Thyroid: Thyroid Nodular Disease & Thyroid Cancer

Question 1

Diffuse nontoxic goiter / simple goiter / colloid goiter is termed “endemic goiter” when it affects >__% of the population.

Answer 1

> 5%

Question 2

Food that are high in goitrogens

Answer 2

Cassava root (contains thiocyanate)

Vegetables of the Cruciferae family (i.e. Brussels sprouts, cabbage, cauliflower)

Milk (from regions where goitrogens are present in the grass)

Question 3

Total thyroid volume on ultrasound that is considered abnormal

Answer 3

> 30 mL

Question 4

What is Pemberton’s sign

Answer 4

Facial and neck congestion due to jugular venous obstruction when the arms are raised above the head, a maneuver that draws the thyroid into the thoracic inlet; suggests that the goiter has increased pressure in the thoracic inlet

Question 5

Usual TFT in simple goiter

Answer 5

Low total T4, normal T3 and TSH (reflecting enhanced T4 to T3 conversion)

Question 6

Treatment of diffuse nontoxic (simple) goiter

Answer 6

Iodine replacement

Surgery if with tracheal compression or obstruction of the thoracic inlet

Question 7

Target TSH level after thyroidectomy for simple goiter

Answer 7

Keep TSH level at lower end of reference interval (to prevent regrowth of the goiter)

Question 8

TRUE OR FALSE: Most nodules within a mutinodular goiter are polyclonal in origin.

Answer 8

TRUE (suggesting a hyperplastic response to locally produced growth factors and cytokines)

Question 9

Usual cause of sudden pain in a multinodular goiter

Answer 9

Hemorrhage into a nodule (but should raise the possibility of invasive malignancy)

Question 10

In multinodular goiter, airway compression must usually exceed __% of the tracheal diameter before there is significant airway compromise.

Answer 10

70%

Question 11

Grayscale sonographic features associated with thyroid cancer (6)

Answer 11

1) Hypoechoic compared with surrounding thyroid
2) Marked hypoechogenicity
3) Microcalcifications
4) Irregular, microlobulated margins
5) Solid consistency
6) Taller than wide shape on transverse view

Question 12

Sonographic feature that is most sensitive for thyroid cancer

Answer 12

Solid consistency (86%)

Question 13

Sonographic feature that is most specific for thyroid cancer

Answer 13

Marked hypoechogenicity (94%)

Question 14

Dosage of 131I in the treatment of multinodular goiter

Answer 14

3.7 MBq (0.1 mCi) per gram of tissue, corrected for uptake (typical dose 370-1070 MBq (10-29 mCi)

Question 15

Usual TFT in toxic multinodular goiter

Answer 15

T3 is often elevated to a greater degree than T4

TSH is low

Question 16

Treatment of toxic multinodular goiter

Answer 16

Radioiodine - treatment of choice

Antithyroid drugs - in elderly or ill patients with limited lifespan

Surgery - definitive treatment

Question 17

Most common mutation in patients with hyperfunctioning solitary nodule

Answer 17

Activating mutations of the thyroid-stimulating hormone receptor (TSH-R) mainly in transmembrane 5 and intracellular loop 3

Question 18

TRUE OR FALSE: In hyperfunctioning solitary nodule, thyrotoxicosis is usually mild and is generally only detected when a nodule is >3cm.

Answer 18

TRUE

Question 19

Treatment of hyperfunctioning solitary nodule

Answer 19

Radioiodine ablation - treatment of choice

Surgical resection - limited to lobectomy

Medical therapy - not an optimal long-term treatment

Question 20

Description of follicular architecture in benign thyroid lesions

Answer 20

Hyperplastic - combination of macro- and microfollicular architecture

Neoplastic - more monotonous microfollicular pattern

Question 21

What is a Hurthle cell adenoma

Answer 21

Term used to denote an adenoma that is composed of oncocytic follicular cells arranged in a follicular pattern

Question 22

The definition of “spongiform” requires the presence of microcystic areas comprising >__% of the nodule volume.

Answer 22

> 50%

Question 23

When can iodine and levothyroxine be given in cases of benign thyroid nodules

Answer 23

In cases of relative iodine deficiency (must maintain TSH at or just below the lower limit of normal, and discontinue treatment if the nodule has not decreased in size after 6-12 months)

Question 24

What is the most common malignancy of the endocrine system?

Answer 24

Thyroid carcinoma

Question 25

TRUE OR FALSE: Thyroid cancer prognosis is worse in older persons (>65 years) and in males.

Answer 25

TRUE

Question 26

Risk factors for thyroid carcinoma in patients with thyroid nodule from history and physical examination

Answer 26

History of head and neck irradiation before the age of 18, including mantle radiation for Hodgkin's disease, and brain radiation for childhood leukemia or other cranial malignancies Exposure to ionizing radiation from fallout in childhood or adolescence Age <20 or >65 years Rapidly enlarging neck mass Male gender Family history of papillary thyroid cancer in 2 ore more first degree relatives, MEN 2, or other genetic syndromes associated with thyroid malignancy (e.g., Cowden's syndrome, familial polyposis, Carney complex, phosphatase and tensin homolog (PTEN) hamartoma tumor) Vocal cord paralysis, hoarse voice Nodule fixed to adjacent structures Lateral cervical lymphadenopathy

Question 27

Staging of PTC and FTC: Cut-off age for staging (Harrison's)

Answer 27

45 years If patient is <45 years, he/she can only be either Stage I or Stage II, depending on the presence of metastasis

Question 28

Which classification of thyroid cancer is always at Stage IV?

Answer 28

Anaplastic thyroid cancer

Question 29

Cancer staging: T

Answer 29

T1a <=1cm T1b >1cm T2 >2cm but <=4cm T3 >4cm or any tumor with extension into perithyroidal soft tissue or sternothyroid muscle T4a invasion into subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve T4b invasion into prevertebral fascia or encasement of carotid artery or mediastinal vessels

Question 30

Cancer staging: N

Answer 30

N0 - absence N1a - level IV central compartment N1b - level II-V lateral compartment, upper mediastinal or retro/parapharyngeal

Question 31

Papillary or Follicular Thyroid Cancer Staging in >45 years old

Answer 31

Stage I - T1N0M0 Stage II - T2N0M0 Stage III - T3N0M0 - T1-T3, N1a, M0 Stage IVA - T4a, any N, M0 - T1-T3, N1b, M0 Stage IVB - T4b, any N, M0 Stage IVC - Any T, any N, M1

Question 32

New age cutoff based on the AJCC guidelines released in 2018

Answer 32

55 years

Question 33

TRUE OR FALSE: Multinodular goiters are polyclonal while thyroid cancers are monoclonal in origin.

Answer 33

TRUE

Question 34

Activation of the _____________ signaling pathway is seen in up to 70% of PTCs.

Answer 34

RET-RAS-BRAF signaling pathway

Question 35

Activation of this cascade is believed to be critical for tumor development in thyroid cancer, independent of the step that initiates the cascade.

Answer 35

Mitogen-activated protein kinase (MAPK) cascade

Question 36

Most common genetic alteration in PTC

Answer 36

BRAF V600E

Question 37

Most common RAS mutations in thyroid neoplasms

Answer 37

NRAS > HRAS > KRAS

Question 38

MTC, when associated with MEN type 2, harbors an inherited mutation in the ___ gene.

Answer 38

RET (point mutations that induce constitutive activity of the tyrosine kinase)

Question 39

Most common type of thyroid cancer

Answer 39

PTC (80-85% of well-differentiated thyroid malignancies)

Question 40

Characteristic cytologic features of PTC

Answer 40

Large, clear nuclei with powdery chromatic ("orphan Annie eye" appearance) with nuclear grooves and prominent nucleoli

Question 41

PTC has a propensity to spread via

Answer 41

Lymphatic system

Question 42

TRUE OR FALSE: Micrometastases, defined as <2 mm of cancer in a lymph node, do not affect prognosis.

Answer 42

TRUE

Question 43

Gross metastatic involvement of multiple 2-3 cm lymph nodes indicates a 25-30% chance of recurrence.

Answer 43

TRUE

Question 44

Which type of thyroid cancer is more common in iodine-deficient regions?

Answer 44

FTC

Question 45

TRUE OR FALSE: The nuclear features of benign and malignant follicular adenomas and carcinomas are different and, hence, FNA can be used to distinguish between the two.

Answer 45

FALSE. The nuclear feature of the two are not different. Histology is required. Follicular carcinoma is diagnosed by the presence of capsular and/or vascular invasion.

Question 46

FTC has a propensity to spread via

Answer 46

Hematogenous route

Question 47

Poor prognostic features of FTC

Answer 47

Distant metastases, age >50 years, primary tumor size >4 cm, Hurthle cell histology, and the presence of marked vascular invasion

Question 48

Treatment of choice for well-differentiated thyroid cancers >1cm

Answer 48

Surgical excision

Question 49

Medication that is a mainstay of thyroid cancer treatment

Answer 49

Levothyroxine (because most tumors are still TSH-responsive, TSH must be suppressed with LT4)

Question 50

Target TSH in patients with thyroid cancer with high risk of recurrence of with known metastatic disease

Answer 50

<0.1 mIU/L

Question 51

Indications for radioiodine treatment in thyroid cancer

Answer 51

Large tumors More aggressive variants of papillary cancer Tumor vascular invasion Extrathyroidal invasion Presence of large-volume lymph node metastases (Radioiodine reduces recurrence and may increase survival for older patients)

Question 52

Prerequisite before thyroid ablation

Answer 52

Radioablation is much more effective when there is minimal remaining normal thyroid tissue, hence it is administered after iodine depletion - Low iodine diet for 1-2 weeks - Elevated serum TSH, ideally >25 mIU/L (give liothyronine then withdraw for 2 weeks, or give recombinant TSH as 2 daily consecutive injections)

Question 53

Surveillance testing after RAI for thyroid cancer

Answer 53

Serum thyroglobulin Neck ultrasound after 6 months Whole body scan if with known iodine-avid metastases or with elevated serum thyroglobulin and negative ultrasound, chest CT, neck cross-sectional imaging, and PET CT

Question 54

Kinase inhibitor that is currently being studied as treatment in progressive metastatic thyroid cancer

Answer 54

Sorafenib

Question 55

Type of cancer that is poorly differentiated and aggressive, wherein most patients die within 6 months of diagnosis

Answer 55

Anaplastic thyroid cancer

Question 56

Thyroid lymphoma often arises in the background of what kind of thyroiditis?

Answer 56

Hashimoto's thyroiditis

Question 57

Most common type of thyroid lymphoma

Answer 57

Diffuse large-cell lymphoma

Question 58

Treatment of choice in thyroid lymphoma

Answer 58

External radiation (highly sensitive; surgical resection should be avoided as initial therapy because it may spread disease)

Question 59

TRUE OR FALSE: MTC is more aggressive in MEN 2B than in MEN 2A, and familial MTC is more aggressive than sporadic MTC.

Answer 59

TRUE

Question 60

Marker of residual or recurrent disease in MTC

Answer 60

Serum calcitonin

Question 61

All patients with MTC should be tested for ___ mutations.

Answer 61

RET mutations

Question 62

Treatment of choice in MTC

Answer 62

Surgery

Question 63

What should be ruled out prior to surgery of MTC?

Answer 63

Pheochromocytoma

Question 64

TRUE OR FALSE: Thyroid nodules are more common in iodine-sufficient areas, in women, and in young individuals.

Answer 64

FALSE. Nodules are more common in iodine-deficient areas, in women, and with aging.

Question 65

Evaluation of a thyroid nodule: First step

Answer 65

Check TSH level

Question 66

Evaluation of a thyroid nodule: Next step if TSH is suppressed

Answer 66

Radionuclide scan

Question 67

Evaluation of a thyroid nodule: Next step if TSH is showed a "hot" nodule

Answer 67

Evaluate and treat for hyperthyroidism; FNA not necessary

Question 68

Evaluation of a thyroid nodule: Next step if TSH is showed a "cold" nodule

Answer 68

Thyroid ultrasound

Question 69

Evaluation of a thyroid nodule: Next step if TSH is normal or elevated

Answer 69

Thyroid ultrasound

Question 70

Size cutoff for FNA of thyroid nodule

Answer 70

1cm 2015 ATA guidelines do not recommend FNA for any nodule <1cm unless metastatic cervical lymph nodes are present.

Question 71

TRUE OR FALSE: The use of levothyroxine to suppress serum TSH is effective in shrinking nodules in iodine-replete populations.

Answer 71

FALSE. The use of levothyroxine to suppress serum TSH is NOT effective in shrinking nodules in iodine-replete populations.

Question 72

Risk of malignancy if thyroid cytology is "I. Nondiagnostic or unsatisfactory"

Answer 72

1-5%

Question 73

Risk of malignancy if thyroid cytology is "II. Benign"

Answer 73

2-4%

Question 74

Risk of malignancy if thyroid cytology is "III. Atypia or follicular lesion of unknown significance (AUS/FLUS)"

Answer 74

5-15%

Question 75

Risk of malignancy if thyroid cytology is "IV. Follicular neoplasm"

Answer 75

15-30%

Question 76

Risk of malignancy if thyroid cytology is "V. Suspicious for malignancy"

Answer 76

60-75%

Question 77

Risk of malignancy if thyroid cytology is "VI. Malignant"

Answer 77

97-100%