What Are the Most Common Hypercalcemia Causes?

Hypercalcemia is an abnormal increase in serum ionized calcium concentration. Because total calcium is usually measured, not ionic calcium, factors that affect ionic calcium must be noted. Serum albumin concentration is the most clinically important factor because albumin is the main calcium-binding protein in the blood circulation. In cases where serum albumin is severely reduced (such as in patients with malignant tumors), normal serum total calcium concentration actually represents an abnormally high ionic calcium concentration. PH also affects the combination of serum calcium and protein. Alkali poisoning can reduce the concentration of ionized calcium, and acidosis can increase it. When the calcium entering the extracellular fluid (intestinal bone) exceeds the excreted calcium (intestinal kidney), hypercalcemia occurs, and the blood calcium concentration is higher than 2.75 mmol / L.

Basic Information

English name: hypercalcemia
Visiting department: Endocrinology
Common causes: Malignant tumor, primary hyperparathyroidism, thiazide diuretics, renal failure, hyperthyroidism, acromegaly, long-term braking

Common symptoms: Anorexia, nausea, vomiting, constipation, fatigue, muscle fatigue, decreased muscle tone, thirst, polyuria, lethargy, unconsciousness, coma
Contagious: no

Causes of hypercalcemia

Malignant tumor

About 20% of patients with malignant tumors (such as breast cancer, lung cancer, kidney cancer, thyroid cancer, and prostate cancer) can develop hypercalcemia especially in advanced stages. These malignancies can metastasize to the bones. Directly destroy bone tissue, release bone calcium, and cause hypercalcemia. In addition, some tumors (such as epithelial-like lung cancer and kidney cancer) can produce parathyroid hormone-like substances, prostaglandin E, vitamin D-like sterols, and osteoclast activating factors, which can cause bone tissue to absorb and release calcium.

2. Primary hyperparathyroidism

Excessive secretion of parathyroid hormone leads to bone tissue absorption, which releases a large amount of calcium and increases blood calcium. Vitamin D or other metabolites are taken too much, which significantly increases the absorption of calcium in the intestinal tract, resulting in hypercalcemia. Too much vitamin A can also cause hypercalcemia by increasing bone resorption.

3. Thiazines diuretics

It can cause excessive discharge of body fluids, cause low blood volume, increase calcium reabsorption in the renal tubules, decrease urinary calcium excretion, and cause hypercalcemia.

4. Renal failure

During the oliguria phase of acute renal failure, calcium cannot be excreted from the urine and is deposited in soft tissues. At this time, the increase in parathyroid hormone caused by hypocalcemia can cause bone resorption, resulting in hypercalcemia. Hypercalcemia can also occur during the polyuria.

5. Hyperthyroidism

Increased thyroid hormone, increased metabolic activity of the body, faster bone turnover, and corresponding increase in bone tissue absorption, leading to hypercalcemia.

6. Acromegaly

It is a type of hyperhypophysis that has increased intestinal calcium absorption and can also cause hypercalcemia.

7. Long-term braking

Such as gypsum fixation and paraplegia, the stress on the bone by the muscle is significantly reduced. Hypercalcemia occurs if the kidneys cannot clear calcium due to reduced bone resorption.

Clinical manifestations of hypercalcemia

Symptoms manifest in the digestive, motor, nervous, and urinary systems. Anorexia, nausea, vomiting, constipation; fatigue, muscle fatigue, decreased muscle tone, thirst, polyuria; lethargy, unconsciousness, and even coma. When the disease course is long, calcium deposition in the tissue can occur, such as conjunctiva, deposition around the joints, and kidney stones. The clinical manifestations of hypercalcemia are related to the magnitude and speed of the increase in blood calcium.

Neuropsychiatric symptoms

The lightest are only weakness, burnout, and indifference; the severe ones have headache, muscle weakness, weakened tendon reflexes, depression, irritability, gait instability, speech impairment, hearing, vision and disorientation or loss, stiffness, abnormal behavior, etc Neuropsychiatric symptoms. Delirium, convulsions, and coma may occur during high calcium crisis. The occurrence of neuropsychiatric symptoms is mainly the toxicity of high calcium to brain cells, which can interfere with the electrophysiological activities of brain cells.

2. Cardiovascular and respiratory symptoms

Can cause elevated blood pressure and various arrhythmias. ECG shows shortened QT interval, ST-T changes, atrioventricular block, and hypokalemia u waves. If left untreated, it can cause fatal arrhythmia. Hypercalcemia can cause increased renal urination and electrolyte disturbances, making bronchial secretions sticky, mucosal cell cilia activity weakened, and bronchial secretions not draining easily, which can easily lead to lung infections, breathing difficulties, and even respiratory failure.

3. Digestive system symptoms

Appeared as loss of appetite, nausea, vomiting, abdominal pain, constipation, severe cases of paralytic intestinal obstruction. Calcium can stimulate gastrin and gastric acid secretion, so hypercalcemia is prone to peptic ulcer. Calcium is ectopically deposited in the pancreatic duct, and calcium stimulates a large amount of pancreatic enzyme secretion, so it can cause acute pancreatitis.

4. Urinary system symptoms

Hypercalcemia can cause damage to the renal tubules, reduce the renal tubular concentrating function, and a large amount of calcium is excreted from the urine, which causes polyuria, thirst, polydipsia, and even water loss, electrolyte imbalance, and acid-base imbalance. Calcium deposits in the renal parenchyma can cause interstitial nephritis, salt-losing nephropathy, and renal calcium deposits, eventually developing into renal failure, and prone to urinary infections and stones.

5. Heterotopic calcium manifestations

Hypercalcemia is prone to ectopic calcium deposits, which can deposit on the vessel walls, cornea, conjunctiva, tympanic membrane, around the joints, and cartilage, which can cause muscle atrophy, corneal disease, red eye syndrome, hearing loss, and joint dysfunction.

6. Hematological symptoms

Because calcium ions can activate coagulation factors, they can lead to extensive thrombosis.

7. Other

Hypercalcemia crisis is when the blood calcium rises to more than 4mmol / L, which manifests as polydipsia, polyuria, severe dehydration, circulatory failure, and azotemia. If not rescued in time, patients may die from renal failure and circulatory failure. A few severe cases may have neurological manifestations including drowsiness, fatigue, and weakened reflexes. Shortening the QT interval of the ECG indicates hypercalcemia. Bradycardia and first degree atrioventricular block have also been reported. Acute hypercalcemia can cause significant blood pressure rises. Gastrointestinal manifestations include weakness constipation and anorexia, nausea and vomiting in severe cases, and hypercalcemia of different causes can be accompanied by acute pancreatitis.

Hypercalcemia test

Measure calcium concentration

(1) Calculate the concentration of calcium in plasma several times, because total serum calcium is interfered by serum albumin, so some people think that it is better to measure plasma ion calcium than to measure total calcium in plasma. However, plasma calcium ions are affected by blood pH, so errors can occur.

(2) Serum albumin should be measured at the same time when measuring total calcium, and blood pH should be measured at the same time when measuring ionized calcium, in order to correct the measured results. In addition, when measuring ionized calcium, pay attention that the pressure vein belt should not be oppressed for too long. If the compression time is too long, the blood pH value can be changed and the blood ionized calcium can be falsely increased.

2. Other auxiliary inspections

Based on medical history and symptoms, B ultrasound, X-ray examination, radionuclide scan and CT examination were selected.

Differential diagnosis of hypercalcemia

To identify with the relevant diseases that can cause hypercalcemia: malignant tumor hypercalcemia. Multiple myeloma. Primary hyperparathyroidism. Sarcoidosis. Vitamin A or D poisoning. Hyperthyroidism. Secondary hyperparathyroidism. Pseudoparathyroidism. Calcium receptor disease and so on.

Hypercalcemia Treatment

Different treatment strategies should be adopted according to the degree of elevated blood calcium.

1. Treatment of mild hypercalcemia

Mild hypercalcemia means that the blood calcium is between 2.75 and 3.0 mmol / L. The goal of hypercalcemia treatment is to reduce blood calcium. There are different opinions on the treatment of hyperparathyroidism. For example, non-life-threatening hypercalcemia and normal bone mineral density can be monitored to observe serum calcium, renal function, bone density and urinary calcium excretion. Surgical treatment should be considered when:

(1) The blood calcium is higher than 2.85mmol / L.

(2) There are life-threatening episodes of hypercalcemia.

(3) Creatinine clearance is reduced to only 70% of healthy people of the same age.

(4) Have kidney stones.

(5) 24-hour urine calcium> 100 mol (400 mg).

(6) Bone mineral density decreases, exceeding 2SD of normal people.

A calcium receptor synergist R-568 can be used. This drug inhibits the secretion of PTH, and the degree of inhibition is dose-dependent. When the maximum dose is used, the blood ion calcium can be reduced, but the exact effect remains to be tested in the long-term clinical trials. Recently, it has been found that the lack of courtship hormone in postmenopausal women is related to hyperparathyroidism. Replacement with matingin treatment can reduce blood calcium (0.125-0.25mmol / L), urine calcium is also reduced, but there is no change in plasma PTH. Courting factors also prevent bone loss and cardiovascular disease. Patients with mild hypercalcemia should avoid using all diuretics. Although diuretics can increase urinary calcium excretion, they also reduce extracellular fluid and increase calcium reabsorption from the renal tubules, thereby increasing blood calcium. Thiazine diuretics should be banned. Such diuretics can reduce urinary calcium excretion. Bisphosphonates have little effect on hypocalcemia due to mild hypercalcemia caused by hyperparathyroidism, so they are not needed.

2. Treatment of moderate hypercalcemia

Moderate hypercalcemia refers to a blood calcium concentration between 3.0 and 3.4 mmol / L. The symptoms of these patients are related to the rate of elevated calcium. In addition to treating the primary diseases that cause hypercalcemia, the following treatment measures that can be taken include:

(1) Intravenous infusion of saline to expand the volume and make the patient slightly "hydrated".

(2) If you want to make blood calcium drop faster, you can use diuretics (but thiazide diuretics are disabled). If there is renal insufficiency, the diuretic dose should be higher. Intravenous infusion of normal saline and diuretics can reduce blood calcium by 0.25 to 0.75 mmol / L within 1 to 2 days. If the decrease in blood calcium is not satisfactory, bisphosphonates can be added orally.

3. Treatment of severe hypercalcemia

Severe hypercalcemia refers to a blood calcium above 3.75mmol / L (13.5mg / dl), which is a hypercalcemia crisis. Urgent treatment is required, with or without symptoms. Treatment options include:

(1) Expansion of blood volume.

(2) Increase urinary calcium excretion.

(3) Reduce bone resorption.

(4) Treatment of primary diseases.

Expanding blood volume can dilute blood calcium and increase urinary calcium excretion. As long as the patient's cardiac function can be tolerated, a large amount of normal saline can be input in the monitoring of blood calcium and other electrolytes and hemodynamic changes. Urine diuretics can increase urinary calcium excretion. Use bisphosphonates to reduce bone reabsorption so that blood calcium is not mobilized into the blood.

4. Treatment of acute hypercalcemia episodes

(1) Intravenous rehydration to increase extracellular volume, followed by sodium diuretics, such as sodium diuretic and furosemide, can increase sodium excretion, and urine calcium excretion will increase accordingly, thereby correcting hypercalcemia. However, patients with renal insufficiency and congestive heart failure are contraindicated.

(2) Intravenous phosphate treatment, which combines calcium with phosphate to form calcium phosphate, and deposits it in soft tissues. In this way, plasma calcium can be quickly reduced; however, it can cause renal failure. Therefore it is rarely used.

(3) Calcitonin and adrenal corticosteroids. Calcitonin can inhibit bone resorption and increase urinary calcium excretion, but some patients fail quickly after use, and some patients have poor results. Corticosteroids can inhibit intestinal calcium absorption and can Enhance the effect of calcitonin.

(4) Cytotoxic drugs, such as radixomycin, can make the bone tissue undergoing absorption directly toxic to the drug, so it is effective for hypercalcemia. However, it can lead to thrombocytopenia, bleeding and renal failure and should be used with caution.

(5) Diphosphate can inhibit bone resorption and inhibit intestinal calcium absorption, so it can correct hypercalcemia. After the reduction of high calcium, then treat the cause.

5. Treatment of chronic hypercalcemia

The cause should be treated. In addition, the calcium content in the diet should be controlled. Drugs can be considered:

(1) Oral bisphosphonates, but patients with renal insufficiency are contraindicated.

(2) Corticosteroid therapy is effective for hypercalcemia caused by malignant tumors, but long-term application has side effects.