Approach to hypocalcemia: Clinical sciences

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Introduction0:00–0:43

Hypocalcemia refers to a serum calcium level that is below the lower limit of normal, which varies among different labs but 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, calcium imbalances such as hypocalcemia often result in abnormal cardiac rhythm and neurologic dysfunction.
Some important causes of hypocalcemia that you should keep in mind include hypomagnesemia, impaired vitamin D conversion, hypoparathyroidism, and secondary hyperparathyroidism.Now, if your patient presents with a chief concern suggesting hypocalcemia, you should first perform an ABCDE assessment to determine if your patient is unstable or stable.

Unstable patient0:43–1:50

If the patient is 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, as well as cardiac telemetry.
Finally, if needed, provide supplemental oxygen.Now, here’s a high-yield fact to keep in mind! If a patient has hypocalcemia, they may experience laryngospasm, seizures, or a prolonged QT interval on an ECG.
This is especially true when the hypocalcemia is severe or develops rapidly. In such cases, administer intravenous calcium gluconate to increase blood calcium levels.
Also, don’t forget that hypomagnesemia often occurs along with hypocalcemia, so consider giving IV magnesium in this situation as well.Now that we're done with unstable patients, let’s go back to the ABCDE assessment and discuss the stable ones.

Stable patient1:50–2:06

If your patient is stable, first obtain a focused history and physical examination, and order labs, including serum calcium and magnesium levels.

History & Physical2:06–3:24

Your patient may report numbness around the mouth, paresthesias of the fingers and toes, and even emotional lability. On the other hand, physical exam can 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 is when inflating a blood pressure cuff over the patient’s arm causes a spasm of their hand.
You can easily remember them as Chvostek for Cheek, and Trousseau for Triceps!Then, the first thing you need to check with labs is calcium.
Clearly, if results reveal a serum calcium level that’s below the lower limit of normal, you should consider, but not diagnose yet, hypocalcemia.
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.
Although ionized calcium reflects the body's calcium stores accurately, measuring it is more complex than measuring total serum calcium.
Also, keep in mind that when measuring total 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.So, to avoid false results and truly diagnose hypocalcemia, you might need to calculate the corrected total serum calcium level.

Corrected calcium levels3:24–3:57

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 obtain the corrected calcium level.
If the corrected serum calcium level is below the reference range, you can confirm the diagnosis of hypocalcemia!Now, once you’ve diagnosed it, your next step is to review the serum magnesium level, and if it’s below the lower limit of normal, diagnose hypocalcemia due to magnesium deficiency.

Magnesium deficiency3:57–4:34

The thing is, magnesium is essential for the production of parathyroid hormone or PTH. In the setting of low serum magnesium, PTH synthesis is reduced, which in turn leads to hypocalcemia.
However, by correcting magnesium levels, we can restore the normal production of PTH, eventually bringing serum calcium levels back to normal.However, if the serum magnesium level is normal, you should order additional labs, including a basic metabolic panel; serum PTH; and 25-hydroxy vitamin D, which is actually the inactive form of vitamin D.

Impaired vitamin D conversion4:34–5:34

review the serum creatinine, and if it’s elevated, check levels of the active form of vitamin D called 1,25-dihydroxy vitamin D levels.
Low values of 1,25-dihydroxy vitamin D are highly suggestive of hypocalcemia due to impaired conversion of vitamin D to its active form.
This typically occurs when there’s an impaired renal function, because, normally, the kidneys convert vitamin D from its inactive to its active form.
However, when there is impaired renal function, this conversion process is also affected, leading to lower levels of serum calcium.On the other hand, if your patient has normal serum creatinine, check PTH levels, and if it’s low or normal, diagnose hypoparathyroidism.

Hypoparathyroidism5:34–6:35

Hypoparathyroidism is most commonly iatrogenic, resulting from damage to the parathyroid glands after surgery or radiation treatment.
Occasionally the parathyroids can be damaged by autoimmune disorders such as polyglandular autoimmune syndrome. Now, here’s a clinical pearl to keep in mind!
A low or normal PTH can also be seen in genetic conditions such as autosomal dominant hypocalcemia. In this particular disorder, a mutation in the calcium-sensing receptor, or CaSR, makes cells more sensitive to calcium levels, resulting in abnormally low PTH secretion.
To screen for this, check the urine calcium to creatinine ratio. If it’s elevated, order genetic testing to confirm the diagnosis.Alright, let's take a step back and take a look at what to do if PTH is elevated.

Secondary hyperparathyroidism6:35–7:46

In this case, diagnose secondary hyperparathyroidism, and consider the possibility of vitamin D deficiency or impaired vitamin D activity.
Next, review your patient's 25-hydroxy vitamin D level. If it's low, then you can diagnose vitamin D deficiency.On the other hand, if the 25-hydroxy vitamin D level is within the normal range, consider pseudohypoparathyroidism, which is a rare genetic condition associated with end-organ resistance to PTH.
To confirm the diagnosis, order genetic testing. If a mutation is detected, then you can diagnose pseudohypoparathyroidism.
Here’s a high-yield fact! Secondary hyperparathyroidism often develops in patients with chronic kidney disease, where a defect in the activation of vitamin D in the kidneys leads to hypocalcemia and hyperphosphatemia, and the parathyroid glands try to compensate by producing more PTH.Alright, as a quick recap… Hypocalcemia refers to a serum calcium level that’s below the lower limit of normal.

Review7:46–8:43

If you suspect hypocalcemia, obtain a focused history and physical exam, as well as labs including a serum calcium and magnesium levels.
Some important causes of hypocalcemia include hypomagnesemia and impaired vitamin D conversion to its active form. If you rule out these two, assess PTH levels.
Low and normal levels are highly suggestive of hypoparathyroidism. On the flip side, elevated PTH levels confirm the diagnosis of secondary hyperparathyroidism, so your next step is to assess 25-hydroxy vitamin D levels.
Low levels of 25-hydroxy vitamin D are associated with vitamin D deficiency, while normal levels are suggestive of pseudohypoparathyroidism.