Clin Invest 2009; 39:699-706

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Benign Malignant

Causes of thyroid nodules

g

Multinodular goiter (colloid adenoma)

Hashimoto’s (chronic lymphocytic) thyroiditis

CystColloidSimpleHemorrhagic

F lli l d

Papillary carcinoma

Follicular carcinoma

Medullary carcinoma

Anaplastic carcinoma

Primary thyroid lymphoma

Metastatic carcinoma Follicular adenomas

Hurthle cell adenomas

breastmelanomarenal cell

Epidemiology – thyroid nodules

Autopsy/

Palpation

Autopsy/ Ultrasound

Mazzaferri 1993 NEJM 328:553-9

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How good are we at finding nodules?Ultrasound vs. Palpation

es fo

und

by U

S

50%

Brander 1992 J Clin Ultrasound 20: 37-42

# N

odul

e

94%

Nodule size by US

Palpable Thyroid Nodules

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Nonpalpable Thyroid Nodules

Not all that is palpable is a nodule…..

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American Thyroid Association Management Guidelines

Thyroid sonography should be performed in all patients with known or suspected thyroid nodules

Recommendation rating: A

Cooper, et al Thyroid 2009

Concerning Clinical Features

High clinical suspicion

• Rapid tumor growthRapid tumor growth• Very firm nodule (rock hard)• Fixation to adjacent structures• Vocal cord paresis• Enlarged regional lymph nodes• Family history of PTC or MEN 2• Distant metastases

Positive Predictive Value (PPV) – good (70-75%)

Negative Predictive Value (NPV) – unacceptable (85%)

•History of radiation exposure to the head/neck

Hamming JF., et al. Arch Int Med 1990; 150:1088Rago T., et al. Clin Endo 2007; 66:13

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History, physical

TSH

High, normal TSH Low TSH

Ultrasound

>1cm<1cm

Thyroid scan

FT4, TT3

Functioning Nonfunctioning>1cm

U/S guided FNARepeat U/S

in 6-24 mo

Functioning

“Hot”

No FNA

Rx hyperthyroidism

Nonfunctioning

“Cold/warm”

Ultrasound-guided

FNA

Imaging

Sipos 7

Size and composition as predictors of malignancy

Characteristic No. benign

No.malignant

% Malignant

pValue

Size (mm) 0.48

11 14 9 135 15 1011-14.9 135 15 10

15-19.9 167 16 8.7

20-24.9 149 19 11.3

25-29.9 112 11 8.9

>30 208 33 13.7

Composition <0.01

Completely solid 330 55 14 3

Frates et al 2006 JCEM 91: 3411-17

Completely solid 330 55 14.3

Predominantly solid 209 24 10.3

Mixed solid and cystic 129 8 5.8

Predominantly cystic 85 2 2.3

Completely cystic 7 0 0

US Predictors of Malignancy for Thyroid Nodules

US feature Mean sensitivity

(range)

Mean specificity

(range)

Increased flow 77 (57-92) 79 (35-97)

Irregular borders 58 (48-78) 85 (74-95)

Taller than wide 58 (33-84) 81 (60-92)

Hypoechogenicity 53 (26 87) 73 (43 94)Hypoechogenicity 53 (26-87) 73 (43-94)

Microcalcifications 42 (29-59) 91 (86-95)

*Review of 15 large studies

Sipos JA, Thyroid 2009;19:1363-1372

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Thyroid Imaging Reporting and Data System(TIRADS)

Horvath, et al. 2009 JCEM 90:1748-51

Park et al 2009 Thyroid 19: 1257-64

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Park et al 2009 Thyroid 19: 1257-64

ElastographyMeasure of tissue stiffness by application of an external force

Elastic=Benign Firm=Malignant

Meta-analysis of 8 studies (mostly European and Asian)

Lippolis PV et al. 2011 JCEM 96(11): E1826-30Bojunga et al 2010 Thyroid 20(10): 1145-50

y ( y p )

n=639 nodules

Sensitivity 92% (88-96%) Specificity 90% (85-95)

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Thyroid Imaging Reporting and Data SystemTIRADS

Russ et al 2013 Eur J Endocrinol 168: 649-55

Thyroid imaging reporting and data systemTI-RADS

Russ et al 2013 Eur J Endocrinol 168: 649-55

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TI-RADS and elastography for predicting benignity

Russ et al 2013 Eur J Endocrinol epub

PET and Thyroid Nodules

18 studies – 55,160 patients

571 (1%) with unexpected focal

Systematic Review

uptake in thyroid

322 underwent “diagnostic confirmation”

33% malignant; 4.7% “indeterminate”

Shie P 2009 Nuc Med Commun 30(9): 742-8

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Fine Needle Aspiration

Indications for FNANodule features Threshold

size for FNARecommendation

rating

HIGH RISK HISTORY

Suspicious US features

>5mm A

No suspicious US features >5mm I

Abnormal LNs All A

Microcalcifications ≥1cm B

NOT HIGH RISK-SOLID NODULE

Hypoechoic

>1cm B

Iso- or hyperechoic ≥1-1.5cm C

MIXED CYSTIC-SOLID NODULE ≥1.5-2cm BMIXED CYSTIC SOLID NODULE

Suspicious US features

1.5 2cm B

No suspicious US features ≥2cm C

Spongiform nodule ≥2cm C

Purely cystic nodule No FNA E

Cooper et al 2009 Thyroid 12:1-48

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Diagnostic yield of sequential aspirations in 120 patients with multiple nodules and cancer

FNA performed on Number of nodules >1cm

2 (n = 73) 3 (n = 27) ≥ 4 (n = 20)

Largest nodule 86.3 51.8 55

Largest 2 nodules 100 81.5 85

Largest 3 nodules 100 95

Largest 4 nodules 100

FNA of only the largest nodule in a patient with 2 nodules would have missed 13.7% of cancers. In patients with 3 nodules, 48.2% of cancers would have been missed by performing an FNA on the largest nodule only.

Frates et al 2006 JCEM 91: 3411-17

Epidemiology of Thyroid Cancer

Aschebrook-Kilfoy 2013 Cancer Epidemiol Biomark Prev 22: 1252-9

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Changing mode of diagnosis in PTMC

• FNA for thyroid nodules has more than doubled from 2006-2011

• Thyroid FNA grew as a percentage of all FNA f 49% t 65%from 49% to 65% Sosa et al 2013 Surgery epub

Hay et al 2008 Surgery 144: 980-7

Papillary microcarcinomaLikelihood of disease progression with observation

Multivariate analysis: Age <40y RR 4 348 (2 293 8 196) Age <40y RR 4.348 (2.293-8.196)

p<0.0001 T≥9mm RR 4.717 (1.961-11.364)

p=0.0005

Ito et al 2013 Thyroid epub

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Natural history—benign nodules

Of 268 benign nodules studied 89% had grown (more than 15%) at five years

Average increase in volume was 69%

Of 74 nodules re-biopsied, only one revealed malignancy

Solid nodules grew more than cystic

Alexander 2003 Ann Internal Med 138: 315-8

Follow up

Repeat U/S 6-18 months after FNA

Repeat FNA if >50% change in volume or 20% change in nodule diameter in at least twochange in nodule diameter in at least two dimensions with minimum increase of at least 2mm

Interval for the next follow-up may be every 3-5 years

Cooper et al 2009 Thyroid 19

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Indications for surgery

Malignant, suspicious, or indeterminate cytologycytology

Compressive symptoms

≥2 “insufficient” FNAs

Cosmetic

Large toxic gnodule/goiter

Graves disease

Enlarging benign nodule

From Lange Endocrinology 7th ed.