Thyroid and Parathyroid Disease

1

What is the incidence of a thyroid nodule?

Clinically palpable nodules occur in 4% to 7% of the population, though the rate of incidental nodule founds on ultrasound is higher (20%–67% of patients), with more than half of thyroids containing more than one nodule. Nodules are more common in women (female-to-male ratio of 4:1). Thyroid cancer occurs in 5% to 10% of palpable nodules.

2

What is the workup of a thyroid nodule?

• Comprehensive history and physical including a visualization of the vocal cords (laryngoscopy) to evaluate recurrent laryngeal nerve function

• Thyroid function assay

• Ultrasound evaluation of nodule

• Possible fine-needle aspiration (FNA) if concern for malignancy

3

What features of thyroid nodules indicate a higher risk of malignancy?

• Age less than 30 and over 60 years old

• Male

• Positive family history

• Radiation exposure

• Hashimoto’s thyroiditis

• Rapid growth

• Pain

• Dysphonia

• Cervical lymphadenopathy

• Firm, fixed nodules

4

What ultrasound features are concerning for malignancy?

• Microcalcification

• Irregular margins

• Solid rather than cystic nodules

• Internal vascularity

• Multiple nodules

• Hypoechoic or isoechoic

• Enlarged cervical lymph nodes, particularly on the same side of the neck

5

What is the diagnostic accuracy of FNA cytology?

• Accuracy 95%; false-negative rate 2.3%; false-positive rate 1.1%.

6

What is the Bethesda Classification for Thyroid Cytopathology and associated risk of malignancy?

• Bethesda I: nondiagnostic or unsatisfactory (n/a)

• Bethesda II: benign (<5%)

• Bethesda III: atypia of undetermined significance (AUS) or follicular lesion of unknown significance (FLUS) (5%–15%)

• Bethesda IV: follicular neoplasm (15%–30%)

• Bethesda V: suspicious for malignancy (60%–75%)

• Bethesda VI: malignancy (97%–99%)

7

What is the role of molecular testing for thyroid cancer?

Genetic molecular testing is used for Bethesda III and IV thyroid nodules to either “rule in” a cancer or “rule out” a benign nodule. These tests should help to further risk stratify patients to improve diagnostic accuracy preoperatively, save unnecessary surgery, and help determine the extent of surgery when indicated.

8

What molecular tests are currently available for thyroid nodules?

• 1.

  Mutation panel testing: Tests for DNA mutations most commonly seen in thyroid cancer, including BRAF V000E, RAS , RET / PTC , and PAX8 / PPARG rearrangements. When these mutations are detected, the test helps to “rule in” cancer with a positive predictive value of 83%.

• 2.

  Gene sequencing classifier testing: tests for RNA expression of several different genes for benign and malignant nodules. Has a greater than 95% negative predictive value and essentially “rules out” cancer.

9

What is the recommended follow-up for benign thyroid nodules?

Pending characteristics on ultrasound, most authors recommend repeat ultrasound at 6 months for concerning nodules. Significant changes often warrant repeat FNA. Suppression with exogenous thyroxine is NOT recommended.

10

What is the differential diagnosis of thyroid cancers?

• Papillary carcinoma: 70%–80%

• Follicular carcinoma: 15%–20%

• Hurthle cell carcinoma: 3%–5%

• Medullary carcinoma: 3%–10%

• Anaplastic carcinoma: less than 2%

• Insular or poorly differentiated carcinoma: rare

• Other: lymphoma, squamous cell carcinoma, metastases from other sites (renal cell carcinoma, melanoma, breast cancer)

11

What is the TNM staging for well-differentiated thyroid cancer?

See Table 16.1 .

12

What is the staging for well-differentiated thyroid cancers?

See Table 16.2 .

13

What are the clinical prognostic indicators for thyroid cancer?

• AMES : Age; Metastasis; Extent and Size of primary tumor

  • Low risk: Age less than 40 (M) or 50 (F); tumor less than 4 centimeters and within thyroid gland

  • High risk: Age over 41 (M) or 51 (F); size >5 centimeters; extrathyroidal extension

• MACIS : Metastasis; Age; Completeness of resection; Invasion; Size of tumor

  • High risk: Age over 40; incomplete tumor resection; local invasion beyond thyroid (recurrent laryngeal nerve, trachea, esophagus, strap muscles) or angioinvasion; size >4 centimeters

14

What is the difference between a total thyroidectomy (TT), hemithyroidectomy or lobectomy, near-total thyroidectomy (NT), and subtotal thyroidectomy?

TT is the complete removal of all visible thyroid tissue. Hemithyroidectomy is complete removal of all thyroid tissue on one side of the thyroid (left or right) with or without isthmusectomy. In an NT, the surgeon elects to leave a very small amount of thyroid tissue around the parathyroid glands or recurrent laryngeal nerve to reduce morbidity. A subtotal thyroidectomy is poorly defined and results in large amounts of thyroid tissue left behind. A subtotal thyroidectomy is NOT an acceptable surgery for thyroid cancer.

15

What is the treatment for early-stage papillary or follicular thyroid cancers?

The treatment for isolated T1 lesions is a typically lobectomy. Guidelines for T2 lesions suggest that either lobectomy or total thyroidectomy can be used to treat, pending concerning features on pathology, contralateral thyroid disease, and patient considerations. Any evidence of macroscopic nodal disease warrants total thyroidectomy to facilitate radioactive iodine (RAI) treatment.

Advantages of total thyroidectomy include allowing for adjuvant RAI ( ¹³¹ I) ablation, improving the specificity of thyroglobulin assays for cancer surveillance, and the use of total body scanning with nuclear medicine scanning. Disadvantages include the need for lifelong thyroid replacement therapy and potentially increased surgical risk.