Approach to hypocalcemia (pediatrics): Clinical sciences

Hypocalcemia refers to a serum calcium level that is below the lower limit of normal, which is often considered below 8.5 mg/dL. Calcium plays a vital role in various body functions, such as cardiac muscle function and nerve signaling, so hypocalcemia can result in abnormal cardiac rhythm and neurologic dysfunction. The evaluation of hypocalcemia depends on whether a patient is a newborn or an older infant or child.

Now, if a pediatric patient presents with a chief complaint suggesting hypocalcemia, you should first perform an ABCDE assessment to determine if your patient is unstable or stable.

If unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, provide supplemental oxygen.

Now, here’s a clinical pearl to keep in mind! Hypocalcemia can occur in the setting of critical illness. In cases where hypocalcemia is severe or develops rapidly, your patient might have stridor secondary to laryngospasm, as well as seizures or a prolonged QT interval on an ECG.

In such cases, you should administer intravenous calcium gluconate to restore blood calcium levels. Also, don’t forget that hypomagnesemia often occurs along with hypocalcemia, so consider giving IV magnesium as well.

Okay, let’s go back to the ABCDE assessment and discuss the stable patients.

If your patient is stable, first obtain a focused history and physical examination, and order a serum calcium level.

Your patient may report weakness, paresthesias of the fingers and toes, and muscle cramps. Additionally, the physical exam might reveal positive Chvostek or Trousseau signs. The Chvostek sign is positive if tapping over the muscles overlying the facial nerve causes facial muscle spasms. On the other hand, the Trousseau sign occurs when inflating a blood pressure cuff over a patient’s arm causes a spasm of their hand. You can easily remember them as Chvostek for Cheek, and Trousseau for Triceps! Finally, labs will be notable for a serum calcium that is below reference range.

At this point, you should consider hypocalcemia so your next step is to order serum albumin and magnesium. Now, if both serum albumin and magnesium are normal you can diagnose hypocalcemia!

However, if the serum albumin is normal but the serum magnesium level is low, you can diagnose hypocalcemia secondary to magnesium deficiency.

Keep in mind that magnesium is required for the production of parathyroid hormone, or PTH, and low levels of PTH lead to hypocalcemia. However, correcting magnesium levels can restore normal PTH production, eventually bringing serum calcium levels back to normal.

Now, let’s go back and discuss cases where the serum albumin is low and the serum magnesium level is normal.

Here, you should consider pseudohypocalcemia, meaning the low albumin level is causing a false result. This is because approximately half of the calcium in the blood is bound to plasma proteins, mainly albumin, while the other half circulates as ionized calcium. So, when you’re measuring serum calcium in the setting of low serum albumin, there's a chance of getting false results since the albumin-bound calcium is also affected.

In this case, you should calculate a corrected serum calcium level. Do this by subtracting the patient's serum albumin level from 4 and multiplying the difference by 0.8. Next, add the product to the measured serum calcium, and you will get the corrected calcium level.

If the corrected serum calcium is normal, your patient does not have true hypocalcemia, and you can diagnose pseudohypocalcemia.

Finally, if the corrected serum calcium is low, again diagnose hypocalcemia. Now, once you diagnose hypocalcemia, the next step is to assess your patient’s age.

If your patient is a newborn, you’ll need to assess the onset of hypocalcemia. Hypocalcemia within four days of life is usually transient and associated with conditions such as birth asphyxia, prematurity, fetal growth restriction, maternal diabetes, or sepsis.

In this case, you should consider early-onset neonatal hypocalcemia, which typically resolves spontaneously; but you can also consider oral calcium supplementation! Next, repeat a serum calcium level. If serum calcium is normal, you can confirm the diagnosis of early-onset neonatal hypocalcemia.

On the flip side, if the hypocalcemia began after the fourth day of life, you should consider genetic causes of hypocalcemia, like DiGeorge syndrome.

In these individuals, prenatal ultrasound might reveal conotruncal heart defect, or cleft lip and palate, with hypertelorism or ear anomalies. If you suspect DiGeorge syndrome, order a fluorescent in-situ hybridization test, or FISH for short. The finding of 22q11.2 microdeletion confirms the diagnosis of DiGeorge Syndrome.

Alright, now let’s switch gears and discuss hypocalcemia in infants and older children. In this case, your next step is to order additional labs, including a basic metabolic panel or BMP and serum phosphate level; as well as a serum PTH level. Additionally, check levels of 25-hydroxyvitamin D, which is the inactive form of vitamin D; and 1,25-dihydroxyvitamin D, which is the active form of vitamin D. Finally, send a urine sample to assess the calcium-to-creatinine ratio.

First, let’s take a look at the urine calcium-to-creatinine ratio. An elevated ratio is suggestive of a calcium-sensing receptor, or CaSR, mutation, so order a genetic mutation analysis. The presence of a gain-of-function mutation in the calcium-sensing receptor confirms a diagnosis of autosomal dominant hypocalcemia type I.