Evaluation of a rapid urine amylase test using post-ERCP hyperamylasemia as a model

OBJECTIVE: The initial diagnosis of acute pancreatitis is often based on clinical criteria together with elevations of serum amylase and lipase. A reliable bedside urine test could facilitate the early diagnosis of pancreatitis. We evaluated a rapid urine amylase test (Rapignost) by using post-ERCP hyperamylasemia as a human model of acute development of hyperamylasemia suggestive of pancreatitis. METHODS: Seventy-five patients undergoing ERCP were prospectively evaluated. Patients with renal insufficiency, hyperlipidemia, or hyperglycemia were excluded. Before ERCP, patients had serum amylase and lipase measured, and urine amylase tested with the Rapignost test strip. At 4 and 16-24 h post-ERCP, a serum and urine (test strip) amylase were measured again; the adequacy of urine collection was verified by measuring a 2-h creatinine clearance. Patients were clinically assessed for the development of clinical pancreatitis. The concordance of the strip result with post-ERCP hyperamylasemia was assessed. RESULTS: The sensitivity of the test strip for the detection of hyperamylasemia was greatest at 16-24 h post-ERCP (78%). Specificity was uniformally high (100% specificity at 16-24 h post-procedure). The test strip was positive in all cases of clinical pancreatitis. Of three cases of clinically evident ERCP-induced pancreatitis, only one was urine test strip positive by 4 h post-procedure. CONCLUSIONS: Using post-ERCP hyperamylasemia as a model, the Rapignost rapid urine amylase test strip was only marginally sensitive but highly specific for hyperamylasemia. The urine test strip was positive in all cases of clinical pancreatitis and may be a useful bedside test for the diagnosis of acute pancreatitis.     

Acute alcohol intoxication: significance of the amylase level

To evaluate the effects of acute alcohol intoxication on serum amylase and isoamylase levels, 58 clinically intoxicated patients with blood alcohol levels greater than 100 mg/dL were studied. Comparisons were made to normal control and a sober chronic alcoholic group. Admitting serum isoamylase levels were determined by cellulose acetate membrane electrophoresis and serum amylase levels measured by the Amylochrome technique. The average blood alcohol level in the intoxicated group was 301 +/- 99 mg/dL. Thirty of the 58 patients had hyperamylasemia (greater than 207 IU). Twenty-five of these 30 patients had hyperamylasemia from nonpancreatic sources (increased salivary isoamylase). Two of the 30 patients had pancreatic hyperamylasemia and three patients had elevated levels of both isoamylases. Neither of the patients with pancreatic hyperamylasemia had clinical evidence of acute pancreatitis. Although nine of the 58 patients had abdominal pain and clinical symptoms suggestive of acute pancreatitis, none of these patients had elevated pancreatic isoamylase. The finding of hyperamylasemia in acutely intoxicated patients is common. This is most frequently due to a rise in the salivary (nonpancreatic) isoamylase. The reliability of the total serum amylase as an indication of pancreatic disease in the intoxicated patient is questioned.     

Prevalence of normal serum amylase levels in patients with acute alcoholic pancreatitis

Acute alcoholic pancreatitis is uncommonly diagnosed when the serum amylase level is normal. We defined acute alcoholic pancreatitis as a clinical syndrome in which hyperamylasemia was not a necessary component and sought support for the diagnosis by ultrasonography and computed tomography of the pancreas. In 68 episodes of acute alcoholic pancreatitis identified in a one-year period, the serum amylase level was normal at the time of hospital admission in 32%. In 40 episodes, we performed ultrasonography and computed tomography within 48 hr of admission. The diagnosis was supported by ultrasonography in 43%, by computed tomography in 68%. Ultrasonography and computed tomography supported the diagnosis as frequently in patients with normal serum amylase levels as in patients with hyperamylasemia. We conclude that patients with acute alcoholic pancreatitis frequently have normal serum amylase levels. The widespread clinical practice of relying solely on hyperamylasemia to establish the diagnosis of acute alcoholic pancreatitis is unjustified and should be abandoned.     

Acute pancreatitis in systemic lupus erythematosus: report of twenty cases and a review of the literature

A retrospective study was undertaken of patients with systemic lupus erythematosus in whom serum amylase had been determined. Sixty-three patients were identified, and of these 53 had abdominal pain at the time of the amylase measurement. Twenty-seven (51 percent) had a normal serum amylase, and 12 of this group had defined reasons for the abdominal pain. Of the 26 patients with hyperamylasemia, 6 had extrapancreatic causes for the elevated amylase. In 20 patients (37 percent of those with abdominal pain) the clinical diagnosis of pancreatitis was made. The amylase levels showed no correlation with renal function nor with dose of corticosteroid. Four patients with pancreatitis were identified in whom no contributing factor other than SLE could be ascertained. No serious complication of the pancreatitis was seen, and recovery occurred despite continued steroid therapy. Pancreatitis is not a rare occurrence in SLE, and may be related in part to the vasculitis seen during periods of disease activity.     

A unique case of breast carcinoma producing pancreatic-type isoamylase

A 71-yr-old woman with a widely metastatic lipid-rich variant of breast cancer was found to have striking hyperamylasemia (85-fold normal). By isoelectric focusing, agarose gel electrophoresis, and a wheat protein inhibitor assay, the predominant serum amylase appeared to be identical to pancreatic isoamylase. Serum trypsin, serum lipase, and an abdominal computed tomography scan were normal, excluding the possibility of pancreatitis. Furthermore, both the primary breast tumor and skin metastases that developed 10 yr later stained immunohistochemically for amylase. Thus, breast carcinoma must be added to the list of tumors causing ectopic hyperamylasemia, and this case shows that nonpancreatic malignancies may produce pancreatic-type hyperamylasemia.     

Elevated Serum Amylase Activity in the Absence of Clinical Pancreatic or Salivary Gland Disease

Elevated serum amylase activity, in the absence of clinically apparent pancreatic or salivary gland disease, has been observed in many seemingly unrelated conditions. In a search for common etiological factors to account for hyperamylasemia in these conditions, a retrospective analysis was performed. Eighty-four episodes of hyperamylasemia (> 300 I.U./l. Phadebas method) occurring in 75 patients over a one-year period ending in June, 1975 were assigned to one of two groups. Group 1 consisted of 56 (67%) episodes of hyperamylasemia with clinical pancreatitis. Group 2 consisted of 28 (33%) episodes of hyperamylasemia in the absence of clinical pancreatitis. Hypoxemia (pO₂ < 75 mm. Hg.) was found in 9/15 patients in Group 2 who had arterial blood gases measured. To assess the possible relationship between acute hypoxemia and amylase activity, a prospective study was initiated. Patients with known causes of pancreatitis or renal failure were eliminated. Hyperamylasemia was found in 3/8 hypoxemic patients. This raises the possibility that acute hypoxemia alone or in combination with other factors may raise serum amylase activity, possibly through ischemic injury to the pancreas or salivary glands or other amylase containing tissues.     

Clinical significance of chronic hyperamylasemia

A longitudinal study of patients with persistent hyperamylasemia was carried out to evaluate the clinical significance of this condition. Twenty-five outpatients were studied by means of serum amylase, isoamylase (wheat germ-inhibition method), and lipase determination; macroamylase detection; and abdominal ultrasonography over a one-year period. Cellulose acetate electrophoresis was carried out to validate the wheat germ-inhibition tests; the results of the two assays were closely correlated, except in three patients with macroamylasemia. At the time of the study, none of the patients had evident signs or symptoms of pancreatic disease. At initial evaluation, wheat germ test demonstrated an elevation of only salivary isoamylase in 16 patients, of both pancreatic and salivary isoenzyme in two, and only pancreatic isoamylase in six patients (three with macroamylasemia). Normal salivary and pancreatic isoenzymes were found in one patient. Serum lipase was elevated in only one patient who had a mixed hyperamylasemia with predominantly pancreatic isoamylase. At the 12-month follow-up, hyperamylasemia had disappeared in six cases and salivary isoamylase elevation in three; pancreatic isoamylase remained abnormally high in all eight patients in whom it was elevated at initial evaluation, and lipase was abnormally high in three patients with elevated pancreatic isoamylase. Of the five patients with true pancreatic hyperamylasemia, one had a juxtapapillary duodenal diverticulum, one showed a slight ultrasound alteration of the pancreas, and one had a past history of acute pancreatitis. In our study, most cases of chronic hyperamylasemia were of nonpancreatic origin. In the patients with elevated pancreatic isoamylase, there was no clinical evidence of pancreatic damage, although a subclinical pancreatic involvement could not be excluded in some.This work was supported by funds from the Italian Ministry of University and of Scientific and Technological Research in 1989.     

Amylase normal, lipase elevated: is it pancreatitis? A case series and review of the literature

OBJECTIVE: This study was undertaken to identify clinical scenarios in which the lipase is significantly elevated (three times above the upper limit of normal) but the amylase is normal, and to examine whether or not pancreatitis is the likely cause for this seemingly unusual constellation of laboratory results. METHODS: Twenty-five patients were retrospectively identified over a 2-yr period, which fulfilled the above criteria. A thorough review of their charts was conducted. In addition, a critical review of the literature was performed. RESULTS: It appears that isolated elevation of lipase in this case series was either related to renal insufficiency (two patients), to nonpancreatic sources of lipolytic enzymes due to malignant tumors (two), to acute cholecystitis (two) or esophagitis (one), to delayed blood withdrawal (at least five patients), to hypertriglyceridemia (two), or to subclinical pancreatitis in patients without abdominal pain (three). CONCLUSIONS: 1. An elevated lipase should not be equated with evidence for pancreatitis if the amylase is normal. 2. A simultaneous determination of both amylase and lipase is recommended for the evaluation of patients with abdominal pain.     

Enzyme immunoassay for serum pancreatic lipase in the diagnosis of pancreatic diseases

To evaluate the diagnostic utility of serum immunoreactive lipase (IRL), serum lipase was determined using an enzyme immunoassay and a turbidimetric method along with total serum amylase in 41 healthy controls, 76 patients with pancreatic disease and 60 with nonpancreatic disease. Serum IRL was elevated in 12 of 13 patients with acute pancreatitis, 12 of 44 with chronic pancreatitis and in 12 of 19 with pancreatic cancer. The IRL was low in 9 of the 44 patients with chronic pancreatitis, which coincided with advanced exocrine pancreatic insufficiency. Overall sensitivities in pancreatic diseases were 59% for serum IRL, 38% for turbidimetric lipase and 51% for amylase, specificities in healthy controls and nonpancreatic diseases were 80% for serum IRL, 86% for turbidimetric lipase and 88% for serum amylase. Serum IRL determination is useful for diagnosis in pancreatic diseases when compared with the conventional determination of serum lipase.     

A simplified method for detecting macroamylasemia by measuring serum amylase activity at different reaction temperatures

Amylase activity in serum and urine, and isoamylase, were measured in 300 patients with abdominal pain to detect cases of macroamylasemia. Of these patients, 9 had hyperamylasemia and 2 were diagnosed as cases of macroamylasemia on the basis of their amylase/creatinine clearance ratio, the gel filtration pattern of their amylase on a dextran column, and results of immunological analysis. Amylase activity in macroamylasemia is reported to show an anomalous response to increase in reaction-temperature. In this report, measurements of the temperature-activity relationships of serum amylase confirmed that the ratio of serum amylase activity at 50 degrees C to that at 25 degrees C (AMY-50 degrees C/AMY-25 degrees C ratio) in patients with macroamylasemia was higher than that in normal subjects or patients with pancreatitis. Moreover, when macromolecular amylase in the sera of patients with macroamylasemia was separated from amylase of normal molecular weight by dextran gel chromatography, it showed a significantly higher AMY-50 degrees C/AMY-25 degrees C ratio than the latter. Measurement of this AMY-50 degrees C/AMY-25 degrees C ratio seems to be a convenient and useful method for differential diagnosis of hyperamylasemia.     

Comparison of serum amylase pancreatic isoamylase and lipase in patients with hyperamylasemia

We compared results of measurements of total serum amylase, pancreatic isoamylase, and lipase measurements in patients with hyperamylasemia. Serial measurements of these three enzyme levels in patients recovering from acute pancreatitis indicated that pancreatic isoamylase and lipase were elevated above normal to a greater extent and remained elevated much longer than did the total amylase. This finding indicates an appreciable sensitivity advantage of the pancreatic isoamylase and lipase over total amylase measurement during the recovery phase of pancreatitis. Comparison of pancreatic isoamylase and lipase levels in selected sera indicated a good correlation (r=0.84) between these two measurements in patients who did not have macroamylasemia. Lipase was normal in sera with amylase elevations due solely to salivary isoamylase. Thus, in nonmacroamylsemic sera, pancreatic isoamylase and lipase appear to be roughly interchangeable markers of the level of pancreatic enzymes in the blood. An advantage of the lipase assay is that this enzyme is normal in hyperamylasemia caused by macroamylasemia, whereas the inhibitor assay indicates that the pancreatic isoamylase is elevated. Development of automated assays for either pancreatic isoamylase or lipase should lead to the routine use of one of these assays in place of the present reliance on total amylase measurements in the diagnosis of pancreatitis.Supported by Veterans Administration Research Funds and National Institutes of Health grant 13309-15.     

Safety advantage of endocut mode over endoscopic sphincterotomy for choledocholithiasis

AIM: To evaluate whether an automatically controlled cut system (endocut mode) could reduce the complication rate of endoscopic sphincterotomy (EST) and serum hyperamylasemia after EST compared to the conventional blended cut mode. METHODS: From January 2001 to October 2003, 134 patients with choledocholithiasis were assigned to either endocut mode group or conventional blended cut mode group at the time of sphincterotomy. The two groups were retrospectively compared for the complications after EST and serum amylase level before and 24 h after the procedure. RESULTS: Of the 134 patients treated, 79 were assigned to conventional blended cut mode group and 55 to endocut mode group. There was no significant difference in age, sex, and serum amylase level before EST between the two groups. Complications were found in 5 patients of the endocut mode group (9%): hyperamylasemia (5 times higher than normal) in 4 and moderate pancreatitis in 1. Complications were found in 13 patients of the conventional blended cut mode group (16%): hyperamylasemia in 12 and moderate pancreatitis in 1. Serum amylase levels were elevated in both groups 24 h after EST (P<0.02). The average serum amylase level 24 h after EST in the conventional blended cut mode group was significantly higher than that in the endocut mode group (P<0.05). CONCLUSION: Endocut mode offers a safety advantage over conventional blended cut mode for pancreatitis after EST by reducing hyperamylasemia.     

Serum Lipase Levels in Nonpancreatic Abdominal Pain versus Acute Pancreatitis

Objective : 1) To determine whether serum lipase is elevated in patients with nonpancreatic abdominal pain, and 2) to compare the levels of serum lipase and serum amylase found in patients with nonpancreatic abdominal pain with those found in acute pancreatitis in order to differentiate between the two groups. Methods : Serum lipase and amylase levels were estimated in 95 patients with nonpancreatic abdominal pain (group A). These levels were then compared with those found in 75 patients with acute pancreatitis (group P). Results : Serum amylase in group A ranged from 11 to 416 U/I. [mean 58 ± 46 (SD)]. Three patients (3.3%) had raised amylase levels. The maximum elevation noted in this group was 416 U/L. Serum amylase in group P ranged from 124 to 13,000 U/L (mean 1620 ± 1976). Twenty of the 75 patients (27%) in group P had levels that overlapped those found in group A. The serum lipase in group A ranged from 3 to 680 U/L (mean 111 ± 101). Ten of the 93 patients (11%) had elevated lipase levels. The maximum elevation noted was roughly 3 times normal (680 U/L). Serum lipase in group P ranged from 711 to 31.153 (mean 6705 ± 7022). None of the patients in group P had levels that overlapped those found in group A. The sensitivity of a serum lipase level > 3 normal in detecting acute pancreatitis was 100% and the specificity was 99%. The corresponding figures for serum amylase were 72% and 99%, respectively. Conclusion : A serum lipase level > 3 normal bas a better diagnostic accuracy than serum amylase in differentiating nonpancreatic abdominal pain from acute pancreatitis.     

Electrophoretic identification of an isoenzyme of amylase which increases in serum in liver diseases.

Isoenzymes of amylase were studied in serum from 72 persons by means of polyacrylamide gel electrophoresis and a direct saccharogenic assay for amylase activity. In 37 normal individuals, there were two major peaks of amylase actvity with mobilities similar to pancreatic and salivary amylases. In 11 patiets with acute pancreatitis, the area of activity corresponding with pancreatic amylases increased disproportionately. Electrophoretic patterns of amylase activity in normal and pancreatitis urine were almost identical to the respective serum patterns from the same persons. In contrast, a prominent slower-moving peak of amylase activity occurred in the serum of 8 of 12 patients who had hyperamylasemia associated with various liver diseases. Traces of this third peak were identifiable in one-third of normal serum specimens, but no increases in its activity were observed in any specimen from 11 patients with pancreatitis or from 12 other patients with hyperamylasemia unassociated with liver disease. The slower-moving peak was absent from the urine of patients whose serum contained it. The origin of the slower-moving serum amylase appearing in patients with liver disease is not established by these studies. It is possible either that a hepatic amylase is liberated from damaged liver cells or that the metabolism of an amylase not originating in the liver is altered as a result of liver dysfunction.     

Serum amylase measured four hours after endoscopic sphincterotomy is a reliable predictor of postprocedure pancreatitis

OBJECTIVE: Acute pancreatitis is a common complication after endoscopic sphincterotomy (ES) and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to detect the time when the peak of serum amylase was predictive for pancreatitis or severe hyperamylasemia, to plan a prolonged follow-up in the hospital and for outpatients. METHODS: In a prospective series of 409 consecutive patients undergoing ES, serum amylase activity was measured immediately before the procedure and 2, 4, 8, and 24 h thereafter; the data obtained at 2, 4, and 8 h were compared with those at 24 h and with the outcome. Sensitivity for long-lasting severe hyperamylasemia (more than five times the upper normal limit) and pancreatitis were also defined for all sampling times. RESULTS: At 24 h after ES, amylase was still more than five times the upper normal limit in 26 patients, 19 of whom had mild/moderate acute pancreatitis. There was a significant difference (p < 0.01 at all sampling times) between the 26 patients with 24-h severe hyperamylasemia and those with lower levels. The sensitivity of amylase measurement in detecting pancreatitis or long-lasting severe hyperamylasemia was highest at 8 h. However, the 4-h assessment appears to be a reliable predictor in practice, as more than two-thirds of cases of pancreatitis (all but one with computed tomography-confirmed pancreatitis) occurred among patients whose 4-h amylasemia was higher than five times the upper normal limit. CONCLUSIONS: Serum amylase assessment 4 h after ES minimizes the likelihood of underestimating the risk of postprocedure pancreatitis. It is therefore a reliable, cost-effective follow-up, particularly in outpatients.     

Amylase inhibitor from wheat: its action and clinical application

The electrophoretic and column chromatographic characteristics of an amylase inhibitor of wheat origin were investigated. Further, the clinical usefulness of this inhibitor for determining the ratio of pancreatic to salivary isoamylase activity in serum was evaluated. Amylase inhibitor inhibits the action of salivary alpha-amylase by making an amylase-inhibitor complex, which is easily separated into its individual component during electrophoresis with full recovery of amylase activity. Using the specific inhibitory effect of this inhibitor on salivary alpha-amylase activity, the ratio of pancreatic to salivary isoamylase activity (P/S) in serum was determined. There was a good correlation in P/S ratio in serum between the results obtained with the inhibitor method and those with electrophoretic method. The P/S ratio in sera from patients with acute pancreatitis was over 8.0, whereas that in sera from patients with salivary-type hyperamylasemia such as mumps, pulmonary diseases and following surgery was less than 0.1. However, hyperamylasemia due to macroamylase or renal failure could not be identified by the inhibitor method.     

Prevalence and nature of hyperamylasemia in acute alcoholism

Determination of serum amylase activity in 100 consecutive patients admitted to an alcohol detoxification unit revealed hyperamylasemia in 39 cases. Further clinical evaluation of 15 of the 39 alcoholic patients with hyperamylasemia was unremarkable except for bilateral enlargement of the parotid glands in two cases. Nine of the 15 patients demonstrated markedly low amylase to creatinine clearance ratio; however, macroamylase complexes were not detected in the sera of any patients. Serum isoamylase separation revealed that the mean salivary isoamylase for the 15 alcoholic patients was significantly (P<0.05) elevated as compared to the control values. Individually, the salivary-type isoamylase was clearly elevated in ten patients while pancreatic type isoamylase was elevated in four. These data indicate that elevated serum amylase activity occurs frequently in alcoholic patients. Hyperamylasemia in a large number of alcoholic patients is nonpancreatic in origin and may be related to the injurious effect of ethanol on salivary glands and other tissues.Presented in part at the 10th annual meeting of the National Council on Alcoholism, held in Washington, DC, April 28, 1979.     

Histological pancreatitis in end-stage renal disease.

To clarify a possible cause of hyperamylasemia in end-stage renal disease (ESRD), histological studies were performed on the pancreatic glands of twenty-seven autopsied patients with ESRD who had received long-term hemodialysis. The findings were compared with those in a similar number of age-matched control subjects. Histological evidence of pancreatitis was found in 51.9% of the ESRD patients as compared with 14.8% in the controls (p < 0.005). The pancreatitis was chronic in nature in 85.7% of the ESRD patients showing changes of pancreatitis. Secretin administration to an additional group of twelve patients with ESRD induced an elevation in the activities of both total and P-type serum amylase in only one patient. These findings suggest that although histological pancreatic alterations are common in patients with ESRD, they are probably not responsible for the P-type hyperamylasemia frequently found in such patients.     

Enzyme immunoassay for serum pancreatic lipase in the diagnosis of pancreatic diseases

To evaluate the diagnositc utility of serum immunoreactive lipase (IRL), serum lipase was determined using an enzyme immunoassay and a turbidimetric method along with total serum amylase in 41 healthy controls, 76 patients with pancreatic disease and 60 with nonpancreatic disease. Serum IRL was elevated in 12 of 13 patients with acute pancreatitis, 12 of 44 with chronic pancreatitis and in 12 of 19 with pancreatic cancer. The IRL was low in 9 of the 44 patients with chronic pancreatitis, which coincided with advanced exocrine pancreatic insufficiency. Overall sensitivities in pancreatic diseases were 59% for serum IRL, 38% for turbidimetric lipase and 51% for amylase, specificities in healthy controls and nonpancreatic diseases were 80% for serum IRL, 86% for turbidimetric lipase and 88% for serum amylase. Serum IRL determination is useful for diagnosis in pancreatic diseases when compared with the conventional determination of serum lipase. This work was supported in part by a research grant for intractable pancreatic diseases and a cancer grant from the Ministry of Health and Welfare, Japan.     

Hyperamylasemia in patients with eating disorders

Hyperamylasemia, which has been reported in patients with the eating disorders anorexia nervosa and bulimia, generally has been thought to result from pancreatitis. To evaluate the mechanisms of hyperamylasemia, we measured amylase, lipase, and isoamylase activity in 17 consecutive patients admitted to the eating disorder unit. Six patients had elevated amylase activity, and 5 of these 6 had isolated increases in salivary isoamylase activity. Six other patients had normal serum total amylase activity but modest elevations in the salivary isoamylase fraction. No patient developed clinical evidence of pancreatitis during hospitalization. Thus, the hyperamylasemia in patients with anorexia and bulimia often is caused by increased salivary-type amylase activity. The appropriate diagnostic test for hyperamylasemia in patients with anorexia or bulimia is the simple measurement of serum lipase or pancreatic isoamylase activity. If these levels are found to be normal, further tests to exclude pancreatitis are unnecessary.