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Endo Repro Exam I > Thyroid Pathology > Flashcards

Thyroid Pathology Flashcards

1
Q

Thyroglobulin is synthesized and stored in ______

______ is transported into the cell, and incorporated into TG

Thyroglobulin is endocytosed and cleaved to release free T3 and T4

A

Colloid

Iodide

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2
Q

Differentiate causes of primary vs. secondary hyperthyroidism

A

Primary (more common) = Diffuse hyperplasia (graves disease), hyperfunctioning multinodular goiter, hyperfunctioning thyroid adenoma

Secondary hyperthyroidism = pituitary adenoma

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3
Q

What will diagnostic labs show in primary vs. secondary hyperthyroidism?

A

Hyperthyroidism is confirmed by elevated T3 and/or T4

To differentiate primary vs. secondary, measure TSH. If TSH is low, it is primary hyperthyroidism. If TSH is high, it is secondary hyperthyroidism

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4
Q

Signs/symptoms of hyperthyroidism

A 
Perspiration
Facial flushing
Nervousness
Excitability
Restlessness
Emotional instability
Insomnia
Palpitations
Tachycardia
Increased appetite
Diarrhea
Tremor
Muscle wasting
Weight loss
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5
Q

In terms of all types of hyperthyroidism, what physical finding is unique to Grave’s disease?

A

Exophthalmos

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6
Q

What is a thyroid storm?

A

Hyperthyroid “crisis” — sudden and severe onset of thyrotoxic manifestations

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7
Q

A thyroid storm is characterized by the Burch Wartofsky score. What are some criteria associated?

A

Fever

Cardiac manifestations (tachycardia, CHF)

GI symptoms (diarrhea, jaundice)

Precipitating history (pregnancy/postpartum, hemithyroidectomy, drugs: amiodarone)

[fever and precipitating hx are really how you distinguish thyroid storm from typical long-term hyperthyroid]

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8
Q

Tx of hyperthyroidism

A

High doses of iodide (Wolff-Chiakoff effect)
Thionamide
Radioiodine ablation
Surgery

To tx manifestations:
Beta blockers
NSAIDs

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9
Q

Most common etiology of hyperthyroidism

A

Graves disease

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10
Q

Classic diagnostic triad of Graves disease

A

Hyperthyroidism with gland enlargement

Infiltrative ophthalmopathy

Pretibial myxedema

[note that this triad is not always present and not all features must be present for dx of Graves]

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11
Q

Pathogenesis of Graves disease affecting the orbit

A
  1. Lymphocytes invade preorbital space
  2. Fibroblasts have TSH receptor
  3. EOM swelling
  4. Matrix accumulates
  5. Adipocytes expand
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12
Q

Infiltrative dermopathy with scaly, indurated skin on the anterior shins that is often seen in hyperthyroidism

A

Pretibial myxedema

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13
Q

Lab test results in graves disease

A

T3/T4 high

TSH low

TSI (thyroid-stimulating Ig) high [this confirms graves as etiology]

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14
Q

Primary etiologies of hypothyroid

A

Hashimoto thyroiditis

Iodine deficiency

Drugs (lithium, iodides, p-aminosalicylic acid)

Postablative (surgery, radioiodine therapy, external irradiation)

Thyroid hormone resistance syndrome (THRB)

Genetic defects in thyroid development (PAX8, FOXE1, TSH receptor mutations)

Congenital biosynthetic defect (dyshormonogenetic goiter)

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15
Q

Secondary etiologies of hypothyroid

A

Pituitary failure

Hypothalamic failure

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16
Q

Congenital hypothyroidism is also known as ______

A

Cretinism

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17
Q

Early infancy/childhood manifestations of cretinism

A

Mental retardation
Growth retardation
Coarse facial features
Umbilical hernias

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18
Q

Cretinism is endemic in areas without ____ supplementation

A

Iodine

[can also be a result of genetic alterations in normal thyroid metabolic pathways]

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19
Q

Cretinism is congenital hypothyroidism and manifestations are dependent upon maternal age of onset.

______ is hypothyroidism in the adult/older child characterized by mental and physical sluggishness, weight gain, cold intolerance, decreased cardiac output, and hypercholesterolemia

A

Myxedema

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20
Q

4 types of thyroiditis

A

Hashimoto thyroiditis

Granulomatous (de Quervain)

Subacute lymphocytic thyroiditis

Reidel

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21
Q

Most common cause of hypothyroidism in iodide-sufficient areas

A

Hashimoto thyroiditis

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22
Q

Hashimoto thyroiditis is autoimmune hypothyroidism characterized by autoantibodies against ____ and _____

A

Thyroglobulin; thyroid peroxidase (TPO)

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23
Q

Morphologically, Hashimoto thyroiditis is characterized by lymphocytic infiltrate with germinal centers, as well as atrophic follicle cells with eosinophilic change known as __________

A

Hurthle cell metaplasia

24
Q

Antibody prevalence in Hashimoto vs. Graves

A

Hashimoto:
TSHR-Ab (TSI) — 10-20%
hTg-Ab — 80-90%
hTPO-Ab — 90-100%

Graves:
TSHR-Ab (TSI) — 80-95%
hTg-Ab — 50-70%
hTPO-Ab — 50-80%

25
Q

Type of thyroiditis in which the patient is typically euthyroid, but they present with very painful thyroid gland

A

Granulomatous thyroiditis (aka de Quervain’s thyroiditis)

26
Q

Fibrosing type of thyroiditis in which fibrotic tissue extends from thyroid into adjacent tissue (i.e., skeletal m.)

A

Riedel thyroiditis

27
Q

Riedel thyroiditis is characterized morphologically by a lot of fibrosis, but also lymphocytes and plasma cells. It is considered a ____-related disease

A

IgG4

[other IgG4-related diseases include autoimmune pancreatitis, inflammatory pseudotumor, Mikulicz’s syndrome, multifocal fibrosclerosis, idiopathic retroperitoneal fibrosis, and inflammatory aortic aneurysm]

28
Q

_____ goiters are more common in females

A

Sporadic

29
Q

Dietary goitrogens

A

Cassava root (thiocyanate)

Brassicaceae — broccoli, cauliflower, cabbage, radish

30
Q

Are diffuse goiters more common in younger or older individuals?

A

Younger; after age 25 tend to be classified as nodular

31
Q

T/F: diffuse goiters are euthyroid

A

True — so presenting symptoms are typically due to mass effect: dysphagia, hoarseness, stridor, SVC syndrome

32
Q

What causes goiters to be multinodular?

A

Hyperplasia, regression (involution) cycle

Varied response of nodules to stimuli

Neoplastic nature of some nodules (adenomas)

33
Q

What is the purpose of doing radioisotope scanning for thyroid nodules?

A

Determines if a specific nodule is responsible for HYPERFUNCTION — if so, it can be treated with excision or ablation

34
Q

T/F: “Hot” thyroid nodules are more likely to be neoplastic, but ultrasound and fine needle aspiration are more useful in that workup

A

False; T/F: “cold” thyroid nodules are more likely to be neoplastic, but ultrasound and fine needle aspiration are more useful in that workup

35
Q

Radioisotope scanning determines if a specific nodule is responsible for hyperfunction.

What test can be used to determine the cellular constituents of a nodule?

A

Fine needle aspiration

36
Q

2 types of benign thyroid nodules

A

Hyperplastic (adenomatoid) nodules

Follicular adenomas

37
Q

4 types of malignant thyroid nodules

A

Papillary thyroid carcinoma

Follicular/Hurthle cell carcinoma

Anaplastic carcinoma

Medullary carcinoma

38
Q

Follicular adenomas are a discrete population of follicular cells with “thyroid autonomy”. What do you need to make sure of in order to confirm they are benign?

A

Capsule is intact (not invaded), so no growth pattern of follicular carcinoma is present

No nuclear features of papillary carcinoma

39
Q

What comprises the majority of malignant tumors of the thyroid gland (85%)?

A

Papillary thyroid carcinoma

40
Q

Age of onset and sx associated with papillary thyroid carcinoma

A

Most occur between 25-50 years of age (remember that staging is based on age of onset)

Typically present without symptoms — may discover palpable nodule, or on thyroid ultrasound

41
Q

How is staging of papillary thyroid carcinoma different based on age?

A

Under 55 years of age — can only be classified stage I or stage II [major difference is whether or not there is metastasis]

55+ years — can be stage I, II, III, IVA, or IVB [stage IVB = stage II in pts under 55]

42
Q

Describe morphology and genetic associations of papillary thyroid carcinoma

A

Papillary architecture

Psammoma bodies

Enlarged nuclei with “clear” appearance: “orphan Annie eye nuclei” — nuclear characteristics are the diagnostic feature allowing for a dx of PTC!!

Associated with RET-PTC mutations, BRAF mutations

43
Q

Describe follicular variant of papillary carcinoma

A

Follicular architecture, but nuclear features of papillary carcinoma

[fewer cases have RET-PTC rearrangements or BRAF mutations; MORE cases with RAS mutations]

44
Q

What variant of papillary carcinoma tends to affect older patients and is aggressive?

A

Tall cell variant

45
Q

What variant of papillary carcinoma tends to affect kids and young adults, with greater incidence of distant metastasis to lung, brain, bone, and liver, but is considered very treatable?

A

Diffuse sclerosing variant of papillary carcinoma

46
Q

Therapeutic options for thyroid carcinoma

A

Surgery

Radioactive iodine (I131)

If refractory, can try chemotherapy

47
Q

Type of thyroid carcinoma that is less common than papillary, but more common in areas with goiter from iodide deficiency

A

Follicular thyroid carcinoma

48
Q

Follicular carcinoma is still considered a differentiated thyroid carcinoma, but with invasive properties as manifested through….

A

Invasion of the capsule (mushroom)

Angioinvasion (allowing for hematogenous metastasis)

49
Q

Type of thyroid carcinoma that is rare, but tends to occur in elderly patients and is highly aggressive — often presenting with mass effect, and pts typically die within 1 year of local invasion

A

Anaplastic thyroid carcinoma

50
Q

The below genetic mutations are associated with what type of thyroid carcinoma:

BRAF gain of function mutations leading to MAP kinase signaling

RET/PTC rearrangements leading to tyrosine kinase activity

A

Papillary carcinoma

51
Q

Genetic mutation associated with anaplastic carcinoma

A

TP53

52
Q

In terms of thyroid histology, follicular cells predominate, but _______ cells are also present, which are responsible for _____ secretion

A

Parafollicular “C”; calcitonin

53
Q

Neuroendocrine thyroid carcinoma derived from C cells

A

Medullary thyroid carcinoma

54
Q

Morphology of medullary thyroid carcinoma

A

Blue cells with dispersed chromatin

Amyloid deposition (apple green birefringence on Congo red stain!)

C-cell hyperplasia

55
Q

T/F: 70-80% of medullary thyroid carcinomas are sporadic, unifocal, and aggressive with mean age of 50. Familial forms have the BEST prognosis of all forms with 100% 15 year survival, tend to be multifocal and affect mean age of 43

A

True

56
Q

Germline mutation identified in association with familial syndromes with medullary thyroid carcinoma

A

RET

[note that somatic mutations of RET are present in a majority of sporadic tumors as well]

Endo Repro Exam I (10 decks)

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