What is Hypercalcemia?
Hypercalcemia simply means that your calcium level in the blood is higher than normal. In our body, there’s a delicate balance between calcium and phosphate, and hypercalcemia indicates that this balance is disrupted. In a healthy person, the total serum calcium level ranges between 8.6-10.4 mg/dL (2.15-2.60 mmol/L; 4.3 – 5.2 mEq/L). The physiologically active form is ionized calcium. In your blood tests, a plasma calcium level exceeding the laboratory’s specified reference range is defined as hypercalcemia.
Classification of Hypercalcemia by Serum Calcium Levels:
Normal serum calcium: 8.5-10.5 mg/dL
Mild hypercalcemia: 10.5-12 mg/dL (often asymptomatic)
Moderate hypercalcemia: 12-15 mg/dL
Severe hypercalcemia: >15 mg/dL (Hypercalcemic Crisis)
Calcium is a vital electrolyte for our body. It plays a key role in many fundamental processes, from the function of our nerves and muscle contraction to the strength of our bones. Our body tightly controls the amount of calcium in the blood.
Hypercalcemia can be asymptomatic or be accompanied by symptoms such as excessive urination (polyuria), vomiting, fluid loss with fever, mental confusion (psychosis), and even coma. When these symptoms occur, we refer to it as a hypercalcemic crisis. A hypercalcemic crisis is a serious, life-threatening condition that requires immediate intervention.
What Are the Causes of Hypercalcemia?
Hypercalcemia can arise from various reasons. It can develop in the body through three main mechanisms:
- Disruption of Bone Metabolism: Increased bone breakdown (resorption) causes osteoclasts to release more calcium into the blood.
- Increased Calcium Absorption from the Intestines: Excessive absorption of calcium from the intestines.
- Decreased Calcium Excretion from the Kidneys: The kidneys are unable to adequately excrete calcium.
The most common causes of hypercalcemia include:
- Primary Hyperparathyroidism: This occurs when at least one of the four parathyroid glands is overactive and secretes too much parathyroid hormone (PTH). This is typically caused by a benign parathyroid nodule (adenoma). PTH increases calcium absorption from the intestines, decreases calcium excretion from the kidneys, and stimulates calcium release from the bones.
- Cancer (Malignant Hypercalcemia): Can occur with any type of cancer and is found in approximately 30% of cancer patients. It is generally a complication of advanced cancer.
- Bone Metastases: The spread of tumors to the bones can directly cause bone destruction and calcium release. This is particularly common in non-small cell lung cancer, breast cancer, multiple myeloma, head and neck cancer, urothelial carcinoma, and ovarian cancer.
- Substances Secreted by Tumors: Many tumors can produce substances that increase bone breakdown, such as parathyroid hormone-related protein (PTHrP). Lymphomas and myeloma cells can produce cytokines like interleukins and tumor necrosis factor, which increase osteoclast activity. Some cancers (e.g., Hodgkin’s disease, T-cell lymphoma) can produce calcitriol (active form of vitamin D), which increases calcium absorption.
- Excessive Vitamin D or Vitamin A Intake: High doses of vitamin D or A supplements can increase calcium absorption and lead to hypercalcemia.
- Medications:
- Thiazide diuretics: Inhibit calcium excretion by the kidneys.
- Lithium: A psychotropic medication that can affect calcium levels.
- Antacids and High-Dose Calcium Intake: Especially in ulcer patients, high doses of calcium and antacids can lead to milk-alkali syndrome.
- Granulomatous Diseases: In conditions like sarcoidosis, tuberculosis, leprosy, and berylliosis, excessive calcitriol production by macrophages forming the granulomas can increase blood calcium.
- Other Endocrine Diseases: Hyperthyroidism (overactive thyroid), acromegaly, or pheochromocytoma can also cause hypercalcemia.
- Immobility: Especially in bedridden or paralyzed patients, the lack of stress on bones can lead to calcium release.
- Acute Kidney Failure: In approximately one-quarter of patients with acute kidney failure resulting from rhabdomyolysis, hypercalcemia can occur due to calcium mobilization from damaged muscle cells.
- Genetic Diseases
What Are the Symptoms of Hypercalcemia?
The symptoms of hypercalcemia vary depending on the speed and degree of calcium elevation. Rapidly developing hypercalcemia leads to more pronounced symptoms, while slowly developing conditions can remain asymptomatic for a long time.
Early and mild symptoms:
- Increased fatigue
- Muscle weakness
- Difficulty concentrating
- Irritability or depression
As calcium levels rise or the condition becomes chronic, more serious symptoms may appear:
- Digestive System Symptoms: Nausea, vomiting, constipation, loss of appetite, abdominal pain, and rarely stomach ulcers or pancreatitis.
- Kidney System Symptoms: High calcium levels lead to polyuria (increased urine output), which can cause dehydration and increased thirst. Prolonged high calcium can lead to nephrocalcinosis (kidney damage) and the formation of calcium stones in the kidneys or urinary tract due due to the accumulation of calcium crystals. Kidney failure may also develop.
- Neuropsychiatric Symptoms: Confusion, emotional outbursts, delirium, hallucinations, and ultimately coma.
- Eye Symptoms: Accumulation of calcium crystals can cause conjunctivitis or keratitis.
- Cardiac Symptoms: Increases heart muscle contractility and can increase the toxicity of digitalis glycosides. In severe cases, heart arrhythmias can occur.
How Is Hypercalcemia Diagnosed?
Hypercalcemia is typically diagnosed during routine blood tests when high serum calcium levels are detected. Once excess calcium is found, further tests are conducted to determine the underlying cause.
These tests include:
- Blood and Urine Tests:
- Parathyroid hormone (intact PTH): Important for diagnosing primary hyperparathyroidism.
- Parathyroid hormone-related peptide (PTHrP): May be high in cancer-related hypercalcemia.
- 1,25-(OH)2-vitamin D3 and 25-OH-vitamin D3: To assess vitamin D excess or granulomatous diseases.
- Phosphate, magnesium, and kidney function tests (creatinine, BUN).
- Evaluation of calcium excretion in urine.
- Imaging Methods:
- Tumor screening: If cancer is suspected, imaging such as abdominal ultrasound, chest X-ray, or mammography may be performed in women.
- Neck ultrasonography, Parathyroid scintigraphy: Used to detect an overactive parathyroid gland in primary hyperparathyroidism.
- Bone scintigraphy or other imaging methods in cases of suspected bone metastasis.
- Genetic Tests: Uzm. Dr. Burcu Meryem Atak Sançmış may order genetic tests if a hereditary cause is suspected (e.g., familial hypocalciuric hypercalcemia).
How Is Hypercalcemia Treated?
The primary goal of hypercalcemia treatment is to lower blood calcium levels and address the underlying cause. Treatment is tailored to the severity of symptoms and the cause of hypercalcemia.
Emergency Treatment (Hypercalcemic Crisis): A hypercalcemic crisis, defined by total calcium levels above 15 mg/dL accompanied by severe symptoms, is a life-threatening emergency requiring immediate reduction of calcium levels in intensive care.
General Treatment Methods: Treatment is planned based on the cause of hypercalcemia. A personalized approach is necessary, as the underlying cause can vary for each patient.
- Fluid Administration: As most patients are dehydrated, intravenous (IV) fluid administration is the most crucial measure to preserve kidney function and accelerate calcium excretion. For mild hypercalcemia, drinking plenty of fluids might also suffice.
- Calcitonin: A hormone that can lower calcium levels within hours. However, its effect may wear off within 2 days due to receptor desensitization in target cells, so it’s not recommended for standalone use. It’s usually used in combination with slower-acting medications to provide a short-term reduction.
- Bisphosphonates: These are the preferred medications for a sustained reduction in calcium levels. They inhibit bone resorption by osteoclasts and calcitriol formation. They can be administered intravenously (IV) or orally. Their effects begin within 48 hours, with maximum effect seen around 6 days, and the effect can last up to 30 days. Pamidronate and zoledronate are commonly used active ingredients.
- Corticosteroids: Particularly effective in patients with granulomatous diseases or vitamin D overload, as they antagonize the effects of calcitriol.
- Cinacalcet: In the presence of hyperparathyroidism with mild symptoms, it can help lower calcium levels by increasing the sensitivity of the calcium receptor.
- Dialysis: In life-threatening, treatment-resistant cases of hypercalcemia, emergency hemodialysis may be required to remove calcium from the patient’s blood. This is a very effective and safe treatment method.
Treatment of the Underlying Cause of Hypercalcemia:
- Primary Hyperparathyroidism: Typically definitively treated by surgically removing the overactive parathyroid gland(s) (parathyroidectomy).
- Cancer-Related Hypercalcemia: Controlling the underlying cancer is essential. Sometimes, medications like denosumab can also help. However, if the cancer cannot be controlled, hypercalcemia may recur.
- Vitamin D/Vitamin A Excess: The condition improves by discontinuing the supplements.
- Medication Use: Discontinuing or adjusting the dosage of medications causing hypercalcemia.
Frequently Asked Questions
Is Hypercalcemia only related to bones?
No, hypercalcemia is not solely related to bones. While increased calcium release from bones is a significant cause, different mechanisms such as increased calcium absorption from the intestines or decreased calcium excretion from the kidneys can also lead to hypercalcemia. Additionally, many different causes, including the parathyroid glands, certain tumors, and vitamin D excess, can cause hypercalcemia.
Does a high calcium level always cause symptoms?
No. Especially if calcium levels rise slowly or if the elevation is mild, individuals may not experience any symptoms. Hypercalcemia is often incidentally discovered during routine blood tests. However, when levels rise rapidly or reach very high values, symptoms become more pronounced.
Can Hypercalcemia be genetic?
Rarely, hypercalcemia can have genetic causes. For example, some genetic disorders like “familial benign hypocalciuric hypercalcemia” can lead to hypercalcemia due to mutations in the receptors that sense calcium levels in the body. Furthermore, some genetic syndromes (e.g., multiple endocrine neoplasia) can predispose to primary hyperparathyroidism.
Can dietary calcium cause hypercalcemia?
Excessive calcium intake from a normal diet typically does not cause hypercalcemia in individuals with healthy kidneys, as the body can excrete the excess. However, very high doses of calcium supplements, especially when combined with antacids or in individuals with impaired kidney function, are known to cause hypercalcemia through conditions like “milk-alkali syndrome.” Excessive vitamin D supplementation can also increase calcium absorption and lead to hypercalcemia. For advice on supplement use and dosage, you can consult with Uzm. Dr. Burcu Meryem Atak Sançmış.
Is exercise or movement beneficial for hypercalcemia?
Physical activity and mobility are important for bone health and can help prevent calcium release from bones. Prolonged immobility (as in paralyzed or bedridden patients) can lead to weakening of bones and increased calcium release into the blood, causing hypercalcemia. Therefore, physical activity, when approved by a doctor and appropriate, is generally beneficial. However, if symptoms such as heart rhythm disturbances or severe muscle weakness are present, activity restriction may be necessary, and medical advice should definitely be sought.
What happens if calcium levels are high?
When your blood calcium level rises, problems such as kidney stones and kidney failure can occur. Additionally, in addition to general symptoms like extreme fatigue, constipation, and muscle weakness, it can lead to more serious conditions like heart arrhythmias and mental confusion. If you experience any of these symptoms, you should absolutely consult your doctor.
What is a hypercalcemic crisis?
A hypercalcemic crisis is a sudden and severe condition where your blood calcium level dangerously exceeds the normal range. This is a life-threatening state that severely impairs bodily functions and requires immediate medical intervention.
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