A patient with a malignancy may present with cancer-associated hypercalcemia late in the course of the disease,


Malignant tumors most often associated with hypercalcemia:

(1) multiple myeloma

(2) breast carcinoma

(3) non-oat cell lung carcinoma

(4) T-cell lymphoma or leukemia

(5) ovarian carcinoma

(6) renal cell carcinoma

(7) transitional cell carcinoma

(8) squamous cell carcinoma of the head and neck, esophagus, cervix or other sites


Some of these tumors are associated with extensive bony metastases; patients with prostate cancer may have extensive bone metastases without hypercalcemia. Some tumors may have hypercalcemia without marked bone involvement.


Common symptoms at presentation:

(1) pain

(2) fatigue

(3) constipation

(4) lethargy, confusion or coma

(5) diminished appetite

(6) nausea

(7) polyuria with urinary frequency

(8) dehydration and thirst


The level of symptomatology is affected by how fast the hypercalcemia develops. A patient with a rapid rise in calcium levels may be symptomatic at a relatively mild elevation of the serum calcium, while a patient with a slow and gradual increase may be symptomatic at a much higher level.


Laboratory testing:

(1) The hypercalcemia in many patients with carcinoma is caused by parathyroid hormone-related protein (PTHrP).

(2) 1,25(OH)2 vitamin D may be elevated in patients with T cell lymphoma or leukemia.

(3) In patients with multiple myeloma, paraproteins may bind calcium, resulting in a high serum total calcium but a lack of symptoms. The ionized (free) calcium can help determine if the patient has functional hypercalcemia.


If hypoalbuminemia is present, then the reported total calcium may be falsely low. This is adjusted (see above) as:


approximate total serum calcium with normal albumin, in mg/dL =

= (current total serum calcium in mg/dL) + (0.8 * (4 - (current serum albumin in g/dL)))


The differential diagnosis includes primary hyperparathyroidism. In cancer-associated hypercalcemia the serum immunoreactive parathyroid hormone is low or normal. A small number of patients may have both cancer-associated hypercalcemia and primary hyperparathyroidism; these patients will elevations of PTH and PTHrP..


Although treatment of the underlying tumor is one way to control the hypercalcemia, many patients with cancer-associated hypercalcemia have advanced tumors with poor response to further therapy.


The prognosis in patients with cancer-associated hypercalcemia is generally poor, with a life expectancy of 1-3 months despite optimum therapy.


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