Thyroid Pathology Singh Flashcards
1
Q
Where is thyroglobulin stored and made, and what does it do?
A
- Tg is made and stored in colloid
- Iodide gets transported to the cell and incorporated into Tg making iodinated tyrosines
- Tg gets endocytosed and cleaved to release T3 and T4
2
Q
How does T3 impact TSH and GH?
A
Incr. Growth hormone and decresase TSH
3
Q
Hyperthyroidism (Thyrotoxicosis) symptoms?
A
- perspiration
- facial flushing
- weight loss
- palpitation/tachy
- diarrhea
- nervousness/excitablitiy/restlessness/insomnia/emotional instablity
- exopthalmos (graves disease not just hyperthyroidism)
4
Q
What causes primary hyperthyroidism?
A
- Grave’s disease
- Hyperfunctioning multinodular goiter
- Hyperfunctioning thyroid adenoma
most common cause of hyperthyroidism
5
Q
What would cause secondary hyperthyroidism?
A
Pituitary adenoma
6
Q
If TSH is low would this indicate primary or secondary hyperthyroidism?
A
Primary because the thyroid hm is negatively inhibiting TSH
7
Q
Apathetic hyperthyroidism?
A
- Older adults with masked symptomatology
- Unexplained weight loss
- CV dz
8
Q
What is Thyroid storm? What is the scoring system?
A
- Sudden severe onset:
- fever
- cardiac → CHF or tachy
- GI → diarrhea, jaundice, pain
- Precipitating history:
- pregnancy
- hemithyroidectomy
- drugs such as amiodarone
Burch Wartofsky Score
9
Q
How do you treat thyroid storm?
A
- Beta blocker (Propranolol) to treat the manifestations
- Treat the underlying disease
- high dose iodide
- thionamide
- radioiodine ablation
- surgery
10
Q
Graves disease diagnostic triad?
A
- Hyperthyroidism with gland enlargement
- Infiltrative opthalmopathy
- Pretibial myxedema
11
Q
How does Graves disease work?
A
- Thyroid stimuolating antibodies bind TSH receptor and increase T3 and T4 release
- Exopthalmos occurs bc fibroblasts become stimulated by these AB’s and increase retro orbital CT mass
12
Q
If you see resorption droplets in histology what would this indicate?
A
- Graves disease
- intracytoplasmic droplets appear representing colloid in endocytotic vesicles
13
Q
What are the expected labs for Grave’s disease?
A
- T3 and T4 → high
- TSH → low
- TSI → high
14
Q
Congenital hypothyroidism (“cretinism”) symptoms, where is it seen, what causes it?
A
- early infancy/childhood
- imparied mental dev, decrease growth, coarse facial features, umbilical hernias
- Seen in endemic areas without iodine supplementation
- depends on time of onset in mother while pregnant
- Can be result of genetic alterations in normal thyroid metabolic paths
15
Q
What causes secondary hypothyroidism?
A
- Pituitary failure
- Hypothalamic failure
both are rare, and everything else is a primary cause
16
Q
Hypothyroidism (myxedema) in the adult/older child symptoms?
A
- edema of face/eyelids
- coarse cool dry yellowish skin
- dry brittle hair
- slow cerebration
- weight gain
- cold intolerance
- cardiac effect → low output, hypercholesterolemia
17
Q
Hashimoto’s thyroiditis?
A
- most common thyroiditis in iodine sufficient areas, it is autoimmunity against thyroglobulin and thyroid peroxidase
- diffuse painless enlargement of thyroid
18
Q
Hashimoto thyroiditis progression?
A
Immune mediated insult → Hyperactivity & elnargement → follicular cell exhaustion
Thisis called hashitoxiocosis
19
Q
What is this
A
- Hashimoto thyroiditis → thyroid is mildly enlarged and painless and path shows lymphocytic infiltrate with germinal centers
- Atrophic follicle cells with eosinophilic change
- Hurthle cell metaplasia
20
Q
what is this
A
Left → hashimoto
Right → graves
21
Q
What antibodies are prevalent in hashimoto’s?
A
- hTg Ab → 80-90%
- hTPO-Ab → 90-100%
- sometimes can see TSHR-Ab (TSI) 5-10%
22
Q
What is Granulomatous thyroiditis?
A
- AKA De Quervain’s thyroiditis
- painful granulomata
- possibly viral in origin
- sometimes lumped with subacute thyroididits
- assoc. with HLA B35
23
Q
Subacute lymphocytic thyroiditis?
A
- transient period of thyroid hm irregularities
- Hypothyroidism, goiter
- painless
can progress to permanent hypothyrodisms
24
Q
What is Riedel Thyroiditis?
A
- Fibrosing process extending from thyoid into adjacent tissues
- you can see invasion into skeletal muscle
- surgeons think it could be cancer as it feels like cement and is a difficult thyroidectomy
- you can see invasion into skeletal muscle
- Excessive fibrosis but you also see lymphocytes and plasma cells (plasma cells → perinuclear hoff)
25
Fill in blanks
26
What is the significance of Riedel's thyroiditis and IgG4 disease?
They are related, so if you diagnose one you need to look for others
27
Diffuse nontoxic goiter
* result of thyroid metabolism issues
* it is an endemic goiter due to iodine deficiency or excess ingestion of thyroid hormones such as broccoli, cauliflower cabbage radish, cassava root
* thyroid swells to get to a euthyroid state
28
Symptoms of diffuse goiters?
* SVC syndrome
* Dysphagia
* Hoarsness
* Stridor
*diffuse goiters are euthyroid and symptoms are due to mass effect*
29
Multinodular goiters?
* Hyperplasia
* can produce the same mass effect as difffuse goiters
* can become massive
30
What is a substernal goiter?
* Goiter that has slipped underneath the sternum and grows within the chest cavity and can reach massive sizes
* *Dr. Singh told the story of the surgeon who told patient they had cancer bc it was so large and “invasive” when it turned out to just be a substernal goiter*
31
What are the benign thyroid nodules
* hyperplastic nodules (adenomatoid)
* Follicular adenoma
32
What are the malignant thyroid nodules?
* Papillary thyroid carcinoma
* Follicular /Hurthle cell carcinoma
* Anaplastic carcinoma
* Medullary carcinoma
*know genetics used for treatment and diagnostics*
33
Describe follicular adenomas
* Clonal population of folllicular cells with thyroid autonomy
* Benign but need to rule out follicular carcinoma and papilllary carcinoma
34
Papillary thyroid carcinoma presentation prognosis?
* Majority of malignant tumors of the thyroid gland (85%)
* Most happen in 25-50 yo
* good prognosis if diagnosed young → remove thyroid
* Typically presents without symptoms
* palpable nodule
35
How does age impact Papillary thyroid carcinoma?
* Tumors behave very well if you are \<55 yo and once you are over 55 they behave aggressively
* you can have Mets under 55 and still be classified as stage II
36
Describe the histo of papillary thyroid carcinioma and diagnostic features?
* Papillary architecture
* Psammoma bodies
* RET-PTC mutations and BRAF mutations
* Diagnostic features are the enlarged nuclei wit h"clear" appearance → “Orphan Annie Eye Nuclei”
37
Describe the variant, Follicular variant of PTC.
* Follicular architecture but nuclear features of papillary carcinoma
* fewer cases have RET-PTC or BRAF
* More cases with RAS mutations
* similar to follicular carcinoma and adenoma
38
Tall Cell Variant of Papillary Carcinoma
* older patients and aggressive
* can be COD even if contained to thyroid
39
Diffuse sclerosing variant of Papillary carcinoma
* Kids and young adults
* Higher incidence of mets
* has high survival rate of 93% at 10 years
40
Follicular carcinoma commonality and mutations?
* Invasive properties
* less common than papillary carcinoma
* more common in areas with goiter from iodide deficiency
* PAX8/PPARG
41
Describe the histology of Follicular carcinoma
* Invasive properties seen with invasion of the capsule (mushroom) and Angioinvasion
42
Therapies for differentiated thyroid carcinoma?
* Surgery
* Radioactive iodine
* If refractory:
* chemo
* tyrosine kinase inhibitor
43
What is anaplastic carcinoma?
* uncommon (~5%) very deadly cancer that occurs in older patients
* presents with mass effect and patients usually die within a year of local invasion
44
Mutations associated with Papillary carcinoma?
* RET/PTC rearrangements
* BRAF gain of function
45
Follicular carcinoma mutations?
PAX8-PPRAG
46
Non specific Follicular neoplasms
RAS and PTEN
47
What mutation is associated with anaplastic carcinoma
TP53
48
What are C cells responsible for?
Calcitonin secretion
49
What are Medullary carcinomas of the thyroid?
* Neuroendocrine carcinoma derived from C cells
* blue cells with dispersed chromatin
* amyloid can be present
* C-cell hyperplasia → stain
50
Genetics and prognosis of Medullary carcinoma?
Familial MTC:
* BEST prognosis (100% 15 year survival)
* Multifocal
* Avg age 43
Sporadic MTC:
* 70-80% of all MTCs
* Unifocal
* avg age 50
* Aggressive (half have LN mets at diagnosis)
MEN syndrome
* worst prognosis (in another lecture)
51
What mutation is associated with medullary carcinoma of the thyroid?
RET
52
How do you diagnose Follicular carcinoma vs follicular adenoma?
If there is invasion into the capsule or angioinvasion you can diagnose carcinoma
