Edmund B. Flink

Magnesium deficiency may complicate many diseases. The causes include the following: inadequate intake during starvation or increased requirement during early childhood, pregnancy, or lactation; excessive losses of magnesium as a result of malabsorption from the gastrointestinal tract or from the kidneys during use of diuretics; and to a combination of the two, as in alcoholism. Most often the etiological factors have been operative for a month or more. Acute hypomagnesemia can occur without previous Mg deficiency after epinephrine, cold stress and stress of serious injury or extensive surgery. The clinical manifestations depend on the age of the patient and may begin insidiously or with dramatic suddenness, or there may be no overt symptoms or signs. The manifestations can be divided into the following categories: totally non-specific symptoms and signs ascribable to the primary disease; neuromuscular hyperactivity including tremor, myoclonic jerks, convulsions, Chvostek sign, Trousseau sign (rarely), spontaneous carpopedal spasm (rarely), ataxia, nystagmus and dysphagia; psychiatric disturbances from apathy and coma to some of all facets of delirium; cardiac arrhythmias including ventricular fibrillation and sudden death; hypocalcemia which is responsive only to Mg therapy; and hypokalemia which is not easily nor completely corrected without Mg therapy. The diversity of etiologies and the multiplicity of manifestations result in confusion and controversy. The documentation of normal renal function is absolutely necessary for maximum doses. The order of magnitude of dose is 1.0 meq Mg/kg on day 1, and 0.3 to 0.5 mEq/kg per day for 3 to 5 days. In emergencies such as convulsions or ventricular arrhythmias, a bolus injection of 1.0 gm (8.1 meq) of MgSO4 is indicated. Therapy of Mg deficiency in the presence of renal insufficiency requires smaller doses and frequent monitoring. Complete repletion occurs slowly.

The morning rise and the nocturnal drop in plasma and urinary levels of 17-hydroxycortieosteroids (17-OH-CS) and in urinary sodium, potassium and endogenous creatinine clearance are described in 8 normal subjects receiving a controlled diet composed of equal feedings every three hours. Magnesium excretion was highest during the period of lowest sodium and potassium excretion (3 A.M. to 6 A.M.). Endogenous creatinine clearance had two peaks (6 P.M. to 9 P.M. and 6 A.M. to 9 A.M.) with two low periods (noon to 3 P.M. and 2 A.M. to 6 A.M.). A definite increase in both sodium and potassium excretion was noted during oral administration of graded dosages of cortisol hemisuccinate in patients with treated adrenal insufficiency. Rapid intravenous injection of 5 mg. of cortisol hemisuccinate every three hours into similar subjects obliterated the variations in creatinine clearance but failed to influence decisively the nocturnal drop in sodium, potassium and magnesium excretion. Magnesium excretion was not influenced by administration of cortisol in either group. Five subjects with Cushing's syndrome due to bilateral adrenal hyperplasia had constant levels of 17-OH-CS in plasma and urine throughout the twenty-four hours. These 17-OH-CS values were most strikingly abnormal when compared to normal nocturnal values. The disturbed rhythm in 17-OH-CS levels in these patients was associated with a disturbance in sodium and potassium excretion, but the noctural excretion peak for magnesium was normal.

Sixteen patients with acute myocardial infarction were subjects of a study of the changes in plasma magnesium and long-chain free fatty acid (FFA) levels. In each patient, there was a sharp fall of magnesium levels and a sharp rise of FFA levels shortly after onset of pain. Magnesium and FFA values returned to normal within three days. An absolute fall in total magnesium level and a probable fall in magnesium ion concentration could be important factors in arrhythmias during the first two days. The simultaneous rise in FFA and fall in magnesium levels in a variety of pathologic and physiologic conditions affords an explanation for divergent changes in FFA and magnesium concentrations in acute myocardial infarction. The FFA rise appears to be the fall in magnesium levels, which has been previously unexplained.

The concentrations of total 17-hydroxycorticosteroid (17-OH-CS) and protein- bound 17-OHCS were determined in plasma from various normal and abnormal subjects. The concentration of nonprotein-bound 17-OH-CS was then calculated by subtraction of the protein-bound value from the total 17-OH-CS value. Elevated plasma total 17-OH-CS concentration in Cushing's syndrome was shown to be due entirely to an increase in the nonprotein-bound 17-OH-CS fraction. Conversely, the elevated plasma total 17-OH-CS concentration in estrogen-treated males without signs of Cushing's syndrome was shown to be due entirely to an increase in the protein-bound 17-OH-CS. In women in the third trimester of pregnancy (with signs of mild adrenocortical hyperfunction) the levels of both protein-bound and nonprotein-bound plasma 17-OH-CS were increased. It is suggested that the nonprotein-bound plasma 17-OH-CS fraction is the immediately active form of cortisol. It probably has high activity because it is able to diffuse readily across capillaries and cell membranes.