Thyroid nodules are common, especially in women and older adults. While most are benign, thyroid cancer occurs in 5-15% of nodules. Risk factors for cancer include age under 18 or over 60, male sex, family history, rapid growth, fixation, hoarseness, lymphadenopathy, and radiation exposure. Tests include thyroid function tests, ultrasound, and fine needle aspiration. Ultrasound features such as hypoechogenicity, irregular borders, microcalcifications, and taller-than-wide shape indicate higher cancer risk. Guidelines from the American Thyroid Association and other groups provide recommendations on evaluation and management of thyroid nodules and cancer.

1. Thyroid Nodules and Cancer

3. Epidemiology
• Thyroid nodules are very common
– Palpable nodules
• 5% of women
• 1% of men
– Ultrasound series
• 19-67%
– Autopsy series
• 37-57%
• The prevalence of nodules increases with age
• Prevalence in women 1.5-1.7 times higher than men
ATA guidelines

4. Etiology of Benign Nodules
• Focal thyroiditis
• Benign adenomas – follicular and hurthle cell
• Thyroid, parathyroid, thyroglossal cysts
• Post surgical/radiation remnant hyperplasia
• Rare: teratoma, lipoma, hemangioma

5. Thyroid Nodules
Thyroid cancer which occurs in 5–15% of nodules
Type Frequency Prognosis
PTC 80% 30-year survival 95%
Follicular (including Hurthle
cell)
10% 30-year survival 85%
Medullary 5% 10-year survival 65%
Anaplastic 3% 5-year survival 5%
Miscellaneous (lymphoma,
fibrosarcoma,SCC, teratomas,
metastatic carcinomas)
1%

6. Thyroid Cancer Risk Factors
– Extremes of Age
• Thyroid nodules in children are twice as likely to be malignant
• In adults, higher rate of malignancy if age > 60
– Sex
• Malignancy rate 2x higher in men compared to women (8% vs 4%)
– Family history
• FHx of a thyroid cancer syndrome (eg, familial polyposis, Carney
Complex, MEN type 2)
• 10-fold increased risk of thyroid cancer in first degree relatives of
thyroid cancer patients
Uptodate: ‘’Overview of thyroid nodule formation’’

7. Thyroid Cancer Risk Factors
Clinical signs
– Rapid growth, fixation of the nodule to surrounding tissues, new onset
hoarseness or vocal cord paralysis, or the presence of ipsilateral
cervical lymphadenopathy
• Radiation Explosure
– Most important RF = radiation exposure during childhood
– ~25% have thyroid nodules
• ~33% have malignant nodules
– No evidence that radiation-associated thyroid cancers are more
aggressive than other thyroid cancers

8. Thyroid cancer risk factors
• Radiation exposure - potential sources:
– Medical uses of radiation (eg, childhood malignancies)
– Atomic weapons (eg, Nagasaki/Hiroshima, Japan 1945), or nuclear
power plant accidents (eg, Chernobyl 1986, Fukushima Daiichi nuclear
disaster 2011)
– Ionizing radiation to treat benign conditions of the head and neck in
1950s

9. Thyroid Function Tests
1. TSH
2. Free T4
3. Free T3
4. Anti-Thyroid Antibodies
5. Nuclear Scintigraphy
6. FNAC of nodule

10. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

11. Investigations
• Laboratory tests
 Serum TSH
 If low  radionuclide thyroid scan
 Either 123I or 99mTc pertechnetate
 Otherwise  Further evaluation for possible FNA
 TSH level correlates to risk of thyroid cancer

12. Thyroid Cancer and TSH
TSH (mU/L) Prevalence of thyroid cancer
(%)
< 0.4 2.8%
0.4 – 0.9 3.7%
1.0 – 1.7 8.4%
1.8 – 5.5 12.3%
> 5.5 29.7%
Boelaert K, Horacek J, Holder RL, et al. Serum thyrotropin concentration as a novel
predictor of malignancy in thyroid nodules investigated by fine-needle aspiration.
J Clin Endocrinol Metab 2006; 91:4295.

13. Investigations
• Laboratory tests
 Serum thyroglobulin (Tg)
 Can be elevated in most thyroid diseases
 Insensitive and nonspecific test for thyroid cancer
 Not recommended as part of the initial evaluation

14. Investigations
• Serum calcitonin
 Screening with calcitonin may detect MTC at an earlier stage (likely
present if level > 100 pg/mL)
 But also detects C-cell hyperplasia and micromedullary carcinoma
(clinical significance uncertain)
 ATA: Cannot recommend either for or against routine measurement
 False-positive results:
 hypercalcemia, hypergastrinemia, neuroendocrine tumors, renal
insufficiency, papillary and follicular thyroid carcinomas, goiter, and
chronic autoimmune thyroiditis
 prolonged treatment with omeprazole (greater than two to four
months), beta-blockers, and glucocorticoids

15. Investigations
• Fine-needle aspiration (FNA)
 Most accurate and cost effective
 Sensitivity 76-98%, specificity 71-100%
 Prior to FNA, only 15% of resected nodules were malignant
 With FNA, malignancy rate of resected nodules > 50%
 False positive and non-diagnostic cytology rates lowered with US guidance

19. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

21. Ultrasound
• Hypoechoic
• Increased central vascularity
• Incomplete halo
• Microcalcifications
• Irregular borders
• Taller than wide (transverse
view)
• Suspicious lymph nodes
• Hyperechoic
• Peripheral vascularity
• Complete Halo
• Comet-tail
• Large, coarse calcifications
High Risk Features Low Risk Features

26. Central Vascularity

27. Microcalcifications

28. Irregular Borders

29. Taller Than Wide

30. Comet-tail Artifact

33. 2014 ATA GUIDELINES ON THYROID NODULES AND DTC

35. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

36. Management of Thyroid Nodules Detected at US

38. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

44. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

46. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

48. Management of Thyroid Nodules Detected at US

49. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

50. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

56. AACE/AME/ETA Guidelines

57. GUIDELINES FOR THE MANAGEMENT OF THYROID CANCER 2014

58. 2015 American Thyroid Association Management Guidelines for Adult
Patients with Thyroid Nodules and Differentiated Thyroid Cancer

59. Guidelines for the management of thyroid cancer
Clinical Endocrinology
pages 1-122, 3 JUL 2014 DOI: 10.1111/cen.12515
http://onlinelibrary.wiley.com/doi/10.1111/cen.12515/full#cen12515-fig-0004

60. Guidelines for the management of thyroid cancer
Clinical Endocrinology
pages 1-122, 3 JUL 2014 DOI: 10.1111/cen.12515
http://onlinelibrary.wiley.com/doi/10.1111/cen.12515/full#