Robbins - Thyroid Flashcards

1
Q

Midline, anterior mass w/ mucinous secretions, lined by epithelium w/ pleomorphic lymphocytic infiltrate

Origin? Leading to a persistent ____

A

Thyroglossal duct cyst

Thyroid tube remnant
Persistent SINUS TRACT

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2
Q

TSH receptor type? Function?

A

Gs

Stimulates thyroid growth and hormone production

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3
Q

2 cell types within the thyroid (w/ functions)

A

Follicular cells - produce thyroglobulin, release T4 (and T3)

Parafollicular cells (C cells) - release calcitonin

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4
Q

Calcitonin - functions

A

Increase calcium absorption by bones, inhibits osteoclasts

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5
Q

What happens to T4 once released into blood?

A

Bound by TBG and transthyretin, then deiodinated to T3 in the periphery, which binds to thyroid hormone receptor

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6
Q

Propylthiouracil (PTU) - functions (2)

Acting as a _____

A
  • Inhibits iodine oxidation –> inhibits T3/T4 production
  • Inhibits T4 deiodination (periphery)

Goitrogen

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7
Q

Iodine (large doses) - function

Acting as a _____

A

Blocks proteolysis of thyroglobulin –> inhibits T3/T4 release

Goitrogen

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8
Q

Elevated circulating levels of T3 and T4 - name?

Causes (3) - general

A

Thyrotoxicosis

  • Hyperthyroidism (primary or secondary)
  • Thyroiditis (excess release)
  • Extrathyroid souce
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9
Q

Excess thyroid hormone:

  • Skin
  • BMR
A
Skin = Warm, flushed, sweating, heat intolerance
BMR = weight loss w/ increased appetite
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10
Q

Excess thyroid hormone:

- Heart

A

Tachy, palpitations, cardiomegaly, A. fib, CHF

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11
Q

Excess thyroid hormone:

- CNS

A

Tremor, hyperactivity, anxiety, insomnia, emotional lability

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12
Q

Excess thyroid hormone:

  • Muscles
  • GI
A

Muscles = proximal mm weakness, decreased mass

GI = diarrhea, malabsorption (overactive)

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13
Q

Excess thyroid hormone:

- Eyes

A

Wide staring gaze, lid lag (overstimulation of sup. tarsal m)

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14
Q

Excess thyroid hormone:

  • Bones
  • Bones microscopically
A

Bone resorption, osteoporosis, fractures

Micro = infiltration of fat and lymphocytes

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15
Q

Excess thyroid hormone:

- Liver

A

Minor enlargement (fatty change in hepatocytes)

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16
Q

Thyroid storm:

  • Symptoms
  • Causes
  • Association
A

Symptoms = fever, tachycardia, arrhythmias (deadly)

Causes = increased catecholamine release (infection, surgery, stress, stopping antithyroid meds)

Association = GRAVE’S DISEASE

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17
Q

Older adult, unexplained weight loss, worsening of heart disease, increase thyroid hormones

A

Apathetic hyperthyroidism

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18
Q

A patient presents w/ thyrotoxicosis. TSH levels are slightly raised. How to determine if it’s secondary (pituitary) hyperthyroidism?

A

TRH stimulation test

- Normal increase in TSH = NEGATIVE = NOT 2º

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19
Q

Primary hyperthyroidism is diagnosed. How to determine the etiology? Result for each? (3)

A

Radioactive iodine test

  • Diffuse uptake = GRAVES
  • Solitary nodular uptake = TOXIC ADENOMA
  • Decreased uptake = THYROIDITIS
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20
Q

Treatment of hyperthyroidism (5)

A
  • Beta blocker (block symptoms)
  • Thionamide (block synthesis)
  • Iodine (block release)
  • T4 deiodination inhibitor (block action)
  • Radioiodine ablation (kill thyroid)
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21
Q

BEST single diagnostic test for ANY thyroid problem suspicion

Why?

A

TSH level

Decreased even at the subclinical level

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22
Q

Infant/child in Asia/Africa, retardation, small, coarse facial features, protruding tongue, umbilical hernia

Most common cause?

A

Cretinism (developmental hypothyroidism)

Usually = dietary iodine deficiency

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23
Q

Older child or adult, normal hypothyroid symptoms - general term

A

Myxedema

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24
Q

Hypothyroidism symptoms

A
  • Fatigue, apathy, mentally slow (CNS)
  • Cold intolerance, cool skin, pale (low blood flow)
  • Overweight (BMR low)
  • SOB, decreased exercise tolerance (reduced C.O.)
  • Increased cholesterol, LDL, CV risk
  • Non-pitting edema (glycan, hyaluronic acid deposition)
  • Coarse facial features (glycan, hyaluronic acid deposition)
  • Enlarged tongue (glycan, hyaluronic acid deposition)
  • Deepening voice (glycan, hyaluronic acid deposition)
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25
Diffuse PAINLESS enlargement of thyroid, major mononuclear infiltrate, germinal centers, atrophic follicles, epithelial cells w/ abundant eosinophilic, granular cytoplasm, fibrosis What are those epithelial cells?
Hashimoto's thyroiditis Hurthle cells
26
Describe Hashimoto's pathogenesis
Breakdown in self-tolerance to thyroid tissue, causing... - CD8 T-cell destruction (Fas-FasL) - CD4 T-cell / Macrophage destruction (cytokines) - Plasma cell / Antibodies / NK cell destruction
27
Hashimoto's autoantibodies
Anti-microsomal, Anti-peroxidase, Anti-thyroglobulin
28
Hashimoto's genetics (2)
CTLA4, PTPN22 - T-reg cell regulators
29
May see what labs at onset of Hashimoto's Term for this?
Increased T3/T4, low TSH, low iodine uptake - increased release of hormones Hashitoxicosis
30
Hashimoto's = increased risks?
- Other autoimmune diseases (Type 1 DM, Autoimmune adrenalitis, SLE, Myasthenia gravis, Sjogren) - Extranodal marginal zone lymphoma
31
What is DIFFERENT about subacute lymphocytic thyroiditis compared to Hashimoto's, symptom-wise? Common presentation of it?
- HYPERthyroidism (mild) POSTPARTUM woman, anti-thyroid-peroxidase antibodies OR family history of autoimmune disorders
32
What is DIFFERENT about subacute lymphocytic thyroiditis compared to Hashimoto's, morphology-wise? What is the SAME?
No fibrosis, no Hurthle cell metaplasia Lymphocytic infiltrate, germinal centers, follicle collapse
33
What is DIFFERENT about Granulomatous Thyroiditis compared to Hashimoto's or Subacute Lymphocytic, symptoms wise? Presentation/history-wise? Prognosis?
PAINFUL thyroid enlargement SUMMER, acute URI viral infection previously SELF-LIMITED (diminishing after 2-6 weeks)
34
Granulomatous thyroiditis - unique morphology (EARLY)
Neutrophilic microabscesses in damaged follicles
35
Granulomatous thyroiditis - unique morphology (LATE)
Multinucleate giant cells around colloid (thyroglobulin)
36
Does damage in granulomatous thyroiditis happen at the same time or in waves?
WAVES - different morphologies w/in the same gland
37
Granulomatous thyroiditis - hyper or hypothyroidism?
HYPERthyroidism
38
Extensive fibrosis of thyroid AND surrounding structures AND maybe other organs What is it?
Riedel thyroiditis Systemic autoimmune IgG4 sclerosing disease
39
Diffuse, symmetric hypertrophy of thyroid, exophthalmos, pretibial myxedema (dermopathy), bruit in neck
Grave's disease
40
Grave's disease - most common antibody Function?
Thyroid-stimulating immunoglobulin (TSI) Binds TSH receptor, mimics its action, released hormones
41
Grave's disease - genetics
CLTA4, PTPN22, HLA-DR3
42
Grave's disease - eyes Why?
Protrusion due to increased connective tissue and EOMs Antibodies stimulate TSH receptor on fibroblasts behind the eye
43
Diffuse enlargement of the thyroid, hypertrophy/hyperplasia of the follicles, papillae w/o fibrovascular cores, lymphocytic infiltrate, germinal centers
Grave's disease
44
Grave's disease - increased risks?
Autoimmune diseases (SLE, pernicious anemia, type 1 DM, Addison's disease)
45
Goiters - fundamental cause How does the enlargement happen? Most common cause?
Impaired synthesis of thyroid hormone Decreased T3/T4 = increased TSH = hypertrophy Iodine deficiency
46
Most (but not all) people w/ goiters have what T3/T4 level? What about TSH level?
NORMAL (compensatory due to increased mass) Elevated TSH Symptoms = mass effect
47
A patient has multinodular goiter. What can be assumed about the history of the disease? Why does this happen?
STARTED AS SIMPLE GOITER, then progressed Episodes of hyperplasia and involution happening simultaneously in different parts of the gland
48
Cause of endemic goiter? Why does prevalence vary in these places?
Iodine deficiency Dietary goitrogens vary from place to place - cabbage, cauliflower, brussel sprouts, turnips, cassava
49
Goiter (large) - symptoms
Airway obstruction, SVC syndrome
50
A patient has had long-term goiter. After 10 years, she develops symptoms of hyperthyroidism. Why?
Plummer syndrome - autonomous "toxic" nodule forms w/in the goiter, producing thyroid hormone
51
Most thyroid neoplasms are ____ (#) and ____ (prognosis)
Solitary, benign
52
Thyroid nodule - neoplasia vs. benign (clues) Common symptoms in all of them (if big enough)
Neoplasia - solitary, young, male, Hx of radiation to H/N Benign - multiple, older, female, functional ("hot") Difficulty swallowing, SVC syndrome
53
Solitary thyroid mass, painless, found on routine exam. Fully encapsulated, well-demarcated, uniform cell population w/ colloid, Hurthle cells occasionally What about hormone production/radioiodine uptake?
Thyroid adenoma Can be "hot" or "cold" - most are nonfunctional ("cold")
54
How to BEST distinguish cause of follicular neoplasm?
Capsule evaluation (adenoma = full, cancer = NOT)
55
Papillary vs. follicular thyroid carcinoma -- History?
Papillary - often radiation exposure | Follicular - often iodine deficiency (think like goiter)
56
4 general types of thyroid carcinoma MOST thyroid carcinomas are what type?
Papillary, follicular, anaplastic, medullary Papillary
57
Follicular carcinoma - genetics Anaplastic carcinoma - genetics Papillary carcinoma - genetics Papillary carcinoma - bad prognostic indicator?
``` Follicular = RAS/PI3K, PTEN, (2;3)(PAX8:PPARG) Anaplastic = SAME (except not the translocation) Papillary = RAS, RET/PTC (fusion gene), BRAF ``` BRAF(V600E)
58
***Solitary thyroid nodule, finely-dispersed chromatin (clear/empty appearance), pseudo-inclusions or invaginations or nuclear grooves, psammoma bodies
Papillary thyroid carcinoma
59
Ground glass or Orphan Annie nuclei
Papillary thyroid carcinoma (clear/empty-looking)
60
Nuclear features of papillary carcinoma, follicular architecture Higher incidence of what genetic thing?
Follicular variant of papillary carcinoma RAS mutation (not BRAF or RET/PTC)
61
Papillary carcinoma nuclei, eosinophilic columnar cells lining the papillae Higher incidence of what genetic things?
Tall-cell variant of papillary carcinoma BRAF mutation, RET/PTC translocation
62
Younger person (even children), papillary carcinoma nuclei, extensive fibrosis throughout the gland, LN (not vascular) metastases Higher incidence of what genetic thing?
Diffuse sclerosing variant of papillary carcinoma RET/PTC translocation (not BRAF)
63
Painless solitary thyroid nodule, small clusters of uniform cells w/ colloid, capsular invasion, small foci of hemorrhage
Follicular thyroid carcinoma
64
Follicular carcinoma - metastasis
Vascular - bone, lungs, liver (NOT LN's)
65
Rapidly enlarging bulky neck mass, extracapsular invasion, dyspnea, dysphagia, hoarseness, cough Prognosis?
Anaplastic thyroid carcinoma Nearly 100% DEATH (no effective therapies)
66
Solitary thyroid nodule, amyloid in the stroma, diarrhea, elevated CEA Cell type? (both types) What else will be seen on labs? (both types)
SPORADIC Medullary thyroid carcinoma ``` Parafollicular cells (C cells) Elevated CALCITONIN ```
67
B/L thyroid nodules, amyloid in the stroma, adrenal or parathyroid masses
FAMILIAL Medullary thyroid carcinoma
68
Sporadic medullary thyroid carcinoma - diarrhea - why?
VIP paraneoplastic secretion
69
Familial medullary thyroid carcinoma - genetics? Syndrome?
RET mutation - MEN2 syndrome