Oct 19, 1992 - Washington University School of Medicine, St. Louis, MO 63110. 2 Current ... fications. Right upper abdominal sonography revealed a partially ...
CLIN. CHEM. 39/2,
234-243
(1993)
(Washington Universiti Case Conference) The Clinical Chemistry Laboratory and Acute Pancreatitis Presentor: Edward C. C. Wong Discussants: Anthony W. Butch and Jerry L. Rosenblum”2 Editors: Jack H. Ladenson and Mitchell G. Scott3
PresentatIon of Cases
Case 2
Case 1
to the hospital forabdominal pain. Two months before admission, the patient had reported right upper quadrant and right A 73-year-old white man was admitted
A 57-year-old white woman presented to the emergency room with a 4-day history of dull, intermittent, and increasing epigastric pain that radiated to her back. She had difficulty keeping down solids or liquids but denied fevers, chills, dyspnea, chest pain, palpitations, or a history of pancreatitis. She also denied recent travel or any history of alcohol or drug abuse. Past medical history was significant for hypertension, impaired glucose tolerance, and hypercholesterolemia. Family and social history were noncontributory. The patient appeared to be a well-developed, well-nourished, but jaundiced woman in moderate distress. Physical examination was remarkable for dry oral mucosa and an obese abdomen with hypoactive bowel sounds, no rebound tenderness, and voluntary guarding upon palpation. Laboratory data (reference values in parentheses) were remarkable for a potassium of 3.2 mmol!L (3.5-5.1 mmolJL), cholesterol 3.83 g/L (2x ULN. tlpaee 5x ULN among these hyperamylasemic patients. 238
CLINICAL CHEMISTRY, Vol.39, No. 2,
1993
much improved in assay time and reproducibility and included turbidimetric/nephelometric, coupled-enzymatic, and titrimetric methods. Three of the four studies used lipase assays that included colipase (18, 60, 87). However, it is unclear whether these improvements in lipase assays resulted in increased lipase specificity. The improvements cannot be simply due to the use of bile salts and colipase because in one study (20) an assay without colipase was used and the lipase specificity was 99%! Furthermore, Lott et al. (61) found similar specificities between assays with and without colipase; however, only a few patients’ samples were assayed by both methods. The study by Orda et al. (87) did not include individual amylase or lipase measurements and could not be evaluated for sensitivity or specificity. Instead, this study presented ranges for amylase and lipase activities of patients with or without pancreatitis. They found that the range of lipase values in patients with pancreatitis did not overlap with the range of lipase values in patients with nonpancreatic disease, whereas the range of amylase values did overlap between the two groups. In the third group of studies, from the late 1980s (13, 14,88), both the sensitivity and specificity of lipase were concluded to be greater than that of amylase (Table 1). However, these studies generally utilized amylase or lipase in the diagnostic workup and, like most studies, had no objective visualization of the pancreas. Selection bias is also clearly evident in these studies. Lin et al. (14), for example, excluded patients known to have nonpancreatic causes of hyperamylasemia and hyperlipasemia. At the same time, patients with amylase values >3x ULN were diagnosed as having pancreatitis. Werner et al. (13) considered that patients with amylase and lipase activities >2x ULN had acute pancreatitis. In the study by Navarro et al. (88), the diagnosis of acute pancreatitis required not only a compatible clinical picture and radiographic or surgical confirmation, but also increased serum immunoreactive trypsin, which has been shown to correlate well with lipase values in patients with suspected pancreatitis (21). Such selection bias may have led to the much higher sensitivity for lipase than for amylase (88) (Table 1). In this third group of studies, the assays used are relatively homogeneous compared with those in the other two groups of studies, and all lipase assays contain colipase. Taken together, the lack of objective criteria, the use of the studied laboratory tests for diagnosis, and changes in the methods make this set of literature extremely confusing regarding the true clinical utility of these tests. Because of the infrequent use of laparotomy to diagnose pancreatitis, Lott et al. (15) attempted to use criteria that were as objective as possible to diagnose patients with or without pancreatitis. Their 78 patients with suspected pancreatitis, defined by an increase of either amylase or lipase, were objectively diagnosed by laparoscopy (n = 46), computed tomography with or without ultrasound (n = 26), ultrasound only (n = 2), or expert clinical judgment (n = 2). Such selection criteria
will overestimate sensitivity and underestimate specificity. Nevertheless, this study carefully examined the type of population that most often presents a diagnostic dilemma. The Ektachem coupled-enzyme (colipase-mediated) assay was used to measure lipase, and the aca saccharogenic assay (Du Pont Clinical Systems, Wilmington, DE 19898) was used to measure amylase. In their study, the sensitivity of lipase was higher, whereas the specificity of lipase was lower than that of amylase when the manufacturer’s “normal” ranges are used. The higher sensitivity of the colipase-mediated lipase assay suggests that this type of lipase assay be considered as a useful adjunct to amylase measurement in patients with acute pancreatitis. Within this population, the specificity of lipase could be greatly improved with minimal effects on sensitivity if higher (2-5x ULN) cutoff values were used. Clavien et al. (19) recently examined 352 consecutive attacks of acute pancreatitis in 318 patients (confirmed radiographically) and found a high percentage (19%) of patients with normoamylasemia. In 68% of these normoamylasemia cases, lipase was above-normal by the Ektachem assay. Unfortunately, the converse evaluation of the number of patients with above-normal amylase but normal lipase was not made. Nevertheless, normal amylase but increased lipase can clearly occur in pancreatitis, which suggests that lipase should always be examined. During the past year, we have become aware of several patients at our institution with computerized tomography-confirmed pancreatitis and lipase values >1000 UIL and amylase values URL
assays
89
138
260
106
221
503
213 653
30 52
108 304
65 75
102
109
20
111
119
16
1112 1116
10th
25th
Du Pont Kodak Amylase
55 57
DuPont Kodak
30 42
45 54
Lipase
Average monthly mean value. Du Pont amylase and lipase assays were performedforthe 4 months of November and December, 1988, and March and April, 1989. Kodak amylase and lipase assays were performedfor the 4 monthsof Novemberand December,1990, and March and April, 1991.
initially compared the aca and Ektachem amylase methods, regression analysis resulted in aca = 1.03 Kodak - 8 (r = 0.98). Thus, it was not surprising that we observed little change in the distribution of values for amylase. These data also suggest that the populations from these two time periodswere similar. Our comparison of the Ektachem lipase and the aca lipase resulted in a poor correlation, r = 0.58. About two-thirds of the compared samples gave similarvalues in both lipase assays, which would be consistent with the similar recommended reference ranges for the two assays (23-203 and 60-240 UIL, respectively). However, about one-third of the patients’ samples in our comparison had values 1.4-4x higher with the KOdak method, probably attributable to the excess colipase included in the Ektachem method. Consistent with this, we observed a marked shift in the distribution of patients’ lipase values. More than half of the values with the Kodak lipase assay were above the ULN of 203 U/L and 25% were 2.5x greater than the ULN (Table 2). In contrast, 14 mmoliL) can result in falsely increased lipase values by the Ektachem procedure (94). Therefore, we determined the glycerol value in this patient’s serum and found it to be 1.1 mmol/L (normal concentration
