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For further information, see CMDT Part 21-10: Hypophosphatemia

Key Features

Essentials of Diagnosis

  • Serum phosphate < 2.5 mg/dL (< 0.8 mmol/L)

  • Severe hypophosphatemia may cause tissue hypoxia and rhabdomyolysis

  • Renal loss of phosphate can be diagnosed by calculating the fractional excretion of phosphate (FEPO4)

  • Parathyroid hormone (PTH) and fibroblast growth factor (FGF23) are the major factors that increase urine phosphate

General Considerations

  • May occur in the presence of normal phosphate stores

  • Serum phosphate levels decrease transiently after food intake, which stimulates endogenous insulin release

  • In patients with depleted phosphate stores, such as alcoholic or malnourished patients, carbohydrate intake can induce severe hypophosphatemia (refeeding syndrome)

  • Acute respiratory alkalosis can lower serum phosphate concentrations by stimulating glycolysis

  • Several medications can impair intestinal absorption of phosphate, particularly

    • Calcium

    • Magnesium

    • Aluminum-containing antacids

  • Elevated PTH causes hypophosphatemia by inhibiting reabsorption in the kidney

  • Vitamin D deficiency decreases intestinal phosphate and calcium absorption with the resultant hypocalcemia stimulating PTH release, increasing urinary phosphate excretion

  • Generalized dysfunction in the proximal tubule, Fanconi syndrome, is characterized by

    • Hypophosphatemia

    • Metabolic acidosis

    • Glucosuria

    • Aminoaciduria

  • Mutations in FGF-23 are associated with urinary phosphorous wasting with rickets or osteomalacia

Etiology

  • Decreased intestinal absorption (Table 21–8)

    • Starvation

    • Parenteral alimentation with inadequate phosphate content

    • Malabsorption

    • Vitamin D–resistant osteomalacia

  • Increased urinary excretion

    • Phosphaturic drugs (diuretics, theophylline, bronchodilators, corticosteroids)

    • Hyperparathyroidism, hyperthyroidism

    • Renal tubular acidosis (eg, monoclonal gammopathy)

    • Alcoholism

    • Hypokalemic nephropathy

  • Transcellular shift of phosphorus

    • Glucose administration

    • Drugs (anabolic steroids, estrogen, oral contraceptives)

    • Acute respiratory alkalosis

    • Salicylate poisoning

  • Electrolyte abnormalities

    • Hypercalcemia

    • Hypomagnesemia

    • Metabolic alkalosis

  • Abnormal losses followed by inadequate repletion

    • Diabetes mellitus with acidosis, especially during aggressive therapy

    • Recovery from starvation

    • Chronic alcoholism

    • Recovery from severe burns

Table 21–8.Causes of hypophosphatemia.

Clinical Findings

Symptoms and Signs

  • Symptoms are rare ...

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