Parathyroid conditions and calcium imbalance: Clinical practice

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Parathyroid conditions and calcium imbalance: Clinical practice

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A 74-year-old woman comes to the emergency department because of altered mental status. Her past medical history includes uncontrolled hypertension and type 2 diabetes mellitus. Her last recorded glomerular filtration rate is 30 mL/min. A radiograph of the patient’s hands shows:
 
Routine blood work is performed. Which of the following series of findings is most likely for this patient?

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Content Reviewers:

Rishi Desai, MD, MPH

There are a number of ways you can measure calcium in the blood.

First, there’s total calcium levels and this is made up of three fractions.

About 40 percent of the calcium is bound to albumin and about 15 percent is bound to minerals and the remaining 45 percent freely circulates the body and it’s called ionized calcium.

Total calcium levels range between 8.5 to 10.5 milligrams per deciliter, while ionized calcium ranges between 4.8 and 5.7 milligrams per deciliter.

When total calcium levels fall below 8.5 milligrams per deciliter, it’s considered hypocalcemia and when total calcium levels rise above 10.5 milligrams per deciliter, it’s considered hypercalcemia.

Okay, let’s start with hypocalcemia.

Individuals with hypocalcemia can be asymptomatic or have symptoms like tetany - which are intermittent muscular spasms - and perioral tingling.

On clinical examination, there may be a positive Chvostek’s sign. That’s when the facial muscles contract in response to tapping the skin over the facial nerve, just 2 centimeters anterior to the ear.

Another sign is the Trousseau sign. That’s where a blood pressure cuff is placed over the individual’s arm and is inflated to a pressure above the systolic blood pressure and is held like that for 3 minutes.

A positive Trousseau sign is when there’s a muscle spasm in the arm and forearm.

Now, the first thing to do in hypocalcemia is redo the lab work to make sure that the reading is accurate.

If hypocalcemia is confirmed, then the next thing is to check albumin levels.

Since most of the total calcium is bound to albumin, any rise or fall in the albumin will affect total calcium levels, leading to pseudohypocalcemia.

Normal albumin levels are 4 milligrams per deciliter and normal total calcium levels are 10 milligrams per deciliter.

For every 1 milligram per deciliter drop in albumin, calcium levels lower by 0.8 milligrams per deciliter. So, based on this, the corrected calcium levels can be calculated.

For example, let’s say that albumin levels are 2 milligrams per deciliter and total calcium levels are 7.8 milligrams per deciliter, which indicates hypocalcemia.

Given that the albumin dropped by 2 milligrams per deciliter, total calcium levels also dropped by 2 times 0.8 milligrams per deciliter, which is 1.6 milligrams per deciliter.

So, the corrected calcium level is 7.8 milligrams per deciliter plus 1.6 milligrams per deciliter, which is 9.4 milligrams per deciliter and that’s in the normal range. That’s an example of pseudohypocalcemia.

Now, if pseudohypocalcemia is ruled out, then ionized calcium levels are also checked, and levels will typically be below 4.8 milligrams per deciliter. At this point, additional labs should be done like PTH levels and phosphate levels.

PTH levels normally range between 10 and 65 picograms per milliliter.

When PTH levels are lower than 10 picograms per milliliter, then there’s also hypoparathyroidism and usually phosphate levels are normal. This is typically caused by the destruction of the parathyroid gland during surgery on the thyroid, parathyroid, or neck surgery for removing a tumor, for example.

Usually it’s transient and the remaining parathyroid glands start functioning again over time.

More rarely, there could be autoimmune destruction of the calcium-sensing receptor in the parathyroids.

Since the receptor can no longer sense calcium levels, PTH levels decrease and as a result, calcium levels decrease as well.

Now, when PTH levels are higher than 65 picograms per milliliter, there are various causes, including vitamin D deficiency, which can be due to inadequate dietary intake, malabsorption, or insufficient sun exposure.

Another cause is chronic kidney disease and it leads to secondary hyperparathyroidism. This happens because with chronic kidney disease, the kidneys aren’t able to properly excrete phosphate- so there’s hyperphosphatemia.

Over time hyperphosphatemia interferes with activation of vitamin D, leading to vitamin D deficiency.

Both hyperphosphatemia and vitamin D deficiency lead to increase secretion of PTH and enlargement of the parathyroid glands.

Then there’s PTH-resistance or PTH-insensitivity, which is where the body is unresponsive to high PTH levels due to some mutation in the PTH receptor.

In this case, PTH levels are high, but the mutation in the PTH receptor, leads to phosphate retention in the kidney, so phosphate levels are also high.

Now, another big cause of hypocalcemia is magnesium depletion. That’s because hypomagnesemia can either induce PTH-resistance or decreases PTH secretion.

Finally, a rare cause of hypocalcemia is acute pancreatitis. The mechanism is unclear, but one theory is that calcium soaps precipitate in the abdominal cavity.

Okay, regarding treatment, when total corrected calcium levels are above 7.5 milligrams per deciliter, oral calcium is given.

When levels of calcium are below 7.5 milligrams per deciliter, 1 or 2 grams of IV calcium gluconate are given over 10 to 20 minutes.

When there’s also vitamin D deficiency, oral vitamin D2 or D3 are given.

When there’s also hypomagnesemia, oral or IV calcium won’t be effective until magnesium levels are normal. Therefore, magnesium depletion is corrected with 2 grams of IV magnesium sulphate over 10 to 20 minutes and is continued until magnesium levels are normal.

Let’s move on to hypercalcemia. Individuals with hypercalcemia can be asymptomatic or can have symptoms like constipation, nausea, and muscle weakness.

There can also be renal symptoms, like polyuria - which happens because the distal tubule isn’t able to properly concentrate the urine.

With hypercalcemia, there’s a high risk for developing kidney stones.

Finally, there can be neurological symptoms like depression and anxiety.

So the first step in hypercalcemia is to redo the lab work to confirm the measurement.

After that, albumin levels are checked and the corrected calcium levels are calculated.

If the corrected calcium levels are in the normal range, then it’s pseudohypercalcemia.

If the corrected calcium level is still high, then the next step is to check PTH levels and phosphate levels.

When PTH levels are high, meaning above 65 picograms per milliliter, then the primary culprit is primary hyperparathyroidism.

With primary hyperparathyroidism, one or more of the parathyroid glands have an adenoma that secretes too much PTH.

Additionally, creatinine levels are checked and eGFR is calculated.

In addition, a 24-hour urinary calcium excretion is measured to calculate the risk for renal complications, like kidney stones.

Most individuals are hypercalciuric, meaning that the urine calcium is greater than 200 milligrams per day.

With primary hyperparathyroidism, phosphate levels are low, because the kidneys aren’t damaged and they’re able to excrete phosphate.

Now, a Sestamibi scan- which is an imaging technique that uses low dose radiation- can be done in order to see which parathyroid glands are overreactive.

Additionally, a DEXA scan can be done to measure bone density, since primary hyperparathyroidism decreases the bone density and increases the risk of pathological bone fractures.

DEXA scans usually check the lumbar spine, total hip, femoral neck or the distal one third of the radius.

Based on the DEXA scan, the T-score is obtained.

When the T score is between minus 1 and minus 2.5, the diagnosis of osteopenia is made.

When the T score is below minus 2.5, then it’s osteoporosis.

In individuals with primary hyperparathyroidism, an abdominal ultrasound or an abdominal CT-scan can be done to look for evidence of kidney stones.