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Appendix > Parathyroids > Flashcards

Parathyroids Flashcards

1
Q

Normal Ca levels?

A

8.5 - 10.5 g/dl

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2
Q

What is active calcium?

A

unbound Ca (about 45%)

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3
Q

Most protein bound Ca associates with what protein?

A

albumin

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4
Q

What happens when someone is hypo-calcemic in terms of symptoms?

A

perioral paresthesia
tingling in fingers and toes
muscle carmps
seizures

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5
Q

Levels of Ca are modulated thru interplay between what other molecules and organ systems?

A

PTH
Vit D
calcitonin

and bone/kidney/GI

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6
Q

What cells in parathyroid gland make PTH?

A

chief cells

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7
Q

Chief cells of parathyroid glands make what hormone?

A

PTH

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8
Q

What effect does PTH have on serum Ca?

A

INCREASES Ca

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9
Q

When serum calcium levels fall low, what does parathyroids do?

A

increase serum Ca

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10
Q

Chief cells of parathyroids release PTH, how does PTH increase serum Ca?

A

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

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11
Q

What does calcitonin do?

A

opposes PTH

tones down Ca

inhibits bone resorption

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12
Q

Where is calcitonin made?

A

parafolicular cells of thyroid

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13
Q

Vit D is ingested or made in precursor form, and it undergoes 2 hydroxylations;

A

1st–>first hydoxylation occurs at C 25 in the liver

2nd–>2nd hydroxylations occurs at C1 in the kidney in response to PTH

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14
Q

What effect does Vit D have on Ca levels?

A

gut–> increase Ca and phosphate resorption

bone–>stimulates bone resorption

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15
Q

Where do we tend to find the superior parathyroid glands vs the inferior parathyroid glands:

A

superior parathyroids–> postero-medial aspect of thyroid near tracheo-esophageal groove

inferior parathyroids–> below area of inferior thyroid artery

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16
Q

Blood supply to parathyroids?

A

inferior thyroid artery–> from thyrocervical trunk–>subclavians

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17
Q

Common sites for ectopic parathyroid glands are?

A

thyrothymic ligament

superior thyroid poles

tracheoesophageal groove

retroesophageal space

carotid sheath

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18
Q

Inferior parathyroids originate from what branchial pouch?

A

3rd branchial pouch

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19
Q

Superior parathyroids originate from what branchial pouch?

A

4th branchial pouch

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20
Q

Relationship of inferior parathyroids as they originate from the branchial pouches;

A

inferior parathyroids–> 3rd branchial pouch

superior parathyroids–> 4th branchial pouch

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21
Q

What cells make up the parathyroid glands?

A

chief cells—> PTH

oxyphill cells

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22
Q

80-90% of primary hyperparathyroidism caused by what?

A

parathyroid adenoma (usually a single gland)

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23
Q

What are three causes of primary hyperparathyroidism?

A

parathyroid adenoma (80-90%)

hyperplasia of parathyroid glands (10-15%)

parathyroid carcinoma (1%)

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24
Q

Whats MEN 1?

A

primary hyperparathyroidism

pancreas lesions

pituitary lesions

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25
Q

Whats MEN2A?

A

primary HPT

medullary thyroid Ca

pheochromocytoma

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26
Q

What do we see with primary hyperparathyroidism?

A

seen in middle aged-older women

characterized by hypersecretion of PTH–> hyper Ca++

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27
Q

What is benign familial hypocalciuric hypercalcemia?

A

benign

AD transmission

can’t be corrected by parathyroidectomy

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28
Q

Superior parathyroids arise from 4th branchial pouch and migrate with what?

A

thyroid anlage

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29
Q

Inferior parathyroids arise from 3rd branchial pouch and migrate with what?

A

thymic remnant

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30
Q

How is PTH secretion controlled?

A

by a negative feedback loop from serum Ca concentrations

parathyroid cells sense extracellular calcium concentrations via G-protein couple recepto

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31
Q

Half life of circulating PTH?

A

2-4 minutes

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32
Q

How is hyperparathyroidism often detected?

A

usually found when pts have high serum Ca on routine blood work

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33
Q

Most common cause of hypercalcemia?

A

primary hyperparathyroidism

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34
Q

Most pts with primary hyperparathyroidism, will have ?

A

a single adenoma as the cause

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35
Q

How do we make diagnosis of primary hyperparathyroidims?

A

elevated Ca

elevated PTH

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36
Q

Difference between primary hyperparathyroidism and benign familial hypocalciuric hypercalcemia?

A

1 HPT–> need parathyroidectomy for symptom relief, don’t see hypo-calciuria

BFHH–> AD, benign, see hypocalciuria, surgery doesn’t do anything,

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37
Q

What causes secondary hyperparathyroidism?

A

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

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38
Q

Pts w/primary hyperparathyroidism would classically present with what symptoms?

A

hypercalcemia
bone pain
fatigue
psychic moans

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39
Q

Difference between subtotal parathyroidectomy and total parathyroidectomy?

A

subtotal–> 3 1/2 glands are removed, other half is transplanted on neck or forearm

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40
Q

What anti-arrhythmic medication can potentiate arrhythmias in setting of hypercalcemia?

A

digoxin

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41
Q

Sometimes pts with primary HPT present with very elevated levels of Ca; in hypercalcemic crises; how do we manage them?

A

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

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42
Q

What’s hypercalcemia of malignancy?

A

elevated Ca levels due to cancer

caused by; due to extensive osseous mets or when some tumors release PTHrelated peptide hormone

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43
Q

In hypercalcemia of malignancy, what meds can we use to lower Ca levels?

A

bisphosphonates

inhibit osteoclast activity for up to 1 month

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44
Q

What do we see with hypoparathyroidism?

A

hypocalcemia

hyper-phosphatemia

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45
Q

MCC of hypoparathyroidism?

A

damage of parathyroids during thyroidectomy

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46
Q

What’s Chvostek’s sign seen in hypoparathyroid pts with hypocalcemia?

A

tapping on facial nerve anterior to ear causes contraction of facial muscles

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47
Q

Sxs of hypocalcemia seen in hypoparathyroidism?

A

low serum calcium levels seen

pts become anxious, peri-oral tingling/numbness, tetany

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48
Q

Carpo-pedal spasm seen in pts with hypoparathyroidism causing hypocalcemia?

A

Trousseu sign

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49
Q

How does DiGeorge’s syndrome cause hypoparathyroidism and hypocalcemia?

A

3rd and 4th branchial pouches develop abnormally, so you get fucked up parathyroids

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50
Q

When do we operate on pts with primary hyperparathyroidism?

A

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

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51
Q

After parathyroidectomy for primary hyperparathyroidism when can we expect to see bone density changes?

A

6months

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52
Q

Single best study to localize the parathyroid glands pre-operatively is?

A

Sestamibi scan

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53
Q

How does a sestamibi scan that localizes parathyroid glands for pre-operative planning?

A

parathyroid glands have a lot of mitochondria

mitochondria uptake technitium 99 avidly

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54
Q

Limitation of sestamibi scan to help localize parathyroid adenomas>

A

if you have co-existence of thyroid pathology or other metabolically active tissue that mimics parathyroid adenomas–> get false +

55
Q

Intra-operatively how can we confirm that parathyroids have been removed?

A

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)

56
Q

With intra-op PTH assays, how do we confirm that surgery was successful and parathyroid tissue was removed?

A

if you get a 50% drop of PTH from baseline

57
Q

Classic surgical approach to primary hyperparathyroidism

A

b/l neck exploration

w/complication rate of 1-2 %

success rate of 95% (success defined as normocalcemia at 6 months)

58
Q

85% of primary hyperparathyroidism is caused by?

A

single adenoma

59
Q

Whats MIP?

A

minimally invasive parathyroidectomy

60
Q

MIP: minimally invasive parathyroidectomy, doesn’t work for what?

A

doesn’t work for multiple adenomas on different sides causing primary HPT

61
Q

Reported rates of injury to the recurrent laryngeal nerves are what post-parathyroidectomy?

A

1-10 %

damage to one causes hoarseness
damage to both causes paralysis

62
Q

Damage to superior laryngeal nerve causes what symptoms?

A

problems with high pitch

can have bad effects in singers/professional speakers

63
Q

Hypoparathyroidism after parathyroidectomy?

A

can cause hypocalcemia after parathyroidectomy

usually from removal of all glands or damage to remaining glands

64
Q

What are some risk factors that lead to hypocalcemia after parathyroidectomy?

A

subtotal parathyroidectomies (removal of 3.5 glands)

b/l neck exploration

thyroidectomy + parathyroidectomy

neck radiation

65
Q

How do you prepare for suspected hypocalcemia post-op parathyroidectomy?

A

start a ca-gluconate drip (30 cc/hr)

long-term can give PO calcium and Vit D

hypomagnesemia needs to be corrected first

66
Q

What are three classes of medications used for hyperparathyroidism?

A

calcimimetics
bisphosphonates
SERMs

67
Q

What are some bisphosphonates used in hyperparathyroidism?

A

atidronate
alendronate
pamidronate

68
Q

Mainstay of management of secondary hyperparathyroidism?

A

calcimimetic agent cinacalcet

69
Q

What causes secondary hyperparathyroidism?

A

kidney failure pts become uremic

leads to hyper-phosphatemia –> leads to hypocalcemia

thus we get 2 -hyperparathyroidism

70
Q

Whats the root cause in all cases of secondary hyperparathyroidism?

A

failing kidney cannot hydroxylate Vit D2 —>D 3

71
Q

What’s renal osteodystrophy?

A

skeletal complications assc/ w ESRD

osteitis fibrosa cystica
osteomalacia

72
Q

What;s osteitis fibrosa cystica and what causes it?

A

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

73
Q

Secondary hyperparathyroidism due to renal failure can cause significant bone dx, how do we diagnose it?

A

bone bx

alk phos levels, PTH, aluminum, bone scintigraphy

74
Q

Calcimimetic drugs like cinacalcet are used for medical management of secondary HPT, how does it work?

A

lower PTH by increasing sensitivity of extra-cellular Ca to the CaSR receptor

75
Q

What’s uremic pruritis and what causes it?

A

Ca-deposits on skin in ESRD uremic pts

these sxs relieved in a few days after parathyroidectomy

76
Q

This is a rare and severe, life-threatening complication of secondary hyperparathyroidism due to calcification of small and medium sized arteries;

A

calciphylaxis

77
Q

What is calciphylaxis?

A

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

78
Q

How do we diagnose calciphylaxis?

A

clinical

can be confirmed by skin biopsy

lesions; mottled and painful, develop into hard plaques with central ulcer, eschar

79
Q

Why is pre-op imaging not indicated for surgical planning in someone with secondary hyperparathyroidism?

A

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

80
Q

Surgical tx commonly done for secondary hyperparathyroidism?

A

total parathyroidectomy with auto-transplantation in forearm

81
Q

For a subtotal parathyroidectomy, which gland is chosen for auto-transplantation?

A

choose a gland that is most easily accessible

usually this will be an inferior parathyroid gland because its more anterior

82
Q

What’s a subtotal parathyroidectomy;

A

removing three glands total

removing 50-75% of last gland and auto-transplanting remaining 50% remnant

83
Q

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?

A

mark it with a titanium clip

can also measure intra-op PTH levels to ensure enough tissue has been resected

84
Q

Why do we need to do a cervical thymectomy in pts who are having surgery for secondary hyperparathyroidism?

A

can have accessory parathyroid tissue in thymus

can cause persistent dx/symptoms

85
Q

Advantage of a subtotal parathyroidectomy with a eutopic parathyroid gland remnant, vs a transplanted parathyroid gland remnant in forearm>

A

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

86
Q

Why is heterotopic parathyroid gland transplant into the forearm preferred over eutopic gland placement?

A

avoids a second neck exploration if needed to re-operate

87
Q

What is a total parathyroidectomy with autotransplantation?

A

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

88
Q

Advantage of SCM/forearm transplantation of parathyroid gland remnant?

A

avoids neck dissection if need to re-operate

can have surgery under local anesthesia if second operation needed to remove more tissue

89
Q

Disadvanatage of implanting parathyroid remnant gland into SCM/forearm?

A

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

90
Q

PReferred surgery in pts with secondary hyperparathyroidism?

A

subtotal parathyroidectomy

91
Q

What is the recurrence rate of secondary HPT?

A

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

92
Q

Where do we see tertiary hyperparathyroidism?

A

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

93
Q

What causes tertiary-HPT?

A

pts with secondary HPT who undergo renal transplant and have autologous working parathyroid glands which cause hypercalcemia after transplant

94
Q

What is MEN1?

A

parathyroid hyperplasia–> causing primary HPT

pancreas lesions

pituitary lesions

95
Q

Parathyroid hyperplasia (causing primary HPT), pancreas lesions, pituitary lesions cause what syndrome?

A

MEN1

96
Q

in MEN1, what causes problems/symptoms first?

A

primary HPT

97
Q

With transplantation of parathyroid tissue in forearm, where is it specifically placed?

A

brachioradialis muscle of non-dominant forearm

98
Q

Initial surgery of choice for pt with MEN1 and primary HPT?

A

total parathyroidectomy or subtotal parathyroidectomy

trans-cervical thymectomy also performed

99
Q

When we do parathyroidectomy surgery, why do we cryo-preserve some parathyroid tissue at time of surgery?

A

transplanted parathyroid remnants can become ischemic and necrose causing permanent hypo-parathyroidism

100
Q

MEN2A?

A

medullary thyroid ca
pheochromocytoma

primary HPT

101
Q

Medullary thyroid Ca, pheochromocytoma, and primary HPT define what entity?

A

MEN2A

102
Q

How does primary HPT in MEN1, compare to MEN2A?

A

MEN2A–> HPT tends to be milder, usually asymptomatic

thus curative resection tends to be less aggressive

103
Q

Most pts with unresectable parathyroid Ca, die from what

A

metabolic effects of hyperCa

see Ca levels > 14

104
Q

After identification of MEN1, what is treated first?

A

primary hyperparathyroidism is treated first

four gland resection with auto-transplanation

(primary HPT in MEN1 due to gland hyperplasia, not adenoma)

105
Q

Ectopic superior parathyroids can be commonly located where?

A

tracheo-esophageal groove & retroesophageal region

106
Q

Ectopic inferior parathyroid glands can be commonly located where?

A

anterior mediastinum in assc/ with thymus and thyroid gland

107
Q

The most common location for a missed gland during surgery is where?

A

normal anatomic location

108
Q

Difference is PTH levels in parathyroid carcinoma vs adenoma?

A

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

109
Q

In terms of comparing PTH Ca vs PTH adenoma, what do we see in the lab values?

A

parathyroid Ca has higher elevations in Ca and PTH compared to adenomas

110
Q

What causes benign familial hypocalciuric hypercalcemia?

A

AD

increase Ca resorption in kidney due to defective PTH receptor

leads to mild hyper Ca, with normal PTH levels

111
Q

Tx for BFHH?

A

no tx

112
Q

What is the genetic defect in MEN2A and 2B?

A

AD dx

defect in ret-proto oncogenes on chromosome 10

113
Q

Genetic defect in MEN2A/B?

A

RET on chrom 10

114
Q

Mutation in MEN1?

A

menin protein mutation

115
Q

MEN2A is what syndrome?

A

medullary thyroid Ca
parathyroid hyperplasia
pheochromocytoma

116
Q

In MEN2A syndrome, what should be done first surgically?

A

pheochromocytoma should be removed first, due to intra-op complications assc with catecholamine surge

once pheo removed, surgical resection of thyroid/parathyroid gland safer

117
Q

Before operating on a pheochromocytoma, what should be done first?

A

a-blockade with phenoxybenzamine

ensure pt does not have a hypertensive crisis

118
Q

Hyperparathyroidism seen in MEN2A is caused by what?

A

parathyroid hyperplasia NOT an adenoma

119
Q

For pt noted to have MEN2A, we recommend total thyroidectomy by what age?

A

5

risk of medullary thyroid Ca

120
Q

RET is a proto-oncogene that encodes a receptor tyrosine kinase protein; and is mutated in what syndrome?

A

MEN2A/B

121
Q

RET mutations are inherited in what fashion in MEN2A?

A

AD

50% risk of giving offspring mutation

122
Q

A pt has primary hyperparathyroidism, what are the indications to operate?

A

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

123
Q

Chemo for parathyroid Ca?

A

not used

radiation has been shown to decrease local recurrence

124
Q

Initial imaging of choice for to localize parathyroid glands?

A

cervical US/

125
Q

Someone has MEN1, and has primary HPT, and you’ve localized the parathyroid adenoma on sestamibi scan and US, what’s the surgical procedure?

A

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

126
Q

Why is FNA contraindicated for someone with suspected parathyroid Ca?

A

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

127
Q

What do you do if you cant find an inferior parathyroid gland during surgery for resection?

A

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

128
Q

The inferior parathyroids arise from 3rd branchial pouch and descend with the ????

A

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

129
Q

How do we treat secondry hyperparathyroidism due to kidneys?

A

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

130
Q

The only reliable criteria for parathyroid Ca are what?

A

local invasion/mets

131
Q

What is the Miami criteria for intra-op PTH assays for parathyroidectomy?

A

> 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

132
Q

What is the treatment for locally recurrent parathyroid carcinoma?

A

re-exploration and resection

**parathyroid tissue is radio-resistant, radiation therapy does not work

133
Q

In pts that have MEN1, whats the most common pancreatic tumors?

A

gastrinomas

then insulinomas

Appendix (39 decks)

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