Parathyroids Flashcards
Normal Ca levels?
8.5 - 10.5 g/dl
What is active calcium?
unbound Ca (about 45%)
Most protein bound Ca associates with what protein?
albumin
What happens when someone is hypo-calcemic in terms of symptoms?
perioral paresthesia
tingling in fingers and toes
muscle carmps
seizures
Levels of Ca are modulated thru interplay between what other molecules and organ systems?
PTH
Vit D
calcitonin
and bone/kidney/GI
What cells in parathyroid gland make PTH?
chief cells
Chief cells of parathyroid glands make what hormone?
PTH
What effect does PTH have on serum Ca?
INCREASES Ca
When serum calcium levels fall low, what does parathyroids do?
increase serum Ca
Chief cells of parathyroids release PTH, how does PTH increase serum Ca?
bone–> stimulates osteoclasts to increase bone resorption
kidney–> stimulates Ca resorption and stimulates production of 1-25 dihydroxyvitamin d
intestine–> stimulates absorption of Ca and phosphate from gut
What does calcitonin do?
opposes PTH
tones down Ca
inhibits bone resorption
Where is calcitonin made?
parafolicular cells of thyroid
Vit D is ingested or made in precursor form, and it undergoes 2 hydroxylations;
1st–>first hydoxylation occurs at C 25 in the liver
2nd–>2nd hydroxylations occurs at C1 in the kidney in response to PTH
What effect does Vit D have on Ca levels?
gut–> increase Ca and phosphate resorption
bone–>stimulates bone resorption
Where do we tend to find the superior parathyroid glands vs the inferior parathyroid glands:
superior parathyroids–> postero-medial aspect of thyroid near tracheo-esophageal groove
inferior parathyroids–> below area of inferior thyroid artery
Blood supply to parathyroids?
inferior thyroid artery–> from thyrocervical trunk–>subclavians
Common sites for ectopic parathyroid glands are?
thyrothymic ligament
superior thyroid poles
tracheoesophageal groove
retroesophageal space
carotid sheath
Inferior parathyroids originate from what branchial pouch?
3rd branchial pouch
Superior parathyroids originate from what branchial pouch?
4th branchial pouch
Relationship of inferior parathyroids as they originate from the branchial pouches;
inferior parathyroids–> 3rd branchial pouch
superior parathyroids–> 4th branchial pouch
What cells make up the parathyroid glands?
chief cells—> PTH
oxyphill cells
80-90% of primary hyperparathyroidism caused by what?
parathyroid adenoma (usually a single gland)
What are three causes of primary hyperparathyroidism?
parathyroid adenoma (80-90%)
hyperplasia of parathyroid glands (10-15%)
parathyroid carcinoma (1%)
Whats MEN 1?
primary hyperparathyroidism
pancreas lesions
pituitary lesions
Whats MEN2A?
primary HPT
medullary thyroid Ca
pheochromocytoma
What do we see with primary hyperparathyroidism?
seen in middle aged-older women
characterized by hypersecretion of PTH–> hyper Ca++
What is benign familial hypocalciuric hypercalcemia?
benign
AD transmission
can’t be corrected by parathyroidectomy
Superior parathyroids arise from 4th branchial pouch and migrate with what?
thyroid anlage
Inferior parathyroids arise from 3rd branchial pouch and migrate with what?
thymic remnant
How is PTH secretion controlled?
by a negative feedback loop from serum Ca concentrations
parathyroid cells sense extracellular calcium concentrations via G-protein couple recepto
Half life of circulating PTH?
2-4 minutes
How is hyperparathyroidism often detected?
usually found when pts have high serum Ca on routine blood work
Most common cause of hypercalcemia?
primary hyperparathyroidism
Most pts with primary hyperparathyroidism, will have ?
a single adenoma as the cause
How do we make diagnosis of primary hyperparathyroidims?
elevated Ca
elevated PTH
Difference between primary hyperparathyroidism and benign familial hypocalciuric hypercalcemia?
1 HPT–> need parathyroidectomy for symptom relief, don’t see hypo-calciuria
BFHH–> AD, benign, see hypocalciuria, surgery doesn’t do anything,
What causes secondary hyperparathyroidism?
w/renal failure we see increased phosphate levels
Vit D can be converted to 1-25 dihyxorvitamin D–> less Vit D means less Ca absorption from GI–> hypocalcemia–> causes PTH release from parathyroids
Pts w/primary hyperparathyroidism would classically present with what symptoms?
hypercalcemia
bone pain
fatigue
psychic moans
Difference between subtotal parathyroidectomy and total parathyroidectomy?
subtotal–> 3 1/2 glands are removed, other half is transplanted on neck or forearm
What anti-arrhythmic medication can potentiate arrhythmias in setting of hypercalcemia?
digoxin
Sometimes pts with primary HPT present with very elevated levels of Ca; in hypercalcemic crises; how do we manage them?
hydrate with NS (299-300 cc/hr) to promote Ca excretion from kidneys
loop diuretics to prevent Ca resorption in loop of henle
pts w/renal failure–> should have HD
steroids–> help lower Ca by inhibiting effects of Vit D
What’s hypercalcemia of malignancy?
elevated Ca levels due to cancer
caused by; due to extensive osseous mets or when some tumors release PTHrelated peptide hormone
In hypercalcemia of malignancy, what meds can we use to lower Ca levels?
bisphosphonates
inhibit osteoclast activity for up to 1 month
What do we see with hypoparathyroidism?
hypocalcemia
hyper-phosphatemia
MCC of hypoparathyroidism?
damage of parathyroids during thyroidectomy
What’s Chvostek’s sign seen in hypoparathyroid pts with hypocalcemia?
tapping on facial nerve anterior to ear causes contraction of facial muscles
Sxs of hypocalcemia seen in hypoparathyroidism?
low serum calcium levels seen
pts become anxious, peri-oral tingling/numbness, tetany
Carpo-pedal spasm seen in pts with hypoparathyroidism causing hypocalcemia?
Trousseu sign
How does DiGeorge’s syndrome cause hypoparathyroidism and hypocalcemia?
3rd and 4th branchial pouches develop abnormally, so you get fucked up parathyroids
When do we operate on pts with primary hyperparathyroidism?
serum Ca concentration > 1 mg/dL above upper limits of normal
Pts <50 y/o with primary hyperparathyroidism
pts in whom medical surveillance is undesirable
bone density T-score -2.5
After parathyroidectomy for primary hyperparathyroidism when can we expect to see bone density changes?
6months
Single best study to localize the parathyroid glands pre-operatively is?
Sestamibi scan
How does a sestamibi scan that localizes parathyroid glands for pre-operative planning?
parathyroid glands have a lot of mitochondria
mitochondria uptake technitium 99 avidly
Limitation of sestamibi scan to help localize parathyroid adenomas>
if you have co-existence of thyroid pathology or other metabolically active tissue that mimics parathyroid adenomas–> get false +
Intra-operatively how can we confirm that parathyroids have been removed?
can do an intra-op PTH assay
blood sample obtained before surgery, immediately have removal to show spike while handling the gland, and then 5-10 minutes after removal
(PTH has half life of 3-4 mins)
With intra-op PTH assays, how do we confirm that surgery was successful and parathyroid tissue was removed?
if you get a 50% drop of PTH from baseline
Classic surgical approach to primary hyperparathyroidism
b/l neck exploration
w/complication rate of 1-2 %
success rate of 95% (success defined as normocalcemia at 6 months)
85% of primary hyperparathyroidism is caused by?
single adenoma
Whats MIP?
minimally invasive parathyroidectomy
MIP: minimally invasive parathyroidectomy, doesn’t work for what?
doesn’t work for multiple adenomas on different sides causing primary HPT
Reported rates of injury to the recurrent laryngeal nerves are what post-parathyroidectomy?
1-10 %
damage to one causes hoarseness
damage to both causes paralysis
Damage to superior laryngeal nerve causes what symptoms?
problems with high pitch
can have bad effects in singers/professional speakers
Hypoparathyroidism after parathyroidectomy?
can cause hypocalcemia after parathyroidectomy
usually from removal of all glands or damage to remaining glands
What are some risk factors that lead to hypocalcemia after parathyroidectomy?
subtotal parathyroidectomies (removal of 3.5 glands)
b/l neck exploration
thyroidectomy + parathyroidectomy
neck radiation
How do you prepare for suspected hypocalcemia post-op parathyroidectomy?
start a ca-gluconate drip (30 cc/hr)
long-term can give PO calcium and Vit D
hypomagnesemia needs to be corrected first
What are three classes of medications used for hyperparathyroidism?
calcimimetics
bisphosphonates
SERMs
What are some bisphosphonates used in hyperparathyroidism?
atidronate
alendronate
pamidronate
Mainstay of management of secondary hyperparathyroidism?
calcimimetic agent cinacalcet
What causes secondary hyperparathyroidism?
kidney failure pts become uremic
leads to hyper-phosphatemia –> leads to hypocalcemia
thus we get 2 -hyperparathyroidism
Whats the root cause in all cases of secondary hyperparathyroidism?
failing kidney cannot hydroxylate Vit D2 —>D 3
What’s renal osteodystrophy?
skeletal complications assc/ w ESRD
osteitis fibrosa cystica
osteomalacia
What;s osteitis fibrosa cystica and what causes it?
bone marrow fibrosis and increased bone remodeling
increased osteoclast activity
we see decrease bone strength–> fractures
high levels of PTH and low calcitriol levels cause this condition
Secondary hyperparathyroidism due to renal failure can cause significant bone dx, how do we diagnose it?
bone bx
alk phos levels, PTH, aluminum, bone scintigraphy
Calcimimetic drugs like cinacalcet are used for medical management of secondary HPT, how does it work?
lower PTH by increasing sensitivity of extra-cellular Ca to the CaSR receptor
What’s uremic pruritis and what causes it?
Ca-deposits on skin in ESRD uremic pts
these sxs relieved in a few days after parathyroidectomy
This is a rare and severe, life-threatening complication of secondary hyperparathyroidism due to calcification of small and medium sized arteries;
calciphylaxis
What is calciphylaxis?
severe, life threatening complication of secondary hyperparathyroidism due to calcification of small to medium sized arteries
see ischemic damage to dermal and epidermal layers
can lead to gangrene, sepsis, death
How do we diagnose calciphylaxis?
clinical
can be confirmed by skin biopsy
lesions; mottled and painful, develop into hard plaques with central ulcer, eschar
Why is pre-op imaging not indicated for surgical planning in someone with secondary hyperparathyroidism?
usually not due to a single adenoma
this is caused by 4-gland hyperplasia due to feedback from low Ca levels in the body
so a b/l neck exploration is often done
Surgical tx commonly done for secondary hyperparathyroidism?
total parathyroidectomy with auto-transplantation in forearm
For a subtotal parathyroidectomy, which gland is chosen for auto-transplantation?
choose a gland that is most easily accessible
usually this will be an inferior parathyroid gland because its more anterior
What’s a subtotal parathyroidectomy;
removing three glands total
removing 50-75% of last gland and auto-transplanting remaining 50% remnant
For a subtotal-parathyroidectomy, where have auto-transplanted a piece of a remaining parathyroid gland, how do we identify it in case we need to re-operate?
mark it with a titanium clip
can also measure intra-op PTH levels to ensure enough tissue has been resected
Why do we need to do a cervical thymectomy in pts who are having surgery for secondary hyperparathyroidism?
can have accessory parathyroid tissue in thymus
can cause persistent dx/symptoms
Advantage of a subtotal parathyroidectomy with a eutopic parathyroid gland remnant, vs a transplanted parathyroid gland remnant in forearm>
a well vascularized eutopic parathyroid gland already has vascular supply and will continue to work
a transplanted parathyroid remnant will need to develop new vascular supply
(avoiding an arm incision to auto-transplant also makes it easier for HD access)
eutopic glands are better for non-compliant pts who wont take their Vit D and C post-op while the transplanted gland develops a new vessel supply
Why is heterotopic parathyroid gland transplant into the forearm preferred over eutopic gland placement?
avoids a second neck exploration if needed to re-operate
What is a total parathyroidectomy with autotransplantation?
removes all identified glands
uses an easily accessible area like forearm and SCM to implant 12-18 1 mm pieces of remaining parathyroid gland into muscle belly
these are marked w/stitch vs clip
neovascularization occurs over several weeks
Advantage of SCM/forearm transplantation of parathyroid gland remnant?
avoids neck dissection if need to re-operate
can have surgery under local anesthesia if second operation needed to remove more tissue
Disadvanatage of implanting parathyroid remnant gland into SCM/forearm?
gotta think about ESRD HD arm access
difficult to visualize glands as they neovascularize into muscle belly
with hetero-topic parathyroid tissue in neck, can have two potential sources of persistent HPT
autograft failure can lead to profound hypoparathyroidism
PReferred surgery in pts with secondary hyperparathyroidism?
subtotal parathyroidectomy
What is the recurrence rate of secondary HPT?
5-17%
depends of length of pt survival
remnant gland in neck/forearm will grow and cause relapsing disease if survival is prolonged and pts dont get kidney transplants
Where do we see tertiary hyperparathyroidism?
seen in subset of pts with 2-HPT who develop autonomous glands and hypercalcemia develops
2nd HPT can persist even in setting of renal transplant, and parathyroids became autonomous
What causes tertiary-HPT?
pts with secondary HPT who undergo renal transplant and have autologous working parathyroid glands which cause hypercalcemia after transplant
What is MEN1?
parathyroid hyperplasia–> causing primary HPT
pancreas lesions
pituitary lesions
Parathyroid hyperplasia (causing primary HPT), pancreas lesions, pituitary lesions cause what syndrome?
MEN1
in MEN1, what causes problems/symptoms first?
primary HPT
With transplantation of parathyroid tissue in forearm, where is it specifically placed?
brachioradialis muscle of non-dominant forearm
Initial surgery of choice for pt with MEN1 and primary HPT?
total parathyroidectomy or subtotal parathyroidectomy
trans-cervical thymectomy also performed
When we do parathyroidectomy surgery, why do we cryo-preserve some parathyroid tissue at time of surgery?
transplanted parathyroid remnants can become ischemic and necrose causing permanent hypo-parathyroidism
MEN2A?
medullary thyroid ca
pheochromocytoma
primary HPT
Medullary thyroid Ca, pheochromocytoma, and primary HPT define what entity?
MEN2A
How does primary HPT in MEN1, compare to MEN2A?
MEN2A–> HPT tends to be milder, usually asymptomatic
thus curative resection tends to be less aggressive
Most pts with unresectable parathyroid Ca, die from what
metabolic effects of hyperCa
see Ca levels > 14
After identification of MEN1, what is treated first?
primary hyperparathyroidism is treated first
four gland resection with auto-transplanation
(primary HPT in MEN1 due to gland hyperplasia, not adenoma)
Ectopic superior parathyroids can be commonly located where?
tracheo-esophageal groove & retroesophageal region
Ectopic inferior parathyroid glands can be commonly located where?
anterior mediastinum in assc/ with thymus and thyroid gland
The most common location for a missed gland during surgery is where?
normal anatomic location
Difference is PTH levels in parathyroid carcinoma vs adenoma?
PTH Ca secretes PTH levels 3-10x normal
PTH adenoma secretes PTH levels 2x normal
Ca levels tend to be higher in PTH Ca–> 3-4 mg/dL higher
In terms of comparing PTH Ca vs PTH adenoma, what do we see in the lab values?
parathyroid Ca has higher elevations in Ca and PTH compared to adenomas
What causes benign familial hypocalciuric hypercalcemia?
AD
increase Ca resorption in kidney due to defective PTH receptor
leads to mild hyper Ca, with normal PTH levels
Tx for BFHH?
no tx
What is the genetic defect in MEN2A and 2B?
AD dx
defect in ret-proto oncogenes on chromosome 10
Genetic defect in MEN2A/B?
RET on chrom 10
Mutation in MEN1?
menin protein mutation
MEN2A is what syndrome?
medullary thyroid Ca
parathyroid hyperplasia
pheochromocytoma
In MEN2A syndrome, what should be done first surgically?
pheochromocytoma should be removed first, due to intra-op complications assc with catecholamine surge
once pheo removed, surgical resection of thyroid/parathyroid gland safer
Before operating on a pheochromocytoma, what should be done first?
a-blockade with phenoxybenzamine
ensure pt does not have a hypertensive crisis
Hyperparathyroidism seen in MEN2A is caused by what?
parathyroid hyperplasia NOT an adenoma
For pt noted to have MEN2A, we recommend total thyroidectomy by what age?
5
risk of medullary thyroid Ca
RET is a proto-oncogene that encodes a receptor tyrosine kinase protein; and is mutated in what syndrome?
MEN2A/B
RET mutations are inherited in what fashion in MEN2A?
AD
50% risk of giving offspring mutation
A pt has primary hyperparathyroidism, what are the indications to operate?
age less than 50
Ca > 1 mg/dL above normal
30% decrease in renal fx
can;t participate in follow up
osteoporosis, nephrocalcinosis, severe psychoneurogenic d/o, nephrolithiasis
urinary Ca > 400 mg/24 hr
Chemo for parathyroid Ca?
not used
radiation has been shown to decrease local recurrence
Initial imaging of choice for to localize parathyroid glands?
cervical US/
Someone has MEN1, and has primary HPT, and you’ve localized the parathyroid adenoma on sestamibi scan and US, what’s the surgical procedure?
b/l neck exploration, removal of 3.5 glands and b/l thymectomy
in pts w/MEN1, all four parathyroid glands have a propensity for hyperplasia, therefore subtotal resection must be performed
these pts also have a greater incidence of ectopic glands and thymic carcinoids so thymectomy needed as well
Why is FNA contraindicated for someone with suspected parathyroid Ca?
tissue obtained via FNA is usually insufficient to make dx
can cause cancer seeding
mainstay of tx–> en bloc resection of suspected mass and nearby tissue with grossly negative margins
ipsilateral neck dissection performed if nodes positive
What do you do if you cant find an inferior parathyroid gland during surgery for resection?
first; mobilize thymus and resect it
second; divide middle thyroid vein and mobilize thyroid lobe to visualize esophagus and trachea
last; thyroid lobectomy done before surgery abandoned
The inferior parathyroids arise from 3rd branchial pouch and descend with the ????
thymus
***therefore missing inferior parathyroid glands that can’t be identified intra-op are frequently found within the thymus
a cervical thymectomy is thus performed on the side of the missing gland
if missing gland not found within thymus tissue (palpation and frozen section), then carotid sheath is explored
How do we treat secondry hyperparathyroidism due to kidneys?
due to chronic renal failure
phosphate retention in kidneys lead to hypocalcemia and we see increase PTH as a response
first line tx–> tx the increased phosphate with binders and diet restrictions
can add Ca supplements, vit D, add Ca in dialysate bath
surgry–> for itching, calciphylaxis, bone pain, anemia, pathologic fxs
The only reliable criteria for parathyroid Ca are what?
local invasion/mets
What is the Miami criteria for intra-op PTH assays for parathyroidectomy?
> 50% drop of PTH level at 10 mins following excision of suspected parathyroid is predictive of surgical cure
if criteria not met at 10 mins post-gland excision, check at 20 mins
if PTH level still has not fallen, explore the remaining parathyroid glands
What is the treatment for locally recurrent parathyroid carcinoma?
re-exploration and resection
**parathyroid tissue is radio-resistant, radiation therapy does not work
In pts that have MEN1, whats the most common pancreatic tumors?
gastrinomas
then insulinomas
