Hypomagnesemia

Article Author:
Alin Gragossian
Article Editor:
Rotem Friede
Updated:
10/27/2018 12:31:39 PM
PubMed Link:
Hypomagnesemia

Introduction

Magnesium is an important electrolyte. It is a key part of many reactions that occur in the human body, affecting cellular function, nerve conduction, and other needs. Normal serum magnesium levels are between 1.46 and 2.68 mg/dL. Hypomagnesemia is an electrolyte disturbance caused when there is a low level of serum magnesium (less than 1.46 mg/dL) in the blood. Hypomagnesemia can be attributed to chronic disease, alcoholism, gastrointestinal losses, renal losses, and other conditions. Signs and symptoms of hypomagnesemia include anything from mild tremors and generalized weakness to cardiac ischemia and death.

Etiology

Hypomagnesemia can be secondary to decreased intake, as seen in:

  • Starvation
  • Alcoholism
  • Critically ill patients who are receiving total parenteral nutrition

It also can be secondary to the following medications:

  • Loop and thiazide diuretics
  • Proton pump inhibitors
  • Aminoglycoside antibiotics
  • Amphotericin B
  • Digitalis
  • Chemotherapeutic drugs, such as cisplatin, cyclosporine

Lastly, hypomagnesemia can be induced by gastrointestinal and/or renal losses, including but not limited to the following conditions:

  • Acute diarrhea
  • Chronic diarrhea (Crohn disease, ulcerative colitis)
  • Hungry bone syndrome (an increased magnesium uptake by renewing bone following parathyroidectomy or thyroidectomy, causing a decrease in serum magnesium)
  • Acute pancreatitis
  • Gastric bypass surgery
  • Inherited tubular disorders (Gitelman syndrome, Bartter syndrome)
  • Familial hypomagnesemia with hypercalciuria and nephrocalcinosis
  • Other rare genetic renal diseases

Epidemiology

The risk of hypomagnesemia depends on multiple characteristics in various healthcare settings, with the following being the latest incidences according to a report published by the Mayo Clinic:

  • 2% in the general population
  • 10% to 20% in hospitalized patients
  • 50% to 60% in intensive care unit patients
  • 30% to 80% in persons with alcoholism
  • 25% in outpatients with diabetes

There have been no recent studies identifying which age groups are at higher risk of hypomagnesemia.

Pathophysiology

Magnesium is a co-factor in many biochemical reactions. Magnesium has a direct effect on various other electrolytes, including sodium, calcium, and potassium. As described above, low levels of magnesium can occur secondary to renal and gastrointestinal losses.

Magnesium homeostasis involves the kidney (primarily through the proximal tubule, the thick ascending loop of Henle, and the distal tubule), small bowel (primarily through the jejunum and ileum), and bone. Hypomagnesemia occurs when something, whether a drug or a disease condition, alters the homeostasis of magnesium.

Magnesium deficiency also can cause hypocalcemia, as the two are inter-related. Decreased magnesium causes impaired magnesium-dependent adenyl cyclase generation of cyclic adenosine monophosphate (cAMP), which decreases the release of parathyroid hormone (PTH). In turn, calcium levels are decreased as well, as PTH regulates calcium levels.

Magnesium also affects the electrical activity of the myocardium and vascular tone, which is why patients with hypomagnesemia are at risk for cardiac arrhythmias. 

History and Physical

Patients with symptomatic magnesium depletion can present in many ways. The major clinical manifestations include neuromuscular and cardiovascular manifestations and other electrolyte abnormalities. Specific signs and symptoms are outlined below.

Neuromuscular Manifestations

  • Tremors
  • Tetany, including positive Trousseau and Chvostek signs, muscle spasms, muscle cramps
  • Seizures
  • Vertical nystagmus
  • Apathy
  • Delirium
  • Coma

Cardiovascular Manifestations

  • Electrocardiogram changes, including widening of the QRS complex, peaked T waves, prolongation of the PR interval
  • Atrial and ventricular premature systoles
  • Atrial fibrillation
  • Ventricular arrhythmias, including torsades de pointes
  • Cardiac ischemia

Other Electrolyte and Hormone Abnormalities

  • Hypocalcemia
  • Hypoparathyroidism
  • Hypokalemia

Evaluation

It is recommended to check the following in a patient suspected of having hypomagnesemia:

  • Serum magnesium, phosphate, calcium level
  • Basic metabolic panel, including serum creatinine/kidney function, glucose levels
  • Electrocardiogram

Once hypomagnesemia is confirmed, the etiology usually can be obtained from the history. If unsure, the distinction between gastrointestinal losses and renal losses can be made by measuring the 24-hour urinary magnesium excretion. In addition, one can calculate the fractional excretion of magnesium (on a random urine specimen) with the following formula where U” and “P” refer to the urine and plasma concentrations of magnesium (Mg) and creatinine (Cr). 

  • FE = [ U x P ]/[ (0.7 x P) x U ] x 100 

If the fractional excretion of magnesium is above 2% in someone with normal renal function, the hypomagnesemia is likely secondary to renal magnesium wasting from drugs such as diuretics, aminoglycosides, or cisplatin.

Treatment / Management

The treatment of patients with hypomagnesemia is based on a patient’s kidney function, the severity of their symptoms, and their hemodynamic stability. If a patient is hemodynamically unstable in an acute hospital setting, 1 to 2 grams of magnesium sulfate can be given in about 15 minutes. For symptomatic, severe hypomagnesemia in a stable patient, 1 to 2 grams of magnesium sulfate can be given over one hour. Non-emergent repletion of the adult patient is generally 4 to 8 grams of magnesium sulfate given slowly over 12 to 24 hours. In pediatric patients, the dose is 25 to 50 mg/kg (with a maximum of 2 grams).

For an asymptomatic patient who is not hospitalized and can tolerate medications by mouth, sustained-release oral replacement should be tried first.

After repletion, serum electrolyte levels must be rechecked (whether in an inpatient or outpatient setting) to ensure that the treatment was effective. Although serum magnesium levels rise quickly with treatment, intracellular magnesium takes longer to replete. Thus, patients with normal renal function should try to continue magnesium repletion for two days after the level normalizes.

Use caution in repleting magnesium in patients with abnormal kidney function (defined as creatinine clearance less than 30 mL/min/1.73 m2). These patients are at risk of hypermagnesemia. Studies recommend reducing the magnesium dose by 50% and closely monitoring magnesium levels in these patients. 

The underlying cause of persistent hypomagnesemia should be addressed and treated. For example, if a patient is consistently having low levels of the electrolyte due to renal losses, they may benefit from amiloride, a potassium- and magnesium-sparing diuretic.

Differential Diagnosis

Always check for other electrolyte abnormalities when suspecting or treating hypomagnesemia. Low levels of magnesium can, in turn, cause low levels of potassium and/or calcium as well. Furthermore, many other electrolyte and hormonal abnormalities can present with similar symptoms.

Prognosis

Prognosis depends on the underlying cause of the hypomagnesemia. Patients with hypomagnesemia from an identifiable cause have a good prognosis for complete recovery.

Complications

It is important to treat hypomagnesemia. Dangerously low levels of magnesium have the potential to cause fatal cardiac arrhythmias, such as torsades de pointes (polymorphous ventricular tachycardia with marked QT prolongation). Moreover, hypomagnesemia in patients with acute myocardial infarction puts them at higher risk of ventricular arrhythmias within the first 24 hours.

Consultations

Consider consulting a nephrologist if suspecting an inherited tubular disorder or in a patient in which magnesium levels are difficult to regulate. If a patient has a cardiac arrhythmia from magnesium deficiency, cardiology can be consulted, and the patient should be monitored closely on a telemetry floor or critical care unit.

Deterrence and Patient Education

Patients with hypomagnesemia should be encouraged to eat the following foods:

  • Green vegetables, such as spinach
  • Beans
  • Peas
  • Nuts
  • Seeds
  • Unrefined grains