Hypomagnesemia Workup

Updated: Jul 19, 2022
  • Author: Tibor Fulop, MD, PhD, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Approach Considerations

Patients whose clinical condition suggests magnesium depletion should have their serum magnesium level measured. Most laboratories use a reference range of 1.5 to 2.5 mg/dL for serum magnesium. Hypomagnesemia reliably indicates reduced total body stores of magnesium.

However, while measurement of serum magnesium is relatively easy, and it has become the method of choice to estimate magnesium content, its ability to evaluate total body stores of magnesium is limited. A person may be intracellularly magnesium depleted and exhibit signs of magnesium deficiency, yet have normal serum levels of magnesium. In this setting, serum magnesium tends to remain within the normal range due to recruitment of intracellular stores, until the point where the intracellular stores cannot keep up.

Unfortunately, no quick, simple, and accurate test is available to measure magnesium at the intracellular level, which is where the major physiologic role of magnesium occurs. Excluding magnesium deposited in bone, which is poorly mobilized, the extracellular fluid space contains only 2% of total body magnesium, and levels there may not always accurately reflect the intracellular magnesium status.

A surrogate for direct intracellular magnesium is the measurement of magnesium retention after acute magnesium loading. A magnesium deficiency is indicated if a patient has reduced excretion (< 80% over 24 h) of an infused magnesium load (2.4 mg/kg of lean body weight given over the initial 4 h). 

This method is useful only when the clinical suggestion of magnesium deficiency is strong (eg, the patient has unexplained cardiovascular or neuromuscular abnormalities) but serum magnesium levels are normal. It is not helpful in the setting of renal magnesium wasting (as seen with diuretics) or in the presence of renal dysfunction.

However, the utility of this test is uncertain. Patients with malnutrition, cirrhosis, diarrhea, or long-term diuretic use typically have a positive result, whether or not they have signs or symptoms referable to magnesium depletion. It seems prudent, therefore, to simply administer magnesium to these patients if they have unexplained hypocalcemia and/or hypokalemia.

Another caveat to estimating serum magnesium levels is that although only free magnesium is biologically active, most methods of assessing the serum content measure total magnesium concentration. Because 30% of magnesium is bound to albumin and is therefore inactive, hypoalbuminemic states may lead to spuriously low magnesium values.

The majority of patients with clinical manifestations of magnesium deficiency have hypomagnesemia. Magnesium assessment can also be made via the following, which are mostly limited to research purposes.

  • Red cell content
  • Mononuclear cell content
  • Skeletal muscle intracellular content
  • 24-hour urinary excretion
  • Fractional excretion (FE) of magnesium
  • Intracellular free magnesium ion concentration with fluorescent dye or nuclear magnetic resonance spectroscopy

Protein, potassium, phosphate, and calcium

Because extracellular magnesium is protein bound, the patient's protein status is an important consideration in interpreting magnesium levels.

Hypomagnesemia contributes to hypokalemia. This condition may be due to a hypomagnesemia-induced decline in adenosine triphosphate (ATP) and the subsequent removal of ATP inhibition of the renal outer medullary K (ROMK) channels responsible for secretion in the thick ascending limb of Henle and collecting duct. In addition, hypophosphatemia has been found in patients with hypomagnesemia.

Hypocalcemia is caused by magnesium depletion, but the reason is not known. Some studies link hypomagnesemia to decreased parathyroid hormone levels and end-organ resistance to parathyroid hormone. Alterations in vitamin D metabolism can contribute to hypocalcemia.


Electrocardiographic (ECG) findings in hypomagnesemia are nonspecific, and include the following:

  • ST segment depression
  • Tall, peaked T waves
  • Flat T waves or depression in the precordium
  • U waves
  • Loss of voltage
  • PR prolongation
  • Widened QRS complex

Excretion Analysis

If hypomagnesemia is confirmed, the diagnosis can usually be obtained from the history. If no cause is apparent, the distinction between gastrointestinal and renal losses can be made by measuring the 24-hour urinary magnesium excretion or the FE of magnesium on a random urine specimen. The latter can be calculated from the following formula:

FEMg = [(UMg x PCr) / (PMg x UCr x 0.7)] x 100

In the above equation, U and P refer to the urine and plasma concentrations of magnesium (Mg) and creatinine (Cr). The plasma magnesium concentration is multiplied by 0.7, since only about 70% of the circulating magnesium is free (not bound to albumin) and therefore capable of being filtered across the glomerulus. The normal renal response to magnesium depletion is to reduce magnesium excretion to very low levels. Thus, daily excretion of more than 2 mEq (1 mmol or 24 mg) or a calculated FE of magnesium above 3% in a subject with normal renal function indicates renal magnesium wasting.