B6-050 CBCL Hyperparathyroidism Flashcards by Felicia Jones

parathyroid glands are located

on the back of thyroid

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cells that produce PTH

chief cells

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chief cells are stimulated to produce PTH by [3]

low calcium
high phosphate
low vitamin D

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PTH stimulates osteoblasts to secrete

RANKL

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RANKL binds to RANK on osteoclasts stimulating them to

resorb bone

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bone resorption releases [2] ions into blood

Ca++
PO43-

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decreased calcium levels stimulates PTH to activate […] to increase calcium levels in the blood

osteoclasts

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PTH stimulates […] in the PCT to activate vitamin D

a-1-hydroxylase

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PTH stimulates a-1-hydroxylase in the […] to activate vitamin D

PCT

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once activated in the kidney, […] stimulates GIT to absorb calcium in the gut

vitamin D

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once activated in the kidney, vitamin D stimulates GI tract to absorb […] in the gut

calcium

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phosphate is excreted from what part of the kidney?

PCT

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how does PTH decrease phosphate ions in blood?

inhibits transporter for reabsorption of Na+ and phosphate in PCT

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decreases the phosphate concentration in blood

PTH

**phosphate trashing hormone

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calcium is reabsorbed from what part of the kidney?

DCT

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PTH can directly stimulate the transporter for reabsorption of […] in the DCT

Ca++

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summarize the effects of PTH on the kidney [4]

increase a-1-hydroxylase
increase PO4 excretion in urine
decrease PO4 in serum
increase calcium in serum

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overall effects of hypersecretion of PTH [2]

hypercalcemia
hypophosphatemia

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primary causes of high PTH [3]

adenomas
hyperplasia
carcinoma

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MEN1 and 2 mutations cause […] hyperparathyroidism

primary

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most common cause of secondary hyperparathyroidism

chronic kidney disease

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causes of secondary hyperparathyroidism [3]

CKD
vitamin D deficiency
low calcium diet

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what stimulates PTH production in CKD? [2]

low calcium
high phosphate

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hyperparathyroidism due to chronic hypocalcemia

secondary

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phosphate binds

free calcium

how does CKD cause hyperparathyroidism?

reduced GFR causes hyperphosphatemia --> hypocalcemia reduced function of PCT causes hyperphosphatemia and hypocalcemia reduced function of DCT causes hyperphosphatemia and hypocalcemia

malabsorptive syndromes like Crohns or celiac can cause

decreased absorption of vitamin D --> secondary hyperparathyroidism

How does pancreatic insufficiency cause secondary hyperparathyroidism?

pancreatic lipase is important for fat absorption, and vitamin D is absorbed with fat --> decreased absorption of vitamin D

how do gallstones cause secondary hyperparathyroidism?

bile is important for fat absorption vitamin D needs fat to be absorbed no bile ---> decreased absorption of vitamin D

decreased sun exposure can cause

secondary hyperparathyroidism **less formation of active vitamin D

chronic hypocalcemic state that progresses over time, past secondary

tertiary hyperparathyroidism

consistent, constant stimulation of the parathyroid leads to

hyperplasia

uncontrolled release of PTH independent of any signaling from feedback regulation

tertiary hyperparathyroidism

mneumonic for primary hyperparathyroidism

bones stones groans thrones psychiatric overtones

PTH liberates [3] things from bones

Ca++ PO43- hydroxyapatites

excessive PTH causes [...] of bone

demineralization **increased risk of fracture

bone density decreases due to constant demineralization

osteoporosis **increased risk of fracture

condition occurring due to increased bone resorption osteoclasts and connective tissues form cavities that look like cyst

osteitis cystica fibrosis **occurs due to primary hyperparathyroidism --> increased osteoclast activity

nephrocalcinosis

calcium and phosphate stones deposit in small parts of kidney tubules or smaller calyxes

nephrolithiasis

calcium and phosphate stones form in ureter/renal calyx

[...]calemia decreases smooth muscle activity

hypercalcemia

how does hypercalcemia decrease smooth muscle activity

increased Ca++ blocks Na+ channels in smooth muscle **results in reduced GI motility

GI symptoms of primary hyperparathyroidism

constipation abdominal pain nausea vomiting

how can primary hyperparathyroidism cause ulcers?

Ca++ activates gastrin and stimulates parietal cells to increase HCl in stomach

how can primary hyperparathyroidism cause pancreatitis?

Ca++ activates pancreatic enzymes in pancreatic ducts --> autodigestion causing significant abdominal pain

how does primary hyperparathyroidism causes nephrogenic diabetes insipidus?

Ca++ inhibits ADH --> less water is reabsorbed

symptoms of nephrogenic DI caused by primary hyperparathyroidism

polyuria: increased urine output polydipsia: to compensate for water lost in bloodstream there is excessive thirst

how does primary hyperparathyroidism cause decreased mental function?

Ca++ can bind to Na+ channels in brain and block electrical activity

neurological manifestations of primary hyperparathyroidism

lethargy depression AMS: can progress to coma due to severe hypercalcemia reduction of deep tendon reflexes

Ca++ in the channel will hinder [...] from entering cells of smooth muscles or neurons

Na+ **causes slow activity and neurological symptoms

Ca++ in the channel will hinder Na+ from entering cells of [...] and [...]

smooth muscle neurons **causes slow activity and neurological symptoms

how does secondary hyperparathyroidism caused by CKD effect the kidneys?

kidney is damaged and unable to resorb calcium

how does secondary hyperparathyroidism caused by CKD effect the GI tract?

kidney damage prevents activation of vitamin D without activated vitamin D, GI tract cannot absorb calcium

how does secondary hyperparathyroidism caused by CKD effect the bones?

increase bone demineralization due to hypocalcemia

group of conditions caused by CKD leading to secondary hyperparathyroidism that damages bone

renal osteodystrophy since PTH cannot get Ca++ from kidneys or GI, it causes massive demineralization of bone

demineralization causing cystic cavities in bone

osteitis cystica fibrosa

[...]calcemia shortens the QT interval

hypercalcemia

seen in secondary and tertiary hyperparathyroidism when there is too much Ca++ and it deposits around the vessels

calciphylaxis

Ca++ deposition around vessels causing ischemia/necrosis of skin lesions

calciphylaxis

calcium in the serum may appear low if [...] is also low

albumin

equation for correction of calcium

serum Ca + 0.8 x (4-albumin)

medications that can cause hypercalcemia

thiazides lithium calcium supplements vitamin D supplements

typically, if calcium is elevated, PTH is

decreased

elevated calcium with normal/high PTH

PTH mediated hypercalcemia

first step in diagnosing hypercalcemia

recheck serum calcium check PTH levels

85% of primary hyperparathyroidism occurs due to

solitary parathyroid adenoma

expected labs for primary hyperparathyroidism

elevated PTH elevated serum calcium elevated urine calcium low phosphate

should you biopsy parathyroid carcinoma?

no, risk for seeding

hypercalcemia caused by a parathyroid carcinoma can be treated with

cinacalcet

primary treatment of parathyroid carcinoma

surgical resection

excessive PTH secretion as a secondary response to hypocalcemia

secondary hyperparathyroidism

chronic hypocalcemia causes parathyroid [...]

hyperplasia

results from progression of secondary hyperparathyroidism

tertiary hyperparathyroidism

prolonged hypocalcemia causes development of autonomous parathyroid function and hypercalcemia

tertiary hyperparathyroidism

in tertiary hyperparathyroidism, [...] remains despite discontinuation of vitamin D and calcium supplements

hypercalcemia

most commonly occurs in CKD or post kidney transplant

tertiary hyperparathyroidism

in tertiary hyperparathyroidism, [...] remains high despite vitamin D therapy and correction of hyperphosphatemia

PTH

inheritance pattern of FHH

autosomal dominant

parathyroid glands and kidney detect serum calcium concentrations via

calcium sensing receptor

FHH is an [....] mutation of CaSR

inactivating

parathyroid gland perceives serum calcium is low due to decreased sensitivity, leading to increased PTH secretion and serum calcium

FHH

paradoxical hypocalciuria in the setting of hypercalcemia

FHH

does FHH resolve with surgery?

mild hypercalcemia since childhood

FHH

Ca/Cr clearance ratio <0.01

FHH

malignancy is the most common cause of

non-PTH mediated hypercalcemia

elevated PTHrP

non-PTH mediated hypercalcemia

metastasis to bone of breast cancer or multiple myeloma causes efflux of calcium from the bone

local osteolytic hypercalcemia **type of non-PTH mediated hypercalcemia

what kind of study is required prior to performing parathyroidectomy?

localization: sestimibi scan thyroid US neck CT

[...] allows determination of the biochemical cure while the patient is undergoing parathyroidectomy

intra operative PTH monitoring

binds to extracellular CaSR on parathyroid cells and decreases their response to low serum calcium

cinacalcet

medication that reduces PTH and calcium but does not affect bone mass

cinacalcet

bisphosphonates [4]

alendronate risidronate ibandronate zolendronic acid

medication that inhibits osteoclast mediated bone resorption

bisphosphonates

medication that does not affect PTH but lowers calcium and improves bone mass

bisphosphonates

primary treatment of malignancy related hypercalcemia

bisphosphonates

vertebral fracture due to low bone density is indication for

parathyroidectomy

serum calcium [...] above the upper limit of normal is indication for parathyroidectomy

greater than 1.0 mg/dl

nephrolithiasis or nephrocalcinosis seen on imaging is indication for

parathyroidectomy

age less than [...] is indication for parathyroidectomy

sites of hydroxylation of Vitamin D and where they occur

25- liver 1 and 24- kidney

[...]calcemia causes inhibition of PTH

hypercalcemia

[...]calcemia results in the secretion of PTH

hypocalcemia

hypercalcemia stimulates osteoblasts to

build more bone lowering serum calcium and phosphate

hypercalcemia will cause the kidneys to increase excretion of

calcium

hypocalcemia will stimulate osteoclasts to

resorb bone increases serum calcium and phosphate

hypocalcemia will cause the kidneys to excrete [...] and retain [...]

excrete phosphorus retain calcium

PTH is synthesized and excreted due to

decreased calcium levels

PTH will cause the bone to release [2]

calcium and phosphorus

PTH will cause the kidneys to

resorb calcium excrete phosphate

PTH will cause the GI tract to

increase calcium and phosphate absorption indirectly via vitamin D

is PTH under hypothalamic control?

no responds directly to calcium

rate limiting enzyme in vitamin D activation

1-a-hydroxylase

inactivates vitamin D during excess calcium and phosphate

24-hydroxylase

PTH acts on osteoblasts to secrete more

RANKL

RANKL binds to RANK on [...] to activate them

osteoclasts

RANKL-RANK bind stimulates

osteoclasts differentiation and activation

osteoblasts secrete [...] which binds to RANKL to prevent it from binding RANK

OPG

what organs hydroxylate vitamin D to its active form?

liver and kidney

in the liver, [...] will hydroxylate the 25 position of vitamin D

25 hydroxylase

in the kidney [...] will hydroxylate the 1 position of vitamin D

1-a-hydroxylase

Vitamin D functions in the gut to

promote calcium uptake and transport into the blood stream

increases the rate of calcium transport

vitamin D (calcitriol)

vitamin D stimulates calcium [...] in bones

resorption

vitamin D acts on the kidneys to

decrease excretion of calcium and phosphate

vitamin D acts on the GI tract to

increase absorption of calcium and phosphate

how many parathyroid glands are typically present?

superior parathyroid glands derive from

4th pharygeal pouch

inferior parathyroid glands derive from

3rd pharyngeal pouch

calcium homeostasis is controlled by [3]

PTH vitamin D calcitonin

increase calcium levels in times of hypocalcemia [2]

PTH and vitamin D

decreases calcium levels in in times of hypercalcemia

calcitonin

PTH [...] and vitamin D [...] renal phosphate reabsorption

PTH decreases and vitamin D increases renal phosphate reabsorption

a mutation in CaSR will stimulate the release of

PTH increasing serum calcium

binds to CaSR and alters its sensitivity resulting in decreased parathyroid responsiveness

cinacalcet

inhibit osteoclast mediated bone resorption resulting in decreased calcium

bisphosphonates

most common cause of primary hyperparathyroidism

parathyroid adenoma

autosomal dominant mutation in CaSR gene

FHH

renal failure and vitamin D cause [...] hyperparathyroidism

secondary

expected labs for primary parathyroidism

hypercalcemia hypophosphatemia

expected labs for secondary parathyroidism

hypocalcemia hyperphosphatemia

refractory hyperparathyroidism resulting from chronic kidney disease

tertiary

expected PTH and Ca+ values in tertiary hyperparathyroidism

elevated PTH elevated Ca+

hyperparathyroidism caused by chronically low calcium and/or elevated phosphate

secondary

expected PTH, calcium, phosphate, ALP labs for secondary hyperparathyroidism

elevated PTH low calcium elevated phosphate (in CKD, may be normal in vitamin deficiency) elevated ALP

MEN1 syndrome involves tumors in [3]

pituitary pancreas parathyroid

primary role of PTH

regulation of calcium and phosphate

How does PTH affect calcium and phosphate metabolism in the kidney?

increases reabsorption of Calcium inhibits reabsorption of phosphate

PTH stimulates the hydroxylation of

25-hydroxy vitamin D

does PTH affect bicarb?

yes, stimulates secretion of bicarb in the kidney

what is the active form of vitamin D?

1,25-OH vitamin D

PTH stimulates [...] to produce 1,25-OH

1a-hydroxylase

1a-hydroxylase in the kidney is stimulated by [3]

PTH low serum calcium low serum phosphate

PTH increases calcium reabsorption in the kidney via a basolateral receptor coupled to [...]

adenylate cyclase

25 hydroxylation of vitamin D occurs in the

liver

activation of vitamin D requires [3]

UV light exposure hepatic function kidney function

cacitonin is induced by [...]calcemia

hypercalcemia

the liver produces what form of vitamin D?

25-hydroxy D3

in CKD, decreased GFR causes the reduced excretion of

phosphate

what medication can have the side effect of elevated serum calcium?

thiazides

how do thiazides lead to elevated serum calcium levels?

block the NaCl channels in the DCT causes hyper polarization of apical membrane, resulting in increased reabsorption of calcium by voltage gated calcium channels

PTH functions at the level of the kidney to [3]

increase calcium reabsorption inhibit phosphate reabsorption induce 1-alpha-OH activity

hypertension fatigue memory issues are symptoms of

hypercalciemia

expected serum PTH, calcium, phosphate, and vitamin D levels in primary hyperparathyroidism

elevated PTH elevated calcium low/normal phosphate normal vitamin D

PTH functions at the level of bone to induce osteoblasts to

secrete RANKL

what does RANKL do?

induces osteoclasts to promote bone reabsorption and increase serum levels of calcium and phosphate

how does PTH stimulate bone reabsorption?

1. induces osteoblasts to secrete RANKL 2. RANKL stimulates osteoclasts to resorb bone

monoclonal antibody used to block the function of RANKL

denosumab

[hyper or hypocalcemia] muscle spasms

hypocalcemia

[hyper or hypocalcemia] tetany

hypocalcemia

[hyper or hypocalcemia] hypotension

hypocalcemia

[hyper or hypocalcemia] trousseau sign

hypocalcemia **carpal spasm when bp cuff is inflated for 2-3min

[hyper or hypocalcemia] chvostek sign

hypocalcemia **twitching of facial muscle when facial nerve is entrapped

[hyper or hypocalcemia] coma

hypercalcemia

[hyper or hypocalcemia] constipation

hypercalcemia

[hyper or hypocalcemia] esophagitis

hypercalcemia

[hyper or hypocalcemia] nephrolithiasis

hypercalcemia

asymptomatic hypercalcemia is associated with

FHH

a calcium to creatinine clearance greater than 0.01 is associated with

hyperparathyroidism

a calcium to creatinine clearance ratio less than 0.01 is associated with

FHH **due to reduced excretion of calcium

formula to calculate fractional excretion of calcium

(Ca urine x Cr plasma) / (Ca plasma x Cr urine)

FHH is due to a mutation in

CaSR **reduces its affinity for calcium

both calcium and PTH mildly elevated patient asymptomatic

FHH

patients diagnosed with FHH will have a family history of

asymptomatic elevated serum calcium and PTH

parathyroid adenoma is the most common cause of

primary hyperthyroidism

causes of secondary hyperparathyroidism [3]

CKD vitamin D deficiency dietary calcium malabsorption

non-PTH mediated hypercalcemia is usually caused by

malignancy

medications that can cause hypercalcemia [2]

thiazides lithium

medications that can be used to treat hypercalcemia if surgery is not an option

cinacalcet alendronate

best option to cure parathyroid adenoma

surgical resection

a patient with primary hyperparathyroidism will have increased [...] in urine [2]

calcium phosphate

describe the expected lab results for primary hyperparathyroidism

elevated Ca low/normal phosphate elevated PTH **30% of patients will have hypercalciuria

the superior and middle thyroid veins drain into the

internal jugular vein

the inferior thyroid vein drains into the

left brachiocephalic

the facial vein drains into the

retromandibular vein --> internal jugular

the external jugular vein is located anterior to the

SCM

nerves located posterior-lateral to the trachea and thyroid glands

recurrent laryngeal nerves

damage to the sympathetic chain during parathyroidectomy results in

Horner's syndrome

damage to the recurrent laryngeal nerves during parathyroidectomy results in

hoarse voice

describe the expected labs in secondary hyperparathyroidism

elevated PTH decreased Ca increased serum phosphate (in CKD) decreased calcitriol

osteoporosis with a bone density score of less than [...] is indication for parathyroidectomy

-2.5

patient age [...] is indication for parathyroidectomy

less than 50

calcium level [...] is indication for parathyroidectomy

greater than 1.0 mg/dl above normal

undetectable PTH indicates

non-PTH mediated hypercalcemia **often caused by malignancy

[....] fracture is indication for parathyroidectomy

vertebral

creatinine clearance [....] is indication for parathyroidectomy

less than 60 mL/min

24 urine calcium [....] is indication for parathyroidectomy

greater than 400 mg/day

[...] or [...] seen on kidney imaging is indication for parathyroidectomy

nephrolithiasis nephrocalcinosis