(See also Overview of Disorders of Phosphate Concentration Overview of Disorders of Phosphate Concentration Phosphorus is one of the most abundant elements in the human body. Most phosphorus in the body is complexed with oxygen as phosphate. About 85% of the about 500 to 700 g of phosphate in the... read more .)
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 alcohol use disorder).
Etiology of Hypophosphatemia
Hypophosphatemia has numerous causes but clinically significant acute hypophosphatemia occurs in relatively few clinical settings, including the following:
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 Hyperparathyroidism Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism, vitamin... read more
Other hormonal disturbances, such as Cushing syndrome Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more and hypothyroidism Hypothyroidism Hypothyroidism is thyroid hormone deficiency. Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. Diagnosis... read more
Electrolyte disorders, such as hypomagnesemia Hypomagnesemia Hypomagnesemia is serum magnesium concentration 1.8 mg/dL ( 0.70 mmol/L). Causes include inadequate magnesium intake and absorption or increased excretion due to hypercalcemia or drugs such... read more and hypokalemia Hypokalemia Hypokalemia is serum potassium concentration 3.5 mEq/L ( 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common cause is... read more
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 Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more (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 alcoholism.
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
Treatment of the underlying disorder and oral phosphate replacement are usually adequate in asymptomatic patients, even when the serum concentration is very low. Phosphate can be given in doses up to about 1 g orally 3 times a day in tablets containing sodium phosphate or potassium phosphate. Oral sodium phosphate or potassium phosphate may be poorly tolerated because of diarrhea. Ingestion of 1 L of low-fat or skim milk provides 1 g of phosphate and may be more acceptable. Removal of the cause of hypophosphatemia may include stopping phosphate-binding antacids or diuretics or correcting hypomagnesemia.
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 Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more , hemolysis, or central nervous system symptoms are present
Oral replacement is not feasible due to underlying disorder
IV administration of potassium phosphate (as buffered mix of K2HPO4 and KH2PO4) is relatively safe when renal function is well preserved. Parenteral 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 Hypocalcemia Hypocalcemia is a total serum calcium concentration 8.8 mg/dL ( 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration 4.7 mg/dL ( 1.17... read more , hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical features... read more , and metastatic calcification due to excessive calcium phosphate product.
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.