Thyroid Parathyroid Disease-Melissa Flashcards
1
Q
Describe how the thyroid develops, its ultimate structure and location:
A
Invagination of pharyngeal mucosa–>
Bilobed organ w isthmus–>
Inferior to thyroid cartilage @ level of cricoid cartilage
2
Q
Describe the histological appearance of the normal thyroid:
A
colloid within matrix of follicular epithelial cells and c cells
3
Q
Define the funciton of colloid, follicular epi cells, parafollicular (c-cells) cells
A
colloid: resevoir for thyroglobulin and thyroid hormone
follicular epi cells: Thyroglobulin–> T4 + T3
C-Cells: secrete calcitonin: inhibit bone resorption; Ca sequestration by bone
4
Q
Describe the process of Thyroid hormone release:
A
TRH (hypothalamous)–>
TSH (anterior pituitary)–>
T3 +T4 (Thyroid)–> Negative feedback on hypothalamus + pituitary
5
Q
Define thryrotoxicosis; what is a possible cause?
A
- Excessive leakage of T3/T4 –> Hyperthyroidism
- can be caused by thyroiditis
6
Q
Hyperthyroidism causes what metabolic imbalance?
How does the condition present (5)?
A
Hypermetabolic state
- GI hypermotility, malabsorption, diarrhea
- ^ sympathetic stimulation
- +/- CHF
- Wide gazing state + Lid Lag
- heat intolerance
7
Q
What are the 5 most common causes of hyperthyroidism?
A
- Graves disease
- Ingestion of hormone
- goiter
- adenoma of thyroid
- Thyroiditises
8
Q
What is a struma ovarii?
A
Ovarian taratoma full of thyroid tissue–possible (RARE) cause of hyperthyroidism
9
Q
What happens in a thyroid storm?
How does it present clinically?
What is the most common cause?
A
- medical emergency
- abrupt onset severe, life threatening thyrotoxicosis
- Tachy, thermoregulatory malfxn, N/V/D
- Seen in GRAVES DISEASE after thyroid surgery
10
Q
How do we screen for hyperthyroidism; describe the lab findings:
A
- ^fT4
- Primary: LOW TSH (check T3)
- Secondary: ^TSH
11
Q
Most cases of hyperthyroidsim are: primary or secondary?
A
PRIMARY
12
Q
What is endemic cretinism? What causes it?
A
- Infants born with hypothyroidism–> MR, protruding tongue, etc.
- Associated with Iodine deficiency or inborn metabolic error
13
Q
What are the symptoms of HYPOthyroidism (6)?
A
- myxedema
- apathy
- cold intolerance
- constipation
- periardial effusion and obsesity
14
Q
What is the most sensitive laboratory test for hypothyroidism?
Which lab test will be decreased in both?
A
TSH = most sensitive test!!!
- Primary (thyroid) = INCREASE
- Secondary (pituitary) = DECREASED
T4 will be DECERASED in both!!
15
Q
Waht is the #1 endogenous form of HYPERTHYROIDISM?
A
Graves disease
16
Q
Graves Disease:
- Population
- Genetic association
A
- females 20-40 yoa
- HLA-DR3, HLAB8
17
Q
How does Graves disease present?
What is the clinical triad?
A
- Exopthalmos (bulging eyes) + hyperthyroid sx.
- Diffuse goiter +/- bruit over thyroid
Clinical Triad:
- thyrotoxicosis
- exopthalmos
- pretibial mydedema
18
Q
How does exopthalmos occur?
With which disease is it associated?
A
Assocated with GRAVES DISEASE:
Mononuclear infiltrate retro-orbital space–> Inflammatory edema of EO mm–>
^ ECM + ^ adipocytes
19
Q
Describe the pathogenesis of Graves disease:
A
Autoimmune attack of thyroid autoantigens (#1= TSH-R)
*Multiple autoabs that ^ TH release
20
Q
***Describe the histo of the graves thyroid (4):
A
- Hypertrophy + hyperplasia
- Crowded follicular cells
- PAPILLAE WITHOUT FIBROVASCULAR CORE*
- Colloid SCALLOPING*
21
Q
Briefly describe how Graves disease manifests in the heart, eyes and skin:
A
- cardiac hypertrophy and ischemia
- exopthalmos w mucopolysaccharide infiltrate
- pretibial myxedema
22
Q
Lab findings associated with Graves (radioiodine, T4/3, TSH):
A
- INCREASED UPTAKE on RADIOIODINE SCAN
- ^T4, ^T3
- DECREASED TSH
23
Q
What is the most common thyroid disease?
What are some symptoms?
A
GOITER–simple enlargement of thyroid
- presents with cosmetic deformity, airway obstruction, dysphasia, etc. (or no complications at all)
24
Q
What is a common cause of goiter?
Where is this a problem geographically?
How do we help it?
A
Iodine deficiency–> Impaired TH synthesis
- common in mountainous regions (low Iodine in soil)
- iodized salt helps
25
What is an ENDEMIC goiter?
- OVER 10% of population has goiter
- common in mountain people
- assocated w Iodine deficiency!
26
What causes SPORADIC goiter?
- many causes both environmental and genetic
| - commonly idiopathic
27
What is Plummer's syndrome?
- HYPERthyroid disorder
- multinodular goiters with hyperfunctioning nodule
- NO optho or derm problems
28
Most goiters are...
EUTHYROID!
| rarely HYPOthyroid, may mask or mimic neoplasm
29
Describe the pathogenesis of a goiter.
| Describe the common lab findings assocated.
DECREASE TH--> ^TSH--> ^Thyroid size--> autonomous cell formation
- T3/T4 wnl
- TSH slightly ^ or wnl
30
Describe the gross morphology of a goiter:
- Hypertrophy and hyperplasia
- stimulation and involution
- nodular/ multinodular
31
What are 4 conditions that can cause thyroiditis?
- nonspecific lymphocytic thyroiditis
- hashimotos thyroiditis
- subacute (granulomatous) thyroiditis
- reidel's thyroiditis
*Infection: acute bacterial, TB, fungal, etc.
32
Nonspecific lymphocytic thyroiditis:
- Population, TH production, Genetic polymorphism
- How does this present?
- middle aged females
- euthyroid, typically incidental finding
- HLA-DR5
**Presents with mild symmetric thyroid enlargement + lymph infiltrate; injury of thyroid follicles may eventually lead to thyrotoxicosis
33
Lab fidnings assocated with nonspecific lymphocytic thyroiditis:
- ^ T4/T3
- LOW TSH
- DECREASED UPTAKE IN RADIOIODINE SCAN
34
If you see germinal centers in the thyroid think...
Hashimotos thyroiditis
35
Hashimotos thyroiditis:
Population?
Associated genetic polymorphisms?
How does this present?
- Older adult females
- HLA-DR5, HLA-DR3 if w atrophy
- Autoimmune HYPOthyroidism w PAINLESS goiter (diffuse or localized)
36
What is HASHITOXICOSIS?
Hashimotos thyroiditis-->Transient Hyperthyroidism
- DECREASED Radioiodine scan
- ^T4/T3
37
Describe the pathogenesis of hashimoto's thyroiditis:
Primary T cell defect-->
Anti-TSH AutoAbs-->
DECERASE TH synth--> HYPOthyroidism
38
Describe the gross/ micro histo assocated with hashimotos thyroiditis:
- Diffuse symmetiric enlargment
- mononuclear infiltrate w GERMINAL CENTERS
- small thyroid follicles
39
Hashimotos thyroiditis is associated with ^ risk for which two malignancies?
- B cell lymphomas
| - Papillary ca of the thyroid
40
De Quervains Thyroiditis:
| Population, cause signs/ sx, histo
- Older adult females
- Viral infection--> PAIN esp w swallowing + infxn sx
- (+/-) transient hyperthyroidism/ gland enlargement
- Typically self limited
Histo: follicles extrude colloid; granulomatous inflammation w/ giant cells, etc.
41
De Quervains Thyroiditis: Lab findings?
- ^ WBC + ^ sed rate
- ^T3/T4
- DECREASED TSH
- DECREASED Radioiodine uprtake
42
What happens in riedel's thyroiditis?
Thyroid becomes hard and fibroses; condition is rare
43
Most thyroid neoplasms are most commonly malignant or benign?
Which population is most likely to get thyroid malignancies?
What is one predisposing risk factor?
BENIGN
- young male patients most likely to have malignancy
- prior radiation therapy ^ risk malignancy
44
Thyroid adenoma:
Pathogenesis + Tissue of origin?
Signs/ Sx?
Histo?
Gs protein mutation --> Chronic ^^^ cAMP--> follicular epi mutates--> BENIGN thyroid adenoma (monoclonal)
- Painless mass, +/- swallowing problems, +/- hyperthyroid
- Histo: ENCAPSULATED lesion, NO papillary change, ^ follicular cells
45
How do we dx thyroid adenoma?
- need more than FNA to see capsule (histo slices)
46
List the 4 types of thyroid carcinoma and identify most common.
Describe the population that gets this disease:
- (#1) papillary
- (#2) follicular
- medullary
- anaplastic
In early and middle adulthood ca more common in F.
In childhood and late adulthood M = F.
47
List three risk factors for ca of the thyroid; one general + two specific
- ionizing radiation
- PTC oncogene --> papillary ca
- RET tyrosine kinase--> medullary ca
48
Papillary ca of thyroid:
- signs + sx.
- Histo***
- How does it met?
Solitary or multifocal mass in thyroid or cervical node(s)
-Mets via LMYPHATICS
Histo: GROUND GLASS/ ORPHAN ANNIE nuclei, papillae WITH FIBROVASCULAR CORE, +/- psammoma bodies
49
Follicular ca of thyroid:
- predisposing factors
- pathogenesis + tx.
+ how does it met (lymphatics vs vasculature)
-goiter/iodine deficiency + adenoma predispose risk
-Mets via VASCULATURE
-Pathogenesis:
Benign Adenoma--> TRANSFORMATION--> INFILTRATES capsule or vasculature
Tx: Surgery, suppression w TH
50
Medullary Ca:
- What type of tumor is this and from where does it derive?
- What does it secrete?
Neoplastic Parafollicular (c-cells)--> Neuroendocrine tumor--> Secretes CALCITONIN +/- VIP, other polypeptide hormones
51
What are they two types of medullary ca and when do they arise?
- sporadic (5th/ 6th decade)
| - MEN IIa, MEN IIb germ line mutations (younger patients; RET protooncogene mutation)
52
What are the signs/ sx of sporadic medullary ca?
| How do we screen for MEN?
Sporadic: presents w dysphasia/ sx of neck mass, +/- diarrhea due to VIP secretion
MEN screening: CALCITONIN levels, RET protooncogene testing
53
Medullary Ca histology; what is common or different between the familial and sporadic types? (4)
Differences:
- Solitary (sporadic) or multiple (familial) nodules
- C cell HYPERPLASIA in FAMILIAL
Both:
- Polygonal spindle shaped cells (nest, trabeculae, follicles)
- AMYLOID calcitonin deposits = CONGO RED STAIN
54
What is the prognosis for medullary ca?
| Which is most aggressive? How does the tumor met?
- Tumors met via vasculature
- Sporadic + MEN IIb are the most aggressive
- Familial tumors NOT MEN asstd. are less aggressive
55
Which thyroid ca is the most aggressive?
| In which population does it occur?
Anapestic ca; elderly patients in areas of endemic goiter
Very poor prognosis: death within year of dx.
56
Describe the histo and morphology or anapestic ca.
| From what must it be distinguished?
- rapidly growing bulky lesion that invades neck structures+ commonly mets to distant sites
- multiple cell types; if small cells present must distinguish from lymphoma
57
From where are the parathyroid glands derived?
What tissue do the glands contain?
How is the gland's function controlled?
- derived from descending pharyngeal pouches
- glands have fat interspersed
- activity controlled by free Calcium
LOW free Ca++ = ^ PTH
^ free Ca++ = LOW PTH
58
Describe the effects of PTH on bone, renal, GI systems:
- ^ osteoclast activity--> ^ free Ca++
- ^ kidney resorption of Ca++, ^ synthesis active Vit D
- ^ urine cAMP, PO4
- ^ GI absorption Ca++ (due to ^ vit D)
***Net effect = ^ free Ca++
59
What are the three potential causes of primary hyperparathyroidism and which is most common?
Which population gets this most?
- Adenoma (#1)
- Hyperplasia
- Carcinoma
**Conditions most common in adult females
60
What are the sx of primary hyperparathyroidism?
- painful bones (osteitis fibrous cystic--hemorrhage +cysts)
- renal stones
- abdominal groans (ulcers)
- psychics overtones
61
What are the three causes of hyperparathyroid adenoma?
- sporadic (95%)
- MEN I
- Parathyroid adenoma 1 mutation (PRAD-1) (10-20%)
62
Describe the details of PRAD-1 mutation:
Inversion of chrom 11--> Cyclin D GOF mutation--> proliferation of PTH producing cells
63
Describe the details of MEN I disorder:
Homozygous LOF tumor suppressor on chrom 11q13
64
Describe the histology of a primary hyperPTH adenoma.
| How do we treat this?
- Circumscribed lesion w loss of fat within rim of compressed normal parathyroid
- Treat with surgical removal
65
Describe the histology of parathyroid hyperplasia:
diffuse enlargement of 2+ glands possibly associated with MEN I or MEN Ia
66
How is parathyroid carcinoma defined?
REQUIRES invasion or mets
67
Describe pathogenesis of secondary hyperparathyroidism.
| What are the signs and sx?
Hypocalcemia--> ^ PTH--> Parathyroid hyperplasia
(associated with ^ PO4 --> direct depression serum Ca++)
Will see bone anomalies, calciphalaxis
68
What is the most common cause of secondary hyperparathyroidism? Three others?
RENAL FAILURE = #1
- poor Ca++ diet
- steatorrhea
- Vit D deficiency
69
Define pathogenesis of calciphalaxis; with what is it associated?
Chronic renal failure--> ^ PO4--> LOW serum Ca++ w/ calcification of vasculature--> ischemia of skin and organs
70
Describe the pathogenesis of tertiary hyperparathyroidism.
| How is it treated?
Treatment for secondary ^ PTH doesn't work -->parathyroid hyperplasia--> secondary ^ PTH becomes autonomous, aggressive, irreversible
Tx: parathyroidectomy
71
What is the most common cause of HYPOparathyroidism?
| What are two others?
- Surgical removal of parathyroid (#1)
- DeGeorge syndrome
- Primary idiopathic (possible autoimmune disease)
72
Familial Hypoparathyroidism:
- When does it present? What is the clinical triad?
- Describe the signs and sx***
Presents in early childhood
* Triad:
- candidiasis
- HYPOparathyroidism
- Adolescent onset adrenal insufficiency
Signs/ Sx:
Tetany (hypocalcemia); (+) Chevostek, (+) Trousseau
73
Define pseudohypoparathyroidism:
manifestations of hypoparathyroidism due to insensitivity to action of PTH or end organ resistance to normal/ ^ PTH
74
* **Pseudohypoparathyroidsm Type I:
- Pathogenesis
- clinical manifestations
Gs LOF mutation or PTH-R mutation--> Diminished cAMP response to PTH--> Hypoparathyroidism
Clinical Findings:
- round facies
- short stature, metacarpals, and metatarsals (Albright hereditary osteodystrophy)
75
Pseudohypoparathyroidsim Type II:
- Pathogenesis
- clinical manifestations
- Normal PTH induced cAMP w/ blunted second messenger response
- Patients do not have developmental defects
