Overview
Hypercalcemia is defined when total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). The normal serum calcium ranges from 8.5 to 10.5 mg/dl (2.2 to 2.7 mmol/L). Normal values and reference ranges may vary among laboratories as much as 0.5 mg/dl.
The main causes of hypercalcemia include hyperparathyroidism, cancer, and vitamin D toxicity.
It can present with symptoms of polyuria (excessive urination), constipation, muscle weakness, and confusion. More seriously, it can lead to coma.
Hypercalcemia is diagnosed by measuring the concentration of serum-ionized calcium and parathyroid hormone.
Treatment aims to increase the excretion of calcium through urine and reduce bone resorption of calcium.
Calcium plays a vital role in nerve transmission, hormone activity, heart function, and blood coagulation.
It is mostly present in the bones as calcium phosphate while a small amount is found in the cells and extracellular fluids.
In the serum, about 45% of calcium is bound to proteins (mostly albumin), 45% exists as free or ionized calcium, while 10% is bound to anions.
Causes
Primary hyperparathyroidism and malignancy account for 90% of hypercalcemia cases.
High parathyroid hormone (PTH) level due to hyperparathyroidism is the most common cause of hypercalcemia and usually, this type is mild, asymptomatic, and persists for years.
On the other hand, hypercalcemia caused by malignancy progresses rapidly. Therefore, rapidly rising calcium levels could indicate malignancy.
The remaining 10% of cases of hypercalcemia are caused by many different conditions.
1. Cancer. The following are the cancers most commonly associated with hypercalcemia.
- Lung cancer
- Breast cancer
- Blood cancer
- Myeloma
2. High PTH levels are caused by
- Primary hyperparathyroidism
- Hereditary-related high PTH levels
- Neonatal hyperparathyroidism
- Kidney transplant
3. Causes related to vitamin D include the following:
- Vitamin D toxicity
- Sarcoidosis
4. Causes related to increased bone turnover include the following:
- Hyperthyroidism
- Prolonged immobilization
- Prolonged use of thiazide diuretic
- Kidney failure
5. Other causes related to particular mechanisms are as follows:
- Increased intestinal calcium absorption
- Decreased renal calcium excretion
- Familial hypercalcemia
- Increased bone resorption
- Dietary phosphate deficiency
- Tuberculosis
Symptoms
The symptoms of hypercalcemia vary with how fast and how far the calcium level has risen and how the patient’s body has responded to these changes.
Mild prolonged hypercalcemia may produce mild or no symptoms. Severe hypercalcemia with sudden onset may cause dramatic symptoms and lead to death.
Central nervous system symptoms include:
- Exhaustion
- Weakness
- Confusion
- Untreated patients with severe hypercalcemia may come in a comatose state
Renal symptoms include the following:
- Polyuria
- Renal stones
- Increased frequency of urination at night
- Dehydration symptoms
Gastrointestinal symptoms include the following:
- Constipation
- Nausea
- Gastric ulcer
Complications
Complications can include:
- Depression
- Kidney stones
- Osteoporosis
- Pancreatitis
- Renal failure
- Gastric ulcers
- Paresthesias
- Syncope
- Arrhythmias
Diagnosis
Hypercalcemia can be classified as:
- Mild hypercalcemia: 10.5 to 11.9 mg/dL
- Moderate hypercalcemia: 12.0 to 13.9 mg/dL
- Hypercalecemic crisis: 14.0 to 16.0 mg/dL
Most cases of hypercalcemia are detected on routine testing.
Diagnostic blood tests for hypercalcemia include testing for levels of the following:
- Sensitive and specific assays should be used to measure parathyroid hormone – will be high
- Calcitonin
- Vitamin D will be high
- Ionized calcium will be high
- Phosphorus will be low
- Magnesium will be high
- Alkaline phosphatase levels will be high
- Renal functions and urinary calcium-creatinine ratio- will be low
Imaging tests
Imaging studies are done to rule out sarcoidosis or lung cancer.
- A mammogram is used to rule out breast cancer
- CT scan is done to rule out renal cancer.
- Ultrasound and MRI are done to investigate the parathyroid glands.
ECG in hypercalcemia will show:
- T wave flattening or inversion
- Mild prolongation of the QRS and PR intervals
- ST-elevation
- Presence of the J wave at the end of the QRS complex
Treatment
If your hypercalcemia is mild, your doctor might choose to watch and wait. At the same time, he will monitor your bones and kidneys.
For severe cases, your doctor will recommend medications for hypercalcemia and to treat the underlying cause.
Medications
In some cases, your doctor might recommend:
- Calcitonin (Miacalcin). Calcitonin controls the calcium levels in the blood.
- Calcimimetics. This helps to control overactive parathyroid glands.
- Cinacalcet (Sensipar) helps manage calcium levels.
- Bisphosphonates. These are intravenous osteoporosis drugs, which quickly lower calcium levels, and indicated more in cases due to cancer.
- Denosumab (Prolia, Xgeva). This drug is often used to treat cancer–related cases that does not respond well to bisphosphonates.
- Prednisone. Short-term use of steroids, such as prednisone is helpful if your hypercalcemia is caused by high levels of vitamin D.
- IV fluids and diuretics. Medical emergency caused by very high calcium levels needs hospitalization and treatment with IV fluids and diuretics to promptly lower the calcium level and to prevent heart rhythm complications and damage to the nervous system.
Surgical and other procedures
If the hypercalcemia is due to overactive parathyroid glands, a special scan is done in which an injection of a small dose of radioactive material helps to pinpoint the gland or glands that aren’t functioning properly.
This can often be cured by surgery to remove the tissue that’s causing the problem.In most cases, only one of a person’s four parathyroid glands is affected, which is then removed.
Outcome
- The outcome depends on whether the cause of hypercalcemia can be treated.
- Hypercalcemia due to hyperparathyroidism tends to be mild but stays prolonged.
- Osteoporosis due to high calcium levels causes the highest morbidity.
- Hypercalcemia due to cancer carries a serious prognosis. Such patients need to be treated aggressively and frequently hospitalized due to severe morbidity and a very poor quality of life.
