Hypercalcemia : Causes, Symptoms, Diagnosis & Treatment

Last Updated: 19/07/2022

Hypercalcemia is an increase in serum concentrations of total calcium greater than 2.8 mmol/l or ionized calcium greater than 1.3 mmol/l. The cause of this condition may be hyperparathyroidism, malignant neoplasm, long-term use of drugs. Symptoms include incipidar syndrome (polyuria, polydipsia), general muscle weakness, neuropsychiatric disorders. For diagnosis, the level of ionized calcium (Ca2+) is more important. For treatment, 0.9% NaCl, loop diuretics, bisphosphonates are used.

Calcium is a vital macronutrient that performs many functions in the human body (ensuring muscle contraction, blood clotting, nerve impulse conduction). Calcium is also the main component of bone tissue. In the regulation of its metabolism, the most important part is calcitriol (vitamin D), parathyroid hormone. Hypercalcemia is a fairly common electrolyte disorder and occurs in about 0.17 to 3.9 cases per 10 people. Gender differences vary among people of different ages. This condition is more susceptible to young men, women over 45 years old.

Causes of hypercalcemia

Hypercalcemia almost always indicates a disease or pathological process. However, sometimes it develops due to physiological causes (in newborns on the 4th day of life, in adults after eating). The pathological causes of this condition are as follows:

  • Hyperparathyroidism. It is an endocrine disease characterized by hypersecretion of parathyroid hormone (PTH). It is the most common cause of hypercalcemia. Hyperparathyroidism is caused by adenoma, hyperplasia of the parathyroid glands, and renal failure. Sometimes hyperparathyroidism occurs as part of an autoimmune polyglandular syndrome or multiple endocrine neoplasias.
  • Oncological diseases. Recognized as the second most common cause of this electrolyte disturbance. In cancer, it occurs through two mechanisms. The first is the destruction of the bone by metastases or the primary focus (leukemia, lymphoma, multiple myeloma). The second mechanism is the synthesis of a PTH-like peptide by cancer cells (cancer of the lung, breast, bladder).
  • granulomatous processes. Chronic diseases characterized by the formation of cellular granulomas in tissues (primarily in the lungs) can also cause hypercalcemia. These include tuberculosis, sarcoidosis, histoplasmosis. Mononuclear phagocytes, which are part of the granulomas, due to the expression of 1-alpha hydroxylase, are able to convert vitamin D into an active form (calcitrirol, 1,25OH-D3), which enhances the absorption of calcium ions by the small intestine.
  • Prolonged immobilization. As a result of a prolonged lack of motor activity, osteoclasts are activated (cells that destroy bone tissue by dissolving mineral compounds). This leads to the release of calcium ions from the bones. Such a phenomenon occurs during forced immobilization after injuries, being in weightlessness (during space flights).
  • Taking medications. First of all, this applies to vitamin D, calcium preparations. Other drugs (thiazide diuretics, theophylline, lithium) can also cause calcium imbalance by enhancing osteodestruction or reabsorption processes in the tubules of the kidney nephrons.
  • Other endocrine disorders. In addition to the pathology of the parathyroid glands, other endocrine diseases sometimes act as the cause of hypercalcemia. For example, an excess of thyroid hormones in hyperthyroidism increases the destruction of bone tissue. In adrenal insufficiency, the inhibitory effect of glucocorticoids on calcium metabolism is reduced.

Pathogenesis

An increase in the calcium content in the blood changes the membrane potential of cells, which leads to inhibition of neuromuscular conduction in skeletal muscles, myocardium, and the gastrointestinal tract. The pathogenesis of neuropsychiatric symptoms is not completely clear. The role of slowing down the conduction of nerve impulses is assumed. Calcification of blood vessels, internal organs, dystrophy, wrinkling of tissues develops.

Due to hypercalciuria (increased filtration of calcium in the tubules of the nephron), the risk of nephrolithiasis increases. Calcium inhibits adenylate cyclase, which suppresses the renal effect of antidiuretic hormone. Also, due to the high extracellular concentration of this cation, the secretion of hydrochloric acid by the parietal cells of the stomach increases, which leads to the development of peptic ulcers.

 

Classification

Along the course, chronic and acute hypercalcemia (hypercalcemic crisis) are isolated. According to the level of the cation (in mmol / l), the following degrees of severity of hypercalcemia are distinguished:

  • Light. The content of total Ca is less than 3, ionized - less than 1.5.
  • Moderate. The level of total Ca is up to 3.5, ionized - up to 1.8.
  • Heavy. Total Ca is above 3.5, ionized - more than 1.8.

Separately, pseudohypercalcemia is considered. Part of the calcium binds to plasma proteins, so diseases such as paraproteinemic hemoblastoses (multiple myeloma), characterized by a high content of protein in the blood, are accompanied by an increase in the level of total calcium. The determination of ionized calcium helps to exclude false hypercalcemia.

Symptoms of hypercalcemia

With a mild degree of pathology, there may be no symptoms at all. With a moderate, severe degree, muscle weakness appears, sometimes reaching such severity that it is difficult for the patient to get out of bed. Symptoms from the gastrointestinal tract are characteristic - nausea, vomiting, abdominal pain. Significantly reduced appetite, constipation occurs. Often there are cardiac symptoms (increased blood pressure, tachycardia).

Even with hypercalcemia of non-oncological origin due to anorexia and muscular dystrophy, the patient loses a lot of weight, acquires a cachectic appearance, which may lead to a false impression that he has a malignant neoplasm. The weakening of the action of antidiuretic hormone on the kidneys causes the appearance of symptoms such as intense thirst, an increase in urination up to 5-6 liters per day.

The neuropsychological symptoms are especially pronounced. First, there is emotional instability, impaired concentration, slight drowsiness. In severe pathology, confusion, delirium, and psychosis develop. Hallucinations are possible. With a long-term high level of calcium, it begins to be deposited in the tissues of the joints (chondrocalcinosis), which causes arthralgia.

Complications

Hypercalcemia has a wide range of adverse effects. The most common complications are osteoporosis (due to increased release of calcium ions from the bones), pathological fractures, and urolithiasis. Less common are acute pancreatitis and intestinal obstruction. The most life-threatening condition is the hypercalcemic crisis, in which the mortality rate reaches 60%. The cause of death is heart or kidney failure.

Another severe but rare complication is calciphylaxis (calcifying uremic arteriolopathy), characterized by ischemic necrosis of the skin and subcutaneous fat. It develops in patients with end-stage renal disease. A prolonged increase in blood calcium can also lead to band keratopathy, calcification of the aorta and heart valves with the formation of heart disease.

Diagnostics

The profile of a medical specialist who supervises a patient with this pathology is determined by the cause that caused this condition. Most often, such patients are observed by endocrinologists, nephrologists, and oncologists. When interviewing a patient, it is imperative to specify which medications he is taking. During the examination, the doctor draws attention to symptoms such as decreased muscle tone, inhibition of tendon reflexes. An additional examination is scheduled, including:

  • Laboratory research. In a biochemical blood test, the level of albumin, urea, and creatinine is measured. From electrolytes, in addition to total and ionized Ca, the concentration of phosphorus and chlorides is determined. The content of vitamin D (25OH-D) is being investigated. PTH, PTH-like peptides. The daily excretion of Ca in the urine is checked. If thyrotoxicosis or hypocorticism is suspected, a blood test for hormones (TSH, free T4, cortisol) is performed.
  • functional tests. Invaluable assistance for the differential diagnosis of the causes of this disorder is provided by special provocative tests. These include samples with native vitamin D, thiazide diuretics, calcitonin. To exclude a process that is not associated with increased secretion of PTH, allows the test of steroid suppression with prednisolone.
  • Instrumental research. To search for adenoma or hyperplasia of the parathyroid glands, their ultrasound, computed tomography, and scintigraphy are performed. In order to determine the mineral density of bone tissue, densitometry is performed, for the diagnosis of nephrolithiasis - ultrasound of the kidneys. If there are symptoms that raise suspicions of an inflammatory process in the lungs or a malignant neoplasm, x-rays, CT scans of the lungs, abdominal organs, and mammography should be prescribed to identify them.

The differential diagnosis should be based on the predominant symptoms. Incipid syndrome must be differentiated from diabetes and diabetes insipidus. Muscle weakness, hypotonia should be distinguished from that in muscular dystrophy, myasthenia gravis, polymyositis. Neuropsychiatric symptoms require the exclusion of psychiatric diseases.

Scintigraphy. parathyroid adenoma

 

Treatment of hypercalcemia

Conservative therapy

Patients with any degree of severity for treatment should be hospitalized in a hospital (endocrinology, nephrology department). Patients with severe neurological symptoms, hypercalcemic crisis should be transferred to the intensive care unit. It is required to stop all drugs that can cause an increase in calcium levels. Treatment of hypercalcemia has the following directions:

  • Increased excretion of calcium in the urine. Adequate rehydration with saline NaCl (0.9%) must first be ensured. This will improve the perfusion of the kidneys, increase the filtration of calcium ions by the renal glomeruli. Additionally, forced diuresis is performed using loop diuretics (furosemide). It is necessary to constantly monitor the level of electrolytes in the blood.
  • Decreased intestinal Ca absorption. Phosphate salts of sodium or potassium are well suited for this purpose. Phosphates are strictly contraindicated for the treatment of secondary hyperparathyroidism caused by renal insufficiency. Also, to suppress the absorption of Ca in the gastrointestinal tract, glucocorticosteroids (prednisolone, hydrocortisone), synthetic antimalarial drugs (hydroxychloroquine, chloroquine) are used.
  • Suppression of bone resorption. An important step in the treatment of hypercalcemia caused by hyperparathyroidism or cancer. The most effective drugs to prevent the progression of osteoporosis are bisphosphonates (pamidronic, zoledronic acid), which inhibit the activity of osteoclasts. A similar mechanism of action, but a faster effect, has the peptide hormone calcitonin, the cytotoxic antibiotic mithramycin.
  • Suppression of the production of PTH and PTH-like protein. For the pathogenetic treatment of primary and secondary hyperparathyroidism, calcimimetics (cinacalcet) are used, which increase the sensitivity of PTG cell receptors, thereby reducing the production of PTH. As a treatment for hypercalcemia caused by a malignant tumor, gallium nitrate is used, which inhibits the secretion of PTH-like protein by tumor cells.
  • Intensive therapy. For the treatment of severe life-threatening conditions (hypercalcemic crisis, calciphylaxis), as well as the ineffectiveness of other conservative methods of therapy, hemodialysis using a low-calcium dialysis solution is an urgent measure for reducing serum Ca.

Surgery

Surgical removal of the parathyroid glands is the main treatment for primary hyperparathyroidism. The main indication for surgical intervention is the Ca level above 2.75 mmol/l. To prevent postoperative hypocalcemia (“hungry bones syndrome”), the patient is prescribed vitamin D, Ca preparations. Malignant tumors are also subject to removal. For the treatment of oncohematological pathologies, bone marrow transplantation is performed.

Experimental treatment

New drugs are being developed to treat this condition. The drug osteoprotegerin, which is a cytokine from the tumor necrosis factor family, is at the stage of clinical trials. It inhibits the differentiation of osteoclasts, stimulates their apoptosis. In in vitro experiments, the calcitriol analogue EB 1089 suppressed the expression of the PTH peptide gene.

Forecast and prevention

Hypercalcemia is a severe, and in some cases (especially in acute course) life-threatening pathological condition. In a hypercalcemic crisis, mortality is very high (60%). The frequency of deaths in chronic course averages 20-25%. However, to a greater extent, the prognosis is determined by the cause of the increase in Ca levels.

Prevention of this pathology lies in the timely diagnosis and proper treatment of diseases against which it develops. Before you start taking vitamin D or other medicines that can increase your blood Ca levels, you should have a blood test to check your calcium levels.

Latest Articles

  1. Noise in ears (September 30)
  2. Stamping gait (September 30)
  3. Wobbly gait (September 30)
  4. Shuffling gait (September 30)
  5. Sneezing (September 30)
  6. Cylindruria (September 30)
  7. Lameness (September 30)
  8. Chorea (September 30)
  9. Cold sweat (September 29)
  10. Chyluria (September 29)