Hypophosphatemia is a serum phosphate concentration < 2.5 mg/dL (0.81 mmol/L). Causes include alcohol use disorder, burns, starvation, and diuretic use. Clinical features include muscle weakness, respiratory failure, and heart failure; seizures and coma can occur. Diagnosis is by serum phosphate concentration. Treatment consists of phosphate supplementation.
(See also Overview of Disorders of Phosphate Concentration.)
Hypophosphatemia occurs in 2% of patients who are hospitalized but is more prevalent in certain populations (eg, it occurs in up to 10% of patients with alcohol use disorder who are hospitalized).
Etiology of Hypophosphatemia
Hypophosphatemia has numerous causes.
Clinically significant acute hypophosphatemia occurs in relatively few clinical settings, including the following:
The recovery phase of diabetic ketoacidosis
Acute alcohol use disorder
Severe burns
When receiving total parenteral nutrition (TPN)
Refeeding after prolonged undernutrition
Severe respiratory alkalosis
Acute severe hypophosphatemia with serum phosphate < 1 mg/dL (< 0.32 mmol/L) is most often caused by
Transcellular shifts of phosphate often superimposed on chronic phosphate depletion
Chronic hypophosphatemia usually is the result of decreased renal phosphate reabsorption. Causes include the following:
Increased parathyroid hormone levels, as in primary and secondary hyperparathyroidism
Other hormonal disturbances, such as Cushing syndrome and hypothyroidism
Electrolyte disorders, such as hypomagnesemia and hypokalemia
Long-term diuretic use
Severe chronic hypophosphatemia usually results from a prolonged negative phosphate balance. Causes include
Chronic starvation or malabsorption, often in patients with alcohol use disorder, especially when combined with vomiting or copious diarrhea
Long-term ingestion of large amounts of phosphate-binding aluminum, usually in the form of antacids
Patients with advanced chronic kidney disease (especially those on dialysis) often take phosphate binders with meals to reduce absorption of dietary phosphate. The prolonged use of these binders can cause hypophosphatemia, particularly when combined with greatly decreased dietary intake of phosphate.
Symptoms and Signs of Hypophosphatemia
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 alcohol use disorder.
Hematologic disturbances of profound hypophosphatemia include hemolytic anemia, decreased release of oxygen from hemoglobin, and impaired leukocyte and platelet function.
Diagnosis of Hypophosphatemia
Serum phosphate levels
Hypophosphatemia is diagnosed by a serum phosphate 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 test results or signs of cirrhosis in patients with suspected alcohol use disorder).
Treatment of Hypophosphatemia
Treat underlying disorder
Oral phosphate replacement
IV phosphate when serum phosphate is < 1 mg/dL (< 0.32 mmol/L) or symptoms are severe
Removal of the cause of hypophosphatemia may include stopping phosphate-binding antacids or diuretics or correcting hypomagnesemia.
Oral treatment
Parenteral treatment
Parenteral phosphate is usually given IV. It should be administered in any of the following circumstances:
When serum phosphate is < 1 mg/dL (< 0.32 mmol/L)
Rhabdomyolysis, hemolysis, or central nervous system symptoms are present
Oral replacement is not feasible due to underlying disorder
potassium phosphate contains 93 mg (3 mmol) phosphorus and 170 mg (4.4 mEq or 4.4 mmol) potassium per mL. The usual dose is 0.5 mmol phosphorus/kg (0.17 mL/kg) IV over 6 hours. Patients with alcohol use disorder may require ≥ 1 g/day during total parenteral nutrition; supplemental phosphate is stopped when oral intake is resumed.
If patients have impaired renal function or serum potassium > 4 mEq/L (> 4 mmol/L), sodium phosphate preparations generally should be used; these preparations also contain 3 mmol/mL of phosphorus and are thus given at the same dose.
Serum calcium and phosphate concentrations should be monitored during therapy, particularly when phosphate 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 phosphate should be given over 6 hours. Close monitoring is done, and more rapid rates of phosphate administration should be avoided to prevent hypocalcemia, hyperphosphatemia, and metastatic calcification due to excessive calcium phosphate product.
Key Points
Acute hypophosphatemia most often occurs in patients with of alcohol use disorder, burns, or starvation.
Acute severe hypophosphatemia can cause serious neuromuscular disturbances, rhabdomyolysis, seizures, coma, and death.
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 chronic depletion can cause anorexia, muscle weakness, and osteomalacia.
Treat the underlying disorder, but some patients require oral, or rarely, IV phosphate replacement.
