The first step in a identifying the etiology of hypomagnesemia is to evaluate fractional urinary excretion of magnesium, Dr. Agus said. A value greater than 4% indicates renal magnesium wasting; values less than 4% point to GI wasting. If the value is less than 2.5%, the cause is typically diarrhea, malabsorption, or familial hypomagnesemia, he noted.
In patients with urinary magnesium excretion greater than 2% or 2.5%, the next step is “to measure the 24-hour urinary calcium,” he said. “A level greater than 250 mg in 24 hours indicates a thick ascending limb defect due to diuretics, nephrotoxins, or an abnormality in paracellin-1.” Paracellin-1 is a protein that regulates permeability of calcium and magnesium.
A 24-hour urinary calcium less than 150 mg indicates a defect in the distal nephron with hypocalciuria. The differential diagnosis in this instance is inhibition of the sodium-chloride co-transporter by thiazides or because of a defective gene (Gitelman’s syndrome).
Gitelman’s syndrome is an autosomal recessive disorder that is often not diagnosed until late childhood or even adulthood. It is an abnormality in the gene coding for the thiazide-sensitive sodium-chloride co-transporter in the distal tubule. The syndrome typically presents as cramps, tetany, hypokalemic alkalosis, hypocalcemia, and hypomagnesemia and may be associated with renal salt-wasting that features polyuria, nocturia, fatigue, and a tendency for low BP.
Signs and symptoms
The signs and symptoms of hypomagnesemia can be nonspecific (i.e., anorexia, nausea, apathy), or they can be mediated by hypocalcemia and manifest as tetany, seizures, or positive Chvostek and Trousseau signs. Hypokalemia can occur via activation of the potassium channel of the thick ascending limb; this activation causes urinary potassium wasting. “That presumably is the reason you see such a high incidence of hypomagnesemia in hospitalized patients who are hypokalemic,” Dr. Agus said.
“The important effect of a fall in intracellular magnesium and activation of the calcium and potassium channels is an increased susceptibility to ventricular arrhythmias during myocardial ischemia,” he said. “The rate of ventricular arrhythmias following myocardial infarction doubles or triples with hypomagnesemia. That alone would be a major reason to try to get it under control.”
The treatment of hypomagnesemia varies with the severity of the clinical manifestations. In the presence of acute symptoms such as tetany, hypocalcemia, and/or arrhythmias, the treatment is 50 mEq of IV magnesium over 24 hours, with the goal of maintaining plasma magnesium greater than 1.0 mg/dL.
“We try to treat asymptomatic hypomagnesemia orally but recognize that magnesium transport in the ascending limb is a function of the serum magnesium,” he said.
Slow oral replacement with a sustained-release magnesium preparation is recommended because approximately 50% of a large bolus given to rapidly increase plasma magnesium will be excreted in the urine. Two to eight tablets of a sustained-release preparation (5-7 mEq per tablet) is suggested for mild-to-severe depletion.
Amiloride, which blocks the sodium channel in the far distal nephron, can enhance magnesium reabsorption. “That’s the only other way to treat these patients,” Dr. Agus said.