Hypercalcemia (High Blood Calcium Levels)

What is hypercalcemia?

Hypercalcemia is the medical term for elevated calcium levels in the blood. Most patients with moderately elevated blood calcium levels are asymptomatic (without symptoms) and hypercalcemia is often detected upon routine blood tests. It can however lead to acute emergencies, often associated with dehydration.

Calcium is an essential mineral for many functions in the body including muscle contraction, blood clotting and nerve impulses. It is transported in the blood either bound to blood proteins like albumin, to other chemicals (anions) like phosphate and citrate or in the most abundant ionized form . The latter is the active form in which it is utilized and can cross the blood capillary membrane.

Meaning of Hypercalcemia

The blood calcium levels are controlled by a number of factors, primarily regulated by the parathyroid hormone. Calcium is absorbed from food and supplements in the small intestine and excess or unused calcium is excreted via the kidneys. Large quantities of calcium are utilized in the formation of bone and can therefore store calcium to some extent. Most of the calcium in the body is found in the bone with smaller quantities in the cells (about 1%) and extracellular fluid (approximately 0.1%).

When there is a disturbance in the regulation of calcium in the body, either due to abnormalities with parathyroid hormone (parathyroid mediated hypercalcemia) or independent of parathyroid hormone (non-parathyroid mediated hypercalcemia), then the levels of calcium in the blood may increases substantially. The kidney may attempt to excrete the excess calcium but if overwhelmed, the blood levels remain elevated for varying periods of time.

Signs and Symptoms of Hypercalcemia

Depending on the severity, excess calcium in the blood may result in the signs and symptoms associated with hypercalcemia or even the underlying disease causing hypercalcemia. Moderate elevations of blood calcium levels may remain asymptomatic in most patients, especially in parathyroid mediated hypercalcemia, although elderly patients may experience a number of symptoms with even a slight elevation.

Some of the signs and symptoms associated with hypercalcemia includes :

• Polyuria – large volumes of urine often characterized by frequent urination
• Polydipsia – excessive thirst
• Nausea – patients may also report dyspepsia (indigestion) and a history of peptic ulcers
• Vomiting
• Renal colic – kidney pain (abdominal/flank pain) often associated with kidney stones
• Constipation
• Drowsiness and/or confusion
• Lethargy
• Depression
• Muscle aches and joint pains
• Headaches

Types of Hypercalcemia

Hypercalcemia is the elevated levels of calcium in the blood. Normal calcium levels in the blood vary between 8.5 mg/dL and 10.2 mg/dL. In hypercalcemia, the levels may be in excess of 14 mg/dL. Calcium levels are regulated primarily by parathyroid hormone (PTH) secreted by the parathyroid gland but also by vitamin D and its derivatives.  Hypercalcemia can be a result of disruption of the calcium regulation mechanism involving the parathyroid hormone or disturbance affecting calcium absorption, excretion and storage of calcium independent of parathyroid hormone.

Hypercalcemia can be classified as :

• Parathyroid mediated hypercalcemia where the increase in blood calcium levels are due to elevated parathyroid hormone.
• Non-parathyroid mediated hypercalcemia where the increase in blood calcium levels is not due to raised levels of parathyroid hormone.

Causes of Hypercalcemia

Parathyroid Mediated Hypercalcemia

The main cause is hyperparathyroidism which is an overactivity of the parathyroid gland leading to elevated levels of parathyroid hormone. Hypercalcemia may be seen with primary, tertiary, drug-induced and familial hyperparathyroidism.

Primary hyperparathyroidism is by far the most common cause of parathyroid mediated hypercalcemia and most cases are due to an adenoma, which is a benign mass on the parathyroid gland.

Non Parathyroid Mediated Hypercalcemia

Malignancy (cancer) is the most common cause of non-parathyroid mediated hypercalcemia. This includes malignant tumors of the breast, lung, kidney, ovary, colon, thyroid gland as well as lymphoma and multiple myeloma. This may be due to destruction of the bone neighboring the tumor or metastasis thereby releasing large quantities of calcium into the blood stream. Another mechanism related to malignancy causes bone resorption and reduced excretion of calcium due to the production and action of a PTH-like protein.

Other causes of hypercalcemia include :

• Thyrotoxicosis (hyperthyroidism – overactive thyroid gland)
• Excessive vitamin D and vitamin A supplementation
• Elevated calcitriol levels due to diseases like HIV, sarcoidosis and other granulomatous diseases.
• Drugs like thiazide diuretics, antacids containing calcium carbonate, milk-alkali syndrome and theophylline.
• Deficiency of glucorticoid (adrenal insufficiency)
• Immobilized especially in patients with Paget’s disease