Parathyroid Pathology Flashcards
The parathyroid glands are derived from what embryological structures?
upper pair from fourth pharyngeal pouch
lower pair from third pharyngeal pouch
What organ do the parathyroid glands descend with?
the thymus
Unrelated, but what happens to the first pharyngeal groove and pouch?
forms inner ear
What happens to the 2nd pharyngeal pouch?
it gets obliterated by the tonsils
What happens to the 5th pharyngeal pouch?
the ultimoibranchial body
What are the two types of cells in the parathyroid gland?
the chief cells and the oxyphil cells
the water clear cells?
What are the 5 main actions of PTH?
- increased bone resorption
- increased renal reabsorption of calcium
- increased renal excretion of phosphate
- increased renal conversion of vitamin D to its active form
- Increased gut absorption of calcium
All of these actions serve to do what?
increase serum calcium
So why does PTH activate vitamin D?
- it stimulats gut to absorb more calcium
- it helps PTH get the calcium out of bone
- It stimulates the kidneys to reabsorb calcium
What enzyme in the liver converts vitamin to 25 (OH)D?
25 hyroxylase
What enzyme in the kidney converts 25(OH)D into active 1,25(OH)2D?
alpha-1 hydroxylase
What controls PTH release?
free calcium
low serum calcium triggers PTH synthesis and release
So what will hyperparathyroidism cause?
hypercalcemia
What are 4 other common causes of hypercalcemia?
- malignancy = metastases or PTH-related protein
- vitamin D overdose
- Thiazide diuretics (reduce excretion)
- Milk-alkali syndrome
What is the MD PIMPS ME mnemonic for hypercalcemia?
Malignancy
Diuretics
Parathyroidism Idiopathic Megadose of vitamin D Paget disease Sarcoidosis
Milk-alkali syndrome
Endocrine (thyrtoxicosis)
What is the most common cause of SYMPTOMATIC hypercalcemia?
malignancy
What is the most common cause of ASYMPTOMATIC hypercalcemia?
hyperparathyroidism
Wht is primary hyperparathyroidism a problem of?
the parathyroid gland itself (usually an adenoma)
What is secondary hyperparathyroidism? What’s the usual cause?
chronic hypocalcemia, leading to hyperparathyroidism
usually from renal failure
What is tertiary hyperparathyoridism?
when there are autonmous parathyroids that don’t listen to other signals
What is pseudohyperparathyroidism from?
PTH-related protein being secreted by a lung cancer
What are the three causes of primary hyperparathyroidism?
parathyroid adenoma
parathyroid hyperplasia
parathyroid carcinoma
As far as epidemiology goes, is primary hyperparathyroidism rare or common?
common - nearly 2.5 cases per 1000 adults
Primary hyperparathyroidism is usually asymptomatic. What are the signs and symptoms when it’s not?
stone: kidney stones
bone: bone pain, brown tumors
groan: GI problems
moan: mental changes
What will the lab findings be in primary hyperparathyroidism?
increased serum PTH
increased serum Ca
decreased serum phosphate
What are the changes that occur in bones with primary hyperparathyroidism?
- osteoclast activation (so bone resorption)
- osteoblast activation
- brown tumors
- osteitis fibrosa cystica
What is the signalling pathway that turns on osteoclasts?
- RANK ligand on the ostoblast binds the RANK receptor on the ostoclast precursor which activates the osteoclast
What is the other pathway?
M-CSF ligand on the osteoblast binds to the M-CSF receptor on the osteoclast precursor which activates the osteoclast
What will bone look like when there’s high osteoclastic activity?
the surface will look eroded
Describe a brown tumor.
The high osteoclast activity chews away at bone, which leads to microfractures and hemorrhage with blood cells coming into clean up the damage. the blood just pools there and turns brown, hence the name
looks like a tumor on imaging, but it’s not really a tumor
What does osteitis fibrosa cystica look like/
When the hyperparathyroidism is long standing, you can start to see punched-out lesions in the skull and between the teeth
What is the commonest cause of primary hyperparathyroidism?
parathyroid adenoma
True or false: Parathyroid adenomas are usually solitary.
true
Some parathyroid adenomas have genetic defects. What are two common ones?
- PRAD 1 overexpression
2. MEN 1 loss or mutation
What does a parathyroid adenoma look like microscopically?
It typically looks like normal parathyroid but there are a few hints
an adenoma will usually have a fibrous capsule (which will NOT be invaded by malignajnt cells) and will be devoid of fat
True or false: parathyroid hyperplasia usually only affects one of the parathyroid glands.
false - usually all four
Parathyroid carcinoma is a super rare cause of primary hyperparathyroidism. What is the main symptom for parathyroid carcinoma?
abrupt onset of bone pain
Parathyroid carcinoma is usually well-differentiated. So what?
This is a problem, because it means that it looks a lot like a benign parathyroid adenoma! It can be really hard to tell them apart
What is the 5 y survival for parathyroid carcinoma?
50-75%
What will parathyroid carcinoma look like microscopically?
It will look just like an adenoma, except there will be cells invading into the surrounding capsule
Renal failure is the most common cause of secondary hyperparathyroidism (chronic hypocalcemia), but what are two others?
- diet poor in calcium
2. vitamin D deficiency
Describe the pathophysiology of why renal failure causes secondary hyperparathyroidism?
- the kidneys can’t ecxcrete phosphate
- serum phosphate goes up
- this makes serum calcium go down
- the hypocalcemia stimulates the parathyroids
What are the three (four) main causes of hypoparathyroidism?
- iatrogenic
- Hereditary: DIGeorge syndrome and agenesis (x-linked)
- idiopathic atrophy
What ais the main cause of iatrogenic hypoparathyoridism?
When they need to surgically remove the thyroid gland and take the parathyroids along with it.
What are the signs ans symptoms of hypoparathyroidism?
neuromuscular irritabiliby (due to the hypocalcemia) with perioral numbness, muscle weakness, cramps, tetany, Chvostek’s sign, Trousseau’s sign
heart arrhythmias
dental abnormalities
What is Chvostek’s sign?
stroke the cheek and it will twitch
What is Trousseau’s sign?
slowly inflate a BP cuff on someone’s arm and it will cramp up