Thyroid: Thyroid Nodular Disease & Thyroid Cancer Flashcards
Diffuse nontoxic goiter / simple goiter / colloid goiter is termed “endemic goiter” when it affects >__% of the population.
> 5%
Food that are high in goitrogens
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)
Total thyroid volume on ultrasound that is considered abnormal
> 30 mL
What is Pemberton’s sign
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
Usual TFT in simple goiter
Low total T4, normal T3 and TSH (reflecting enhanced T4 to T3 conversion)
Treatment of diffuse nontoxic (simple) goiter
Iodine replacement
Surgery if with tracheal compression or obstruction of the thoracic inlet
Target TSH level after thyroidectomy for simple goiter
Keep TSH level at lower end of reference interval (to prevent regrowth of the goiter)
TRUE OR FALSE: Most nodules within a mutinodular goiter are polyclonal in origin.
TRUE (suggesting a hyperplastic response to locally produced growth factors and cytokines)
Usual cause of sudden pain in a multinodular goiter
Hemorrhage into a nodule (but should raise the possibility of invasive malignancy)
In multinodular goiter, airway compression must usually exceed __% of the tracheal diameter before there is significant airway compromise.
70%
Grayscale sonographic features associated with thyroid cancer (6)
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
Sonographic feature that is most sensitive for thyroid cancer
Solid consistency (86%)
Sonographic feature that is most specific for thyroid cancer
Marked hypoechogenicity (94%)
Dosage of 131I in the treatment of multinodular goiter
3.7 MBq (0.1 mCi) per gram of tissue, corrected for uptake (typical dose 370-1070 MBq (10-29 mCi)
Usual TFT in toxic multinodular goiter
T3 is often elevated to a greater degree than T4
TSH is low
Treatment of toxic multinodular goiter
Radioiodine - treatment of choice
Antithyroid drugs - in elderly or ill patients with limited lifespan
Surgery - definitive treatment
Most common mutation in patients with hyperfunctioning solitary nodule
Activating mutations of the thyroid-stimulating hormone receptor (TSH-R) mainly in transmembrane 5 and intracellular loop 3
TRUE OR FALSE: In hyperfunctioning solitary nodule, thyrotoxicosis is usually mild and is generally only detected when a nodule is >3cm.
TRUE
Treatment of hyperfunctioning solitary nodule
Radioiodine ablation - treatment of choice
Surgical resection - limited to lobectomy
Medical therapy - not an optimal long-term treatment
Description of follicular architecture in benign thyroid lesions
Hyperplastic - combination of macro- and microfollicular architecture
Neoplastic - more monotonous microfollicular pattern
What is a Hurthle cell adenoma
Term used to denote an adenoma that is composed of oncocytic follicular cells arranged in a follicular pattern
The definition of “spongiform” requires the presence of microcystic areas comprising >__% of the nodule volume.
> 50%
When can iodine and levothyroxine be given in cases of benign thyroid nodules
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)
What is the most common malignancy of the endocrine system?
Thyroid carcinoma
TRUE OR FALSE: Thyroid cancer prognosis is worse in older persons (>65 years) and in males.
TRUE
Risk factors for thyroid carcinoma in patients with thyroid nodule from history and physical examination
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
Staging of PTC and FTC: Cut-off age for staging (Harrison’s)
45 years
If patient is <45 years, he/she can only be either Stage I or Stage II, depending on the presence of metastasis
Which classification of thyroid cancer is always at Stage IV?
Anaplastic thyroid cancer
Cancer staging: T
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
Cancer staging: N
N0 - absence
N1a - level IV central compartment
N1b - level II-V lateral compartment, upper mediastinal or retro/parapharyngeal
Papillary or Follicular Thyroid Cancer Staging in >45 years old
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
New age cutoff based on the AJCC guidelines released in 2018
55 years
TRUE OR FALSE: Multinodular goiters are polyclonal while thyroid cancers are monoclonal in origin.
TRUE
Activation of the _____________ signaling pathway is seen in up to 70% of PTCs.
RET-RAS-BRAF signaling pathway
Activation of this cascade is believed to be critical for tumor development in thyroid cancer, independent of the step that initiates the cascade.
Mitogen-activated protein kinase (MAPK) cascade
Most common genetic alteration in PTC
BRAF V600E
Most common RAS mutations in thyroid neoplasms
NRAS > HRAS > KRAS
MTC, when associated with MEN type 2, harbors an inherited mutation in the ___ gene.
RET (point mutations that induce constitutive activity of the tyrosine kinase)
Most common type of thyroid cancer
PTC (80-85% of well-differentiated thyroid malignancies)
Characteristic cytologic features of PTC
Large, clear nuclei with powdery chromatic (“orphan Annie eye” appearance) with nuclear grooves and prominent nucleoli
PTC has a propensity to spread via
Lymphatic system
TRUE OR FALSE: Micrometastases, defined as <2 mm of cancer in a lymph node, do not affect prognosis.
TRUE
Gross metastatic involvement of multiple 2-3 cm lymph nodes indicates a 25-30% chance of recurrence.
TRUE
Which type of thyroid cancer is more common in iodine-deficient regions?
FTC
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.
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.
FTC has a propensity to spread via
Hematogenous route
Poor prognostic features of FTC
Distant metastases, age >50 years, primary tumor size >4 cm, Hurthle cell histology, and the presence of marked vascular invasion
Treatment of choice for well-differentiated thyroid cancers >1cm
Surgical excision
Medication that is a mainstay of thyroid cancer treatment
Levothyroxine (because most tumors are still TSH-responsive, TSH must be suppressed with LT4)
Target TSH in patients with thyroid cancer with high risk of recurrence of with known metastatic disease
<0.1 mIU/L
Indications for radioiodine treatment in thyroid cancer
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)
Prerequisite before thyroid ablation
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)
Surveillance testing after RAI for thyroid cancer
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
Kinase inhibitor that is currently being studied as treatment in progressive metastatic thyroid cancer
Sorafenib
Type of cancer that is poorly differentiated and aggressive, wherein most patients die within 6 months of diagnosis
Anaplastic thyroid cancer
Thyroid lymphoma often arises in the background of what kind of thyroiditis?
Hashimoto’s thyroiditis
Most common type of thyroid lymphoma
Diffuse large-cell lymphoma
Treatment of choice in thyroid lymphoma
External radiation (highly sensitive; surgical resection should be avoided as initial therapy because it may spread disease)
TRUE OR FALSE: MTC is more aggressive in MEN 2B than in MEN 2A, and familial MTC is more aggressive than sporadic MTC.
TRUE
Marker of residual or recurrent disease in MTC
Serum calcitonin
All patients with MTC should be tested for ___ mutations.
RET mutations
Treatment of choice in MTC
Surgery
What should be ruled out prior to surgery of MTC?
Pheochromocytoma
TRUE OR FALSE: Thyroid nodules are more common in iodine-sufficient areas, in women, and in young individuals.
FALSE. Nodules are more common in iodine-deficient areas, in women, and with aging.
Evaluation of a thyroid nodule: First step
Check TSH level
Evaluation of a thyroid nodule: Next step if TSH is suppressed
Radionuclide scan
Evaluation of a thyroid nodule: Next step if TSH is showed a “hot” nodule
Evaluate and treat for hyperthyroidism; FNA not necessary
Evaluation of a thyroid nodule: Next step if TSH is showed a “cold” nodule
Thyroid ultrasound
Evaluation of a thyroid nodule: Next step if TSH is normal or elevated
Thyroid ultrasound
Size cutoff for FNA of thyroid nodule
1cm
2015 ATA guidelines do not recommend FNA for any nodule <1cm unless metastatic cervical lymph nodes are present.
TRUE OR FALSE: The use of levothyroxine to suppress serum TSH is effective in shrinking nodules in iodine-replete populations.
FALSE. The use of levothyroxine to suppress serum TSH is NOT effective in shrinking nodules in iodine-replete populations.
Risk of malignancy if thyroid cytology is “I. Nondiagnostic or unsatisfactory”
1-5%
Risk of malignancy if thyroid cytology is “II. Benign”
2-4%
Risk of malignancy if thyroid cytology is “III. Atypia or follicular lesion of unknown significance (AUS/FLUS)”
5-15%
Risk of malignancy if thyroid cytology is “IV. Follicular neoplasm”
15-30%
Risk of malignancy if thyroid cytology is “V. Suspicious for malignancy”
60-75%
Risk of malignancy if thyroid cytology is “VI. Malignant”
97-100%
