How to Diagnose Calcium and Magnesium Problems for the Physician Assistant Exam

Understanding the evaluation of abnormal calcium and magnesium levels is rather straightforward and important for the Physician Assistant Exam (PANCE). Knowing how to treat these electrolyte abnormalities, especially hypercalcemia, is really important. Calcium metabolism is intricately involved with the parathyroid gland. Magnesium is an important co-factor for more than 300 enzymatic reactions in the body. Having labs that are wonky can affect the heart, increasing the risk of dysrhythmias.

Hypercalcemia

A normal calcium level on reference labs is usually 8.5 to 10.2 mg/dL. Higher levels than this are called hypercalcemia. The symptoms of hypercalcemia depend on the calcium level:

  • At levels of around 11 to 12 mg/dL, common complaints include fatigue, weakness, and constipation.

  • At levels around 14 to 16 mg/dL, someone may experience changes in mentation, difficulty thinking, and polyuria. There can also be abdominal pain.

Because calcium is a potent vasoconstrictor, very high levels can cause peptic ulcer disease and pancreatitis as well. Hypercalcemia can also be a cause of acute kidney injury (AKI).

Causes of hypercalcemia

The two most common causes of hypercalcemia are primary hyperparathyroidism (PHP) and malignancy. Remember the triad of primary hyperparathyroidism:

  • The calcium level is normal or elevated.

  • The parathyroid gland value is normal or elevated. (Note: In the setting of hypercalcemia, the intact parathyroid hormone [PTH] level should be depressed, so even a normal level would be abnormal in this situation.)

  • The 24-hour urinary calcium level is elevated (hypercalciuria).

The most common cause of primary hyperparathyroidism is a parathyroid adenoma, which usually affects one of the parathyroid glands. The initial evaluation, in addition to biochemical testing, can include obtaining an ultrasound of the neck as well as a nuclear scan to get a better look at the parathyroid glands.

The treatment is usually surgical removal of the parathyroid adenoma once identified. Common indications for parathyroid surgery include an elevation in the serum creatinine level, recurrent kidney stones, osteoporosis, and hypercalcemia.

Many of the malignancies that cause hypercalcemia are solid-organ tumors and do so either by directly invading the bone or by secreting a parathyroid-like hormone. This is why part of the workup for hypercalcemia can involve checking not only an intact PTH level but also a PTH-related peptide.

Examples of common malignancies that can cause hypercalcemia include lung, breast, and prostate cancer. In addition, if a solid-organ malignancy is suspected, a “metastatic workup” is undertaken. It can involve CT scans of the thorax, abdomen, and pelvis; a bone scan; and brain imaging.

Here are a few key points concerning the evaluation of hypercalcemia:

  • Differential diagnoses for a high calcium level include a plasma cell dyscrasia like multiple myeloma, vitamin D or vitamin A excess, and medications like hydrochlorothiazide, lithium, and theophylline.

  • Granulomatous diseases such as sarcoidosis can also cause hypercalcemia and hypercalciuria. The mechanism of hypercalcemia is increased 1,25-hydroxyvitamin D3 from the granulomas themselves. Thus, checking a 1,25-hydroxyvitamin D3 level can be part of the initial lab evaluation for hypercalcemia.

  • On an ECG, hypercalcemia can cause a shortening of the QT interval.

  • Milk alkali is a funky cause of hypercalcemia that consists of the triad of ingesting lots of milk, taking a lot of antacids, and having kidney failure or kidney stones. Many patients also have a metabolic alkalosis.

How to treat hypercalcemia

Many, if not all, patients who present with hypercalcemia are significantly volume-depleted. The first line of treatment consists of intravenous hydration with normal saline.

Other treatments include the use of furosemide (Lasix) and calcitonin-salmon (Miacalcin). Give this subcutaneously if and only if you first do an intradermal test dose and it’s negative. In addition, bisphosphonates can be administered intravenously. In rare instances, if the calcium level is very high (that is, > 20 mg/dL), the patient may need dialysis to remove the calcium.

The bisphosphonates administered intravenously, including pamidronate disodium and zoledronic acid, both have the potential to cause acute kidney failure. If kidney disease is present, the doses may have to be reduced or delayed until the kidney function is better. And if the GFR is < 30 mL/min, these medications should not be given.

Which one of the following represents symptoms and/or complications of hypercalcemia?

(A) Diarrhea
(B) Psychoses
(C) Gallstones
(D) Hypertension
(E) Proteinuria

The answer is Choice (D). Hypercalcemia is a vasoconstrictor and can cause hypertension.

Hypocalcemia

Hypocalcemia, usually defined as a corrected calcium level < 8.5 mg/dL, is relatively uncommon. However, you should be aware of some key points about hypocalcemia:

  • If the corrected calcium level is low, first check a magnesium level. A very low magnesium level (usually <= 1.4 mg/dL) can cause hypocalcemia.

  • Your initial workup includes checking vitamin D levels, phosphorous, magnesium, and an intact PTH level.

Hypomagnesemia

Hypomagnesemia is defined as a magnesium level of < 1.6 mg/dL. Very low magnesium levels can contribute to both low potassium and low calcium levels. Like hypocalcemia, low magnesium levels can cause QT interval prolongation on the ECG.

The most common cause of hypomagnesemia is renal losses, usually from medications like diuretics, amphotericin B, and cisplatin.

GI losses like those found in certain malabsorption syndromes and inflammatory bowel disease (IBD) can also cause hypomagnesemia.

Therapy consists of either oral magnesium replacement such as magnesium oxide or intravenous replacement with magnesium sulfate. You need to watch some of the oral magnesium replacements because they can cause diarrhea.

Hypermagnesemia

The kidney is the main organ of excretion for magnesium, and normally your kidney is pretty good at getting rid of it. Thus, the primary cause of hypermagnesemia is excessive magnesium intake in the setting of kidney failure. Therapies to help with the renal excretion of magnesium include intravenous fluids, high dose furosemide (Lasix), and, when needed, dialysis.

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