A 69-year-old female presented with an itchy throat and a family history of thyroid cancer. An ultrasound revealed an 8mm nodule in her left thyroid lobe. Further investigations would include a fine needle aspiration biopsy of the nodule. The doctor would explain to the patient that the small nodule size is reassuring but not completely benign, and recommend follow up ultrasound scans. If the nodule was larger, such as 15mm or 30mm, the risk of cancer would be higher and surgery may be considered.

1. Dr. Prabin Bhattarai
2nd Year MD Resident
Internal Medicine
2079/07/14

2. Case Scenario
A 69 years old female, otherwise healthy presented with itchy throat. Her sister had
thyroid cancer for which surgery was done. Having peristent symptoms for a week, she
visited a general practitioner with fear of some cancer. Her GP didn’t find any palpable
lump and thus ordered a Thyroid Ultrasound that revealed a nodule of 8mm in her left lobe
of thyroid.
1. What further investigations would you like to do?
2. How would you explain to her? Is it worrisome?
3. Follow up? Surgery?
4. What wud change in management if size was
15mm, 30 mm ?
2

3. Contents
• Anatomy
• Introduction, Epidemiology and Causes
• Approach
• Investigations
• Diagnosis
• Categorization and Classification
• Management
• Algorithms
• Special Scenarios
3

4. Thyroid Gland
4

5. Introduction
• Discrete lesion within thyroid gland that is radiologically distinct from surrounding
parenchyma
• Noted by patient or clinical examination or incidentally during carotid ultrasonography,
neck or chest computed tomography (CT), magnetic resonance imaging (MRI), or
positron emission tomography (PET) scanning
• Palpable (5% of adults) or impalpable
• Functioning or non functioning
• 4 to 6.5 percent are malignant
5
Ref :ATA Guidelines 2015

6. Epidemiology
• 35-59 years of age
• Palpable nodules in 5% women and 1% men living in iodine-sufficient region
• Incidence F>M, but aggressiveness M>F
• Pregnancy increases risk
• Children may present with more advanced disease
• Prevalence increases with
• Age ( present in up to 50% individuals aged >50 years)
• Exposure to ionizing radiation
• Iodine deficeincy region
6

7. Causes : Wide Spectrum
7

8. Thyroid incidentalomas
• Nonpalpable thyroid nodules that are detected during other imaging procedures.
• Same risk of malignancy as palpable nodules, increased risk if >45 years
• May have history of childhood head or neck irradiation
• Thyroid nodules ≥1 cm with focal FDG uptake that are discovered incidentally on PET
scans require ultrasound-guided FNA biopsy as many are malignant
• Thirty-five percent of Graves disease have nodules, and 3.3 percent have thyroid cancers.
• The majority of cystic thyroid nodules are benign, degenerating thyroid adenomas
8

9. Factors that increase risk of malignancy *
• Children
• Adults < 30 years of age
• Head and neck irradiation
• Family history of thyroid cancer
• Nonpalpable nodules (incidentalomas) have the same risk of malignancy as palpable
nodules of the same size
9

10. Approach
History
Physical Examination
TSH and Ultrasonography
Thyroid Scintigraphy
Fine Needle Aspiration
Follow Up and Surgery
10

11. History
• A neck mass
• Symptoms of hyperthyroidism and hypothyroidism
• Throat or neck pain (hemorrhage into benign nodule, rarely carcinoma)
• Features suggestive of malignancy
 History of rapid growth of a neck mass
 Childhood head and neck irradiation
 Family history of thyroid cancer
 Compressive or invasive symptoms
 Thyroid cancer syndromes (MEN2, FAP, Cowden syndrome)
11

12. Physical examination
• Palpation of thyroid (solitary or dominant nodule in multinodular gland )
• Firm nodule: 2-3 times increased risk of carcinoma
• Substernal extension estimated by relationship of inferior aspect of mass to clavicle
• Thoracic inlet obstruction by Pemberton maneuver
• Suggestive of cancer
 Fixed hard mass
 Cervical lymphadenopathy
 Vocal cord paralysis
12

13. Lab investigations
• CBC, ESR: Inflammatory or infectious thyroiditis
• TFT: Most are euthyroid
• TSH: Independent risk factor for predicting malignancy
• Anti TPO antibodies in patients with high TSH (Hashimoto's thyroiditis)
• Anti Thyroglobulin Antibodies : No routine use, no role in malignancy identification
• Serum calcitonin : controversial for routine use, elevated in MTC
• 24-hour urine for metanephrines and catecholamines
• Serum calcium to exclude hyperparathyroidism
13

14. Serum TSH for all
• Higher prevalence of malignancy associated with higher TSH level
• <0.4 mU/L : 2.8%
• 0.4 to 0.9 mU/L : 3.7%
• 1 to 1.7 mU/L : 8.3%
• 1.8 to 5.5 mU/L : 12.3%
• >5.5 mU/L : 29.7%
• Thyroid cancer with higher TSH associated with a more advanced stage
14
Ref : Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA. Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle
aspiration. J Clin Endocrinol Metab. 2006;91(11):4295-4301.

15. Thyroid Stimulating Hormone
Low TSH
• Hyperfunctioning nodule
• Thyroid scintigraphy
• Evaluation for hyperthyroidism
TSH Normal or High
• Hypofunctioning nodule
• If sonographic criteria met →
Ultrasound-guided FNA biopsy
• Do not meet sonographic criteria for FNA →
Monitoring
• Evaluation for hypothyroidism
15

16. Thyroid ultrasonography for all
• Not recommended as screening tool to detect nonpalpable thyroid cancers
• Size and anatomy of the thyroid gland and adjacent structures in the neck
• Identify additional nonpalpable nodules
• Confirm if the palpable nodule is indeed a nodule
• Identify posterior nodules
• Identify predominantly cystic nodules
• Helps select nodules for FNA
• Suspicious ultrasonographic findings of cancer
16

17. Ultrasonographic features and malignancy
Increased risk
• Hypoechogenicity
• Solid composition
• Punctate echogenic foci
(microcalcifications)
• Infiltrative/irregular margins
• Taller-than-wide shape
• Associated suspicious
lymphadenopathy
Lower risk
• Isoechoic or hyperechoic
• Spongiform appearance
• Simple cysts
• Comet-tail artifact within a cystic
nodule
• Uninterrupted eggshell calcification
17

18. Thyroid scintigraphy : for functional status
• Cannot be used to select patients for surgical resection
• Contraindicated during pregnancy
• Breastfeeding should be suspended
• Utilizes 123-I or technetium-99m pertechnetate
• Most benign and virtually all malignant thyroid nodules
concentrate both radioisotopes less avidly (cold) than
adjacent normal thyroid tissue
18

19. Scintigraphy results : Based on tracer uptake
1. Nonfunctioning → cold → FNA
2. Autonomous → Hyperfunctioning → hot (5 to 10 percent of palpable nodules), few are
cancer and fewer are aggressive
3. Indeterminate
• Small, nonfunctioning nodules (majority) anterior or posterior to normal tissue
• Autonomous nodules that produce insufficient thyroid hormone to suppress TSH
• Need FNA if they meet sonographic criteria for sampling
• Can also be assessed by suppression scanning
19

20. Hyper functioning - ‘‘HOT’’
Uptake is greater than surrounding thyroid
(~5% malignant)
Iso-functioning - ‘‘WARM’’
Uptake is equal to surrounding thyroid
(~10% malignant)
Non-functioning - ‘‘COLD ’’
Uptake less than surrounding thyroid
(~20% malignant)
20

21. Radioimaging : Not routinely done
Chest Xray
Tracheal deviation, compression,
metastases, Calcifications
CT Scan
Substernal extension
Lymphadenopathy
Better structure relation and visualization
MRI
Recurrent or persistent tumor from
postoperative fibrosis
21

22. FNAC : Procedure of choice
Advantages
• Minimally invasive
• Improved diagnostic accuracy
• Higher malignancy yield at the time of
surgery
• Significant cost reductions
• Specifity : 72 – 100%
• Sensitivity : 65 – 98%
Disadvantages
• False-positive results (difficulties in
interpreting cytology)
• Hashimoto thyroiditis
• Graves disease
• Toxic nodules
• Cannot distinguish follicular adenoma
from carcinoma
22

23. Benign Vs Malignant Nodule
Benign Nodule
• Benign on FNAC
• Soft Mobile nodule
• Simple cystic nodule <4cm in USG
• Hyperfunctioning hot nodule
• High Serum antibodies
• Suppressed TSH
Malignant Nodule
• Suspicious or malignant FNAC
• Hard fixed nodule
• Ipsilateral cord paralysis
• Ipsilateral lymph nodes
• Solitary solid nodule or complex cyst
>4cm on USG
• Hypofunctioning cold nodule
23

24. Risk stratification systems (RSS)
• Risk estimates for thyroid cancer based on certain sonographic patterns
• Specific size cutoff criteria differ
• Lower size cutoffs have higher sensitivity and lower specificity for thyroid cancer
diagnosis
• All have been shown to reduce unnecessary FNAs by at least 45%
 American College of Radiology [ACR] Thyroid Imaging Reporting and Data System [TI-
RADS] : Preferred, Selective, Superior, Complex
 American Thyroid Association
 European Thyroid Association [EU-TIRADS]
24

25. 2015 ATA Guidelines (less selective)
25

26. 26

27. ACR TI-RADS
27

28. Entirely or nearly entirely cystic Spongioform
28

29. Solid or almost completely solid Mixed cystic solid
29

30. ACR TI-RADS Classification
30

31. Fine Needle Aspiration
• FNA (if achievable) in any TR5 nodule (regardless of size) if
• Subcapsular locations adjacent to the recurrent laryngeal nerve (RLN) or trachea
Extrathyroidal extension
• Extrusion through rim calcifications
• Associated with sonographically abnormal cervical lymph nodes
• Thyroid nodules under 5 mm : Technically difficult, nondiagnostic result, reliability of a
negative result should be discussed
• FNAC of abnormal lymph node if thyroid nodule is not amenable to FNA.
31

32. FNA of subcentimetric nodules
• Strong family history of differentiated thyroid cancer
• Known syndromes associated with thyroid cancer
• Young age
• History of therapeutic childhood head and neck or whole body radiation
• Preference for FNA over observation
32

33. Monitoring of nodules that do not meet FNA criteria
• Ideal candidates for observation of suspicious subcentimetric nodules include
• older patients (age >60 years)
• solitary nodules with well-defined margins and a >2 mm rim of normal thyroid
parenchyma
• All adult patients and those with multiple nodules (same risk of malignancy as those with
a single nodule)
• TIRADS Based decisions made at every USG checkpoint
33

34. Periodic follow up ultrasonography
(A) Nodules with high suspicion US pattern
Repeat US in 6–12 months
(B) Nodules with low to intermediate suspicion US pattern
Consider repeat US at 12–24 months
(C) Nodules >1 cm with very low suspicion (including spongiform nodules) and pure cyst
Utility and time interval of surveillance US for risk of malignancy is not known
If US is repeated, it should be at ≥24 months
(D) Nodules ≤1 cm with very low suspicion (including spongiform nodules) and pure cysts
Do not require routine sonographic follow-up
34

35. Bethesda System : for uniform FNAC reporting
35

36. Benign Nodules : Bethesda II : Follow Up
• Uncertanity in Frequency of ultrasound imaging
• Less frequent monitoring of cytologically benign nodules may be warranted *
• 12 to 24 months initially → Every 3-5 years based on size and usg findings
• Reaspiration after a benign biopsy within 12 months if #
• Substantial growth (more than a 50 % change in volume or 20 % increase in nodule
diameter with a minimum increase in two or more dimensions of at least 2 mm)
• Appearance of suspicious ultrasound features
• New symptoms are attributed to a nodule
36
* Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA. 2015;313(9):926-935
# Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American
Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133.

37. Bethesda and management
Bethesda Category Comment Management
Nondiagnostic
(Bethesda I)
Cytologically inadequate Repeat the FNA in 4-6
weeks
Core Needle Biopsy
Benign
(Bathesda II)
Malignancy is rare USG Follow Up
Indeterminate cytology
(Bethesda III and IV)
Molecular testing should be done first Follow Up vs Surgery
Suspicious for malignancy
(Bethesda V)
Suggestive of, but not definitive for, papillary
thyroid cancer, or other malignancies, NIFTP
Surgery
Malignant
(Bethesda VI)
Papillary cancer, medullary thyroid cancer (MTC),
thyroid lymphoma, anaplastic cancer, and cancer
metastatic to the thyroid
Surgery
37

38. Some extra nodules and techniques
• Autonomous nodules : controversial; if hyperthyroidism : radioiodine, surgery, or long-
term antithyroid drugs.
• Cystic thyroid nodules : difficult; nondiagnostic cytology can be followed; recurrent
bleeding or cyst reformation may be a source of discomfort, anxiety, or rarely obstructive
symptoms.
Ablation techniques
• Benign, autonomous, and cystic thyroid nodules
• Ultrasound-guided injection of ethanol or sclerosing agents
• Ultrasound-directed physical energy
38

39. Thyroid Nodule and Pregnancy
• FNA of clinically relevant nodule should be performed in eu/hypothyroid pregnant
• If suppressed serum TSH levels that persist beyond 16 weeks gestation, FNA may be deferred
until after pregnancy and cessation of lactation.
• Pregnancy does not appear to modify microscopic cellular appearance, thus standard
diagnostic criteria should be applied for cytologic evaluation
• Thyroid nodules enlarge slightly throughout gestation and that’s not malignant
transformation
• Evaluation of clinically relevant nodule in a pregnant is same as for a nonpregnant , with the
exception that a radionuclide scan is contraindicated
• In addition, for patients with nodules diagnosed as DTC by FNA during pregnancy, delaying
surgery until after delivery does not affect outcome.
• Surgery performed during pregnancy is associated with greater risk of complications, longer
hospital stays, and higher costs
39

40. 40

41. ATA 2015
Algorithm
41

42. Take Home Message
• Benign vs Malignant
• Hypofunctioning vs Hyperfunctionig
• ACR-TIRADS followed for proceeding further
• USG guided FNA Biopsy is the Key to diagnosis
• Bethesda categorization is the key to cytology and management
42

43. Case Scenario
A 69 years old female, otherwise healthy presented with itchy throat. Her sister had
thyroid cancer for which surgery was done. Having peristent symptoms for a week, she
visited a general practitioner with fear of some cancer. Her GP didn’t find any palpable
lump and thus ordered a Thyroid Ultrasound that revealed a nodule of 8mm in her left lobe
of thyroid.
1. What further investigations would you like to do?
2. How would you explain to her? Is it worrisome?
3. Follow up? Surgery?
4. What wud change in management if size was
15mm, 30 mm ?
43

44. 44

45. References
• (2022). Harrison's Principles of Internal Medicine. McGraw Hill LLC.
• (2019). Williams Textbook of Endocrinology. Elsevier.
• Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS. The Diagnosis and
Management of Thyroid Nodules: A Review. JAMA. 2018;319(9):914–924.
• Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association
Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated
Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid
Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133.
• Thyroid Ultrasound Reporting Lexicon: White Paper of the ACR Thyroid Imaging,
Reporting and Data System (TIRADS) CommitteeATA 2015 Guidelines
45