work-up and management of hypercalcemia in hospitalized patients jessica thom pgy-3
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Work-up and Management of Hypercalcemia in Hospitalized Patients
Jessica ThomPGY-3
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Let’s start with a caseMrs. 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.
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Symptoms of hypercalcemiaCognitive dysfunction
Confusion, lethargy, coma (in severe cases)
GI disturbancesConstipation, nausea, anorexia
Renal dysfunctionPolyuria, acute/chronic renal failure, nephrolithiasis
Musculoskeletal symptomsMuscle weakness, bone pain
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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?
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Start with PTHPTH-dependent causes
(mid-high normal/elevated levels)
Primary hyperparathyroidism
Familial benign hypocalciuric hypercalcemia
Chronic renal failure (3° hyperparathryoidism)
PTH independent causes(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, thiazides, lithium
Immobilization
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Indications for treatmentNo 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 patientsAcute rise in calcium levelsCalcium levels >3.5mmol/L
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4 Main Treatment Strategies for Hypercalcemia
1. Delivery of calcium to kidneys
2. Calcium reabsorption from kidneys (therefore excretion)
3. Bone resorption
4. Calcium absorption from intestines
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1. Increasing calcium delivery to kidney
Isotonic saline – increases GFR (ie. Ca delivery to kidney). 1st line tx for hypercalcemia
2. Decreasing calcium reabsorption in kidneys
Loop diuretics – Decrease Na & Cl reabsorption, which decreases passive calcium reabsorption
Hypercalcemia Treatment in the Kidney
Remember that calcium is re-absorbed passively in the ascending limb of the loop of Henle (via electrochemical
gradients created by NaCl absoprtion)
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Hypercalcemia Treatment in the Bones
Very effective strategy at treating hypercalcemia
Agents that are effective in decreasing bone resorption:CalcitoninBisphosphonates (ex. pamidronate)
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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
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Other treatments of hypercalcemia
DialysisWith little or no calcium in dialysateReserved for severe, symptomatic hypercalcemia
(4.5-5mmol/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.
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How effective are these treatments?
Intravenous fluidsFirst line treatmentLowers calcium within hoursRarely lowers calcium levels in patients with >
mild hypercalcemia
LasixNo 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.
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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.
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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.
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TO RECAP: Initial treatment of severe hypercalcemia
IV hydration with isotonic salineWorks immediatelyRate of 200 too 300 cc/hr (less in elderly patients)Target UOP 100 to 150 cc/hr
Salmon calcitoninMaximal activity in 4 to 6 hrs
BisphosphonateMaximal activity 2 to 4 days
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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.