Transcript Management of Hypercalcemia in Hospitalized Patients

Work-up and Management of
Hypercalcemia in Hospitalized
Patients
Jessica Thom
PGY-3
Let’s start with a case
Mrs. S is a 74 year old female with a history of COPD who
presents to the ER with confusion and acute renal failure.
Her calcium on presentation is 3.13mmol/L with a
creatinine of 175micromol/L. Chest X-ray reveals a large
right hilar mass.
Symptoms of hypercalcemia
 Cognitive dysfunction
 Confusion, lethargy, coma (in severe cases)
 GI disturbances
 Constipation, nausea, anorexia
 Renal dysfunction
 Polyuria, acute/chronic renal failure, nephrolithiasis
 Musculoskeletal symptoms
 Muscle weakness, bone pain
What is the most likely cause
of hypercalcemia?
 Inpatient setting – Malignancy
 Outpatient setting – Primary hyperparathyroidism
If no malignancy…how do you approach the work-up of
hypercalcemia?
Start with PTH
PTH-dependent causes
PTH independent causes
(mid-high normal/elevated levels)
 Primary hyperparathyroidism
(low levels)

Malignancy
 PTHrp (squamous cell ca)
 1,25(OH)2D secretion (lymphoma)
 Osteolytic (breast, multiple myeloma)

Granulomatous dx (secrete 1,25(OH)2D)
 Sarcoidosis
 Mycobacerial/fungal dx

Non-parathyroid endocrine dx
 HyperT4, pheo, adrenal insufficiency

Medications
 Milk-alkali syndrome, vit A/D toxicity,
 Familial benign hypocalciuric
hypercalcemia
 Chronic renal failure (3°
hyperparathryoidism)
thiazides, lithium

Immobilization
Indications for treatment
 No treatment:
 Asymptomatic or mildly symptomatic (ex. constipation)
with acute calcium levels <3.0mmol/L
 Asymptomatic with chronic calcium levels 3.0 to
3.5mmol/L
 Treatment:
 Symptomatic patients
 Acute rise in calcium levels
 Calcium levels >3.5mmol/L
4 Main Treatment Strategies for
Hypercalcemia
Blood
1
2
4
3
Intestines
1. DeliveryTreatment
of calcium
to kidneys
strategies involve
the following:
1. Increase delivery of calcium to the kidney, thus increasing calcium excretion
2.  Calcium Isotonic
reabsorption
from kidneys (therefore  excretion)
saline increases the glomerular filtration rate, and thus the delivery of
calcium to the kidney. It should be used as first-line treatment of
hypercalcemia, since high calcium levels induce urinary salt wasting and
volume depletion.
3. Bone resorption
2. Decrease calcium reabsorption, thus increasing calcium excretion
4. Calcium absorption
from intestines
Recall that calcium is reabsorbed passively in the proximal tubule and
ascending limb of the loop of Henle (affected by electrochemical gradients
created by sodium and chloride absorption) and actively in the distal tubule.
Both isotonic saline and a loop diuretic will reduce sodium and chloride
Hypercalcemia Treatment in the Kidney
1.
Increasing calcium delivery
to kidney

2.
Isotonic saline – increases
GFR (ie. Ca delivery to
kidney). 1st line tx for
hypercalcemia
Decreasing calcium
reabsorption in kidneys

Loop diuretics – Decrease
Na & Cl reabsorption,
which decreases passive
calcium reabsorption
Remember that calcium is re-absorbed passively in the ascending
limb of the loop of Henle (via electrochemical gradients created by
NaCl absoprtion)
Hypercalcemia Treatment in the Bones
 Very effective strategy at treating hypercalcemia
 Agents that are effective in decreasing bone resorption:
 Calcitonin
 Bisphosphonates (ex. pamidronate)
Hypercalcemia Treatment in the
Intestines
Decreasing calcium absorption:
 Only effective in the treatment of hypercalcemia secondary to
granulomatous diseases and occasionally in lymphomas (where
there is increased calcitriol production that enhances intestinal
calcium absorption).
Treatments:
 Glucocorticoids – Decrease calcitriol production by activating
mononuclear cells in the lungs/lymph nodes.
 Low calcium diet
Other treatments of hypercalcemia
Dialysis
 With little or no calcium in dialysate
 Reserved for severe, symptomatic hypercalcemia (4.55mmol/L) with neurologic symptoms and severe renal
failure (CrCl <10-20ml/min).
 Can also be considered severe hypercalcemia and heart
failure, in which can not safely give IV fluids.
Target the underlying cause…
 Treat the underlying malignancy, sarcoid, stop offending
drug etc.
How effective are these
treatments?
 Intravenous fluids
 First line treatment
 Lowers calcium within hours
 Rarely lowers calcium levels in patients with > mild
hypercalcemia
 Lasix
 No randomized controlled trials to assess efficacy. Use
based on old case reports/series prior to the use of
bisphosphonates.
 Not recommended as first line therapy unless patient has
or is at risk of fluid overload with hydration.
How effective are these
treatments?
 Calcitonin
 Weak antiresorptive
 Works rapidly: reduces calcium levels by 0.5 mmol/L within 4 to
6 hours.
 Limited to use within the first 2 days because of risk of
tachyphylaxis
 Bisphosphonates
 More potent than calcitonin
 Normalizes calcium in >70% of patients with hypercalcemia of
malignancy
 Maximum effect in 2-4 days
 Particularly useful in reducing bone pain & pathological
fractures if administered regularly in patients with skeletal
metastases or multiple myeloma.
How effective are these
treatments?
 Bisphosphonates (cont’d)
 Zolendronic acid slightly more effective than pamidronate
but may have more renal toxicity.
 Pamidronate: maintains normocalcemia for 2 to 3 weeks
(up to 4 weeks)
 Zoledronic acid: lasts for ~ 4 weeks.
 Glucocorticoids (Prednisone 20-40mg/day)
 Decreases calcium levels within 2-5 days.
TO RECAP: Initial treatment of
severe hypercalcemia
 IV hydration with isotonic saline
 Works immediately
 Rate of 200 too 300 cc/hr (less in elderly patients)
 Target UOP 100 to 150 cc/hr
 Salmon calcitonin
 Maximal activity in 4 to 6 hrs
 Bisphosphonate
 Maximal activity 2 to 4 days
Preventing recurrence of
hypercalcemia
 Mainstay or therapy is treat underlying cause (ex.
malignancy)
 If no response to tumor therapy:
 Infuse bisphosphonates every 2 to 4 weeks to maintain
normocalcemia and prevent skeletal complications.