Parathyroid Hillard Flashcards
the superior parathyroid glands develop from the ?
the inferior parathyroid glands develop from the?
fourth pharyngeal pouch
thrid pharygenal pouch
they can be ectopically located like in the mediastinum or the lateral neck
what does a normal parathyroid gland look like grossly and how much does it typically weigh
rounded red brown structure that weighs less than .5cm
gross weight will clue you into if the parathyroid is normal or if there is hyperplasia
describe the histology of the normal parathyroid gland
gland is surrounded by a thin capsule with adipose tissue and 2 cell types: chief and oxyphil
describe what a chief cell looks like
what do they produce?
chief cells have pink to clear cytoplasm with secretory granules
they produce parathyroid hormone
what do oxyphil cells look like and what is their function?
they have pink granula cytoplasm due to mitochondria
they are less endocrinogically active
similar to hurtle cells in the thyroid
the parathyroid gland produces _ when it senses low _
parathyroid hormone
low calcium
PTH affects bone by increasing _ activity through differentiation of progenitor cells into its mature type.
osteoclast (break down bone, releasing calcium)
PTH has affects on the kidney where it causes it to _ calcium at the distal convoluted tubule and collecting duct and _ phosphate reasbsorption
resorb (increase calcium)
decrease phosphate resobrptoion (pee it out)
PTH activates _
vitamin D
how does PTH activate vitamin D
it upregulates 1-alpha hydroxylase in the kidney converting inactive vitamin D to its active form calcitriol (1,25, dihydroxy vitamin D)
how does vitamin D increase calciim serum concentrations
increase kidney reabsorption, and GI abosrption of calcium
an elevated serum calcium will _ secretion of parathyroid hormone
decrease
the parathyroid hormone senses calcium levels through the?
Calcium sensing receptor
explain the ca sensing receptor
the extracellular receptor will bind calcium if levels are adequate/high in the blood and this causes PTH to be downregulated
it is a rapid continous moniotr that responds to mild changes
what causes sprimary hyperparaythroidism
parathyroid adenoma (most common)
parathyroid hyperplasia
parathyroid carcinoma
a parathyroid adenoma typically affects how many glands?
a single gland
parathyroid hyperplasia affects how many glands
multiple parathyroid glands, usually all 4
parathyroid carcinoma will present as?
a large mass lesion
what is primary hyperparathyroidism
this is when the parathyroid gland produces too much parathyroid hormone
1/3 of parathyroid adenomas have what mutation?
sporadic MEN1 mutations
a somatic mutation
rare germline mutation in _ can also cause parathyroid adenomas and affect every single cell in the body
MEN1 which will cause them to develop MEN-1 syndrome
MEN1 can lead to?
pituitary adenomas, pancreatic and endocrine tumors, parathyroid hyperplasia and rarely parathyroid adenomas
what cell cycle regulator mutation can lead to parathyroid adenomas
Cyclin D1 (CCDN1)
what is mutated in parathyroid carcinomas
CDC73
(jaw ossifying tumors as well)
what are the symptoms of primary hyperparathyroidsim
usually asymptomatic and picked up on a BMP rotuine calcium screen
if unchecked though it can cause
BONES, STONES, ABDOMINAL GROANS AND PSYCHIC MOANS
with no calcium in bones it can lead to osteoporosis and osteitis firbosis cystica (cystic areas of bony destruction)
increased circulating calcium can cause renal stones (nephrolithiasis) and gall stones along with constipation.
hypercalcemia reduces neuromusclar excitability- abdominal groans
high calcium can also lead to physciatric symptoms
lack of calcium in the bones, more calcium in the blood circulating
PTH increases osteoclastic activity in the bone, what can happen as a result of this
increased osteoclastic activity can cause a decrease in bone density, thinning of the trabeculae, and borwn tumors in the eroded bone.
PTH can cause “brown tumors” of the eroded bone, what is this?
this is when there is a loss of trabeculae in the bone and it is replaced with fibrosis, microfractures, and hemorrhage
can mimic a neoplastic process–> they progress to become completely cystic
when PTH causes the bone to become completely cystic what is this process termed
osteitis fibrosis cystica aka von recklinghuasens disease
when osteoclasts burrow centrally and destroy trabeculae it is referred to as?
dissecting osteitis
most of the time primary hyperparathyroidism is picked up by what?
routine elevated calcium
why is phosphorus low in primary hyperparathyroidism
PTH causes a decrease in phosphorous reabsorption by the kidney
imaging for primary parathyroid disease are used to help plan _
surgery
what imaging techniques can we use to visualize the parathryoid (when we have a known elevated calcium and PTH)
sestamibi scintigraphy- technetium-99m is used (radioactive)
SPECT-CT
ultrasound
the most reliable feature to distinguise a parathyroid adenoma from hyperplasia is?
the number of glands involved
1 gland in adenoma
multiple glands in hyperplasia
the enlargement between glands in parathyroid hyperplasia can be
asymmetric
normal weight of a parathyroid adenoma
.5 to 5 grams
multpile large parathyroid adenomas should clue you in to think?
MEN syndrome
histology of parathyroid hyperplasia and adenoma
both: can be hard to distinguish between the two that is why gross appearance is so important. they will have little adipose tissue with abundant chief cells and scattered oxyhphil cell nests
adenoma: can have both cells are consist of only 1 cell type; rim of normal compressed parathyroid tissue above a hypercellular nodule
how do you treat parathyroid hyperplasia
partial parathyroidectomy
- 3 1/2 of the gland is removed and the remannt can be implanted into the forearm
how do you trear parathyroid adenoma
excision
how do surgeons gauge if they have removed all of the parathyroid tissue (hyperplasia/adenoma)
they use intraoperative parathyroid hormone levels
assess in real time
adenoma: marked drop
hyperplasia: stepwise drop with excisio of each hyperplastic gland
what is the averaage weight of a parathyroid carcinoma
19grams (large mass lesion)
is atypia a reliable criteria seperating benign tumors from malignant ones?
NO!
what are the features of malignancy for the parathyroid neoplasm
vascular invasion, invasion of adjacent structures, metastasis
parathyroid carcinoma is often _ _ and difficult to resect
poorly circumscribed
secondary hyperparathyroidism occurs when ?
there is a disease or condition outside of the parathyroid gland and gives low calcium levels
what is the most common cause of secondary hyperparathyroidism ?
renal failure/insufficiency
how does renal failure cause decreased calcium levels but hyperparathyroidism
functional and absolute hypocalcemia
hypocalcemia- decreased renal production of the active form of vitamin D which decreases intestinal calcium absorption
decreased phosphate excretion also drives calcium levels down even further by complexing with calcium
secondary hyperparathyroidism is compensatory _ secretion due to prolonged _
PTH
prolonged hypocalcemia
what are some other causes of secondary hyperparathyroidism?
inadequate calcium intake
pancreatitis
vit D def.
baractic surgery
how does secondary hyperparathyroidism look grossly and histologically
grossly: all 4 glands enlarged
histologically- diffuce cellular hyperplasia due to a hypocalemic state
what are the symptoms of secondary hyperparathyroidism
signs of renal failure (if this is the cause)
apparent and picked up at a earlier stage than primary
bone pain, increased fracture incidence ( due to increased PTH)- renal osteodystrophy - + renal failure
calciphylaxis
what is renal osteodystrophy
bone pain and fractures in the setting of renal failure
what is calciphylaxis
increased vessel calcifications which cause vascular compromise and necorsis usually of the skin, fat, of lower leg
associated with secondary hyperparathyroidism
calciphylexis is associated with?
hyperphosphatemia
increased calcium and phosphate complexes deposit in the skin
what is tertiary hyperparathyroidism?
perisisten secretion of PTH after longstanding secondary hyperparathyroidism
descirbe the pathology of tertiary hyperparathyroidism
longstanding hypocalcemia from secondary hyperparathyroidism will cause marked parathyroid gland hyperplasia and cause them to act on their own to create PTH despite calcium levels.
there is a chnage in calcium sensitivity
really high PTH, high calcium
what are the signs of teritary hyperparathyroidism ?
calcipheyxis, abdominal gorans, moans, stones, cystic brown tumors, etc.
what is the most common cause of hypercalcemia not related to parathyroid hormone?
hypercalcemia of malignancy
what is hypercalcemia of malignancy
increased calcium with no increase in pth
PTH-related peptide tumor secretion (paraneoplastic process)
cytokine induced bone resorption by a tumor metastasis
tumors producing calcitriol that induces osteoclastic reabsorption
what are some other causes of hypercalcemia with no increase PTH
excess vitamin D ingestion
excess calcium
thaizides
immobilization
GRANULOMATOUS DISEASE- EXCESS CALCITRIOL (SARCOIDOSIS)
what is sarcoidosis
a non-caseating granulomatous disease that is seen in black people and bilateral hilar lymphadenopathy
involves the skin, joints, eyes, subcutenous nodules
histology of sarcoidosis
giant cells with no necrosis and non-caseating granulomas
macrophages in the granulomas of sarcoidosis creates _ which causes formation of calcitriol and forms hypercalcemia (calcitriol induces osteoclastic reabsorption)
1 alpha hydroxylase
in the case of hypoparathyroidism PTH and calcium are _
low
what is the primary cause of acquired hypoparathyroidism
removal or too much pararthyroid (iatrogenic)
what is another cause of acquired hypoparathyroidism
autoummune hypoparathyroid
autoimmune parathyroid sydnrome 1*
what is autoimmune hypoparathyroidism (autoimmune parathyroid syndrome 1)
a sydnrome that presents with mucocuteneous candiadisis in childhood followed by hypoparathyroidism and then adrenal insufficiency
AIRE mutation
what are the congenital causes of hypoparathyroidism
digeorge syndrome
autosomal dominant hypoparathyroidism
familil isolated hypoparathyroidism
what is familial associated hypoparathyroidism
issue with the production of secretion of PTH
what are the clinical findings of hypocalcemia
tetany (involuntary muscle contractions, hyperstimulated peripheral nerves)- seizures, spasms
chvostek sign
troussaeu sign
anxiety
prolonged QT
paradoxical calficications
what is chvostek sign
this is when you tap the facial nerve and there is contraction of the muscles that it innervates (eye, mouth nose)
whar is trosseau sign
this is when you occlude the blood supply of the arm for a couple of minues and induce transient ischmeia and hypocalcemia will cause a carpal spasm to occur
what is digeorges syndrome?
this is deletion of the long arm of chromosome 22 and developmental defect of the 3rd and 4th pharyngeal pouch
what are the symptoms of digeorge syndrome
CATCH22
cardiac anomalies
abnormal facies
thymic aplasia
cleft palate
hypocalcemia
hypocalecmia is due to underdevelopment of the pouches and therefore the parathyroid glands, this lowers PTH and ultimately calcium as well
22q11 deletion
what is autosomal dominant hypoparathyroidism
a mutation in CASR gene that increases in sensivity to calcium
PTH is inhbited even at low calcium levels
pth- low
calcium- low
usually PTH is ibhibited when calcium levels are high and bind to CASR
what is pesuedohyperthryoidism?
a childhood disorder that results in end organ resistance to parathyroid hormone
hypocalcemia, hyperphosphtemia, hyperparathyrodism
what is the mutation in pseudohypoparathyrodism and what else can it cause?
g protein receptor , there is resistence to PTH at end organs
affects other g protein receptors too: TSH , FSH, LH, GHRH
this means there will be hypothyroidism, infertility, short stature
albright hereditary osteodystrophy
what is the transmission of multiple endocrine neoplasia syndromes
autosomal dominant (MEN)
what are the different types of MEN syndromes
MEN-1
MEN2A
MEN2B
MEN4
what organs are affected in MEN 1
remember the p’s
pituitary adenoma, parathyroid adenoma/hyperplasia, pacreatic/gestroenteric tumors (gastrinomas/insulinomas)
what are the main abnormalities MEN4 can cause
pituitary adenomas and parathyroid hyperplasia
MEN2A affects what
remember PM PHEO
parathyroid hyperplasia
medullary thyroid carcinoma
phernochromocytoma
MEN 2B affects what
remember MMM Pheo
mucosal neuromas
marfanoid body
medullary thyroid carcinoma
pheochromcytoma
MEN 1 syndrome is also known as?
mutation in?
first presentation?
wermer syndrome
MEN 1
hyperparathyroidism
symptoms of men1
hyperparathyroidism
bones, stones, abdominal groans and psychic moans
gastrinomas
_ _ syndrome is frequently seen in MEN1 syndrome and it presents as an increased gastrin from a gastrinoma
zollinger-ellison syndrome
describe gastrinomas in men1 syndrome/zollinger ellision
the gastrinoma creates gastrin which stimulates gastric acid secretion from parietal cells and form peptic ulcer, reflux esophagitis, and diarrhea
another presentation of men1 syndrome is a pituitary adenoma _
features
could be other adenoma types also like ACTH
prolactinoma
which causes galactorhea and amenorrhea in females and imptence in males (ED)
what do the pancreatic tumors in men1 syndrome present with
an insulinoma which produces insulin and causes hypoglycemia (weakness, pale, confusion)
when should you suspect MEN1
how do you test for it
suspect if: they have 2 or more primary tumors: pituitary adenoma, parathyroid adenoma, pancreatic, gastric tumor)
MEN1 DNA testing
MEN 2A is also known as?
sipple syndrome
what is the mutation in MEN2A
gain of function in RET proto-ooncogene
what drive mortality in MEN2
medullary thyroid carcinoma
what is medullar thyroid carcinoma
a mlaignant tumor of c cells in the thyroid (aka parafollicular cells)
what are c cells/parafollicular cells of the thyroid
a neuroendocrine cell that secretes calcitonin to help lower lower blood calcium (prevents osteoclasts from reasorbing bone)
what is often seen in histology of medullar thyroid carcinoma
amyloid due to the abundance of calcitonin polypeptides
c-cell hyperplasia
positive IHC: calcitonin
parathroid hyperplasia presentation
medullary carcinoma presentation
pheochromocytoma presentation
all in MEN2
parathroid hyperplasia presentation: asymptomatic; incidental finding
medullary carcinoma presentation: thyroid nodule/lymphadenopathy
pheochromocytoma presentation - bilateral and secrete epinephrine
pheochromocytoma: episodic heacaches, sweating, tachycardia
what is the mutation in MEN2B
germline missense mutation in RET
more aggressive than MEN2A
MEN2b and MN 2B overlap with pheohromcytoma, and medullary thyroid carcinoma
what is specific to men2b
medullary thyroid carcinoma in MEN2b is miltifocal
mucocutenous neuromas
marfanoid hyperxtensible joints
no aortic abnormalities like in MARFANs
almost all MEN2 patients develop _
medullary thyroid carcinoma
all indivduals with medullary thyroid carcinoma should be tested for?
RET
MEN2B presents earlier (around 10) then MEN2A
