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by James L. Lewis, III, MD

Hypophosphatemia is serum phosphate (PO 4 ) concentration < 2.5 mg/dL (0.81 mmol/L). Causes include alcoholism, burns, starvation, and diuretic use. Clinical features include muscle weakness, respiratory failure, and heart failure; seizures and coma can occur. Diagnosis is by serum PO 4 concentration. Treatment consists of PO 4 supplementation.


Hypophosphatemia occurs in 2% of hospitalized patients but is more prevalent in certain populations (eg, it occurs in up to 10% of hospitalized patients with alcoholism).

Hypophosphatemia has numerous causes, but clinically significant acute hypophosphatemia occurs in relatively few clinical settings, including the following:

  • The recovery phase of diabetic ketoacidosis

  • Acute alcoholism

  • Severe burns

  • When receiving TPN

  • Refeeding after prolonged undernutrition

  • Severe respiratory alkalosis

Acute severe hypophosphatemia with serum PO 4 < 1 mg/dL (< 0.32 mmol/L) is most often caused by transcellular shifts of PO 4 , often superimposed on chronic PO 4 depletion.

Chronic hypophosphatemia usually is the result of decreased renal PO 4 reabsorption. Causes include the following:

  • Hyperparathyroidism

  • Other hormonal disturbances, such as Cushing syndrome and hypothyroidism

  • Electrolyte disorders, such as hypomagnesemia and hypokalemia

  • Theophylline intoxication

  • Long-term diuretic use

Severe chronic hypophosphatemia usually results from a prolonged negative PO 4 balance. Causes include

  • Chronic starvation or malabsorption, especially when combined with vomiting or copious diarrhea

  • Long-term ingestion of large amounts of PO 4 binding aluminum, usually in the form of antacids

Ingestion of aluminum is particularly prone to cause PO 4 depletion when combined with decreased dietary intake and dialysis losses of PO 4 in patients with end-stage renal disease.

Symptoms and Signs

Although hypophosphatemia usually is asymptomatic, anorexia, muscle weakness, and osteomalacia can occur in severe chronic depletion. Serious neuromuscular disturbances may occur, including progressive encephalopathy, seizures, coma, and death. The muscle weakness of profound hypophosphatemia may be accompanied by rhabdomyolysis, especially in acute alcoholism. Hematologic disturbances of profound hypophosphatemia include hemolytic anemia, decreased release of O 2 from Hb, and impaired leukocyte and platelet function.


  • Serum PO 4 levels

Hypophosphatemia is diagnosed by a serum PO 4 concentration < 2.5 mg/dL (< 0.81 mmol/L). Most causes of hypophosphatemia (eg, diabetic ketoacidosis, burns, refeeding) are readily apparent. Testing to diagnose the cause is done when clinically indicated (eg, suggestive liver function test results or signs of cirrhosis in patients with suspected alcoholism).


  • Oral PO 4 replacement

  • IV PO 4 when serum PO 4 is < 0.5 mEq/L or symptoms are severe

Oral treatment

Treatment of the underlying disorder and oral PO 4 replacement are usually adequate in asymptomatic patients, even when the serum concentration is very low. PO 4 can be given in doses up to about 1 g po tid in tablets containing Na or K PO 4 . Oral Na or K PO 4 may be poorly tolerated because of diarrhea. Ingestion of 1 L of low-fat or skim milk provides 1 g of PO 4 and may be more acceptable. Removal of the cause of hypophosphatemia may include stopping PO 4 binding antacids or diuretics or correcting hypomagnesemia.

Parenteral treatment

Parenteral PO 4 is usually given IV. It should be administered in any of the following circumstances:

  • When serum PO 4 is < 0.5 mEq/L (< 0.16 mmol/L)

  • Rhabdomyolysis, hemolysis, or CNS symptoms are present

  • Oral replacement is not feasible due to underlying disorder

IV administration of KPO 4 (as buffered mix of K 2 HPO 4 and KH 2 PO 4 ) is relatively safe when renal function is well preserved. NaPO 4 (rather than KPO 4 ) preparations generally should be used in patients with impaired renal function. The usual parenteral dose of KPO 4 is 2.5 mg (0.08 mmol)/kg IV over 6 h. Patients with alcoholism may require 1 g/day during TPN; supplemental PO 4 is stopped when oral intake is resumed. Serum Ca and PO 4 concentrations should be monitored during therapy, particularly when PO 4 is given IV or to patients with impaired renal function. In most cases, no more than 7 mg/kg (about 500 mg for a 70-kg adult) of PO 4 should be given over 6 h. Close monitoring is done and more rapid rates of PO 4 administration should be avoided to prevent hypocalcemia, hyperphosphatemia, and metastatic calcification due to excessive Ca× PO 4 product.

Key Points

  • Acute hypophosphatemia most often is caused by alcoholism, burns, or starvation.

  • Chronic hypophosphatemia may be due to hormonal disorders (eg, hyperparathyroidism, Cushing syndrome, hypothyroidism), chronic diuretic use, or use of aluminum-containing antacids by patients with chronic kidney disease.

  • Hypophosphatemia is usually asymptomatic, but severe depletion can cause anorexia, muscle weakness, and osteomalacia.

  • Treat the underlying disorder, but some patients require oral, or rarely, IV phosphate replacement.

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