Thursday, September 5, 2013

Interpreting and Correlating Abnormal Laboratory Values : Glucose Abnormalities

The major purpose of performing analyte determinations in the clinical laboratory is to aid in the diagnosis and management of patients with disease and individuals in health assessment. In this regard, the clinical pathologist/Clinical Biochemist/Clinical Microbiologist are often called upon as a consultant to explain abnormal laboratory values, especially those that do not seem to correlate with one another, and to recommend or even to order laboratory tests that may lead to the correct diagnosis in the work-up of patients for particular medical problems.

For evaluation of test results, the laboratory computer is an invaluable aid. Virtually all such systems perform daily checks for patient values that lie significantly outside of their established reference intervals or that have undergone large changes over a 24-hour period. These are often reported as ‘failed delta checks.’ Thus patients with significantly abnormal laboratory findings can be identified.

Fundamental Principles in Interpretation of Values

Before embarking on a discussion of specific conditions giving rise to abnormal values, certain precepts should always be followed, encapsulated as follows:   
  1. Never rely on a single (out-of-reference range) value to make a diagnosis. It is vital to establish a trend in values. A single sodium value of, for example, 130 mEq/L does not necessarily indicate hyponatremia. This single abnormal value may be spurious and may reflect such factors as improper phlebotomy technique, laboratory variability, etc. Rather, a series of low sodium values in successive serum samples from a given patient does indicate this condition. Thus it is vital to follow trends in particular values. 
  2. Osler's Rule. Especially if the patient is under the age of 60 years, try to attribute all abnormal laboratory findings to a single cause. Only if there is no possible way to correlate all abnormal findings should the possibility of multiple diagnoses be entertained.  
Abnormalities in Clinical Chemistry:

Fig. Abnormal glucose result
Glucose Abnormalities
The normal reference interval for fasting serum glucose is generally between 70-110 mg/dL. As described in Chapter 16 , the two basic abnormalities that occur with serum glucose levels are hyperglycemia, almost always associated with diabetes mellitus, and hypoglycemia due to iatrogenic (overdose with insulin in the diabetic patient) or to other underlying causes (such as reactive hypoglycemia due to ‘hypersensitivity’ to insulin, insulinoma, etc.). 

To establish hyperglycemia, it is vital to determine whether the patient has 
(1) a fasting serum glucose level greater than or equal to 126 mg/dL, or 
(2) a serum glucose level greater than or equal to 200 mg/dL and classic symptoms of diabetes, or 
(3) a 2-hour postload plasma glucose concentration greater than or equal to 200 mg/dL during an oral glucose tolerance test. Any one of the above findings is diagnostic, if it can be confirmed by repeat testing on a subsequent day. In the glucose tolerance test, after giving the patient, who has not eaten for 12 hours overnight, a well-defined amount of glucose orally, the blood and urine glucose levels are followed. Normally, serum glucose levels rise and then fall within about a 2-hour period. If the glucose levels remain elevated, however, the diagnosis of diabetes mellitus may again be made. Also, if glucose is detected in the urine at any point, evidence for this condition is also obtained, although absence of urinary glucose does not in any way rule out diabetes mellitus.

High levels of serum glucose also result in the glycosylation of hemoglobin. Glycosylated hemoglobin levels change slowly over time and therefore constitute a stable and reliable indicator of serum glucose levels over the past 2-3 months. Glycosylated hemoglobin levels that are greater than 7% are considered to be indicative of diabetes mellitus, and efficacy of treatment is gauged by whether this serum level is reduced to less than 7. Of all of the methods for diagnosing and especially for monitoring treatment of diabetes mellitus, measurement of glycosylated hemoglobin levels is perhaps the most accurate and should be measured in conjunction with blood glucose determinations.

Other Abnormal Laboratory Findings in Diabetes Mellitus
As discussed in the electrolyte section above, under the influence of insulin, whenever glucose is transported into the cell, it is accompanied by potassium. In diabetes, in the absence of insulin, blood glucose is elevated as is potassium. Due to increased metabolism of fats, there is a build-up of acetoacetic acid, leading to a metabolic acidosis. In diabetes where the blood glucose becomes exceptionally elevated, i.e., >300 mg/dL, serum osmolality becomes dangerously high and can cause nonketotic, hyperosmolar coma. In this condition, red (and white) cell water flows from the cells into the vascular volume, tending to dilute analytes such as sodium. Thus the nonketotic, hyperosmolar coma patient may have a hyperosmolar serum, hyperglycemia, hyperkalemia and hyponatremia. In ketotic states, the patient will have, additionally, a metabolic acidosis and a large anion gap.

In hypoglycemia, serum glucose levels of < 60 mg/dL on a series of random fasting serum specimens strongly indicate this condition. Glucose tolerance tests show that after an initial sharp rise of serum glucose levels, there is an abnormally rapid drop to levels substantially below 60 mg/dL. If hypoglycemia is suspected, it is advisable to give the patient a 5-hour glucose tolerance test because the hypoglycemic ‘dip’ often is not seen until after 3 hours. Glucose tolerance tests on patients with suspected hypoglycemia should be performed with great caution because the procedure can induce severe reactive hypoglycemia causing loss of consciousness and even shock.

(Source: McPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed.)

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