Hypophosphatemia in Hospitalized PatientsDavid Juan, MD, Mohamed A. Elrazak, MD

Hypophosphatemia is common in hospitalized patients and occursunder a variety of circumstances other than parathyroid hormone excess.Charts of 100 inpatients with hypophosphatemia were reviewed and thepatients divided into five groups on the basis of serum phosphate level: 18,2.1 to 2.4 mg/dL; 49, 1.6 to 2.0 mg/dL; 20, 1.1 to 1.5 mg/dL; 12, 0.6 to 1.0mg/dL; 1, 0.1 to 0.5 mg/dL. The effect of glucose ingestion on serumphosphate level was shown in one normal patient. Whenever carbohydratewas administered intravenously (45 cases), this was considered the primarycause of the hypophosphatemia. Other causes were as follows: diuretics,hyperalimentation, alcoholism, respiratory alkalosis, dialysis, insulin, corti-costeroids, diabetic ketoacidosis, vomiting, phosphate-binding antacid,Gram-negative sepsis, primary hyperparathyroidism, saline, epinephrine,gastrointestinal malabsorption, and unknown. Hypophosphatemia in hospi-talized patients may have multiple causes.

(JAMA 242:163-164, 1979)

HYPOPHOSPHATEMIA is a com¬mon finding in clinical medicine.Gilbert and co-workers' in Birming¬ham, Ala, reported that the incidencewas 21.6% in a population of 18,088inpatients. The purpose of our retro¬spective study was to investigate thevarious causes of hypophosphatemiain hospitalized patients.

METHODIn this retrospective study, 100 inpa¬

tients with hypophosphatemia (serumphosphate level, <2.4 mg/dL) at two medi¬cal centers (the Medical College of Ohioand the St Vincent Hospital and MedicalCenter) in Toledo were reviewed. In our

laboratory, the normal range of phosphateconcentration is 2.5 to 4.5 mg/dL. Since itis known that carbohydrate intake affectsserum phosphate level, we studied theeffects of a standard five-hour glucose

tolerance test on serum phosphate level ina normal subject. Glucose and phosphatedeterminations were done by the standardmethods.23

RESULTSEffect of Glucose on

Serum Phosphate LevelThe effect of a 100-g dose of glucose

on serum phosphate level is shown inthe Figure. The glucose load promptlyled to a decline in serum phosphatelevels, reaching a nadir at 120minutes, soon after the insulin peak.At the end of 300 minutes, the phos¬phate value was back to pretestlevel.

Causes of HypophosphatemiaOn the basis of serum phosphate

value, five groups of hypophospha¬temia patients were distinguished: 18,2.0 to 2.4 mg/dL; 49,1.6 to 2.0 mg/dL;20, 1.1 to 1.5 mg/dL; 12, 0.6 to 1.0mg/dL; 1, 0.1 to 0.5 mg/dL.The Table shows the causes of

hypophosphatemia found in thisretrospective study. Intravenous ad¬ministration of carbohydrate ac¬counted for 45%. Diuretic use, hyper-alimentation, and alcoholism eachaccounted for 7%.

COMMENT

This retrospective study of inpa-tients from both surgical and medicalservices showed that hypophospha¬temia could be due to a variety ofcauses other than parathyroid hor¬mone excess. In fact, primary hyper-parathyroidism was a cause of hypo¬phosphatemia in only 2% of thepatients in our study. In one otherpublished study of the causes of hy¬pophosphatemia in hospitalized pa¬tients," the investigators reportedthat intravenous use of carbohydrateaccounted for 40% of cases, a figurevery similar to ours. They alsoreported that the cause was unknownin 26%, whereas in our series wecould not account for only 6% of thecases.It is well established that, in

normal subjects, serum phosphatevalue can vary as much as 2 mg/dL,primarily because of carbohydrateingestion. Our study confirms thatglucose-induced hypophosphatemiacan occur in a normal subject given a

100-g glucose load and in hospitalizedpatients given carbohydrate intrave¬nously. The mechanism of carbohy¬drate-induced (especially glucose) hy¬pophosphatemia is due to insulinrelease, which enhances both influx ofglucose and phosphate into skeletalmuscle, liver, and other tissues.5 Theclinical implications of this phenome-

From the Medical College of Ohio and the StVincent Hospital and Medical Center, Toledo.

Reprint requests to Medical College of Ohio,PO Box 6190, Toledo, OH 43614 (Dr Juan).

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Effect of 100-g glucose load on serum phosphate level (solid circles). Open circles indicateimmunoreactive insulin; solid squares, glucose.

Causes of Hypophosphatemia

No. ofPatients

Cause (N 100)Intravenously givencarbohydrate 45

Diuretics 7Hyperaltmentation 7Alcoholism 7Unknown 6Respiratory alkalosis 5Dialysis 5Insulin 3Corticosteroids 2Diabetic ketoacidosis 2Vomiting 2Phosphate-binding antacid 2Gram-negative sepsis 2Primary hyperparathyroidism 2Saline infusion 1Epinephrine 1Gastrointestinal malabsorption 1

non are several. First, it is knownthat a patient with diabetic ketoaci¬dosis is at great risk for the adverseeffects of phosphate depletion. Meta¬bolic acidosis, glycosuria, ketouria,and polyuria lead to decrease in phos¬phate reabsorption. In addition toinsulin, hyperglucagonemia causes

enhanced influx of phosphate fromextracellular compartments into cells.The effect of hypophosphatemia onRBC 2,3-diphosphoglycerate and oxy¬gen dissociation is well known.6 It is acommon practice to administer phos¬phate to patients with diabetic keto¬acidosis.' Second, intravenously givencarbohydrate is widely used in hospi-

talized patients. Since hypophospha¬temia has been shown to cause

depression in myocardial function,respiratory failure, and increasedincidence of sepsis, patients undergo¬ing coronary bypass, patients withchronic obstructive lung diseases, andpatients with poor host defense are atgreat risk for the adverse effectsof carbohydrate-induced hypophos¬phatemia."' It is advisable in thesehigh-risk groups to monitor serum

phosphate levels regularly if carbohy¬drates are being administered.Diuretic use has been shown to lead

to increased phosphate excretionfrom the urine.10 Hyperalimentation-related hypophosphatemia is mainlysecondary to administration of an

inadequate amount. Increased inci¬dence of sepsis in patients receivinghyperalimentation has been etio-logically associated with hypophos¬phatemia." The mechanism of eth-anol-induced hypophosphatemia iscomplex. Alcohol may directly lead toincreased phosphate excretion.12 Inaddition, hypomagnesemia, hypocal-cemia, and alcoholic ketosis maydirectly or indirectly lead to hypo¬phosphatemia."14 Recently publishedreviews on hypophosphatemia con¬tain a more detailed discussion of theless common causes as well as thesystemic effects associated with thisabnormality.15"1

CONCLUSIONThis retrospective study of 100

hypophosphatemic inpatients showedthat intravenous carbohydrate ad¬ministration accounted for 46% of allcases. Diuretics, hyperalimentation,and alcoholism each accounted for7.0%. Since hypophosphatemia de¬creases RBC 2,3-diphosphoglycerate(thus impairing oxygen delivery totissue), impairs bactericidal activi¬ties, and causes depression in myocar-dial contractibility, the physicianshould monitor serum phosphate lev¬els more closely in high-risk groups.

This research was supported in part by theDouglass Foundation, St Vincent Hospital andMedical Center, Toledo.

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