Thyroid Flashcards
1
Q
What is this?
A
normal thyroid gland
2
Q
What is this?
A
Normal thyroid (usu 10-30gm)
3
Q
What is the function of TSH?
A
1) stimulates T3/T4 production via Iodination of Thyroglobulin
2) stimulates release of T3/4 (by cleavage from Iodinated Thyroglobulin), it than binds Thyroid Binding Globulin in serum
4
Q
What is the function of Thyroid Peroxidase?
A
1) responsible for the iodination of thyroglobulin
2) readies the Iodine into Iodide
5
Q
Where do thyroid hormones (T3/T4) carry out its function?
A
It passes to cells where it works intranuclearly: binding the Thyroid Hormone receptor forming a complex
6
Q
What does the complex of thyroid hormone with thyroid hormone receptor goes on to do?
A
binds Thyroid Response Elements (TRE) in the genome, thereby upregulating transcription (despite it being a peptide derivative!!!)
7
Q
How does goitrogens affect the thyroids?
A
lead to thyroid enlargment
8
Q
How does goitrogen work?
A
Inhibit thyroid hormone release in the blood
9
Q
Explain the two mechanisms for how goitrogens work.
A
1) One mechanism (Iodides) prevents cleavage of thyroglobulin, thus Iodinated Thyroglubulin continues to be stored in the colloid, and low serum T3/T4 leads to increased TSH secretion promoting proliferation of thyroid tissue-> goiter! {includes both Drugs & certain foods}
2) Another mechanism is preventing of Iodine uptake -> leads to Goitrous Hypothyroid
10
Q
What are the 3 broad classifications of thyroid disease?
A
Hyperparathyroidism
Hypothyroidism
Mass Lesions
11
Q
How is thyrotoxicosis and hyperthyroidism similar?
A
Thyrotoxicosis is the hypermetabolic state of excess T3/T4; it is most commonly caused by hyperfunction of the Thyroid gland itself (=Hyperthyroidism, thus often used interchangeably)
12
Q
Contrast thyrotoxicosis and hyperthyroidism.
A
Thyrotoxicosis may also be due to increased release of hormone (as in Thyroiditis) or even extra-thyroidal source (tumor); thus, strictly, hyperthyroidism is a FORM of thyrotoxicosis
13
Q
What are the most common causes of thyrotoxicosis and hyperthyroidism?
A
Diffuse Hyperplasia (eg: Graves), Hyperfuctional Multinodular Goiter, Hyperfunctionnal Adenoma of Thyroid
14
Q
What generally happens with elevated thyroid hormones?
A
Increased basal metabolic rate (BMR), sweating, warm skin, weight loss, decreased appetite, lymphandenopathy
15
Q
What happens cardiovascularly with elevated thyroid hormones?
A
Palpitations, Tachycarddia, arrythmia, even CHF in patients w/ previous CHD
16
Q
What happens neuromuscularly with elevated thyroid hormones?
A
anxious, tremor, hyperactive, proximal muscle weakness, poor concentration, insomnia
17
Q
What happens gastrointestinally with elevated thyroid hormone?
A
SNS hyperstimulation -> increased motility, diarrhea, reduced absorption (-> weight loss)
18
Q
What happens ocularly with elevated thyroid hormone?
A
exopthalmia (more specific to Graves)
19
Q
What happens skeletally with elevated thyroid hormones?
A
increased bone resorption & osteoporosis (if chronic)
20
Q
What is a thyroid storm?
A
abrupt onset of hyperthyroidism (elevated thyroid hormone); febrile & tachy; occurs due to underlying disease (graves & stress); medical emergency, can die of arrhythmia
21
Q
What are 3 causes of thyrotoxicosis?
A
Hyperthyroid, T3/4 Spilling, Tumor
22
Q
List 5 primary causes of excess thyroid hormone.
A
- Diffuse Toxic Hyperplasia (Graves)
- Hyperfxning Multinodular Goiter
- Hyperfxning Thyroid Adenoma
- Hyperfxning Thyroid Carcinoma
- Iodine-Induced Hyperthyroidism
*all of these have down-regulated TSH*
23
Q
What leads to neonatal thyrotoxicosis?
A
associated w/ Maternal Hyperthyroid/Thyrotoxic Disease
24
Q
What is a secondary cause of elevated thyroid hormone?
A
TSH Secreting Pituitary Adenoma (rare); in this case TSH will be elevated along w/ high T3/T4
25
What is primary hyperthyroidism?
Primary is associated w/ increased T3/T4 due to thyroid overproduction; Low TSH
26
What is secondary hyperthyroidism?
Secondary is associated w/ increased T3/T4 due to upregulation of thyroid; extrinsic to thyroid; High TSH
27
How effective is TSH as a screening test for hyperthyroidism?
TSH is the best measure as it is lowered (by neg feedback) even in the very early stages of disease; this is assoc w/ an incrd T4/T3 level {TSH could be high if TSH tumor though!}
28
What comes up after TSH as a screening procedure?
Follow up w/ radioactive Iodine studies to determine etiology
29
What's the link between iodine and Grave's disease?
whole gland increased Iodine uptake
30
What's the link between iodine and adenoma?
single region of increased Iodine uptake (increased assumes Hyperfunction adenoma)
31
What's the link between iodine and adenocarcinoma?
single cold spot (Follicular can be hot)
32
What's the link between iodine and thyroiditis?
decreased Iodine uptake; T3/4 spilling & overproduction is not the issue
33
What is primary hypothyroidism?
due to failure of the Thyroid itself
34
What is secondary hypothyroidism?
due to failure of the Pituitary to make TSH
35
What is tertiary hypothyroidism?
due to failure of the Hypothalamus to make TRH (Rare)
36
List the major causes of hypOthyroidism.
Developmental (thyroid dysgenesis: due to PAX-8, TFF-2, or TSH receptor mutations)
Congenital biosynthetic defect in T3/T4 synthesis
Thyroid Hormone Resistance Syndrome (TR-beta mutation at tissues)
Ablative (Qx/Removal, Radioactive Iodine, Radiation exposure)
Autoimmune (Hashimoto’s)
Iodine Deficiency (3rd world countries)
Drugs (Iodides, a Goitrogen)
Pituitary Defect (secondary Hypo)
Hypothalamic defect (tertiary Hypo)
37
What is cretinism?
Cretinism is hypothyroidism that develops in infancy or early childhood; may be due to iodine deficiency or defective synthesis (congenital enzyme defect as above)
38
What are the clinical features of cretinism?
impaired development of skeleton & CNS: mental retardation, short stature, coarse fascies, protruding tongue, umbilical hernia
degree of abnormality varies based on maternal levels early (normal is high) & late (normal is low) in pregnancy
39
What is myxedema?
Hypothyroidism occurring in older child or adult; thus, often acquired
40
What are some clinical features of myxdema?
Features include slowed mental & physical activity; which may be more apparent in child & indolent in adult (long course for clinical suspicion); other traits are opposite of those seen in Hyperthyroidism along with: edema, coarse features, deepened voice, enlarged tongue-\> all due to GAG & Hyaluronic Acid deposition
41
How is hypothyroidism diagnosed?
TSH levels are also important for diagnosis; it will be high in primary hypo, but low in 2ndry or 3ry hypo
42
What are the 3 most common and clinically significant forms of thyroiditis?
Hashimoto’s (Chronic Lymphocytic)
Subacute Granulomatous
Subacute Lymphocytic
43
List the typical age of onset, male:female ratio, and HLA associations of Hashimoto thyroiditis.
45-65yrs, 10:1 or even 20:1 Female:Male; HLA-DR3 & HLD-DR5
44
Patients with Hashimoto's Disease have _________ risk of developing (exocrine and non-exocrine) autoimmune diseases.
increased
45
What other diseases will patients with Hashimoto's be at risk for?
Endocrine autoimmune (Type I DM)
non-endocrine autoimmune (SLE, Myasthenia, Sjogren)
Non-Hodgkin's Lymphoma
NO specific link to thyroid neoplasms
46
What are 3 autoantibodies produced by B lymphocytes in Hashimoto thyroiditis?
Anti-TSH Receptor, Anti-Thyroglobulin, Anti-Thyroid Peroxidase
47
Three mechanisms of Thyrocyte Death
1. CTL mediated cell death
2. CD4 mediated cytokine release (INF-γ) that activates Macros leading to cell death
3. Anti-Thyroid Antibodies mediated cell death
48
What are the functions of anti-thyroid antibodies?
All three lead to Ab-Dependent Cell-mediated Cytotoxicity (ADCC)
They will all alter T3/T4 production & release, and Anti-TSH-R blocks TSH
49
What is this?
Hashimoto's Thyroditis
50
What do you expect to see on micro slide for Hashimoto's thyroiditis?
Thyroid gland w/ Lymphoid Follicles (mononuclear cells); Atrophic Thyroid follicles; Hurthle Cells
In addition, Fibrous variants may demonstrate broad, kelloid like fibrosis
51
What are Hurthle cells?
cells w/ eosinophilic granular cytoplasm found in Hashimoto's thyroiditis
52
Describe the clinical course of Hashimoto thyroiditis.
Gradual autoimmune destruction of the thyroid gland; it is the most common cause of hypothyroidism where Iodine intake is sufficient; it presents painlessly,
Initial Thyrotoxicosis/Hashitoxicosis (incrd T3/4 & decrd TSH) -\> Euthyroid -\> Hypothyroid (decrd T3/4 & incrd TSH)
53
List the typical age of onset and male:female ratio of Granulomatous Thyroiditis
30-50 yrs; 3:1 or 5:1 Female:Male (again women favored)
54
Discuss the proposed etiology of Granulomatous Thyroiditis
Occurs secondary to antecedent viral infection (cocksackie, mumps, measles, adenovirus), w/ a summer predilection
One hypothesis is that viral infection leads to release of an Ag (viral or thyroid is unclear) that leads to CTL mediated attack on Thyrocytes (follicular cells); this is in contrast to Auto-immune diseases due to the viral induced component
55
What's the most common cause of endogenous hyperthyroidism? What's its frequency?
Graves Disease
It occurs in 1.5-2% of women in US; w/ incr’d incidence in families
56
What's the "Classic Triad" of Grave's disease?
1. Hyperthyroidism (leads to Hyperplasia of thyroid)
2. Opthalmopathy – Exopthalamus
3. Dermatopathology – Localized & infiltrative: Pretibial Myxedema in some ptnts
57
What's the difference between myxdema or pretibial myxdema?
Myxedema refers to Adult HYPOthyroid, but Pretibial Myxedema can occur in Graves (disease of hyperthyroidism)
58
List the typical age of onset, Male:female ratio, and HLA associations of Graves disease
20-40 yrs; 7:1 Female:Male; HLA-B8 & HLA-DR3; CTLA-4 defects have also been noted (CTLA-4 normally reduces response of T-cells to self-Ag, binds B7)
59
State the underlying etiology of Graves disease
Various Auto-Ab may be present in the serum, most important of which is the TSH Receptor stimulating Ab (opp of TSH-R blocking Ab, 1 of 3 seen in Hashimoto’s)
60
What are the 3 autoantibodies found in Grave's disease (similar to Hashimoto's)?
Auto-Abs targeted against TSH receptors, thyroid peroxidase, and thyroglobulin
61
What are the auto-antibodies reserved for Grave's disease?
(All three binds to TSH receptors)
1. Thyroid Stimulating Immunoglobulin
2. Thyroid Growth Stimulating Immunoglobulin (stimulates growth of tissue itself)
3. TSH-Binding Inhibitor Immunoglobulins (blocking TSH from binding - stim or inhib - may be related to the presence of spontaneous hypothyroidism sometimes seen in Graves)
62
Compare and contrast Hashimoto's with Grave's.
Opposite extremes of the autoimmune disease spectrum (Hashimoto's - hypO; Grave's - hypER)
Hashimoto's occur later (55s) than Grave's (30s)
Both can have CROSSOVER during progress (patient may be concurrently both diseases).
Also, both have a strong link with other autoimmune diseases and **intrathyroidal lymphoid infiltrate**
63
What's expected grossly in Graves?
\>80g; smooth and soft
64
What's expected microscopically with Graves?
“Too Many Cells”; **hypertrophied follicles**, w/ tall columnar epi, **scalloped edge colloid**, and **papillary-like insertions of epithelium** into the colloid due to overgrowth; as above, **Intrathyroidal Lymphoid Infiltrate** (T’s, B’s, Plasma) & even **germinal centers** (as in Hashimoto’s)
65
What's particularly special about the eyes in Graves?
exopthalamos! eyeballs will show edema
66
Describe clinical course of Graves.
General changes assoc w/ Thyrotoxicosis apply, but also…
Hyperplasia of thyroid, Opthalmopathy, Dermatopathology (eg: pretibial myxedema - thickening, peau d'orange, induration, slight pigmentation)
Weakened extraocular muscles due to Exopthalmia (persists even w/ Graves treatment)
67
Lab findings of Graves?
elevated T3/4 w/ low TSH; incrd & diffuse uptake of Radioactive Iodine
68
Treatment of Graves?
ablation of tissue: Qx/removal, Propylthiouracil (a goitrogen), radioiodine
69
Why do we get goiters?
thyroids enlarged due to **compensatory hyperplasia** in attempt to maintain euthyroid state when there's impaired synthesis of thyroid hormone (GRAVE'S EXCEPTION)
\*MOST COMMON MANIFESTATION OF THYROID DISEASE\*
70
What's goitrous hypothyroidism?
when the compensation of a goiter is insufficient
71
Define diffuse goiter.
the goiter formation is diffuse within the thyroid & no nodularity; assoc w/ **Endemic or Sporadic Goiter**
72
Define multinodular goiter.
**_chronic_** cycles of hyperplasia & involution lead to irregular enlargement of the thyroid; arise from diffuse (simple) goiters which recur, thus can also be assoc w/ **Endemic or Sporadic**; cause the **largest goiters**, and may be **confused for neoplasia**
73
What's endemic goiter?
Areas where 10% of the population has a goiter related to poor availability of Iodine in the soil, water, & food (mountainous areas like: Alps, Andes, Himalayas)
In these areas, Goitrogenic foods (cassava, cabbage, brussel sprouts, turnips) may exacerbate
74
What's the accepted theory of multinodular goiter development?
Due to **variations in responsiveness of follicular cells to growth factors** (eg: trophic hormones, mutations in TSH response pathway proteins may be involved) - some cells may have a **growth advantage** and may even become **autonomous** (similar to thyroid Adenomas)
nodules may be **poly & monoclonal**; uneven growth may lead to rupture of follicles & vessels, which can create fibrosis & perpetuate a 2nd rupture
75
What's seen grossly in multinodular goiter?
**Asymmetric, nodular** hyperplasia of thyroid; 2,000g’s is possible
Large size may impede on neck & mediastinal structures (**Mass Lesion**)
76
What's seen microscopically in multinodular goiter?
colloid filled follicles, w/ low columnar epi & hyperplastic epi; hemorrhage, fibrosis, calcification, & cysts are signs of degenerative change (grow so fast!)
77
Describe clinical course of goiter.
For both types, main problem is **Mass Effect** on structures of neck, thoracic outlet, and mediastinum
Both show **high TSH** (trying to maintain euthyroid) and **increased radioiodine uptake** in **"Hot" zones** of hyperplasia
Most cases are **euthyroid** (a few mutlinodular can be hyper or hypothyroid)
\*if hyperthyroid - does not have opthalmopathology or dermatopathology\*
78
Discuss the male:female ratio and clinical significance of a Solitary Thyroid Nodule.
4:1 Female:Male; it is a palpable mass in an otherwise normal thyroid
Possibility of neoplasia in a solitary nodule is a major concern when detected; luckily 10:1; benign:malig
79
State the frequency and general overall prognosis of thyroid malignancy
Rare ; good prognosis
80
What are the 5 clinical criteria of thyroid nodule?
1. **Solitary vs. Multiple** (solitary more likely neoplastic)
2. **Young** (more likely neoplastic)
3. **Males** (more likely neoplastic)
4. **Radiation of head and neck** (increased risk of neoplasm)
5. **Hot nodules** (more likely BENIGN - exception is follicular carcinoma which may be hot or cold - think: INFLAMMATION)
Summary: Solitary “Cold” nodule in a young male with a history of radiation is most likely to be neoplastic
81
Describe the derivation of typical thyroid adenoma.
derived from _follicular epithelium_, aka: **Follicular Adenomas**
A small portion may produce T3/4 autonomously, aka **Multinodular Goiters**
82
What's grossly seen in typical thyroid adenoma?
grey-white to yellow-brown; encapsulated; can be reminiscent of Multinodular Goiter w/ calcification, hemorrhage, fibrosis, & cystic change; normally a single foci & will compress adjacent tissue (both v. Multinodular Goiter)
83
What's seen microscopically in typical thyroid adenoma?
distinct pattern of clonal follicular cells; NO papillary arrange (suggests malig!)
84
What's seen clinically in thyroid adenoma?
Painless Cold Nodule
Sx may include dysphagia due to mass effect; possibility of Hyperfxnal or Toxic Adenoma (rare Hot Nodule)
They **take up less Radioactive Iodine** = Cold nodules (differ from Multinodular goiter); but, _not all cold nodules are adenoma (some cold nodules may be malignant, 10%)_
85
What's important in the diagnosis of thyroid adenoma?
Fine needle aspiration & most importantly surgical specimen (tell if benign/malignant)
86
What's the significance of a "cold" thyroid nodule?
takes up **LESS Radioactive Iodine** than normal tissue
87
What's the significance of a "hot" thyroid nodule?
takes up **MORE Radioactive Iodine** than normal tissue
88
List and rank by **frequency** the 4 major subtypes of thyroid cancer.
List and rank by **prognosis** the 4 major subtypes of thyroid cancer.
**frequency:** papillary \> follicular \> medullary \> anaplastic
"please forgive my aunt"
THE EXACT OPPOSITE for **prognosis**
89
What are the 3 proven/suspected risk factors for thyroid carcinoma?
genetics, radiation exposure, long standing multinodular goiter (growth factor response)
90
List the typical age of onset and risk factors for Papillary Carcinoma of the thyroid.
**20-40yrs** (same as Graves), most commonly assoc w/ exposure to **Ionizing Radiation**
91
What's seen microscopically in papillary carcinoma?
1. **Papillary appearance w/ Fibrovascular core** (infiltrating or fairly well delimited)
2. Clear to Empty look of the nuclei (**Orphan Annie Eye Nuceli**)
3. **Psammoma Bodies** – concentrically calcified structures w/in the lesion; used for discrimination from Follicular v. Medullary Carcinoma
4. **Lymphatic invasion** is common, blood vessel invasion is not
92
What is this?
papillary carcinoma
93
What is this?
Papillary Carcinoma
94
What's the classic presentation of papillary carcinoma?
most are **asymp** thyroid nodules; may show up as **metast to cervical node**, but still good prog; **Mass Effect** if big (eg: dysphagia); **possible lung metast** also
95
What are the Scintscan findings of papillary carcinoma?
most are “Cold” lesions; Fine needle aspiration is also useful (Orphan Annie)
96
What's the prognosis of papillary carcinoma?
GOOD
## Footnote
10yr survival 95%; 5-20% recur; 10-15% metast; also depends on Age (\>40 is worse), extrathyroidal extension, & metastasis
97
List the typical age of onset and proposed risk factors for Follicular Carcinoma.
**40-50yr** old women most common; possibly assoc w/ **Nodular Goiters in endemic** iodine deficient regions; **ras mutations** correlate Follicular Adenoma & Carcinoma
98
Discuss the significance of a thyroid malignancy presenting as a "Hot" nodule.
This is a hyperfxnal lesion, and thus may lead to Thyrotoxicosis (hyperthyroidism)
99
What carcinoma is a neuroendocrine tumor?
**Medullary Carcinoma,** as it is derived from the **Parafollicular or C-cells**; assoc w/ **MEN2**
100
What's the most typical secretory product of Medullary Carcinoma
Calcitonin (although, VIP, SS, 5HT also possible)
101
What is acellular amyloid deposits associated with?
medullary carcinoma
102
ID the clinical course of medullary carcinoma.
Present as **mass in neck**, sometimes w/ mass effect; may demonstrate 1st as **Paraneoplastic Syndrome** due to VIP, SS, 5HT; but surprisingly, **Hypocalcemia is _NOT_ common**!
103
Identify the prognosis of Anaplastic Carcinoma of the thyroid gland
BAD
## Footnote
No effective therapy, **almost uniformly fatal w/in a year** due to rapid growth & Mass Effect compressing vital neck structures; it is the worst of the Thyroid Carcinomas
104
State the most common clinically significant congenital anomaly of the thyroid gland
Thyroglossal Duct Cysts
105
What's the clinical significance of thyroglossal duct cyst?
May convert into **abscess cavities**, and in **rare** instances can demonstrate **premalignant potentional**
