Fredrick L. Kiechle, MD, PhD
Q. Physicians occasionally request “random” blood glucose measurements. What is the suggested reference range for this? I’m inclined to use “critical value,” upper and lower.
A. It is not clear why the physicians are requesting “random” blood glucose measurements. The most frequently encountered disorder of glucose homeostasis is hyperglycemia caused by diabetes mellitus, which affects approximately nine percent of the U.S. adult population.1 The incidence of hypoglycemia is unknown, but it is rare in patients who do not have drug-treated diabetes.2 Hypoglycemia is a blood glucose concentration below the fasting value, but it is difficult to define a specific limit.3 The most widely suggested cutoff in adults is 50 mg/dL. Neonatal blood glucose concentrations are much lower than those in adults.4
Diabetes is most commonly diagnosed by detecting increased glucose in the blood, either in the fasting state or after a glucose challenge (oral glu-cose tolerance test, or OGTT). The cur-rent diagnostic criteria for diabetes5 are: 1. fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L), 2. 2-h plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT, or 3. symptoms of hyperglycemia and casual plasma glucose ≥ 200 mg/dL (11.1 mmol/L). (Casual is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycemia include polyuria, polydipsia, and unexplained weight loss.) In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeating the test on a different day.
Therefore, there is no true reference interval for “random” blood glucose. The values are virtually impossible to interpret in the absence of symptoms. The American Diabetes Association (and World Health Organization) criteria, not the reference interval, are used for the diagnosis of diabetes. As mentioned above, the threshold for diagnosis of hypoglycemia is variable. The reference interval is not useful to diagnose either of these condi-tions.
1. Cowie CC, Rust KF, Ford ES, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006. Diabetes Care. 2009;32: 287– 294.
2. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94:709–728.
3. Service FJ. Hypoglycemic disorders. N Engl J Med. 1995;332:1144–1152.
4. Sacks DB: Carbohydrates. In: Burtis CA, Ashwood ER, Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. St. Louis, Mo.: Elsevier Saunders;2006:837–902.
5. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care. 2009;32(suppl 1):S13–61.
David B. Sacks, MBChB
Associate Professor of Pathology
Harvard Medical School
Medical Director of Clinical Chemistry
Director of Clinical Pathology
Brigham and Women’s Hospital
Member, CAP Chemistry
Q. Are yeast sensitivities indicated in urine cultures?
A. Among yeast, Candida sp. are the most commonly identified in urine samples. The microbiology of candiduria differs from that of candidal infections at other sites in that Candida albicans remains the most common species found in cases of candiduria. C. glabrata is emerging as a nosocomial pathogen with a predilection for the urinary tract. In addition, several reports have demonstrated the predominance of non-albicans species in candiduria, indicating that the fungal species causing candiduria might be shifting to the non-albicans spectrum.
The clinical importance of candiduria is unclear. Candiduria is not common in the healthy population but has been frequent among people admitted to the hospital, especially in those in whom indwelling foley catheters are used. The most common hospital-acquired infection has been urinary tract infection, of which up to 15 percent are caused by Candida species. Part of the decision about whether to treat patients who have Candida species in their urine relates to the possibility of complications developing with untreated infection. Most patients with Candida in urine should not be treated with antifungal agents. Treatment is indicated with antifungals with fungemia or persistence after foley removal, or evidence of symptomatic infection such as fever, leukocytosis, and pyuria that cannot be attributed to another etiology.
The mainstay of managing candiduria continues to be the removal of urinary catheters, as this has shown to have high eradication rates. Routine susceptibility testing is not currently done because the information is not used in management, and a correlation between results of in vitro susceptibility tests and outcome of Candida urinary tract infection is not well established.
Although most studies report a relatively low percentage of concomitant candidemia in patients with Candida in the urine, candiduria that persists after catheter removal may be a surrogate marker of more serious infections. For more serious candidal infections, recent innovations in management include the identification of the Candida sp., as each species demonstrates a unique susceptibility pattern to antifungals.
1. Kauffman CA. Candiduria. Clin Infect Dis. 2005;41:S371–376.
2. Paul N, Mathai E, Abraham OC, et al. Emerging microbiological trends in candiduria. Clin Infect Dis. 2004;39:1743–1744.
3. Rex JH, Pappas PG, Karchmer AW, et al. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy of candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis. 2003;36(10):1221–1228.
Katherine Reyes, MD
Fellow, Infectious Diseases
Henry Ford Hospital
Q. Is it necessary to test lipase and amylase when you can test for pamylase to aid in the diagnosis of pancreatitis?
A. Pancreatitis is an important cause of acute abdominal pain. The annual incidence of acute pancreatitis ranges from 4.9 to 35 per 100,000 population in various reports. The overall mortality in hospitalized patients diagnosed with acute pancreatitis ranges from two to 22 percent and reaches 30 percent in severe cases. The most common biochemical assays to aid in the diagnosis of acute pancreatitis are serum amylase and lipase. However, a new biochemical assay, differentiating pancreatic amylase from other isoenzymes, is postulated to aid in the diagnosis of acute pancreatitis.
Serum amylase rises over the first six to 12 hours after the onset of acute pancreatitis, peaks at 48 hours, and is rapidly cleared from the blood-stream, with an approximate half-life of 10 hours. Serum amylase, in uncomplicated cases, returns to normal ranges within three to five days. In the appropriate clinical setting in a patient with symptoms associated with pancreatitis, serum amylase has a high positive and negative predictive value. Amylase has two dominant isoenzymes, s-amylase and p-amylase (also referred to as alpha amylase), which aid in the breakdown of starches in the salivary glands and pancreas, respectively. The assay is limited in patients with pancreatitis with concurrent hypertriglyceridemia (causing normal serum amylase) or alcoholism (elevated salivary amylase). Also, elevated amylase levels are not specific to pancreatitis, as they can be observed in other conditions such as inflammation of the salivary glands, perforated peptic ulcer (transperitoneal absorption of amylase), macroamylasemia (normal serum amylase bound to abnormal serum protein to form a macroamylase complex), or renal insufficiency (decreased clearance). To account for the nonspecific nature of this enzyme, a value three times the upper reference limit of normal is often used to diagnose acute pancreatitis.
Serum lipase is derived from pancreatic acinar cells and rises four to eight hours after onset of acute pancreatitis, peaking at approximately 24 hours. Lipase typically remains elevated for a longer duration compared with serum amylase (about eight to 14 days). The earlier appearance, peak, and longer half-life make serum lipase more sensitive and specific than serum amylase for the diagnosis of acute pancreatitis. Although lipase may be elevated in disorders outside of the pancreas, including cholecystitis and gastroenteritis, several studies have shown that elevated pancreatic lipase correlates more strongly than amylase with the diagnosis of acute pancreatitis.
The lack of a readily available gold standard for the diagnosis of acute pancreatitis and the variability of chemical methods makes it difficult to calculate sensitivity and specificity for amylase and lipase precisely.
All lipases are inhibited by bile acids. The activity of pancreatic lipase depends on the presence of colipase, which facilitates attachment to triglyceride droplets and prevents bile salts from deactivating pancreatic lipase. Lipase assays commonly use bile acids and colipase in reagents to activate only pancreatic lipase, creating a specific assay for the pancreatic isoform. The sensitivity of serum lipase for the diagnosis of pancreatitis ranges from 85 percent to 100 percent in various reports. However, the specificity of lipase is still more reliable than compared with that of serum amylase.
Commonly used serum amylase assays do not differentiate between pancreatic and salivary isoenzymes. In 1997, Kemppainen, et al., found the sensitivity and specificity of amylase to be 85 percent and 91 percent, respectively. P-isoamylase represents 35 percent to 50 percent of normal serum amylase and can be used to improve diagnostic accuracy. However, colorimetric assays specific for pancreatic amylase are much more expensive at this time than conventional serum amylase and lipase assays. The other option is to identify amylase isoenzymes by electrophoresis, a time- and la-bor-intensive method that is impractical for clinical use.
For the above-stated reasons, the most time-, cost-, and labor-efficient, as well as specific, laboratory diagnosis of pancreatitis will utilize current lipase assays using colipase in their reagents. Amylase testing is unnecessary and redundant. However, physicians are accustomed to ordering amylase testing, often in conjunction with lipase. Changing this established practice will prove challenging.
1. Corsetti JP, Cox C, Schulz TJ, et al. Combined serum amylase and lipase determinations for diagnosis of suspected acute pancreatitis. Clin Chem. 1993;39:2495–2499.
2. MacPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. China: Elsevier Saunders;2007.
3. Kemppainen E, Hietaranta A, Puolakkainen P, et al. Time course profile of serum trypsinogen-2 and trypsin-2-alpha1–antitrypsin in patients with acute pancreatitis. Scand J Gastroenterol. 2000;35(11):1216–1220.
4. Smith RC, Southwell-Keely J, Chesher D. Should serum pancreatic lipase replace serum amylase as a biomarker of acute pancreatitis? ANZ J Surg. 2005;75:399– 404.
5. Treacy J, Williams A, Bais R, et al. Evaluation of amylase and lipase in the diagnosis of acute pancreatitis. ANZ J Surg. 2001;71:577–582. http://www.uptodate.com/online/content/abstract.do?topicKey=pancdis/7667&refNum=14.
Madelyn Lew, MD
Massachusetts General Hospital
Kent Lewandrowski, MD
Associate Chief of Pathology
Director of Clinical Services
(Anatomic and Clinical Pathology)
Massachusetts General Hospital
Harvard Medical School
Dr. Kiechle is medical director of clinical pathology, Memorial Healthcare, Hollywood, Fla.