Hypercalcemia: what is it, causes, symptoms, treatment, prognosis

What is hypercalcemia?

Hypercalcemia Is a high level of calcium (Ca2 +) in the blood serum. The normal range is 2.1–2.6 mmol / L (8.8–10.7 mg / dL, 4.3–5.2 meq / L), and levels over 2.6 mmol / L are defined as hypercalcemia. Patients with a moderate increase in Ca2 +, which slowly developed, are usually asymptomatic. In people with higher or faster onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, nephrolithiasis or an abnormal heart rhythm, including cardiac arrest.

Most cases are associated with primary hyperparathyroidism or cancer. Other causes include sarcoidosis, tuberculosis, Paget's disease, multiple endocrine neoplasia (MEN), toxicity vitamin D, familial hypocalciuric hypercalcemia, and certain drugs such as lithium and hydrochlorothiazide. The diagnosis should usually include a calcium test and be confirmed one week later. Specific changes such as a shortened QT interval and a prolonged PQ interval can be seen on an electrocardiogram (ECG).

Treatment may include intravenous fluid, furosemide, calcitonin, or pamidronate in addition to treating the underlying cause. However, the evidence for the use of furosemide is insufficient. Patients with very high Ca2 + levels may require hospitalization. Patients who do not respond to these treatments may need dialysis. Patients with vitamin D toxicity may benefit from steroids. Hypercalcemia is relatively common. Primary hyperparathyroidism occurs in 1-7 people per 1000 people, and hypercalcemia - in 2% of cancer patients.

Causes and risk factors

Causes of hypercalcemia may include:

• Hyperparathyroidism: One or more of the four parathyroid glands secrete too much parathyroid hormone, which controls the amount of calcium in the blood.
• Too much calcium intake: Sometimes hypercalcemia occurs in patients with peptic ulcersif they consume a lot of milk and take antacids containing calcium. The resulting disease is called lactic-alkaline syndrome.
• Too much vitamin D intake: When very high daily doses of vitamin D are taken for several months, the amount of calcium absorbed from the digestive tract is significantly increased.
• Oncological diseases: At lung cancer, kidney and ovarian cells can secrete large amounts of protein, which, like parathyroid hormone, increases blood calcium levels. These disorders, called cancer humoral hypercalcemia, are considered paraneoplastic syndrome. Calcium also enters the bloodstream when cancer spreads (metastasizes) to the bones and destroys bone cells. This destruction of bones usually occurs with prostate cancer, breast cancer and lungs. Multiple myeloma (bone marrow cancer) can also lead to bone destruction and hypercalcemia. Other cancers can raise blood calcium levels in an as yet unclear way.
• Bone diseases: When bone breaks down (resorption), calcium enters the bloodstream, sometimes causing hypercalcemia. At Paget's disease bone destruction is observed, but blood calcium levels are usually normal. However, calcium levels can rise too high if people with Paget's disease are dehydrated or spend too much time sitting or lying down when their bones are not supporting their body weight. Heavy hyperthyroidism can also cause hypercalcemia by increasing bone resorption.
• Sedentary lifestyle: Rarely in sedentary patients, such as those who are paralyzed or who are bedridden for a long time time, hypercalcemia develops due to the fact that calcium from the bones moves into the blood when the bones do not hold body weight for a long time.

Granulomatous disorders, drugs, endocrine disorders, and several other diseases can also cause hypercalcemia.

Hyperparathyroidism

The parathyroid glands produce parathyroid hormone, which increases the absorption of calcium from digestive tract, causes less calcium excretion by the kidneys and leads to calcium accumulation bones.

Parathyroid hormone causes the kidneys to excrete more phosphate and also moves phosphate from the bones into the blood. The balance of these two processes determines whether phosphate levels are normal or decreased.

If the parathyroid glands produce too much parathyroid hormone, hyperparathyroidism occurs. In patients with hyperparathyroidism, calcium levels are significantly elevated and blood phosphate levels are normal or low.

- Primary hyperparathyroidism.

At primary hyperparathyroidism the disease causes the production of an increased amount of parathyroid hormone. Approximately 90% of patients with primary hyperparathyroidism have a benign tumor (adenoma) in one of the parathyroid glands. In the remaining 10%, the glands simply enlarge and produce too much hormone. In rare cases, parathyroid cancer causes hyperparathyroidism.

Primary hyperparathyroidism is more common in women than in men. It occurs more often in the elderly and in patients who have received radiation therapy for neck problems. Sometimes the violation occurs as part of multiple endocrine neoplasia, a rare hereditary disease.

Primary hyperparathyroidism is usually treated with surgery by removing one or more of the parathyroid glands. The goal of the surgery is to remove the parathyroid tissue that produces an increased amount of the hormone. Surgical intervention is effective in almost 90% of cases.

- Familial hypocalciuric hypercalcemia.

Familial hypocalciuric hypercalcemia syndrome is another inherited disorder that develops as a result of parathyroid glands underestimate the amount of calcium in the blood and in response, mistakenly produce too much parathyroid hormone. In this disorder, parathyroid surgery is not beneficial and other treatment is usually not needed.

- Secondary hyperparathyroidism.

In secondary hyperparathyroidism, an increased amount of parathyroid hormone is produced in response to a significant decrease in blood calcium levels, which is usually observed with chronic kidney disease and lack of vitamin D.

Tertiary hyperparathyroidism.

In tertiary hyperparathyroidism, excess parathyroid hormone is produced regardless of the amount of calcium in the blood. Tertiary hyperparathyroidism usually occurs in people with long-term secondary hyperparathyroidism.

Symptoms and Signs

Hypercalcemia usually has few symptoms. The earliest symptoms of hypercalcemia usually include constipation, nausea, vomiting, abdominal pain, and loss of appetite. Patients have increased urine output, which leads to dehydration and increased thirst.

Very severe cases of hypercalcemia often cause brain dysfunction and disorientation, emotional disturbances, delirium, hallucinations and coma. Muscle weakness and abnormal heart rhythms can occur, and death can also follow.

Prolonged or severe hypercalcemia usually results in calcium-containing kidney stones. In rare cases, it develops renal failurebut it usually goes away after treatment. However, if enough calcium builds up in the kidneys, the damage is irreversible.

Epidemiology

The prevalence of hypercalcemia in the general population ranges from 1% to 2%. Most cases (90%) of hypercalcemia are secondary to primary hyperparathyroidism and hypercalcemia associated with malignant neoplasms. The prevalence of primary hyperparathyroidism in the general population ranges from 0.2% to 0.8% and increases with age. Overall, 2% of all cancers are associated with hypercalcemia, but in the pediatric age group, the prevalence is between 0.4% and 1.3%.

Pathophysiology

Calcium concentration is regulated by the plasma membrane calcium receptor, PTH and its receptor, calcitonin and its receptor, and by the action of vitamin D on the kidneys, bones and intestines. PTH mobilizes calcium directly, enhancing bone resorption, and indirectly, by stimulating one alpha hydroxylase, which increases production of vitamin D3, which in turn leads to increased absorption of calcium from the intestines and increased bone resorption. Primary hyperparathyroidism occurs due to solitary adenoma or diffuse glandular hyperplasia. In this condition, there is an abnormal setpoint relationship between calcium and PTH levels and calcium-independent PTH secretion. Familial hypocalciuric hypercalcemia is inherited in an autosomal dominant manner and arises from an inactivating mutation in the gene for a calcium-sensitive receptor. Granulomatous lesions cause ectopic vitamin D production. Transient neonatal hypercalcemia is rare in babies born to mothers with hypoparathyroidism.

Hyperkacemia from hyperparathyroidism is mild and can last for years and be asymptomatic. Hypercalcemia caused by malignant neoplasms is associated with a rapid increase in calcium levels.

Diagnostics

Hypercalcemia is usually diagnosed during routine blood tests.

Once hypercalcemia is detected, additional tests may be required to determine the cause. Additional blood and urine tests may be done. A chest x-ray may also be needed. Genetic testing may be done to check for a hereditary cause.

Treatment

You can cure a mild form of hypercalcemia by getting rid of its cause. Patients with normal kidney function and mild hypercalcemia or diseases that can cause hypercalcemia are usually advised to drink plenty of fluids. The fluid stimulates the kidneys to excrete calcium and prevents dehydration.

Doctors may prescribe mineral supplements that contain phosphate, which prevent calcium from being absorbed.

If calcium levels are elevated or if symptoms of brain dysfunction or muscle weakness are present, fluids and diuretics are given through a vein (intravenously) until kidney function returns to normal. Dialysis is a highly effective, safe and reliable treatment, but it is usually only used for patients with severe hypercalcemia that cannot be treated with other treatments.

Certain drugs (including bisphosphonates, calcitonin, corticosteroids, and rarely plicamycin) are sometimes used to treat hypercalcemia. These drugs reduce the excretion of calcium from the bones.

Cancer-related hypercalcemia is particularly difficult to treat. Sometimes a drug called denosumab. If cancer does not respond to treatment, hypercalcemia usually returns despite treatment.

Forecast

Hypercalcemia, when it occurs after a benign disease, has a good prognosis, but when the cause is secondary to a malignant neoplasm, the prognosis is poor. Patients with malignant hypercalcemia are often symptomatic and require frequent hospitalization. When hypercalcemia is due to ectopic production of a PTH-associated protein, most patients die within a few months. Osteolytic metastatic lesions cause fractures, nerve compression, and paralysis.

Complications

Complications include:

• depression;
• stones in the kidneys;
• bone pain;
• constipation;
• pancreatitis;
• renal failure;
• stomach ulcers;
• paresthesia;
• fainting and arrhythmias;
• changes in mental state.