Hypercalcemia Flashcards
Asymptomatic and mild hypercalcemia value
<12 mg/dl
moderate hypercalcemia value
12-14 mg/dl
severe hypercalcemia value is
>14 mg/dl
treatment of mild hypercalcemia (<12)
no immediate treatment needed avoid thiazide diuretics, lithium and volume depletion or prolonged bed rest
treatment of moderate hypercalcemia 12-14
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
treatment of severe hypercalcemia (both short term and long term)
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.
most common cause of hypercalcemia >13 is from
malignancy that degree of hypercalcemia are volume depleted from vomiting and renal salt and water wasting.
Benefit of calcitonin in hypercalcemia
it is administered early in management because it can rapidly lower Ca and it only lasts for 48 hrs it helps decrease bone resorption.
When should you give bisphosphonate when trying to lower hypercalcemia?
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
Why do we like zoledronic acid for lower hypercalcemia
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
What is denosumab?
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)
why do we try to avoid loop diuretics with hypercalcemia
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) .
when do we use corticosteroids (methylprednisolone) for hyper calcemia
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
most common cause of hypercalcemia
primary hyperparathyroidism and hypercalcemia of malignancy
what kind of cancers can cause hypercalcemia of malignancy by a PTH mimic?
squamous cell,
renal and bladder cell
breast and ovarian cancer
What do we see on hypercalcemia of malignancy labs?
low PTH and high PTHrP and it’s a PTH mimic
What causes hypercalcemia of malignancy of bone metastases?
breast and multiple myeloma See this via mechanism or osteolysis and bone metastases
what do we see on labs of hypercalcemia of malginancy via osteolysis?
low PTH and low vitamin D
PTHrP is high?
What kind of cancer causes hypercalcemia by increased calcium absorption?
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.
what kind of labs do we see of hypercalcemia on lymphoma and vitamin D driven hypercalcemia?
low PTH and increased vitamin D and this is from higher calcium absorption.
mild asymptomatic hypercalcemia at a young age should get ?(which labs)
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).
PTH dependent hypercalcemia is often a result of
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.
what causes FHH or familial hypocalciuric hypercalcemia?
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
What do you do with a 24 hr urine calcium and Cr in someone suspicious for FHH?
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.
treatment of choice for primary hyperparathyroidism?
paarathyroidectomy Primary hyperparathyroidism - if there’s high secretion of PTH resulting in hypercalcemia from overactivity of parathyroid glands
Is familial hypocalciuric hypercalcemia dangerous
no it’s a benign condition
algorithm for hypercalcemia evaluation
how does sarcoidosis cause hypercalcemia?
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.
most common cause of hypercalcemia
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).
which granulomatous diseases can cause hypercalcemia and how do they do it?
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.
how high is hypercalcemia related to cancer?
generally its 13-14 or very high.
does osteoporosis cause hypercalcemia?
no.
What are the granulomatous diseases that cause hypercalcemia?
Algorithm for hypercalcemia
pt with hypercalcemia (anorexia nausea polyuria and constipation) who has CXR with bilateral hilar adneoapthy. What is driving their hypercalcemia?
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
Treatment of hypercalcemia and hypercalciuria from granulomatous disorders is
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.
best way to treat cancer pts with severe hypercalcemia (Ca>14mg/dl)
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
what is cinacalcet or Sensipar?
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)
triad of PTH independent hypercalcemia (low or normal PTH) and renal insufficiency and alkalosis is consistent for
milk alkali syndrome
Milk alkali syndrome is from
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
what medications can increase risk for milk alkali syndrome?
ACEi/ARBs and NSAIDs
Treatment of milk alkali syndrome?
isotonic saline infusion and lasix corrects hypercalcemia right away
milk alkali syndrome manifestations
see incidental hypercalcemia, to acute symptomatic hypercalcemia to chronic kidney disease with metastatic calcification.
how do we know if it’s HCTZ induced hypercalcemia or PTH dependent hypercalcemia?
Ca 11.1
PTH: 60 (range is 10-65)
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)
Remember PTHrP acts
like PTH
so will cause high ca and low phosphate and low PTH levels.
