Hypercalcemia

Overview: What is hypercalcemia?

Hypercalcemia means that a person has too much of the mineral calcium in the blood. Examples include malignant tumors (cancer), increased release of parathyroid hormone (involved in calcium metabolism) from the parathyroid gland (hyperparathyroidism), or certain medications.

We can detect hypercalcemia by blood test. A slightly elevated calcium level usually does not yet cause any symptoms and is usually not dangerous to health. The situation is different for more elevated calcium levels, which can upset various metabolic processes. Symptoms can be seen in various organs: the gastrointestinal tract, heart, nervous system, muscles and kidneys. Extremely high blood calcium levels can even be life-threatening. This hypercalcemic crisis is an emergency in which we must act immediately. The aim is to lower the amount of calcium in the blood as quickly as possible.

Treatment depends on the cause and the level of calcium in the blood. The first thing we always do is treat the underlying disease that leads to the high calcium level, for example, cancer.

Hypercalcemia – frequency and age

Hypercalcemia is relatively common in the physician’s office, hospital, and emergency department. The three most common causes of upward calcium derailment are cancer, hyperparathyroidism, or vitamin D over-supplementation. Together, they account for about 90 percent of all cases of hypercalcemia. In principle, elevated calcium levels can occur in the context of all types of cancer, but we particularly often find the disorder in patients with lung and breast cancer, as well as disease of the blood cells.

An exact age cannot be determined for hypercalcemia. Elevated calcium levels can occur in principle at any age – from children to senior citizens.

Hypercalcemia: causes and risk factors

The causes of hypercalcemia can be very diverse. There are usually other underlying conditions that cause blood calcium levels to spike. The two main causes are:

• Malignant tumors – hypercalcemia can be concomitant with all types of cancer. In most cases, the cancer is already more advanced by then. Bone metastases in lung or breast cancer but also renal cell cancer are typical. The bone is broken down by the bone metastases and releases calcium. But blood calcium levels can also increase in blood cell disease, head and neck tumors, multiple myeloma – a cancer of the blood cells, or cancer of the genitourinary tract.
• Hyperparathyroidism – an overactive parathyroid gland. In the process, it releases more of the so-called parathormone, which is crucially involved in calcium metabolism. The parathormone increases the calcium level in the blood via various processes and simultaneously lowers the phosphate levels.
• Over-supplementation of vitamin D – taking too much vitamin D also often leads to hypercalcemia.

In addition, hypercalcemia may have other causes, but these are less common. Examples are:

• Overactive thyroid (hyperthyroidism)
• Tuberculosis
• Familial hypocalciuric hypercalcemia – a congenital disorder resulting in mild hypercalcemia.
• Sarcoidosis – an inflammatory disease of the connective tissue that often affects the lungs.
• Addison’s disease – a rare disease of the adrenal cortex in which it loses its function
• Medications, such as lithium (for mental illness), thiazide diuretics (diuretic, draining agents), or tamoxifen (for hormone-sensitive breast cancer).
• Immobilization, in children and adults who physiologically have a high bone turnover, after long periods of bed rest (e.g., paraplegia, back surgery), there may be an imbalance between new bone formation and resorption, resulting in hypercalcemia.

Symptoms: Hypercalcemia affects multiple organs

The symptoms of hypercalcemia depend on how much the calcium levels in the blood are elevated. In addition, whether calcium levels rise rapidly or slowly over several weeks plays a role in the severity of symptoms. Age or the use of medication (for example, tranquilizers, neuroleptics) are also thought to influence the type and intensity of symptoms. Often the complaints are very unspecific and are not always easy to classify, for example in the case of advanced cancer.

Hypercalcemia – at what levels?

• In an adult person, normal calcium values range from 2.09 – 2.54 mmol/l. A slightly elevated calcium level usually does not yet cause any symptoms.
• Calcium levels of more than 2.7 mmol/l (millimoles per liter of blood) are usually the first signs.
• If the values rise to 3 mmol/l and above, severe symptoms occur. We refer to a hypercalcemic crisis at a level of 3.5 mmol/l, which is an emergency and requires immediate treatment. The condition is life-threatening.

Hypercalcemia – symptoms at a glance

The symptoms of hypercalcemia can be seen in several organs: the digestive tract, heart, nervous system, muscles, and kidneys. The following symptoms may indicate elevated calcium levels:

• gastrointestinal tract: loss of appetite, nausea, vomiting, constipation, abdominal pain, pancreatitis, peptic ulcer
• Kidneys: great thirst, frequent urination, nocturnal urination, dehydration, kidney stones.
• Heart: cardiac arrhythmias, hypertension, changes in electrocardiogram (ECG).
• Nervous system and musculature: fatigue, lassitude, lack of strength, decreased performance, muscle weakness, decreased reflexes, impaired concentration, depression, confusion, disorientation, behavioral disturbances, clouding of consciousness, coma.

Hypercalcemia: diagnosis by us

The diagnosis of hypercalcemia always begins with a discussion between the physician and the person concerned about the patient’s medical history (anamnesis). For example, the following questions are important:

• What exactly are your symptoms?
• When did they first appear?
• How intense are the complaints?
• Did the symptoms develop rapidly or slowly over time?
• Do you have any known underlying diseases? For example, cancer disease, hyperparathyroidism, hyperthyroidism?
• Are you taking any medications? If yes: Which ones and since when? For example, lithium, vitamin D, thiazides?

This is followed by a physical examination, during which we listen to the heart and lungs with a stethoscope, for example, and palpate the body and test certain bodily functions, such as reflexes.

A blood test will show the levels of total and free active calcium in the blood. Laboratory physicians analyze a blood sample for this purpose. The following values apply (“Ca” is the chemical abbreviation for calcium = calcium):

• Hypercalcemia: Ca ≥ 2.6 mmol/l
• Mild to moderate hypercalcemia: Ca ≥ 2.6 – 3.4 mmol/l
• Severe hypercalcemia: Ca ≥ 3.5 mmol/l

Usually we additionally determine the blood values for:

• Phosphate
• Albumin
• Creatinine
• Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP).
• Vitamin D

An electrocardiogram (ECG) allows conclusions to be drawn about cardiac function. In the ECG, for example, we can detect cardiac arrhythmias based on the altered spikes and curves.

In some cases, imaging techniques are used to detect changes in the bones. Examples are:

• X-ray examination
• Computed tomography (CT) – an X-ray examination that provides cross-sectional images of the body.
• Magnetic resonance imaging (MRI = magnetic resonance imaging): It works with strong magnetic fields and records the body “slice by slice”. This also provides the radiologist with detailed cross-sectional images.
• SPECT/CT: This scintigraphic method can be used to detect parathyroid adenomas in hyperparathyroidism.
• Choline PET/MR or PET/CT: This highly sensitive hybrid technique is used to detect very small (and previously undetected) parathyroid adenomas in hyperparathyroidism.

Hypercalcemia: prevention, early detection, prognosis

There are no known specific measures you can take to prevent hypercalcemia. However, you should always ensure an adequate supply of calcium, because there is also the opposite: hypocalcemia, an undersupply of calcium. So it’s a matter of finding the right balance. and be careful not to take vitamin D supplements without a medical prescription and supervision. If you are unsure, seek advice from a nutritionist (oecotrophology).

The most common causes of hypercalcemia are cancer and hyperparathyroidism – an overactive parathyroid gland. If they are taking vitamin D and calcium supplements, they should have their calcium levels checked regularly by a health care professional.

There are also no special measures for early detection of hypercalcemia. The determination of calcium levels in blood serum is not a routine examination in healthy people. However, in affected individuals with an existing disease, we usually determine the values alongside other blood values. Be sure to come to us if you experience symptoms such as fatigue, loss of appetite, nausea, vomiting, constipation or abdominal pain.

Course and prognosis in hypercalcemia

The course and prognosis for hypercalcemia depend on the severity and cause of the calcium levels. Usually, the prognosis is favorable if we quickly lower the calcium level sufficiently. It should be noted that hypercalcemia is often associated with severe, advanced cancer. This also influences life expectancy. Age, the use of medication and other existing diseases also have an influence on the course and prognosis.

Hypercalcemia: treatment depending on the cause

The therapy of hypercalcemia depends on the cause. First, we always treat the underlying disease – then calcium levels often return to normal. This could be cancer, bone metastases, hyperparathyroidism (excessive levels of parathyroid hormone due to hyperparathyroidism), or hyperthyroidism. If medications are the triggers of the elevated calcium levels, we try to discontinue them and find alternatives for these drugs. In addition to treatment of the cause, additional measures such as intravenous fluid administration and intravenous medication and, in the most extreme case, dialysis are often necessary in acute cases to quickly lower calcium levels. Hypercalcemic crisis is an emergency in which we must act immediately. Affected persons must seek inpatient treatment at the hospital.