1. Management of thyroid nodule
American Thyroid Association guidelines Mohammed Alessa mbbs,frcsc Assistant professor consultant otolaryngology , head & neck surgery

2. Introduction.
Guidelines recommendation.
Thyroid nodule work up.
Genetic work up
Medical therapy in thyroid nodule
Thyroid nodule in children
Thyroid nodule in pregnancy .

3. Introduction It is a common clinical problem, ( 50% in adult) .
Female : 5% & male : 1%.
High-resolution ultrasound (US) can detect thyroid nodules in 19–67%.
Thyroid Carcinoma occurs in 5-15% of any thyroid nodule (1).
Well differentiated thyroid CA represent 90% of all thyroid CA.
(1) Hegedus L 2004 Clinical practice. The thyroid nodule. N Engl J Med 351:1764–1771.
iodine-sufficient parts of the world

4. Occult carcinoma in 6 – 35 % of glands at autopsy
(usu 4-10 mm)
– Biologic behavior difficult to predict
12,000 new thyroid cancers / year
1000 deaths / year
Surgically removed nodules:
– % colloid nodules
– % adenomas
– 8-17 % carcinomas

5. Carcinoma ( subtypes) Histological subtype Papillary 70%
Follicular 15%
Medullary 5-10%
Anaplastic 5%
Poorly differentiated 1%
Lymphoma 5%
Mets ( breast , lung ,GI , melanoma)

6. Radiation : as risk factor
Appears to be dose-dependent :
– ERR 7.7 at 100 cGy
Maximum risk approximately 30 years later
Nodule in radiated patient: 35-40% cancer
Data suggest no more agggresive behavior over spontaneously-occuring cancers, but may be larger at presentation.
Only unequivocal environmental cause of thyroid cancer

7. Radiation : as risk factor
Younger age – greater risk
Suppression may help decrease risk:
– One study: 35.8% %
I-131: risk of leukemia with high doses

8. Thyroid nodule work up
What is the appropriate evaluation of clinically or incidentally
discovered thyroid nodule(s)?
What laboratory tests and imaging modalities are indicated?
What is the role of fine-needle aspiration (FNA)?
What is the role of medical therapy of patients with
benign thyroid nodules?
How should thyroid nodules in children and pregnant
women be managed?

9. Strength of Panelists’ Recommendations
(A) : Strongly recommends. The recommendation is based on good evidence that the service or intervention can improve important health outcomes.
(B) : The recommendation is based on fair evidence that the service or intervention can improve important health outcomes.
(A) well-designed, well-conducted studies in
representative populations that directly assess effects on health outcomes.
(B) The evidence is sufficient to determine effects on health outcomes, but the strength
of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to
routine practice; or indirect nature of the evidence on health outcomes

10. Eitology of thyroid nodule ( Others) :
Higher rate of nodules found in patients:
Who have hyperparathyroidism
Are undergoing hemodialysis

11. Strength of Panelists’ Recommendations
(C) : based on expert opinion.
(D) : Recommends against : based on expert opinion.
(E) : Recommends against : based on fair evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits.
(F) : Strongly recommends against: based on good evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits

12. Strength of Panelists’ Recommendations
(I) : Recommends neither for nor against:
If the evidence is lacking that the service or intervention improves important health outcomes, the evidence is of poor quality, or the evidence is conflicting. As a result, the balance of benefits and harms cannot be determined.

13. Thyroid nodule
Discrete lesion within the thyroid gland that is radiologically distinct from the surrounding thyroid parenchyma.
What is Incidentalomas?
Nonpalpable nodules detected on US or other anatomic imaging studies.
PET % thyroid nodule
risk of malignancy is 33%

14. Thyroid nodule work up size as a factor
Nodules >2 cm hold a higher risk of cancer (15%) .
only nodules >1 cm should be evaluated.
If nodules <1 cm that require evaluation.
Thyroid cancer in one or more first-degree relatives.
History of head and neck irradiation.
Lymphadenopathy on examination or imaging studies .
Suspicious US findings.

15. Thyroid nodule site as risk factor
Isthmus (carcinoma proven biopsy )
LN Mets ( isthmus vs lobes) (83% vs. 66%).
LN involvement on the both sides of the neck (50%)

16. Thyroid nodule work up Complete history & physical exam .
Risk factors .
Serum TSH
US thyroid .
Radionuclide Thyroid scan if TSH low normal or subnormal.
If TSH high normal : increased risk of malignancy in a thyroid nodule.
Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA 2006 Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endo Metab91:4295–4301.

17. History : Age Gender Exposure to Radiation
Signs/symptoms of hyper- / hypo- thyroidism
Rapid change in size
– With pain may indicate hemorrhage into nodule
– Without pain may be bad sign

18. Gardner Syndrome (familial adenomatous
polyposis)
– Association found with thyroid ca
– Mostly in young women (94%) (RR 160)
– Thyroid ca preceded dx of Garners 30% of time
Cowden Syndrome
– Mucocutaneous hamartomas,
keratoses,fibrocystic breast changes & GI polyps
– Found to have association with thyroid ca (8/26
patients in one series)

19. History Familial h/o medullary thyroid carcinoma
– Familial MTC vs MEN II
Family hx of other thyroid ca
H/o Hashimoto’s thyroiditis (lymphoma

20. History Elements suggestive of malignancy: Progressive enlargement
Hoarseness
Dysphagia
Dyspnea
High-risk (fam hx, radiation)
Cervical lymphadenopathy
Fixation into adjsent structures
Vocal cord paralysis
PET (high uptake)
• Not very sensitive / specific

21. Clinical findings & FNA

22. Recommendation
Measure serum TSH . If subnormal, a radionuclide thyroid scan.( A)
US thyroid should be performed in all patients
with known or suspected thyroid nodules.(A)

23. Laboratories investigations:
TSH – first-line serum test
– Identifies subclinical thyrotoxicosis
T4, T3
Calcium ( MTC)
Thyroglobulin (post cancer Rx surveillance)
Calcitonin (MTC)
Antibodies – Hashimoto’s
RET proto-oncogene

24. Imaging
U/S
CT vs MRI
Radio nucleotide scan
PET

25. U/S Neck ( Thyroid)
Ultrasound remains the most important imaging modality in the evaluation of thyroid cancer:
Primary tumor
 Cervical lymph node basins

26. Thyroid nodule suspicious US finding
Size > 2 cm
Microcalcifications. ( 38%)
Solid
Hypoechoic.
Increased nodular vascularity.
infiltrative margins.
Absence of halo.
taller than wide on transverse view.
Lymphadenopathy
Spongiform nodules ?

27. Malignant LN ( US finding)
Round
Hilum not visible
Hypoechoic/heterogeneous
Micro calcifications
Irregular margins
Multiple
Invasion of surrounding tissues

28. Imaging : CT scan indications
Lymphadenopathy
Revision cases ( selected)

29. CT/MRI Retrosternal extension
Soft tissue invasion ( trachea , esophagus ,vessels)
ultrasound expertise is not available.

30. Radionuclide Thyroid scan:
Concept
Uses
Metabolic studies
Imaging
Iodine is taken up by gland and organified
Technetium trapped but not organified
Follicular cell only.

31. Radioisotope
I-131
I-123
I-125
Tc-99m
Thallium-201
Gallium 67

32. Tc-99m Most commonly used isotope (some authors)
99m: “m” refers to metastable nuclide
•Decay product of Molybdenum-99
•Long half-life before decaying into Tc-99
Administered as pertechnate (TcO4-)
Images can be obtained quickly
• “One-Stop” evaluation
Hot nodules need f/u Iodine scan
Discordant nodules higher risk of malignancy

33. Tc-99m
Hot nodule

34. Iodine scan 127 – only stable isotope of iodine
123 – cyclotron product
• Half-life 13.3 hr
• Expensive, limited availability
• Low radiation-exposure to patient

35. Iodine scan 131 – fission product • Half-life 8 days
• Cheap, widely available
• Better for mets (diagnostic and therapeutic) (high radiation exposure)
125 – no longer used
• Long half-life (60 days); high radiation exposure with poor visualization

36. Radionuclide Thyroid scan: 99mTcO4 Thyroid Scintigraphy
TSH <0.4 mU/L
TSH ( 0.4 – 0.6 mU/L)
Iodine deficiency ( endemic areas)
Background MNG
Avoid unnecessary FNAs

37. FDG-PET Main indication
Post therapy surveillance ( localization) :
Positive tumor markers (stim Tg> 10 ng /ml)
&
Negative anatomical & functional imaging

38. FDG-PET relative indication
Initial staging & follow up in poorly differentiated thyroid CA.
Disease specific mortality ( known cases of distant metastasis ).
Identification of patient with poor response to RAI Rx .
Post Rx response ( EBRT, surgery , chemotherapy or embolization)

39. Recommendation
FNA is the procedure of choice in the evaluation of thyroid nodules. (A)
US guidance FNA: .(B)
> 50% cystic,
Nonpalpable,
Located posteriorly in the thyroid lobe
Initial FNA non diagnostic

40. FNA Biopsy Technique: 25-gauge needle Multiple passes
Ideally from periphery of lesion
Reaspirate after fluid drawn
Immediately smeared and fixed
Papanicolaou stain common

41. FNA Biopsy Hamberger study: addition of FNA
– Changed # pts undergoing surgery ( %)
– Carcinoma yield %
– Reduced cost per pt 25%
Campbell & Pillsbury: pooled 10 studies
– All pts operated on regardless of FNA:
• False neg rate: 2.4%
• False pos rate: 1.2%

42. Thyroid nodule work up High Low Normal TSH Hx, P/E, TSH TSH Thyroid US
Non functioning
123I or 99Tc Scan
Nodule
Do FNA
No nodule
Hyper
functioning
Elevated TSH
Normal TSH
Evaluate and Rx
for
Hyperthyroidism
Evaluate and
Rx for
Hypothyroidism
FNA not
Indicated

43. Bethesda system thyroid cytopathology

44. Thyroid FNA be Follow up Benign Consider 123I Scan if TSH Low Normal
Indeterminate
(FLUS)
10-20%
Follicular
Neoplasm
Hurthle cell neoplasm
Suspicious or malignant PTC
Surgery
Pre op US
Close follow up ( US /6 month) or surgery
Non diagnostic
Repeat US guided FNA
Non diagnostic

45. Thyroid FNAC benign pathology
Follow up with serial US ( 6-18 months): (B)
Volume by 50 %.
FNA
Dimensions of two nodule by 20% with
minimal increase of 2mm in solid nodules.

46. Benign FNA : Long term F/u
Disadvantages:
Does not improve the cancer detection rate
Increase the use of U/S or repeat fine needle aspirations,
consideration should be given to stopping further follow-up after 3 years.

47. FNA & Gentic work up (Afirma)
Specialized cytopathology with unique molecular analysis.
Advantage:
Avoid unnecessary surgeries ( 90% reduction in number of surgeries)
Single clinic visit ( One FNA)
Reduce healthcare cost
Inform surgery choice ( TT&level VI ND, TT or hemi thyroidectomy) Afirma BRAF & MTC

48. Afirma ( GEC) Indication : FLUS . Disadvantage:
Result : 17 days ( average)
Suspicious result:
60% ( false positive) .
Sensitivity : 90%
Specificity : 50%

49. Medical therapy benign thyroid nodule
Thyroid hormone in doses that suppress the serumTSH to subnormal levels may result :
Nodule size.
Prevent the appearance of new nodules in regions of the world with borderline low iodine intake.

50. Thyroid nodule in children
Thyroid CA % all pediatric malignancies
Malignant nodule %.
10% thyroid cancer age <21
More likely to present with neck mets
Most common cause thyroid enlargement is
chronic lymphocytic thyroiditis

51. Thyroid nodule in children
Medullary Thyroid Carcinoma:
FMTC, MEN 2A, MEN 2B
RET proto-oncogene (chromosome 10)
Calcium / Pentagastrin stimulation
Prophylactic thyroidectomy recommended age 2-6

52. Thyroid nodule in children
The diagnostic and therapeutic approach to one or more thyroid nodules in a child should be the same as it would be in an adult (clinical evaluation, serum TSH, US, FNA).
( A)

53. Thyroid nodule in pregnancy
Pregnancy increases risk
One study: u/s detection nodules :
• 9.4% nulliparous women
• 25% women previously pregnant
Attributed to increased renal iodide excretion
and basal metabolic rate
Rosen: Nodules presenting during pregnancy :
• 30 patients, 43% were cancer
• HCG may be growth promoter (TSH-like activity)

54. Thyroid nodule in pregnancy
Nodules discovered in pregnant women are more likely to be malignant than those found in nonpregnant women.
Euthyroid
Hypothyroid FNA should be performed in pregnancy .
Hyperthyroid Radionuclide scan after pregnancy & cessation of lactation .

55. Malignant thyroid nodule in pregnancy
PTC early in pregnancy
US monitoring
Stable in size
Grow substantially
Surgery after delivery
Surgery
2nd trimester

56. Malignant thyroid nodule in pregnancy
If suspicious for PTC :
LT4 to keep TSH 0.1–1mU/L

57. Case : 35 YOF Cc: L thyroid nodule Risk : none No Compressive symptoms
Clinically euthyroid
Exam unremarkable except ( L thyroid lobe nodule 3 cm )

58. Case
TSH : 1.7
U/S neck : well defined hypoechoic L lobe nodule (2.5 * 0.9 * 1 cm ), no calcifications , increase vascularity , presence of halo . No lymphadenopathy
FNA : AUS
what is the management ?

59. Case L hemithyroidectomy Pathology :
Follicular thyroid carcinoma (2 vascular invasion & micro capsular invasion ) , size : 3 cm
What is your proposed plan ?

60. Case Completion thyroidectomy.
Completion & Central compartment dissection.
I 131 abltion.
Observation.

61. FTC subtypes :
MIFTC with capsular invasion only, with limited (< or =3) vascular invasion.
Rx : hemithyroidectomy
Encapsulated FTC with extensive (>3) vascular invasion
Broadly invasive FTC with extensive invasive growth.
Rx : Total thyroidectomy
2005 by Rosai