Malignancy associated hypercalcemia
is the most common cause
of non-parathyroid hormone
It is typically severe in that patients present
with elevated calcium greater than 14 mg/dL.
It's often the result of a
tumor-produced PTH-related protein
or PTHrP leading to extensive
resorption of the bone.
Renal carcinoma, breast cancer and squamous
cell cancers are associated with PTHrP release.
Rarely, local mediated osteolysis from
its extensive skeletal metastases,
typically in multiple myeloma and breast cancer
may cause the efflux of calcium from bone
resulting in significant
Let's talk about the
management of hypercalcemia.
This is really dependent on the
severity of the elevation of calcium.
If it is mild, say under 12 mg/dL,
treatment of the underlying disorder,
for example, hyperparathyroidism,
once you perform a parathyroidectomy.
This is usually sufficient and continuous monitoring
of patient's calcium continuous after to surgery.
Treating calcium levels above 12 mg/dL usually requires
hospitalization especially if patient's asymptomatic.
The key features to look at for are the presence
of kidney disease and mental status changes.
Initial treatment of severe hypercalcemia consist
of aggressive hydration to replete volume loss
and to increase the kidney's
excretion of calcium.
Loop diuretics are not recommended unless the patient
manifest with kidney failure or heart failure.
For the acutely symptomatic patient, subcutaneous
calcitonin should be applied as well.
Bear in mind that the half-life of
the drug wanes withing 48 hours
Calcium levels should be re-checked
and re-dosing may be considered.
Long-term management of hypercalcemia may
require intravenous bisphosphonate therapy
to prevent mobilization of
calcium from the skeleton
but also requires
adequate kidney function.
Always check the creatinine before
prescribing a bisphosphonate.
Glucocorticoids and restriction
of calcium and vitamin D intake
are also beneficial in vitamin
D dependent hypercalcemia.
Hemodialysis is reserved for the treatment of severe
hypercalcemia in patients who are unable to produce urine
and would not respond to fluid
resuscitation or diuretics.
Vitamin D-dependent hypercalcemia is associated
with normal to elevated serum phosphorus.
Vitamin D enhances intestinal absorption
of phosphorus and suppresses PTH secretion
which reduces kidney
This is in fact, the opposite in hyperparathyroidism
where one sees reductions in serum phosphorus.
In vitamin D-dependent hypercalcemia,
the pathophysiology going on
is the unregulated conversion of
25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.
This is seen classically in the
granulomatous diseases which include:
fungal infections, tuberculosis,
sarcoid and lymphomas.
What occurs is increased
intestinal absorption of calcium.
These conditions are associated
with inappropriately normal
or frankly elevated 1,25-dihydroxyvitamin
D level and a supressed PTH.
Decreased serum and urine calcium after intake
of calcium and vitamin D is restricted.
Or rapid decrease in calcium after glucocorticoid
therapy is consistent with these disorders.
Of note here that the treatment of hypercalcemia
and sarcoidosis is to give steroids.
Let's talk about
PTH mediated hypercalcemia
occurs with lithium.
Non-PTH mediated hypercalcemia occurs
with thiazide diuretics, classically.
And then excessive ingestion of calcium or vitamin
D can also elevate serum calcium levels
and should always be
ruled out on history.
Let's go through a summary of the causes
of hypercalcemia that we've discussed.
Primary hyperparathyroidism most
commonly from a parathyroid adenoma
is the most common cause of
In this case, the PTH is elevated in 80%, the phosphorus
is classically low and the vitamin D levels are high.
Creatinine is usually normal and the parathyroid
hormone releasing peptide is negative.
Clinical clues are symptoms and
signs of hypercalcemia and xrays
which are classic findings including
osteitis fibrosa cystica.
Humeral hypercalcemia of malignancy is the
most common cause if in-patient hypercalcemia.
In this condition, the PTH level is low, the phosphorus
level is normal or low, vitamin D levels are normal or low
and the creatinine can be increased depending
upon whether or not there is calciuresis.
Parathyroid hormone releasing
peptide is positive.
Symptoms and signs of malignancy
will be found clinically.
weight loss, bone pain, etc.,
may also be manifestations.
Multiple myeloma is a clinical condition in
which parathyroid hormone manifest as low,
Serum phosphorus may be high, vitamin
D levels are usually normal.
Creatinine is elevated if the
condition also affects the kidney.
and parathyroid hormone
releasing peptide is negative.
Symptoms and signs of malignancy are usually the common
presentation usually with bone pain and weight loss.
Granulomatous diseases as we discussed,
the classic example being sarcoidosis.
Here, the parathyroid hormone is low, the phosphorus
levels are high, vitamin D levels are high,
Creatinine, if the kidney is affected by the underlying
condition will manifest as an increased creatinine
or alternatively, if the patient has a very
high level of calcium and they are dehydrated,
may manifest with the pre-renal state which would
be another cause of an elevation of creatinine.
And then finally, PTHrP
will be negative.
The clinical features of sarcoidosis and
TB vary but mostly affect the lungs.
Hyperthyroidism, interestingly enough, will not cause any
derrangements in PTH, phosphorus, vitamin D or creatinine.
The PTHrP will be negative but they may
be the direct stimulation of osteoclasts
by thyroid hormone leading
And then finally, the very rare condition
of familial hypocalciuric hypercalcemia
where all of the
tests are negative.
One makes the diagnosis by checking
a 24-hour urine calcium excretion.
Here, this will be low in the setting
of an elevated serum calcium.
Checking a family history is usually
indicated and these patients
will then require managements depending
upon the severity of the hypercalcemia.