What is Hypercalcemia?
Hypercalcemia is an elevated calcium (Ca2+) level in the blood (Normal range: 8.5–10.0 mg/dL). It can be due to excessive skeletal calcium release, increased intestinal calcium absorption, or decreased renal calcium excretion. It is an asymptomatic laboratory finding most of the time, but because an elevated calcium level is often indicative of other diseases, a workup should be undertaken if it persists. Most cases are picked up on routine labs and are asymptomatic. When symptomatic the most common symptoms include stones (kidney or biliary), bone pain, abdominal pain, nausea, vomiting, increased urination, depression (30-40%), anxiety, cognitive dysfunction, insomnia, coma and cardiac arrest in severe cases. Severe hypercalcemia can lead to EKG changes that mimic a myocardial infarction and can cause peptic ulcers.
What are the causes of Hypercalcemia?
Primary hyperparathyroidism (see separate section) and malignancy account for 90% of cases of hypercalcemia with primary hyperparathyroidism being the most common cause in the outpatient setting and malignancy being the most common cause when discovered in a hospitalized setting.
Abnormal parathyroid gland function
▪ Primary hyperparathyroidism (see separate section)
▪ Lithium use
▪ Familial hypocalciuric hypercalcemia (FHH)/ familial benign hypercalcemia
▪ solid tumors with metastasis (e.g. breast cancer or squamous cell carcinoma)
▪ solid tumors with humoral mediation of hypercalcemia (e.g. lung cancer, kidney cancer, pheochromocytoma)
▪ hematologic malignancy (multiple myeloma, lymphoma, leukemia)
Vitamin-D metabolic disorders
▪ hypervitaminosis D (vitamin D intoxication)
▪ elevated 1,25(OH)2D levels (e.g. sarcoidosis and other granulomatous diseases)
Disorders related to high bone-turnover rates
▪ hyperthyroidism (see separate section)
▪ prolonged immobilization
▪ thiazide diuretic use
▪ vitamin A intoxication
▪ severe secondary hyperparathyroidism
▪ aluminium intoxication
▪ milk-alkali syndrome
How is Hypercalcemia treated?
The key is to address the underlying etiology. For the most severe and acute cases the following is the treatment of choice. Most cases of hypercalcemia discovered in the outpatient setting will not require such aggressive intervention.
Initial therapy: fluids and diuretics
- hydration, increasing salt intake, and forced diuresis.
- hydration is needed because many patients are dehydrated due to vomiting or renal defects in concentrating urine.
- increased salt intake also can increase body fluid volume as well as increasing urine sodium excretion, which further increases urinary calcium excretion (In other words, calcium and sodium (salt) are handled in a similar way by the kidney. Anything that causes increased sodium (salt) excretion by the kidney will, en passant, cause increased calcium excretion by the kidney)
- after rehydration, a diuretic such as furosemide (lasix) can be given to permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and pulmonary edema. In addition, diuretics tend to depress renal calcium reabsorption thereby helping to lower blood calcium levels
- can usually decrease serum calcium by 1–3 mg/dL within 24 h
- caution must be taken to prevent potassium or magnesium depletion
Additional therapy: bisphosphonates and calcitonin
- biphosphonates are used to treat osteoporosis with high affinity for bone, especially areas of high bone-turnover.
- they are taken up by osteoclasts (cells involved in remodeling of bones) and inhibit osteoclastic bone resorption
- all patients with cancer-associated hypercalcemia should receive treatment with biphosphonates since the ‘first line’ therapy (above) cannot be continued indefinitely nor is it without risk. Further, even if the ‘first line’ therapy has been effective, it is a virtual certainty that the hypercalcemia will recur in the patient with hypercalcemia of malignancy. Use of bisphosphonates in such circumstances, then, becomes both therapeutic and preventative
- patients in renal failure and hypercalcemia should have a risk-benefit analysis before being given biphosphonates, since they are relatively contraindicated in renal failure.
- Calcitonin blocks bone resorption and also increases urinary calcium excretion by inhibiting renal calcium reabsorption
- Usually used in life-threatening hypercalcemia along with rehydration, diuresis, and bisphosphonates
- Helps prevent recurrence of hypercalcaemia
- rarely used, or used in special circumstances
- plicamycin inhibits bone resorption (rarely used)
- gallium nitrate inhibits bone resorption and changes structure of bone crystals (rarely used)
- dialysis usually used in severe hypercalcemia complicated by renal failure. Supplemental phosphate should be monitored and added if necessary
- glucocorticoids increase urinary calcium excretion and decrease intestinal calcium absorption
- no effect on calcium level in normal or primary hyperparathyroidism
- effective in hypercalcemia due to osteolytic malignancies (multiple myeloma, leukemia, Hodgkin’s lymphoma, breast cancer) due to antitumor properties
- also effective in hypervitaminosis D and sarcoidosis