Hypercalcemia

Question 1

Asymptomatic and mild hypercalcemia value

Answer 1

<12 mg/dl

Question 2

moderate hypercalcemia value

Answer 2

12-14 mg/dl

Question 3

severe hypercalcemia value is

Answer 3

>14 mg/dl

Question 4

treatment of mild hypercalcemia (<12)

Answer 4

no immediate treatment needed avoid thiazide diuretics, lithium and volume depletion or prolonged bed rest

Question 5

treatment of moderate hypercalcemia 12-14

Answer 5

usually no immediate treatment unless symptomatic and treatment is similar to severe hypercalcemia See dehydration so give IVFs may see hypokalemia related to osmotic diuresis of body trying to get rid of calcium

Question 6

treatment of severe hypercalcemia (both short term and long term)

Answer 6

short term (immediate treatment) IVFs plus calcitonin (only works for 48 hrs) avoid loop diuretics unless volume overload (heart failure exists) long term treatment: bisphosphonates like zoledronic acid.

Question 7

most common cause of hypercalcemia >13 is from

Answer 7

malignancy that degree of hypercalcemia are volume depleted from vomiting and renal salt and water wasting.

Question 8

Benefit of calcitonin in hypercalcemia

Answer 8

it is administered early in management because it can rapidly lower Ca and it only lasts for 48 hrs it helps decrease bone resorption.

Question 9

When should you give bisphosphonate when trying to lower hypercalcemia?

Answer 9

give at the same time you give calcitonin and IVFs. it takes about 2-4 days to start dropping calcium levels and provides a sustained calcium lower effect

Question 10

Why do we like zoledronic acid for lower hypercalcemia

Answer 10

this bisphosphonate is ok to use with renal dysfunction. Not typically used for osteoporosis. But zoledronic acid is ok to use for Cr <4.5 and can be considered if higher than 4.5. Alendronate can’t be used for renal dysfunction

Question 11

What is denosumab?

Answer 11

this is monoclonal antibody that stops osteoclastic maturation and slowed down bone breakdown. Not used as 1st for hypercalcemia of malignancy but can be used for those with severe renal impairment (Cr>4.5)

Question 12

why do we try to avoid loop diuretics with hypercalcemia

Answer 12

furosemide has been advocated to promote urinary calcium excretion BUT not recommended b/c

it can cause hypokalemia

worsen hypovolemia.

only meant for pts who develop volume overload (like have CHF already) .

Question 13

when do we use corticosteroids (methylprednisolone) for hyper calcemia

Answer 13

only if treating hyperabsorptive hypercalcemia related to vitamin D toxicity, lymphoma, and granulomatous disease (sarcoidosis)

this response is variable and not recommended for treatment of hypercalcemia emergencies of unknown origin

Question 14

most common cause of hypercalcemia

Answer 14

primary hyperparathyroidism and hypercalcemia of malignancy

Question 15

what kind of cancers can cause hypercalcemia of malignancy by a PTH mimic?

Answer 15

squamous cell,

renal and bladder cell

breast and ovarian cancer

Question 16

What do we see on hypercalcemia of malignancy labs?

Answer 16

low PTH and high PTHrP and it’s a PTH mimic

Question 17

What causes hypercalcemia of malignancy of bone metastases?

Answer 17

breast and multiple myeloma See this via mechanism or osteolysis and bone metastases

Question 18

what do we see on labs of hypercalcemia of malginancy via osteolysis?

Answer 18

low PTH and low vitamin D

PTHrP is high?

Question 19

What kind of cancer causes hypercalcemia by increased calcium absorption?

Answer 19

Lymphoma and Hodgkin’s lymphoam.

• makes more 1 alpha hydroxylase which can in turn increase the formation of 1.25 dihydroxyvitamin D that leads to excessive GI absorption of calcium.

on labs will see high 1,25 vitamin D level and high Ca.

Question 20

what kind of labs do we see of hypercalcemia on lymphoma and vitamin D driven hypercalcemia?

Answer 20

low PTH and increased vitamin D and this is from higher calcium absorption.

Question 21

mild asymptomatic hypercalcemia at a young age should get ?(which labs)

Answer 21

after confirming it to be a true calcium elevation, get these labs:

PTH,

24 hr urine calcium

Cr level

PTH dependent hypercalcemia will have elevated PTH or inappropriately mid high normal (if high Ca should have low PTH).

Question 22

PTH dependent hypercalcemia is often a result of

Answer 22

familial hypocalciuric hypercalcemia (FHH) -

seen in young pts and patients who have a strong family history of hypercalcemia or pts with recurrent hypercalcemia after parathyroidectomy.

Question 23

what causes FHH or familial hypocalciuric hypercalcemia?

Answer 23

from an inactivating mutation in the calcium sensing receptor that results in lower urine calcium and higher setpoint in serum calcium. It’s a benign condition that does not need treatment

Question 24

What do you do with a 24 hr urine calcium and Cr in someone suspicious for FHH?

Answer 24

urinary calcium/cr clearance ratio will show if pt has FHH. THe proposed cuttoff of <1% suggests FHH. Less likely if urinary calcium >3% and ruled out by elevated urinary calcium. Ultimately if FHH consideration needs genetic testing.

Question 25

treatment of choice for primary hyperparathyroidism?

Answer 25

paarathyroidectomy Primary hyperparathyroidism - if there’s high secretion of PTH resulting in hypercalcemia from overactivity of parathyroid glands

Question 26

Is familial hypocalciuric hypercalcemia dangerous

Answer 26

no it’s a benign condition

Question 27

algorithm for hypercalcemia evaluation

Answer 27

Question 28

how does sarcoidosis cause hypercalcemia?

Answer 28

multi systemic granulomatous disease with non caseating tissue granulomas and see activated pulmonary macrophages that make calcitriol which causes hypercalemia and hypercalciuria.

will see higher than normal 1.25 hydroxy vitamin D.

Question 29

most common cause of hypercalcemia

Answer 29

primary hyperparathyroidism

• usually asymptomatic and present with incidental hypercalcemia on routine lab testing.

Pts who have primary hyperparathyroidism and HCTZ can have synergistic effect in raising Ca level (12).

Question 30

which granulomatous diseases can cause hypercalcemia and how do they do it?

Answer 30

sarcoidosis, fungal infections (Histoplasma) and TB can cause hypercalcemia

• they cause an extrarenal production of 1 alpha hydroxylase which in turn increases the formation of 1,25 OH vitamin D.

Question 31

how high is hypercalcemia related to cancer?

Answer 31

generally its 13-14 or very high.

Question 32

does osteoporosis cause hypercalcemia?

Answer 32

no.

Question 33

What are the granulomatous diseases that cause hypercalcemia?

Answer 33

Question 34

Algorithm for hypercalcemia

Answer 34

Question 35

pt with hypercalcemia (anorexia nausea polyuria and constipation) who has CXR with bilateral hilar adneoapthy. What is driving their hypercalcemia?

Answer 35

sarcoidosis (granulomatous dx) that creates extra renal production of 1-hydroxylase which results in excessive conversion of 25 vit D to 1,25 vit D (calcitriol)

This calcitriol then in turn increases intestinal calcium absorption and bone resorption.

may also see hypercalcuria with sarcoidosis leading to nephrolithiasis

Question 36

Treatment of hypercalcemia and hypercalciuria from granulomatous disorders is

Answer 36

decreasing calcium and oxalate intake and avoidance of sun exposure (which aggravates hypercalcemia in some pts)

In sarcoidosis, treat with low dose glucocorticoid therapy (lowering serum calcium levels by decreasing calcitriol production) and this takes about 2-5 days.

Question 37

best way to treat cancer pts with severe hypercalcemia (Ca>14mg/dl)

Answer 37

give calcitonin for reduction in serum calcium levels by decreasing bone resorption but effect is short lived and then give bisphosphonates.

Not helpful for treatment of granulomatous diseases

Question 38

what is cinacalcet or Sensipar?

Answer 38

its a calcium mimetic drug that acts on calcium sensing recpetors of parathyroid cells to decrease secretion of parathyroid hormone. Only helpful in pts who have hypercalcemia due to hyperparathyroidism (prmary or tertiary)

Question 39

triad of PTH independent hypercalcemia (low or normal PTH) and renal insufficiency and alkalosis is consistent for

Answer 39

milk alkali syndrome

Question 40

Milk alkali syndrome is from

Answer 40

excessive intake of calcium and absorable alkali from calcium carbonate preparations for osteoporosis and heart burn.

See resulting hypercalcemia which results in renal vasoconstriction with decreased GFR and leads to increased natriuresis with eventual volume depletion and metabolic alkalosis due to increased renal tubular bicarbonate resorption.

also see low phosphate due to phosphate binding action of calcium carbonate

Question 41

what medications can increase risk for milk alkali syndrome?

Answer 41

ACEi/ARBs and NSAIDs

Question 42

Treatment of milk alkali syndrome?

Answer 42

isotonic saline infusion and lasix corrects hypercalcemia right away

Question 43

milk alkali syndrome manifestations

Answer 43

see incidental hypercalcemia, to acute symptomatic hypercalcemia to chronic kidney disease with metastatic calcification.

Question 45

how do we know if it’s HCTZ induced hypercalcemia or PTH dependent hypercalcemia?

Ca 11.1

PTH: 60 (range is 10-65)

Answer 45

normally even with mild hypercalcemic like Ca 11.2, it can suppress PTH to low levels of <20. SO inappropriately normal PTH means that this is driven by PTH process.

Likely driven by primary hyperparathyroidism.

HCTZ can help to unmask primary hyperparathyroidism.

Can also see this with familial hypocalciuric hyperaclemia (low urine calcium because it holds onto calicium)

Question 46

Remember PTHrP acts

Answer 46

like PTH

so will cause high ca and low phosphate and low PTH levels.