Are You Sure the Patient Has Hypophosphatemia?
Musculoskeletal symptoms: weakness, bone pain.
Central nervous system symptoms: irritability, apprehension, weakness, numbness, paresthesias, dysarthria, confusion, obtundation, seizures and coma.
Cardiac symptoms: dyspnea, and orthopnea.
Proximal muscle weakness, diaphragmatic weakness.
Laboratory findings: hypophosphatemia (low serum phosphorus <2.5 mg/dL in males and females > 18 years of age; refer to gender and age specific lower limits of normal in patients < 18 years of age).
What Else Could the Patient Have?
Many diseases are associated with hypophosphatemia (see
Laboratory Tests, Outcomes and Interpretation Abbreviations: Ca = calcium; Pi = inorganic phosphorus; PTH = parathyroid hormone; 25(OH)D = 25-hydroxyvitamin D; 1,25(OH)2D = 1, 25-dihydroxyvitamin D; FGF-23 = fibroblast growth factor 23; TmP/GFR = tubular maximum for phosphate/glomerular filtration rate; AA = amino acids
A partial list of conditions associated with hypophosphatemia includes:
Decreased dietary intake.
Decreased intestinal absorption seen in patients with vitamin D deficiency, malabsorption syndromes, secretory diarrhea, and the use of phosphate binders.
A shift of phosphate into the intracellular compartment seen in patients with:
respiratory alkalosis in the context of sepsis, heatstroke, hepatic coma, salicylate poisoning, gout, panic attacks.
administration of or elevated concentrations of hormones such as insulin, glucagon, epinephrine, androgens and cortisol.
administration of nutrients such as glucose, fructose, glycerol, lactate and amino acids.
Increased cellular uptake seen in the context of hypothermia, lymphoma, leukemia, treatment of pernicious anemia, and the "hungry bone syndrome" after parathyroidectomy.
Increased urinary excretion of phosphorus seen in the context of hyperparathyroidism, Fanconi syndrome, X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia, tumor-induced osteomalacia and post-kidney transplantation.
Other Tests That May Prove Helpful Diagnostically
Skeletal X-rays will demonstrate evidence of osteomalacia in adults and rickets in children in patients with long-standing hypophosphatemia. On occasion, hypophosphatemia is due to tumors which elaborate substances that induce urinary phosphate wasting. Such tumors can sometimes be detected by radiological methods.
Tumors causing hypophosphatemia are generally small but can be detected by whole-body magnetic resonance scanning, computed X-ray tomography (CT), technetium 99m scintigraphy, radiolabeled octreotide scanning, or F-18 fluorodeoxyglucose positron emission tomography. If a mass can be palpated or detected by various scanning methods, biopsy and histological examination may show the presence of histology typical for mesenchymal phosphaturic tumors.
Management and Treatment of the Disease
Every effort should be made to identify the cause of hypophosphatemia and to avoid situations that would precipitate it. Besides the administration of phosphorus, therapy will need to be tailored to the underlying cause of the hypophosphatemia. Comments which follow pertain to the administration of phosphorus in individuals who may have phosphorus deficits as a result of nutritional impairment.
Severe hypophosphatemia (less than 1 mg/dL) can occur even though body phosphorus stores are not severely depleted. Furthermore, it is difficult to estimate overall deficits based on serum phosphorus concentrations. If the patient is symptomatic and the hypophosphatemia is of recent origin, phosphorus should be administered orally at an initial dose of 0.08 mmol per kilogram body weight (2.5 mg per kilogram body weight).
If the hypophosphatemia is prolonged in duration and has multiple causes, an initial oral dose of 0.16 mmol per kilogram body weight (5 mg per kilogram body weight) can be administered. Parenteral therapy can be given if the patient is severely symptomatic and serum phosphorus concentrations are less than 1 mg/dL (0.32 millimoles per liter).
In these circumstances, an initial dose of 0.08 mmol per kilogram body weight (2.5 mg per kilogram body weight) intravenously over a period of 6 hours can be administered. Serum phosphorus and serum calcium concentrations should be checked every 2 hours after the initiation of parenteral phosphorus therapy. No more than 0.24 mmol per kilogram body weight (7.5 mg per kilogram body weight) or a total of 16.9 mmol (525 mg) for a 70 kg adult should be administered.
Some investigators have used higher doses of parenteral phosphorus. For example, in the context of critically ill patient is receiving parenteral nutrition, IV doses of phosphorus were given according to the serum concentration of phosphorus: 0.73-0.96 mmol/L (0.32 mmol/kg, low dose), 0.51-0.72 mmol/L (0.64 mmol/kg, moderate dose), and 0.5 mmol/L or less (1 mmol/kg, high dose). According to the report, none of the patients develop hypocalcemia or other complications. While higher doses of phosphorus can be given parenterally, this author uses more conservative and lower amount of phosphorus intravenously.
In chronic hypophosphatemia, phosphate therapy can be given orally so as to administer initially 1 g of phosphate per day (approximately 33 mmol per day). Depending upon the response, phosphorus intake can be increased to 2-3 g per day. If correction of renal phosphorus losses does not occur with oral phosphorus supplements, calcitriol (1, 25-dihydroxyvitamin D) can be added at doses of between 0.5 and 2 mcg per day.
What’s the Evidence?/References
Lentz, RD, Brown, DM, Kjellstrand, CM. "Treatment of severe hypophosphatemia". Ann Intern Med. vol. 89. 1978. pp. 941-4.(An excellent overview of hypophosphatemia and its treatment.)
Clark, CL, Sacks, GS, Dickerson, RN, Kudsk, KA, Brown, RO. "Treatment of hypophosphatemia in patients receiving specialized nutrition support using a graduated dosing scheme: results from a prospective clinical trial". Crit Care Med. vol. 23. 1995. pp. 1504-11.(An excellent overview of hypophosphatemia and its treatment.)
Popovtzer, MM, Knochel, JP, Kumar, R, Schrier, RW. "Disorders of Calcium, Phosphorus, Vitamin D and Parathyroid Hormone Activity". Renal and Electrolyte Disorders. Lippincott-Raven. 1997. pp. 241-319.(A discussion regarding the pathogenesis of hypophosphatemia.)
Taylor, BE, Huey, WY, Buchman, TG, Boyle, WA, Coopersmith, CM. "Treatment of hypophosphatemia using a protocol based on patient weight and serum phosphorus level in a surgical intensive care unit". J Am Coll Surg. vol. 198. 2004. pp. 198-204.(Guidance regarding treatment of hypophosphatemia.)
Brown, KA, Dickerson, RN, Morgan, LM, Alexander, KH, Minard, G, Brown, RO. "A new graduated dosing regimen for phosphorus replacement in patients receiving nutrition support". JPEN J Parenter Enteral Nutr. vol. 30. 2006. pp. 209-14.(Guidance regarding treatment of hypophosphatemia.)
Kumar, R, Folpe, AL, Mullan, BP. "Tumor-Induced Osteomalacia". Translational Endocrinology and Metabolism. vol. 2. 2011. pp. 1-23.(A discussion of the etiology and diagnostic approach to tumor induced osteomalacia.)
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