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Hypomagnesemia
Hypomagnesemia Syndrome

Hypomagnesemia is a condition characterized by lower than normal levels of magnesium in the blood. It is found to be prevalent among hospitalized patients, particularly those in intensive care units.

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WIKIDATA, Public Domain

Presentation

Hypomagnesemia is associated with a number of biochemical abnormalities and hence it is hard to point out specific clinical manifestations for the condition. Two organ systems commonly affected by the deficiency are the cardiovascular system and the nervous system. Hyperactive neuromuscular functioning is a characteristic feature of this condition. Neuromuscular manifestations of the deficiency include seizure, muscular weakness, horizontal and vertical nystagmus, cortical blindness, tremors and paresthesias [10].

Abnormalities in ECG and arrhythmias are the main cardiovascular symptoms of the condition. Hypokalemia and hypocalcemia are also noted in patients with low levels of magnesium. Conduction system of the heart also shows symptoms of neuromuscular hyperactivity, indicated by disturbances in cardiac rhythm like atrial fibrillation, atrial flutter, and tachycardia. Some patients complain of gastrointestinal distress like anorexia and nausea.

The normal levels of magnesium in adults is 1.5-2.5 mEq/L. As the level drops lower than 1 mEq/L, the patient may present with tremors and hyperactive deep-tendon reflexes. Vertical nystagmus and muscular fibrillations are also common. The patient may show high irritability or be disoriented. Depression and psychosis are evident in some patients. In severe cases, respiratory muscle fibers show impaired function.

Gastrointestinal

  • Abdominal Cramps

    However, high doses of magnesium from dietary supplements or medications often result in diarrhea that can be accompanied by nausea and abdominal cramping [ 1 ]. [ods.od.nih.gov]

Cardiovascular

  • Irregular Heart Rhythm

    You may also notice "jerky" movements, high blood pressure, and irregular heart rhythms with severely low blood magnesium levels. [chemocare.com]

    Those with very low levels of magnesium may have muscle weakness, reduced reflex, tremors, hypertension, and irregular heart rhythms. Some people may also have abnormal eye movements. [symptoma.com]

Musculoskeletal

  • Muscle Cramp

    Severe magnesium deficiency associated with proton pump inhibitors (PPIs) has been described recently with clinical presentations varying from life-threatening conditions to muscle cramps and paresthesias. Probably milder cases go undetected. [ncbi.nlm.nih.gov]

    Symptoms can include muscle weakness, tremor, muscle cramps, carpopedal spasm, tetany, seizures, and cardiac conduction disturbances and arrhythmias. [secure.medicalletter.org]

    cramps Muscle fasciculations Chvostek's sign (fascial muscle spasms induced by tapping the branches of the facial nerve) Neurologic Vertigo Nystagmus Aphasia Hemiparesis Depression Delirium Choreoathetosis Cardiovascular Ventricular arrhythmias Torsade [physio-pedia.com]

    This leads to various neuromuscular manifestations such as seizures, muscle cramps, hyperreactive reflexes, depression, nausea and vomiting. [healthhype.com]

  • Chvostek Sign

    Confusion Delirium Tremors Seizures Tachyarrhythmias (particularly VT and VF) Tetany Chvostek sign Trousseau sign ECG changes Widening QRS complexes Peaking T-waves (which vanish in very severe hypomagnesemia) Prolonged PR interval Associated biochemical [derangedphysiology.com]

    Chvostek sign is an involuntary twitching of the facial muscles elicited by a light tapping of the facial nerve just anterior to the exterior auditory meatus. [merckmanuals.com]

    signs despite normal ionized calcium Weakness / fatigue Vertical nystagmus Tetany Seizures Reversible blindness CVS Arrhythmia, especially torsades des pointes (resistant to cardioversion) ECG Changes similar to hypokalemia Digitalis toxicity Metabolic [lifeinthefastlane.com]

  • Muscle Twitch

    When to call your healthcare provider Call your provider right away or go to the emergency room if you have any of the following: Muscle twitching, spasms, or cramps Fatigue Confusion Loss of consciousness or fainting Dizziness Irregular or fast heartbeat [saintlukeskc.org]

Urogenital

  • Polyuria

    In this report, we present a seven-year-old girl with polyuria and polydipsia. She was the daughter of consanguineous parents with a history of neonatal hypomagnesemic convulsion. [ncbi.nlm.nih.gov]

    Some Of The Causes For Hypomagnesemia Are: Excessive intake of alcohol Excessive burns in the body Chronic diarrhea Polyuria Hypercalcemia Hyperaldosteronism Celiac disease Inflammatory bowel disease Malnutrition Sweating What Are The Symptoms Of Hypomagnesemia [epainassist.com]

    Hyperaldosteronism High blood calcium levels (hypercalcemia) Malabsorption syndromes, such as inflammatory bowel disease and celiac disease Medications (amphotericin, cyclosporine, cisplatin,diuretics, aminoglycoside antibiotics etc) Excessive urination (polyuria [hxbenefit.com]

Neurologic

  • Seizure

    INTERVENTION: Child was given oral magnesium supplementation and the seizures got controlled. MESSAGE: Familial hypomagnesemia should be considered in any child with recurrent or refractory hypocalcemic seizures. [ncbi.nlm.nih.gov]

  • Tremor

    […] hypomagnesemia /hy·po·mag·ne·se·mia/ ( -mag″nes-ēm´e-ah ) abnormally low magnesium content of the blood. hypomagnesemia [hī′pōmag′nisē′mē·ə] an abnormally low concentration of magnesium in the blood plasma, which causes nausea, vomiting, muscle weakness, tremors [medical-dictionary.thefreedictionary.com]

    We report the first Japanese case of hypomagnesemia associated with chronic use of PPIs in a 64-year-old man hospitalized for nausea, bilateral ankle arthritis, and tremor of the extremities who had convulsions 3 days after admission. [ncbi.nlm.nih.gov]

    Clinical features are often due to accompanying hypokalemia and hypocalcemia and include lethargy, tremor, tetany, seizures, and arrhythmias. Treatment is with magnesium replacement. [merckmanuals.com]

  • Paresthesia

    Severe magnesium deficiency associated with proton pump inhibitors (PPIs) has been described recently with clinical presentations varying from life-threatening conditions to muscle cramps and paresthesias. Probably milder cases go undetected. [ncbi.nlm.nih.gov]

    Neuromuscular manifestations of the deficiency include seizure, muscular weakness, horizontal and vertical nystagmus, cortical blindness, tremors and paresthesias. [symptoma.com]

    Some of the signs and symptoms of hypomagnesemia therefore includes : Abnormal sensations particularly on the hands and legs known as paresthesias. Muscle weakness, twitching, cramps and tremors. Seizures (convulsions). [healthhype.com]

  • Vertigo

    Laryngeal stridor Seizures Respiratory depression Cardiac arrhythmia Cardiac arrest Dysphagia Nausea Vomiting Anorexia Drowsiness Confusion Vertigo Leg and foot cramps Assessment-Physical Findings Tachycardia Hypertension (see Clinical effects of hypomagnesemia [quizlet.com]

    Presentation Electrolyte abnormalities Hypokalemia Hypocalcemia Neuromuscular Hyperirritability Carpopedal spasm Tetany Muscle cramps Muscle fasciculations Chvostek's sign (fascial muscle spasms induced by tapping the branches of the facial nerve) Neurologic Vertigo [physio-pedia.com]

  • Hyporeflexia

    The patient may also develop muscle weakness, paralysis, and hyporeflexia or areflexia. ECG changes include prolonged QT interval, bradycardia, and heart blocks. [nursingcenter.com]

Workup

Measuring the serum magnesium levels is the accepted method for assessing deficiency of magnesium. It may also be done by assessing the intracellular magnesium content of red cell, mononuclear cell, or skeletal muscle. Other methods to measure the levels of magnesium include fractional excretion of magnesium, intracellular concentration of magnesium ions, and nuclear magnetic resonance spectroscopy.

Apart from direct measurement of magnesium in the serum, magnesium retention may also be checked for assessment. But this method may not be useful in case of renal loss of the cation. Magnesium levels are also interpreted by assessing the levels of proteins in extracellular fluid. Some non-specific changes in the ECG also suggests probability of magnesium deficiency, including ST segment depression, peaked T waves, PR prolongation and broad QRS segment. Urinary magnesium excretion is used to distinguish between hypomagnesemia caused by gastrointestinal and renal losses. The normal blood and urine tests used in the diagnosis of condition include calcium levels, comprehensive metabolic panel, for magnesium and potassium, and urine magnesium tests.

Serum

  • Magnesium Decreased

    Magnesium deficiency also results in decreased release of parathyroid hormone leading to hypocalcemia. [symptoma.com]

QT, RR, ST Intervals

  • Prolonged QT Interval

    The others had electrocardiogram abnormalities (prolonged QT interval, ST depression, and U waves). Concomitant hypokalemia (potassium, 2.8 +/- 0.1 mEq/L) was considered the trigger for these arrhythmias. [ncbi.nlm.nih.gov]

    EKG shows a prolonged PR and QT interval. [medbullets.com]

    ECG changes include prolonged QT interval, bradycardia, and heart blocks. [nursingcenter.com]

    ECG signs may include wide QRS complexes, a prolonged QT interval, flattened T waves and the presence of U waves. Associated metabolic abnormalities as above. Investigations for hypomagnesaemia [ 11 ] Serum Mg level should be tested. [patient.info]

Treatment

Prompt and appropriate treatment helps to resolve the condition in most of the cases. Replenishment of magnesium helps to improve the symptoms. Diet rich in magnesium-containing foods is suggested. Green leafy vegetables, beans, nuts, seeds and whole grains are good sources of magnesium.

Magnesium repletion is done using different routes based on the severity of the symptoms. For those who have hypocalcemia or hypokalemia with hypomagnesemia, intravenous magnesium is suggested. The dose is monitored to keep the concentration above 0.8mEq/L. Patients with substantial deficiency may require sustained replenishment of the ion. Oral replacement is suggested for patients who are asymptomatic. Magnesium is usually given in divided doses with two to four tablets for mild cases of hypomagnesemia. Those who have hypocalcemia or hypokalemia as concomitant conditions with magnesium deficiency, are given calcium and potassium replenishments as well.

If magnesium deficiency is caused by medications like diuretics, it should be immediately discontinued. If a diuretic cannot be discontinued in any of the cases, it should be changed to potassium-sparing diuretic. Serum magnesium levels of all the patients should be monitored continuously and if deficiency persists, oral magnesium supplementation is recommended.

Prognosis

In general, prognosis depends on the actual cause, severity of the symptoms and early treatment. Prognosis is very good if the cause of the deficiency is clear. And in most of the cases, complete recovery is reported. For those with chronic deficiency of magnesium, care should be taken for continuous replenishment.

Etiology

Some of the most common etiologic factors of hypomagnesemia include:

  • Dietary deficiency
  • Redistribution of the cation between intracellular and extracellular space
  • Gastrointestinal and renal loss of magnesium

Hypomagnesemia is seen in malnourished individuals or those who have inadequate intake of the cation in diet. About 30% of alcoholics also have hypomagnesemia [2]. Alcohol induces tubular dysfunction resulting in excessive secretion of magnesium. This condition is reversed with few weeks of alcohol abstinence. Dietary deficiency, pancreatitis, and diarrhea in alcoholics may also lead to hypomagnesemia.

Serum magnesium levels may fall due to redistribution of the cation from extracellular space to intracellular fluid or bones [3]. In patients with diabetic ketoacidosis, insulin therapy may result in shifting of magnesium back into the cells from extracellular fluid [4]. When malnourished patients are fed with carbohydrate-loaded food, extracellular volume increases while levels of magnesium, phosphate and potassium reduces. Parathyroidectomy and thyroidectomy may lead to hungry bone syndrome, characterized by removal of magnesium from extracellular fluid.

Defective or impaired absorption of magnesium results from malabsorption of ions, chronic diarrhea, and bypass surgery of the intestine. Use of proton pump inhibitors (PPIs) is also associated with reduced absorption of magnesium. Magnesium is wasted through excretion in many renal tubular disorders as well. Gitelman syndrome is one of the autosomal disorders that cause hypomagnesemia. Other inherited disorders including antenatal Bartter syndrome, autosomal-dominant hypocalcemia and hypercalciuria also lead to hypomagnesemia.

Certain drugs like loop diuretics and aminoglycosides are known to increase excretion resulting in deficiency of magnesium in blood. Lower level of magnesium is also associated with abnormalities in the transport of calcium and potassium as in hypercalciuria and hypocalciuria. Surgery may result in this condition [5] when the cation chelates with circulating free fatty acids. Some other causes of hypomagnesemia include hyperaldosteronism and hyperglycemia.

Epidemiology

Prevalence of this electrolyte imbalance ranges from 1.5% to 15% in the general population. Incidence of hypomagnesemia is about 12% in hospitalized patients while it is very high, to the order of 60% to 65%, in critically ill patients. About 25% of patients with diabetes show clinical manifestations of hypomagnesemia. Alcoholics also have increased risk of developing this condition. About 30% to 80% of the patients with alcohol dependency develop hypomagnesemia. Information on incidence of this condition in different age groups is sparse. Neonates are considered to have a higher risk of developing this condition when compared to other age groups.

Pathophysiology

Hypomagnesemia results in a number of metabolic abnormalities including decreased levels of potassium in serum. Decreased levels of magnesium lead to differential conductance of K+ ions with more of these ions excreted in the renal tubules [6]. Magnesium deficiency also results in decreased release of parathyroid hormone leading to hypocalcemia [7]. Decreased levels of magnesium affect the ion exchange at the surface of bones with increased absorption of calcium from the serum and increased release of magnesium from bones.

Effect of magnesium deficiency on electrical activity and contraction of myocardium result in a number of cardiovascular effects including arrhythmia [8]. This is mainly due to impaired sodium-potassium pump and increased outflow of potassium. Increases in intracellular magnesium content raise the vascular tone and total peripheral resistance. This may lead to hypertension and this is supported by the fact that magnesium replenishment provide hypotensive effects. Studies also show that magnesium deficiency in serum play an important role in myocardial infarction.

When serum levels of magnesium decrease, axon stabilization threshold reduces. This increases the excitability of both muscles and nerves. Secretion and sensitivity of insulin decrease with magnesium deficiency [9]. Hypomagnesemia is also associated with other diseases like hypertension and hyperlidemia. Migraine is also known to be related to low levels of magnesium. This deficiency is linked to many other conditions including sudden death in athletes, chronic fatigue syndrome, and sudden infant death syndrome.

Prevention

Treating the underlying condition that causes hypomagnesemia goes a long way in preventing the condition. Having a balanced diet, quitting alcohol consumption, controlling diabetes and taking magnesium supplements are all helpful in improving the symptoms. As in many other diseases, prompt diagnosis and start of treatment is very important in preventing complications.

Summary

Hypomagnesemia is an electrolyte imbalance characterized by low levels of the cation magnesium in the blood. This condition has important clinical consequences as magnesium is essential in maintaining the functioning of heart and nervous system. Magnesium also plays a role in energy transfer and storage, and metabolism of fat and carbohydrates [1].

Hypomagnesemia is found to be prevalent among hospitalized patients, particularly those in intensive care units. Low levels of magnesium can affect many organs and may even lead to sudden death. Replenishing the levels of this cation is the most appropriate treatment modality to avoid complications. Prognosis is good if the cause of the condition is clearly defined.

Patient Information

Hypomagnesemia is a condition characterized by lower than normal levels of magnesium in the blood. Normal adults have about 1.5-2.5 mEq/L magnesium in serum. This ion is very important in maintaining the functioning of heart and nervous system in the body. In general population, prevalence of this condition is about 2%. In most of the cases, people have lower amounts of magnesium in the diet than what is recommended.

Under normal conditions, body regulates the level of magnesium by different methods. In some cases, more amount of magnesium is shifted into the cells from the serum resulting in a deficiency. Damage or disorders in the kidney may result in excessive secretion of magnesium in urine leading to a decrease in the levels. Having insufficient amounts of magnesium in the diet, gastrointestinal problems that affect absorption of the ion from food, alcoholism, certain medications, and endocrine disorders may all result in this electrolyte imbalance. Some people may remain without any obvious symptoms even when the blood report shows low levels of magnesium. Those with very low levels of magnesium may have muscle weakness, reduced reflex, tremors, hypertension, and irregular heart rhythms. Some people may also have abnormal eye movements.

A thorough physical examination will help the doctor in identifying the underlying cause of the condition. Other tests that are normally used for confirmatory diagnosis of the condition include ECG, blood calcium levels, blood potassium levels, and level of magnesium in urine.

Treatment of the condition is based on the severity of symptoms and level of deficiency. Patients with mild symptoms may show improvement with oral replacement of magnesium. When the symptoms are acute, intravenous replenishment is recommended. If cardiac problems are seen as symptoms, intravenous magnesium sulfate is suggested. If the deficiency is caused by the use of certain medications, doctors might recommend discontinuation of the same till symptoms improve. If hypomagnesemia is seen with any other conditions like low levels of calcium or potassium, supplements will be given to remove the deficiency. Dietary management of the condition involves having more of magnesium-containing foods including green leafy vegetables, legumes, nuts, seeds and whole grains. The outcome of treatment is good if magnesium is replenished appropriately. If any underlying condition is the actual cause of the disease, treating the same helps to remove the deficiency.

References

  1. Konrad M. Disorders of magnesium metabolism. In: Geary D, Shaefer F. Comprehensive Pediatric Nephrology. Philadelphia PA: Mosby Elsevier; 2008:461-475.
  2. Elisaf M, Merkouropoulos M, Tsianos EV: Pathogenetic mechanisms of hypomagnesemia in alcoholic patients. J Trace Elem Med Biol 1995;9: 210-214.
  3. Brasier AR, Nussbaum SR. Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med. 1988;84(4):654-60.
  4. Chrun LR, João PR. Hypomagnesemia after spinal fusion. J Pediatr (Rio J). 2012;88(3):227-32.
  5. Aglio LS, Stanford GG, Maddi R: Hypomagnesemia is common following cardiac surgery. J Cardiothorac Vasc Anesth 1991;5 : 201-208.
  6. Hebert SC, Desir G, Giebisch G, Wang W. Molecular diversity and regulation of renal potassium channels. Physiol Rev. 2005;85(1):319-71.
  7. Rude RK, Oldham SB, Singer FR. Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Clin Endocrinol (Oxf). 1976;5(3):209-24. 
  8. Khan AM, Lubitz SA, Sullivan LM, Sun JX, Levy D, Vasan RS. Low serum magnesium and the development of atrial fibrillation in the community: the Framingham Heart Study. Circulation. 2013;127(1):33-8.
  9. Lima Mde L, Cruz T, Rodrigues LE, Bomfim O, Melo J, Correia R, et al. Serum and intracellular magnesium deficiency in patients with metabolic syndrome--evidences for its relation to insulin resistance. Diabetes Res Clin Pract. 2009;83(2):257-62.
  10. Drueke TB, Lacour B. Magnesium homeostasis and disorders of magnesium metabolism. In: Feehally J, Floege J, Johnson RJ, eds. Comprehensive Clinical Nephrology. 3rd ed. Philadelphia, PA: Mosby; 2007:136-8.
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