AssessmentsParathyroid conditions and calcium imbalance: Clinical practice
USMLE® Step 2 style questions USMLE
A 55-year-old female presents to her family physician with pain in the fingers of her right hand. She is mildly confused and is unsure exactly how long she has had this pain. The patient's daughter, who accompanied her mother to the visit, says that the patient has complained about this pain for about a month and has been progressively more confused over the last week. She also says that her mother has been complaining of increased nausea for the last few months. An X-ray of the right hand shows thin bones with brown tumors. Based on the patient's history and symptoms, what is the most likely cause of her condition?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Anca-Elena Stefan, MD
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.
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.
Okay, let’s start with hypocalcemia.
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.
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.
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.
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.
There can also be renal symptoms, like polyuria - which happens because the distal tubule isn’t able to properly concentrate the urine.
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.
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.
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.
The parathyroid glands are four small glands in the neck that produce parathyroid hormone (PTH), which plays a major role in regulating calcium in the body. High levels of PTH lead to hyperparathyroidism, whereas low levels can lead to hypoparathyroidism. Hyperparathyroidism leads to an increase in blood calcium levels, resulting in symptoms like fatigue, muscle weakness, bone pain, osteoporosis, and kidney stones.
Hypoparathyroidism leads to a decrease in blood calcium levels. This can cause symptoms like tingling in the fingers and toes, muscle cramps, and seizures. Hyperparathyroidism is treated by surgically removing the overactive parathyroid gland; whereas in hypoparathyroidism, calcium and vitamin D supplementation, and hormone replacement therapy can help manage the symptoms.