Hypocalcemia

Symptoms Of Hypocalcemia

Hypocalcemia that develops gradually is most likely to be asymptomatic but acute hypocalcemia can result in severe symptoms requiring hospitalization. Some of the symptoms of hypocalcemia include: 

• Paresthesia (burning or prickling sensation)

• Tetany (involuntary muscle contractions)

• Cramps

• Circumoral numbness (absent or reduced sensory perception around the mouth)

• Seizures

• Twitching in your hands, face, and feet

• Numbness

• Tingling 

• Depression 

• Memory loss 

• Scaly skin

• Changes in the nails 

• Rough hair texture

• Delayed tooth eruption

• Increased dental caries

• Dysphagia (difficulty in swallowing)

• Abdominal pain

• Dyspnea (shortness of breath)

• Wheezing

• Subcapsular cataracts ( a type of cataract)

• Papilledema (swelling of the optic nerve)

Often, treating hypocalcemia may relieve these symptoms immediately. If hypocalcemia is caused by another condition, there might be additional symptoms like: 

• Laryngospasm (spasm of the vocal cords)

• Trouble remembering, learning new things, or concentrating

• Electrocardiographic changes that resemble heart attack

• Prolonged QT intervals on ECG

• Personality disturbances

• Heart failure

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Causes Of Hypocalcemia

The levels of calcium are controlled by Vitamin D, parathyroid hormone, calcitonin, and fibroblast growth factor-23 (FGF23). 

• Parathyroid hormone (PTH) enhances bone resorption and reabsorption of calcium. PTH also stimulates the conversion of Vitamin D (25 hydroxyvitamin D) to the active form (1,25-dihydroxy Vitamin D) and renal excretion of phosphate. 

• Vitamin D stimulates intestinal absorption of calcium, renal absorption of calcium and phosphate and also bone reabsorption. 

• Calcitonin, on the other hand, lowers levels of calcium by inhibiting bone resorption. 

• FGF23 inhibits the conversion of Vitamin D to its active form, thus reducing intestinal calcium absorption.

A number of causes that can cause hypocalcemia are divided into three broad categories:

•  Parathyroid hormone (PTH) deficiency
•  High parathyroid hormone (PTH)
•  Other causes

1. Parathyroid hormone (PTH) deficiency

Hypoparathyroidism or low normal serum PTH occurs as a result of decreased PTH secretion, which can be due to the following reasons:

Post-surgical: This is the most common cause of hypoparathyroidism. It can occur after removal of thyroid gland (thyroidectomy), removal of parathyroid glands (parathyroidectomy), or radical neck surgery. The resulting hypoparathyroidism is usually transient but can also be permanent with subsequent transient or permanent hypocalcemia. 

In cases surgery is required for severe hyperparathyroidism with significantly elevated PTH levels, the abrupt drop in PTH levels after surgery can lead to severe hypocalcemia causing significant calcium uptake into the bones. This condition is termed ‘Hungry Bone Syndrome."

Autoimmune: Autoantibodies against the parathyroid gland are the main cause of autoimmune hypoparathyroidism eventually leading to hypocalcemia.

Abnormal development of the parathyroid gland: Some genetic aberrations can cause abnormal parathyroid gland development. This can be isolated or associated with complex hereditary syndromes like DiGeorge syndrome.

Parathyroid gland destruction: This can also be due to rare diseases of the parathyroid gland like hemochromatosis (absorption of too much iron), Wilson disease (accumulation of excess copper in the liver), or irradiation. Human immunodeficiency virus (HIV) infection is also a rare cause of symptomatic hypoparathyroidism.

2. High PTH levels

Absolute or relative Vitamin D deficiency: Vitamin D deficiency or resistance can occur because of lack of sun exposure, inadequate dietary intake, intestinal malabsorption (steatorrhea), live or kidney disease, osteomalacia and rickets.

Certain medications phenytoin, phenobarbital, and rifampin can also alter Vitamin D metabolism.

Vitamin D dependency results from the inability to convert Vitamin D to its active form or decreased responsiveness of end-organs to adequate levels of the active vitamin. This can lead to decreased calcium absorption and bone resorption. The resulting hypocalcemia leads to a compensatory increase in PTH secretion (secondary hyperparathyroidism).

Vitamin D deficiency is becoming a lifestyle problem all over the world. Learn about 6 signs and symptoms of Vitamin D deficiency.
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Chronic kidney disease: Long term kidney diseases can cause severe hypocalcemia due to abnormal renal loss of calcium and decreased renal conversion of Vitamin D to its active form.

This drives PTH secretion and can cause secondary hyperparathyroidism. However, due to impaired Vitamin D metabolism and high phosphorus level, the serum calcium remains low despite the high PTH.

Pseudohypoparathyroidism (PHP): It is an uncommon group of genetic disorders characterized not by hormone deficiency but by end organ resistance to PTH. It is characterized by hypocalcemia, hyperphosphatemia, and elevated PTH concentration.

3. Other causes

Apart from the above mentioned causes, other causes that can lead to hypocalcemia include:

• Acute pancreatitis: Hypocalcemia is often associated with acute pancreatitis as inflammation of pancreas leads to calcium deposition in the abdominal cavity.

• Hypoproteinemia: Refers to lower-than-normal levels of protein in the body. This reduces the protein-bound fraction of serum calcium.

• Magnesium depletion: This can cause relative PTH deficiency and end-organ resistance to PTH action, usually when serum magnesium concentrations are < 1.0 mg/dL [< 0.5 mmol/L] leading to lower calcium levels.

• Severe sepsis or critical illness: Severe sepsis can lead to hypocalcemia through ways that are not clear. Proposed mechanisms include impaired PTH secretion, dysregulation of magnesium metabolism, and impaired calcitriol secretion. Recent reports also indicate that hypocalcemia is associated with severe Covid-19 infection.

• Hyperphosphatemia: This is an uncommon cause of hypocalcemia which is mostly caused by extravascular (outside a blood or lymph vessel) deposition of calcium phosphate products.

• Massive blood transfusion: Transfusion of >10 units of citrate-anticoagulated blood can cause hypocalcemia. Citrate binds with calcium leading to an acute decline in ionized calcium.

• Radiocontrast agents: These contain the chelating agent ethylenediaminetetraacetate (EDTA) which can decrease the concentration of bioavailable ionized calcium while total serum calcium concentrations remain unchanged.

• Pregnancy: Hypocalcemia is seen during pregnancy, mostly related to poor diet, extreme and persistent nausea, vomiting, or any underlying diseases.

Risk Factors For Hypocalcemia

Hypocalcemia can be due to environmental or genetic factors. Some of the common risk factors in the development of hypocalcemia include:

• Vitamin D deficiency 

• Parathyroid hormone (PTH) deficiency

• Hypomagnesemia

• Hypoalbuminemia

• Hyperphosphatemia

• Newborn babies with diabetic mothers

• Family history of parathyroid disorders

Less common risk factors in the development of hypocalcemia include:

• Surgical removal of parathyroid glands

• Side effects of medications

• Anion chelation (binding of negatively charged ions)

• Pseudohypoparathyroidism

• Hepatic (liver) disease

• Acute pancreatitis

• Increased protein binding

• Critical illness

• Severe sepsis

• History of gastrointestinal disorders

• Tumor lysis syndrome (TLS) is when a large number of cancer cells die within a short period, releasing their contents into the blood

• Osteoblastic metastases (characterized by deposition of new bone, seen in certain types of cancers)

• Anxiety disorders

Diagnosis Of Hypocalcemia

If the cause of hypocalcemia is not clinically obvious the most important investigation is to measure serum parathyroid hormone. A standard biochemical profile, a parathyroid hormone measurement, and a clinical history will usually provide the likely cause of hypocalcemia. The tests required to confirm the diagnosis include:

Laboratory tests

1. Calcium

Hypocalcemia is diagnosed by a total serum calcium concentration < 8.8 mg/dL (< 2.2 mmol/L). However, because low plasma protein can lower total, but not ionized, serum calcium, ionized calcium should be estimated based on serum albumin concentration.

2. Parathyroid hormone

In true hypocalcemia, intact parathyroid hormone concentrations should be high in case of reduced negative feedback of calcium by parathyroids or low if these glands are the cause of the problem.

A high concentration of parathyroid hormone in the presence of normal renal function suggests a deficiency of Vitamin D or calcium malabsorption. 

3. Alkaline phosphatase

A raised serum alkaline phosphatase suggests osteomalacia as a result of Vitamin D deficiency. Parathyroid hormone stimulates clearance of phosphate through the kidneys, so serum phosphate should be low in non-parathyroid disease but high in parathyroid hormone deficiency.

4. Vitamin D

Vitamin D concentrations are useful in confirming Vitamin D deficiency when it presents atypically, and it should be assessed in patients with possible pseudohypoparathyroidism.

Vitamin D helps our body absorb calcium and phosphorus. Diagnosing Vitamin D deficiency is very important and it may require complete workup. Read about Vitamin D profile.
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5. Magnesium

Serum magnesium is important to estimate the normal functioning of the parathyroid gland. In hypomagnesemia, the release of parathyroid hormone is inhibited, leading to (potentially severe) hypocalcaemia. Recognition of hypomagnesemia is important because it is difficult to reverse hypocalcemia without getting back the magnesium levels to the normal range.

6. Phosphate

Low to low normal serum phosphate levels can be due to deficient actions of Vitamin D, loss of calcium in the urine, and deposition of calcium in bone. Hypocalcemia with high normal to high serum phosphate levels includes chronic renal failure and hypoparathyroidism.

Imaging

These may include:

• Plain radiography: Radiographs can diagnose bone disorders like rickets or osteomalacia. It can also disclose the spread of certain tumors to the bones (eg : breast, prostate, and lungs), which can cause hypocalcemia.

• Computed tomography (CT): CT scans of the head may show calcification of basal ganglia (structures linked to the thalamus of the brain).

• Echocardiogram (ECG): The ECG hallmarks of hypocalcemia can be used to determine degree of hypocalcemia.

Prevention Of Hypocalcemia

The main cause of hypocalcemia is the deficiency of calcium and Vitamin D. This can be prevented by:

• Eating foods rich in calcium such as dairy products

• Choosing low-fat or fat-free options to reduce your risk of heart disease

• Including calcium in the diet every day. The dietary need for calcium is as follows:

  • 2,000 mg per day for men and women 51 years of age and above

  • 2,500 mg per day for men and women 19 to 50 years of age

• Adding multivitamin supplements along with the diet

• Understanding the Vitamin D need by consulting the doctor

• Increase your calcium intake, by adding food rich in Vitamin D to the diet. These include:

  • Fatty fish like salmon and tuna

  • Fortified orange juice

  • Fortified milk

  • Mushrooms

  • Eggs

• Exposing oneself to enough sunlight to boost Vitamin D levels

• Making certain lifestyle changes like:

  • Maintaining a healthy body weight

  • Exercising regularly

  • Limiting alcohol intake

  • Restricting tobacco use

Specialist To Visit

The primary cause of hypocalcemia is the abnormal functioning of the parathyroid gland and Vitamin D deficiency. The symptoms can be mild or can be due to an underlying disorder. The doctors that can help are:

• General physician 

• Endocrinologist

• Nephrologist

An endocrinologist who treats metabolic and hormone disorders. A nephrologist focuses on kidney diseases.

Seek medical advice from our world-class professionals to diagnose and treat the symptoms of hypocalcemia. 
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Treatment Of Hypocalcemia

The treatment and management of hypocalcemia can be divided into acute and chronic (long-term) management. They are as follows:

Acute management of hypocalcemia

Acute hypocalcemia can result in severe symptoms requiring hospitalization. The treatment consists of:

• Intravenous calcium if serum calcium levels are below 1.9 mmol/L, ionized calcium levels are less than 1 mmol/L, or if patients are symptomatic.

• Oral calcium supplements and calcitriol (0.25 to 1 μg/day) as needed.

• Correction of magnesium deficiency or alkalosis.

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Chronic management of hypocalcemia

Hypocalcemia that develops gradually is more likely to be asymptomatic, but some of the common symptoms include paresthesia (burning or prickling sensation), tetany (involuntary muscle contractions), cramps, muscle spasms, circumoral numbness (absent or reduced sensory perception around the mouth), and seizures. Its management consists of:

• Calcium carbonate and calcium citrate supplements as they have the greatest proportion of elemental calcium (40% and 28% respectively) and are easily absorbed.

• Calcium supplement dosages are 1 to 2 g of elemental calcium 3 times daily.

• Elemental calcium supplements can be started at 500 mg to 1000 mg 3 times daily and titrated upward.

• Asymptomatic electrocardiography changes usually normalize with calcium and calcitriol supplementation.

• Magnesium supplementation corrects hypomagnesemia-related hypocalcemia.

• Thiazide diuretics decrease urinary calcium excretion by increasing distal renal tubular calcium reabsorption.

• Combining diuretics with a low-salt, low-phosphate diet, and phosphate binders is beneficial.

• Serum calcium, phosphorus, and creatinine should be measured weekly to monthly during initial dose adjustments, with quarterly or twice-yearly measurements once the therapy protocol has stabilized.

Correcting Vitamin D inadequacy

If hypocalcemia is due to malabsorption of Vitamin D, physicians should treat the underlying cause (eg implementing a gluten-free diet for patients with celiac disease). It consists of:

• Correcting the deficiency with ergocalciferol (Vitamin D2) or cholecalciferol (Vitamin D3). 

• Ergocalciferol can be given in doses of 50,000 IU weekly or twice a week with an assessment of levels 3 months later, titrating up until a normal Vitamin D level is reached.

• Alternatively, 300,000 IU of ergocalciferol can be administered intramuscularly, with the first 2 injections spaced 3 months apart, followed by regular injections every 6 months.

• Administrating 100,000 IU of Vitamin D3 once every 3 months is also effective in maintaining adequate Vitamin D levels.

• Vitamin D analogs, particularly calcitriol or alfacalcidol, can be used.

Replacement with PTH for hypoparathyroidism

Replacement therapy with PTH is optional, as it corrects hypercalciuria (decreased amount of calcium in the urine) and potentially reduces the risk of nephrocalcinosis (too much calcium deposited in the kidneys), nephrolithiasis (mineral and salt deposition in the kidneys), and renal insufficiency. It also reduces the wide fluctuation in serum calcium.

Also, PTH reduces urinary calcium excretion that can help in the reduction of the dose of calcium and Vitamin D. PTH has also been studied and might become a valuable addition to current treatment options.

Home-care For Hypocalcemia

Calcium plays a vital role in strengthening the bones and teeth. It also helps in the proper functioning of nerves and muscles. Mild cases of hypocalcemia can be managed by adding foods rich in calcium and certain lifestyle modifications. They are as follows:

• Milk or yogurt can be added to fruit smoothie

• Add greens to the soups or pasta dishes

• Make sure that the vegetable intake is increased in every meal 

• Nuts and seeds such as almonds and sesame seeds can be added to the diet

• Use yogurt instead of vegetable dips

• Take Vitamin D and calcium supplements

• Expose the skin in natural sunlight

• Choose proper clothing and sunscreen to avoid complete blockage of sunlight

• Try UV lamps because when the skin is exposed to UV-B it produces its own Vitamin D

• Eat fortified foods

• Exercise regularly

• Talk to a doctor about medications that can cause hypocalcemia and avoid them

• Include egg yolks in diet

Complications Of Hypocalcemia

Hypocalcemia can be asymptomatic in mild cases to presenting as an acute life-threatening crisis. It is to detect calcium regulating hormones like parathyroid hormone (PTH), Vitamin D, and calcitonin through their specific effects on the bowel, kidneys, and skeleton. The complications are as follows: 

Neurological complications

Neurological complications occur due to the presence of co-morbidities and other electrolyte imbalances. They include:

• Seizures: Hypocalcemia can cause seizures because low ionized calcium concentrations in the cerebrospinal fluid (CSF) can cause increased excitability in the central nervous system. 

• Status epilepticus: A seizure that lasts longer than 5 minutes, or having more than 1 seizure within a 5 minutes period, without returning to a normal level of consciousness between episodes.

• Uremic encephalopathy: It is cerebral dysfunction due to the accumulation of toxins resulting from acute or chronic renal failure. Studies have shown that this can be a complication of hypocalcemia.

• Cerebral edema: It is swelling of the brain. It is a relatively common phenomenon with numerous etiologies including hypocalcemia.

• Coma: With a Glasgow coma scale (used to objectively describe the extent of impaired consciousness in all types of acute medical and trauma patients) of less than 9/15 is seen in severe cases.

Cardiac complications

Numerous case reports associate hypocalcemia with life-threatening cardiac complications such as: 

• Reversible heart failure: Hypocalcemia caused by hypoparathyroidism and hypomagnesemia can cause heart failure in severe cases that can be reversed.

• Torsades de pointes: It is a specific type of fast heart rhythm (heart rate over 100 beats a minute) that begins in the ventricles of the heart.

• Arrhythmias: When hypocalcemia is severe it can predispose to life-threatening arrhythmias. In such cases, a rapid admission to hospital and correction of electrolyte imbalance are needed.

An arrhythmia is a condition in which the heartbeat is irregular. Arrhythmia can occur along with a regular or an irregular heart rate. Read more about its signs, symptoms, causes, risk factors and treatment.
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Alternative Therapies For Hypocalcemia

There is no alternative treatment to hypocalcemia, but mild symptoms can be managed by adding food substances that are rich in calcium and Vitamin D. Some of them include:

1. Dairy products: Increase your intake (in moderation) of milk, cheese, cottage cheese, yogurt, and ice cream as they are rich in calcium.

2. Nuts: Seeds and nuts including almonds and sesame seeds act as vegan dietary sources of calcium.

3. Beans: In addition to being rich in fiber and protein, beans and lentils are good sources of calcium as well. 

4. Broccoli: It provides a generous amount of calcium along with other minerals like beta-carotene (the precursor to Vitamin A) and Vitamins C and K1.

5. Black-eyed peas (lobia): One half-cup serving of black eyed peas contains 8 percent of the daily recommended intake of calcium.

6. Figs (anjeer): They are a good source of both calcium and potassium. These minerals can work together to improve bone density.

7. Oranges: They help in boosting the immune system and are rich in calcium and Vitamin D.

8. Salmon: Fatty fish and seafood are among the richest natural food sources of Vitamin D.

Living With Hypocalcemia

Hypocalcemia is a metabolic disorder that can be asymptomatic or cause mild symptoms. In rare cases, it can lead to a severe life threatening crisis. The treatment of hypocalcemia depends on the cause, the severity, the presence of symptoms, and how rapidly it has developed (acute or chronic).

Most cases of hypocalcemia are clinically mild and require only supportive treatment and further laboratory evaluation. Some of the tips that can help manage mild cases are:

• Eating calcium-rich foods

• Avoiding foods that are high in trans fat

• Reducing alcohol intake

• Making sure there is enough sun exposure

• Not being indoors most of the times

• Choosing sunscreens and clothes that does not block sun exposure completely

• Adding foods that are rich in Vitamin D to the diet

• Exercising regularly

• Quitting smoking

• Maintaining a healthy weight

• Taking Vitamin D and calcium supplements

• Understanding if there is an underlying cause by talking to a doctor