LabMed

Pseudohypoglycemia

At a Glance

Sometimes, you get a low (or even critically low) glucose test result back that just doesn't make sense. The patient has no history of diabetes, is taking no hypoglycemic agents, and has absolutely no symptoms suggestive of hypoglycemia during the office visit. You wonder, “Could the lab test just be wrong?”

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Genuine hypoglycemia may not be accompanied by any symptoms, but a more common occurrence may be "pseudohypoglycemia," the situation in which the measured blood glucose concentration does not reflect the glucose concentration in the blood at the time the specimen was drawn.

Pseudohypoglycemia should not be confused with a laboratory measurement error. Most laboratories retain samples for several days, so the first thing you should do is arrange to have the test repeated on the same sample. If the result is different, then a true measurement error occurred. But, in most cases, the low glucose result will be confirmed, in which case the hypoglycemia reported reflects the true concentration in the sample.

Red blood cells (RBCs) are capable of metabolizing glucose at an appreciable rate. At room temperature, the glucose concentration in a typical blood sample will decrease by about 7 mg/dL/hour as a result of this metabolism. So, a fasting sample whose glucose concentration started at 80 mg/dL could have a concentration as low as 52 mg/dL if left at room temperature for four hours.

The rate of metabolism will, of course, be higher in patients with polycythemia. In some cases, very high white blood cell counts (e.g., >100,000 cells/mm3), whether benign or malignant, can cause pseudohypoglycemia.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

There are at least three ways to prevent this metabolism from occurring:

  1. separating the serum/plasma from the RBCs by centrifugation

  2. keeping the sample at refrigerator temperature until analysis (or centrifugation)

  3. collecting the sample in a special tube containing a chemical (e.g., sodium fluoride) that prevents glycolysis

The first two options are not fool-proof. If centrifugation does not take place relatively soon after sample collection (e.g., less than an hour), then some glycolysis will have taken place. Furthermore, there is no way to be sure how long a delay occurred. Similarly, if refrigeration is delayed or is not continuous (e.g., taking the sample out of the refrigerator to be transported at room temperature to the laboratory for analysis), glycolysis will occur and there will no way to tell how long the sample was not at refrigerator temperature.

In contrast, using a special tube to inhibit glycolysis is virtually fool-proof. Essentially no glycolysis occurs, as the inhibition of the enzymes begins as soon as the sample is drawn. There is no need to centrifuge or cool the sample. The only downside to this solution is that the only analyte that can be measured using this type of collection tube is glucose. If other tests are needed, a separate tube will have to be drawn.

What Lab Results Are Absolutely Confirmatory?

Samples for glucose drawn in a fluoride-containing tube will almost always be accurate.

What Factors, if Any, Might Affect the Confirmatory Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Modern blood gas analyzers may be used to measure parameters other than the traditional PO2, PCO2, and pH, such as electrolytes, free calcium, glucose, and lactate. An advantage of such instruments for these determinations is very short turnaround times, because the analyses are done on whole blood rather than on serum or plasma, both of which require centrifugation. In addition, the analysis is typically done at 37°C.

An unusual phenomenon may occur in patients with polycythemia or very high white blood cell (WBC) counts, whose samples are submitted for analysis on blood gas instruments. Since the RBCs and WBCs remain in the sample and the sample is warmed to 37°C for analysis, the glucose concentration will steadily decrease over the course of time. The instruments will typically give an error message, since they are programmed to wait for a steady endpoint. In such cases, the true glucose concentration is the initial concentration displayed at the beginning of the analysis.

Also, in some cases of pseudohypoglycemia secondary to abnormal WBCs, the fluoride inhibition does not work well. In these cases, one must obtain and keep the sample cold and centrifuge it immediately to prevent the in vitro metabolism of glucose.

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