TOC  |  Lytes  

Hypercalcemia               SX  |  Diff-DX  |  RX  

* Hospitalize patients with any degree of hyercalcemia and polyuria, polydipsia, dehydration, altered mental status, and all patients with serum levels greater than 13.0 mg/dL, regardless of clinical presentation.

EKG :decreased ST segment & QT interval, wide T waves ("wide QT interval"), 1st AV block, bradycardia.
GI : N/V, constipation, anorexia
Renal: polyuria, polydipsia
CNS :apathy, drowsiness, cognitive difficulty, stupor/coma.

Diff. Dx:
A. Primary hyperparathyroidism:  Sporadic or Clinical variants & familial syndromes

B. Neoplastic diseases:      1. Local osteolysis    2. Humoral hypercalcemia of malignancy    3. Other factors: prostaglandins, vit. D like sterols

C. Endocrinopathies:   Thyrotoxicosis, Adrenal insufficiency, Pheochromocytoma

D. Medications:  Thiazide diuretics, Vit. D & A, Milk alkali syndrome, Lithium

E. Sarcoidosis & other granulomatous diseases

F. Miscellaneous conditions
     1. Immobilization
     2. Acute renal failure
     3. Idiopathic hypercalcemia of infancy; Familial hypocalciuric hypercalcemia


Differential Diagnosis of Hypercalcemia    (REF:  ACP - PIER 2002)          

Primary hyperparathyroidism
Most often seen as an incidental finding in the absence of obvious symptoms. Prevalence of symptoms depends on the intensity by which they are sought, particularly vague symptoms of being unwell. Infrequently shows as acute symptomatic hypercalcemia Calcium elevated.

Humoral hypercalcemia of malignancy
The most common cause of hypercalcemia in patients with cancer, even in those with skeletal metastases Calcium is elevated.

Metastatic bone disease
True prevalence uncertain. Hypercalciuria without hypercalcemia is much more prevalent but infrequently evaluated or monitored Calcium is elevated.

Multiple myeloma
The most common cause of hypercalcemia in patients with hypercalcemia, decreased GFR, and anemia. Alkaline phosphatase is generally normal because there is only a limited osteoblastic response to myelomatous infiltrate in the marrow Calcium is elevated.

Granulomatous disease (sarcoidosis and tuberculosis are the most frequently considered but hypercalcemia has been reported to complicate granulomatous disease from all etiologies)
Prevalence varies from region to region around the world. Felt by some to be related to vitamin nutritional status with hypercalcemia being more prevalent in countries with higher amounts of annual sunlight Calcium elevated.

Milk-alkali syndrome
Allegedly becoming more prevalent with increased use of calcium supplements. Should be considered in seemingly healthy people in whom primary hyperparathyroidism has been excluded Calcium elevated.

Benign familial hypocalciuric hypercalcemia
Constitutive overexpression of the calcium sensing receptor gene. Homozygote has fatal neonatal primary hyperparathyroidism. Heterozygote has benign familial hypocalciuric hypercalciuria Calcium elevated.

Diuretic phase of acute renal failure
Most often seen when acute renal failure resulted from rhabdomyolysis. Felt to be mobilization of extra-cellular calcium-phosphate deposits released into the circulation during acute phase of rhabdomyolysis Calcium elevated.

Prevalence uncertain.  Generally only occurs in persons with high bone turnover before immobilizing event (growing children, untreated primary hyperparathyroidism, hyperthyroidism, Paget's disease of bone) Calcium elevated.

A frequent, but usually incidental finding in hyperthyroidism. Results from direct action of thyroxine or tri-iodothyronine to stimulate osteoclasts. In those rare patients where the hypercalcemia is severe, usual symptoms and signs of hyperthyroidism are masked Calcium elevated.

Addison's disease
A rare cause of hypercalcemia. Mechanism unclear Calcium elevated.


Causes of Hypercalcemia, by age:   

From birth to age 20 years:

From older adolescence to age 40 years 

From age 40 years and older 

Therapy for Hypercalcemia                      (Ref: NEJM 1992/4/30;325:1196)  

Consider the need for treatment of dehydration and altering of exogenous calcium intake in patients with hypercalcemia, depending on the underlying etiology.

Acute Rx of Hypercalcemia : Drug Therapy of Hypercalcemia
Consider drug therapy, in addition to rehydration, to lower serum calcium in patients with hypercalcemia.

1. IV Hydration 2 - 4 liters of normal saline accordingly.
    Furosemide (Lasix) 20-100 mg IV or PO as needed to prevent fluid overload of IV hydration.
Normal saline - Promotes calcium diuresis - 200 mg/h, IV, per hour
Benefits: Corrects dehydration. Lowers serum calcium rapidly (hour) but incompletely
Side effects: May promote fluid overload, particularly in the elderly with preexistent cardiac dysfunction
NOTE: Fluid status should be carefully monitored preferably in an ICU. Serum calcium should be monitored every 6 hours during therapy for acute hypercalcemia. Furosemide therapy should only be used to correct fluid overload, not to prevent it. Such therapy may contribute to negative sodium balance that would hinder a calcium diuresis. Furosemide is not therapy for hypercalcemia per se.

2. Specific Rx of Hypercalcemia:

4. Phosphate as IV Na phosphate can lower Calcium rapidly & profoundly.
This Rx is very dangerous because of the risk that cal phosphate complexes
will be deposited in blood vessels, lungs, & kidneys.

5. Dialysis for severe or symptomatic hypercalcemia !

Mild, chronic hypercalcemia  11 to 12 mg/dL (2.8 to 3 mmol/L)
— In general, patients with even mild, asymptomatic hypercalcemia who have serum calcium concentrations in the range of 11 to 12 mg/dL (2.8 to 3 mmol/L) should be treated when there is associated hypercalciuria because of the risk of nephrolithiasis and nephrocalcinosis. The most effective therapy depends mostly upon the cause of the hypercalcemia:

More severe or symptomatic hypercalcemia  >12 mg/dL (3 mmol/L)
— Acute therapy consists of a three-pronged approach:

The calcitonin plus saline-furosemide regimen should result substantial reduction in serum calcium concentrations within 12 to 48 hours, whatever the cause of the hypercalcemia.

The bisphosphonate will be effective by the second to fourth day, thereby maintaining control of the hypercalcemia. Follow-up therapy is aimed at preventing recurrence of hypercalcemia.

Tumors may respond to chemotherapy or radiation therapy leading to resolution of the hypercalcemia. In patients whose primary disease cannot be cured, oral etidronate, oral phosphates, low-dose glucocorticoids and aggressive oral hydration may be tried. These therapies are rarely effective for very long. In these situations, hypercalcemia can be prevented with infusions of pamidronate at two to three week intervals, administered on an outpatient basis.

Severe hypercalcemia   18 to 20 mg/dL (4.5 to 5 mmol/L)
— Additional, more aggressive measures are necessary in the rare patient with severe, symptomatic hypercalcemia.
should be considered, in addition to the above treatments, in patients who have serum calcium concentrations in the range of 18 to 20 mg/dL (4.5 to 5 mmol/L) and neurologic symptoms but a stable circulation.

REF: Uptodate Medicine 08-2001


Laboratory and Other Studies for Hypercalcemia   (REF:  ACP - PIER 2002)