Hypocalcemia

What is Hypocalcemia?

The balance of calcium in our bodies is a complex process that involves a variety of hormones, regulatory proteins, receptors, and blood chemistries. The main actors in this process are several hormones including parathyroid hormone (PTH), activated vitamin D or calcitriol, fibroblast growth factor 23 (FGF23), and calcitonin. Other important elements are the calcium-sensing receptor (CaSR), and serum calcium and phosphorus levels.

The level of calcium in our blood is kept within a very specific range. Around 45% of our body’s calcium is attached to plasma proteins, primarily a protein called albumin. About 15% is linked with small ions like phosphate and citrate, while 40% is freely floating around, which is the active form. Most labs report the total amount of calcium in the blood, which is usually between 8.5 to 10.5 mg/dL (2.12 to 2.62 mmol/L). We can also measure the free calcium, and the normal range is 4.65 to 5.25 mg/dL (1.16 to 1.31 mmol/L). Numbers below this range indicate low calcium levels, or hypocalcemia. Since most of our body’s calcium is bound to albumin, total calcium levels should be adjusted based on albumin levels to accurately diagnose hypocalcemia. For example, a 1g/dL (10 g/L) decrease in albumin concentration will result in approximately a 0.8 mg/dL (0.25 mmol/L) decrease in total calcium concentration.

The processing of calcium and phosphorus are closely connected. The main hormones controlling this are PTH hormone made by parathyroid glands and calcitonin made by thyroid C-cells. PTH increases calcium levels by increasing the activity of cells called osteoclasts that break down bone to release calcium into blood, while calcitonin does the opposite by inhibiting osteoclasts. There are also many intricate feedback loops where calcium and activated vitamin D decrease PTH secretion and elevated phosphorus levels increase PTH secretion.

Calcium processing disorders are somewhat common in regular clinical practice. Low calcium or hypocalcemia is not as common as high calcium or hypercalcemia, but it can be life-threatening if not recognized and treated promptly. Most causes are down to acquired conditions but some may be inherited. Patients with these conditions can vary from showing no symptoms at all to being at risk of life-threatening heart rhythm problems or seizures.

What Causes Hypocalcemia?

Hypocalcemia, or low levels of calcium in the blood, can be caused by a variety of factors that may be grouped into three categories: PTH deficiency, high PTH and other causes.

PTH Deficiency

PTH, or parathyroid hormone, helps regulate the amount of calcium in the blood. When levels of this hormone are low, it can be due to damage to the parathyroid glands (from surgery or an immune response), problems with how PTH is produced and released, or issues with the development of the parathyroid glands. Surgery is usually the most common cause of this problem and if you have low levels of PTH, your doctor can diagnose this by checking your blood calcium levels at least two weeks apart.

In very rare cases, damage to the parathyroid glands can result from certain diseases or treatments, like HIV infection or chemotherapy drugs.

High PTH Levels

Vitamin D deficiency: Vitamin D helps to maintain normal levels of calcium in the blood and a deficiency can lead to a compensatory increase in PTH. This deficiency could be caused by inadequate diet or sun exposure, liver or kidney disease, or decreased metabolism of the vitamin.

Chronic kidney disease (CKD): CKD leads to problems with phosphate excretion and vitamin D metabolism, which can increase PTH levels. However, due to impaired vitamin D metabolism and high phosphorus levels, calcium levels in the blood can remain low despite high PTH.

Other Causes

False low calcium: If your blood protein levels are low, it can appear as though you have low levels of calcium. In this case, the levels of ionized calcium, or calcium that is readily available for use in the body, are usually normal.

Acute pancreatitis: This condition can lead to low levels of calcium as the calcium combines with free fatty acids, leading to a decrease in blood calcium levels.

Severe sepsis/trauma: Severe infections or trauma can lead to low calcium levels through various mechanisms, including problems with PTH secretion and regulation of other minerals like magnesium.

Hypomagnesemia/hypermagnesemia: Having too little or too much magnesium in your blood can also lead to low calcium levels by impacting the function of PTH.

Cancer: Certain cancers can cause low calcium levels due to increased calcium uptake in the bones.

Drugs: Some medications, including those used for cancer and osteoporosis, can cause low levels of calcium in the blood.

Excessive blood transfusion: Getting a large amount of blood transfusion can lead to a sudden drop in calcium levels due to how calcium interacts with certain substances in the donated blood.

Certain conditions during pregnancy, and conditions that increase the activity of cells that build up bone (osteoblasts), such as prostate cancer, can also cause low levels of calcium.

Risk Factors and Frequency for Hypocalcemia

Detailed information about the occurrence of hypocalcemia, a condition of low calcium levels in the blood, is not readily available in the medical literature. However, it’s known that low calcium levels can temporarily occur in about 6.9% to 49% of people after thyroid surgery, and permanently in about 0.4% to 33% of cases. Some common causes of hypocalcemia are surgery, chronic kidney disease, lack of vitamin D or magnesium, and severe inflammation of the pancreas (acute pancreatitis). Additionally, while smoking is believed to affect certain hormone levels related to calcium, it’s not certain how it affects the actual calcium levels in the body.

• Hypocalcemia data in the general population is not comprehensive.
• Between 6.9% and 49% may experience temporary low calcium levels after thyroid surgery.
• Post-thyroid surgery, permanent hypocalcemia may occur in 0.4% to 33% of people.
• Common causes of hypocalcemia include surgery, chronic kidney disease, vitamin D deficiency, magnesium deficiency, and acute pancreatitis.
• Smoking is suspected to influence hormone levels related to calcium, but its impact on calcium levels is not clear.

Signs and Symptoms of Hypocalcemia

Hypocalcemia, or low calcium levels in the blood, can have a range of effects on the body, from none at all to severe symptoms like seizures, heart failure, or spasms of the voice box. The way it shows up can also depend on how fast the levels drop and how long the condition lasts. Doctors examining someone with hypocalcemia will do specific tests to provoke symptoms. Conditions linked to hypocalcemia can include:

• Seizures: These can happen when hypocalcemia is very severe. Sometimes, they may be the only symptom or they might be part of a larger group of symptoms.
• Tetany: Rapid drops in the amount of calcium that is free in the blood can cause this condition. It’s usually seen when there’s too little acid in the body, which can lead to hypocalcemia. This condition is typically more dangerous.
• Paresthesias: This can mean tingling around the mouth or in the arms and legs.
• Psychiatric Symptoms: Sometimes, people with hypocalcemia might experience anxiety, depression, or quick mood changes.
• Hand Spasm: Known as Trousseau’s sign, this occurs when there’s too much nerve stimulation. It’s characterized by the thumb, wrist, and joints in the hand bending towards the palm while the fingers extend when a blood pressure cuff is inflated above systolic blood pressure for 2 to 3 minutes.
• Chvostek’s Sign: Similar to Trousseau’s sign, this is another indication of too much nerve stimulation. Tapping of the facial nerve in front of the ear causes the muscles on the same side of the face to contract.
• QTc Prolongation: This refers to changes in the heart rhythm that can lead to a specific type of dangerous irregular heartbeat known as torsades de pointes.

In figuring out the cause of hypocalcemia, doctors will look into things like recent head or neck surgery, a family history of low calcium levels, gut or kidney disease, or alcohol use leading to low magnesium levels.

Testing for Hypocalcemia

If you have low levels of calcium in your blood, or hypocalcemia, your doctor will need to perform a series of steps to accurately diagnose and treat you:

Firstly, they’ll confirm that you do indeed have hypocalcemia. This is done by checking a protein in your blood called serum albumin level or directly measuring the level of calcium ions in your blood. Your total calcium level can be influenced by serum albumin level, so for every 1 gram per deciliter decrease in albumin below 4 grams per deciliter, an additional 0.8 milligrams per deciliter should be added to your total calcium level to get a correct reading.

Next, they’ll check your heart’s health using an ECG (electrocardiogram). This test looks for something called QTc prolongation – a heart rhythm condition that can increase your risk of severe irregular heartbeats. If this is found, it’s often treated with a medication given through a vein, known as IV magnesium.

After these steps, your doctor will try to find out what’s causing your hypocalcemia. This might involve checking other elements in your blood such as magnesium and phosphorus levels, as well as hormone called PTH (parathyroid hormone), and vitamin D levels. Sometimes, the cause can be obvious, like if you’ve recently had surgery on your thyroid or parathyroid glands. Other times, additional tests might be needed based on your symptoms or medical history like a serum lipase test if pancreatitis (inflammation of the pancreas) is suspected.

Finally, your doctor might perform imaging tests, like X-rays, on your skeletal system. These can reveal diseases that affect your bones like osteomalacia (softening of the bones), rickets (a condition in children caused by vitamin D deficiency), or metastatic disease (cancer that has spread to the bones).

Treatment Options for Hypocalcemia

Treating low calcium levels, or hypocalcemia, depends on several factors such as how severe the symptoms are, the cause, and the degree of the condition. Here, we’ll look at few approaches used for its management.

Intravenous calcium: This is a method where calcium is directly administered into your bloodstream. It is often recommended for people who are having severe symptoms of hypocalcemia, or have developed hypocalcemia suddenly and are displaying no symptoms. Calcium gluconate or calcium chloride are typically used for this. If hypocalcemia continues, a continuous infusion of these solutions may be advised. Calcium gluconate is generally favoured since it is less likely to cause tissue damage if it leaks outside of the vein. It’s important to avoid mixing these solutions with ones that contain bicarbonate or phosphorus, as this could cause calcium salts to precipitate or form solid particles.

Oral calcium: This is calcium taken in tablet form. It’s generally used when the symptoms of hypocalcemia are mild. The calcium is typically provided as calcium carbonate or calcium citrate. The aim is to consume between 1500 to 2000 mg of calcium per day, with doses taken 2-3 times per day to limit potential side effects. It is often recommended that Vitamin D supplements are also taken as it helps the body to absorb calcium more efficiently and is often deficient in patients with hypocalcemia.

Recombinant human parathyroid hormone: This is a lab-made version of a hormone made by the parathyroid glands. It is approved for use in chronic cases of hypoparathyroidism and some genetic diseases resulting in low levels of parathyroid hormone (PTH). However, its use can be limited due to cost and availability, and there are potential long-term side effects to consider such as bone pain and overactive parathyroid glands. Other PTH preparations are currently being developed as an alternative treatment for chronic hypocalcemia caused by low PTH levels.

Disease-specific treatment:

– Post-surgical hypoparathyroidism: After thyroid or parathyroid surgery, most patients will temporarily have low calcium levels due to lowered production of PTH, called hypoparathyroidism. Taking calcium after surgery is sometimes recommended to prevent severe symptoms of hypocalcemia. Calcium levels should be regularly checked after surgery and adjusted as needed.

– Hyponagnesemia: If your blood levels of magnesium are low too, these should be adjusted before treating your hypocalcemia.

– Vitamin D deficiency: If you have hypocalcemia due to a lack of Vitamin D, the Vitamin D deficiency must be treated before the hypocalcemia can be corrected.

Chronic Kidney Disease (CKD): If you have CKD, your hypocalcemia is usually due to a lack of Vitamin D. In this case, taking activated Vitamin D (calcitriol) usually corrects hypocalcemia. If your vitamin D levels are significantly low, taking a high-dose vitamin D supplement each week for 8 to 12 weeks is recommended, followed by a lower daily dose. If you have a history of kidney stones, it’s worth noting that this treatment may increase the risk of developing more stones. To lower this risk, some methods include drinking more water, eating less sodium and eating less animal protein.

What else can Hypocalcemia be?

When a patient has lower-than-normal levels of calcium in their blood, known as hypocalcemia, doctors have to consider a number of conditions that could be causing it. These include:

• Low levels of albumin in the blood (hypoalbuminemia)
• Sudden inflammation of the pancreas (acute pancreatitis)
• A severe bacterial infection (sepsis)
• Sudden damage to the kidneys (acute kidney injury)
• High levels of phosphate in the blood (hyperphosphatemia)
• Low levels of magnesium in the blood (hypomagnesemia)
• Overactive parathyroid glands (hyperparathyroidism)

It’s often difficult to figure out the root cause of the low calcium levels because these conditions can affect and be related to each other.

What to expect with Hypocalcemia

The outlook for people with hypocalcemia, which is low calcium levels in the blood, is generally positive because it can be corrected easily. However, in rare cases, patients who have had their parathyroid glands completely removed might need very high doses of calcium and vitamin D supplements to maintain a normal calcium level.

People who have had gastric bypass surgery, which is a surgical procedure that helps you lose weight by changing the way your stomach and small intestine handle the food you eat, can often have malabsorption. This means their body can’t absorb nutrients from the food they eat as well. These patients may also need very high doses of calcium and vitamin D to correct their low calcium levels.

It’s important to note that taking high doses of vitamin D supplements is commonly associated with nephrolithiasis and nephrocalcinosis. Nephrolithiasis is the medical term for the condition commonly known as kidney stones, while nephrocalcinosis refers to a condition in which excess calcium is deposited in the kidneys.

Possible Complications When Diagnosed with Hypocalcemia

People with extremely low calcium levels, less than 7 mg/dl, or a sudden drop in calcium levels can end up having seizures or critical heart rhythm disorders. It’s crucial in these instances that a heart test is done and calcium levels are adjusted urgently. Individuals who can’t manage their low parathyroid hormone condition well are more likely to develop problems with their kidneys. This includes kidney stones and long-term kidney disease, which can generally lower a person’s quality of life.

Common risks associated with low calcium levels include:

• Seizures
• Life-threatening heart rhythm disorders
• Kidney stones
• Chronic kidney disease
• Decreased general quality of life

Preventing Hypocalcemia

Patients with low calcium levels in their blood, called hypocalcemia, or those who may develop this condition should be informed about its symptoms. They also need to understand the importance of sticking to their prescribed treatment to decrease the risks of experiencing severe symptoms or life-threatening complications. If patients are taking heavy doses of calcium, they should be made aware of the risk of developing kidney stones, also known as nephrolithiasis.