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The normal ratio of these clearance is between 3% and 5%, while a result of less than 1% suggests macroamylasemia [13]. The final confirmatory test is electrophoresis or polyethylene glycol precipitation test and chromatography [14]. As these are methods used in specialized laboratories and are rarely used routinely, most authors agree that the calculation of ACCR ratios can be considered diagnostic, although there are some discrepancies that [7,13,15,16].

CASE REPORT: Patient P.Ž. The 65-year-old comes for a gastroenterological examination on July 10, 2019. due to an occasional feeling of bloating in the abdomen and elevated serum amylase in the laboratory findings. The problems last from October 2018 and occur occasionally, approximately once in 7-10 days, usually after meals and discounts after bowel movements. It denies severe and hereditary diseases in personal and family history. He received symptomatic therapy (spasmolytics) which he used as needed. During the physical examination, an orderly objective finding is ascertained. In the laboratory reports that the patient brings - complete blood count, erythrocyte sedimentation rate, and C-reactive protein level were within the reference values. Tumor marker CA19 / 9 was 31.6U / ml (normally up to 37 U/ml). Serum amylase levels were elevated - 235 IU / L (reference range: up to 100 IU / L). Other results in biochemical parameters, including serum lipase, nitrogen retention, aminotransferases, bilirubin, and serum iron were normal. Ultrasound and computed tomography of the abdomen showed a normal finding. An ultrasound examination of the neck (parotid gland region) is also normal. Laboratory parameters were monitored after 3 months (30.10.2019) including erythrocyte sedimentation rate, CRP, lipase, aminotransferase, bilirubin and serum iron as well as anti-tissue transglutaminase-IgA (anti-tTG-IgA). All findings were within normal limits. Elevated serum amylase remained 197 IU / l. Urine amylase was also at reference values of 32 IU / l. We determined serum creatinine 75 umol / L and urine creatinine 7003 umol to calculate ACCR. The ACCR is 0.174.

Based on the clinical picture of the performed diagnosis and calculated ACCR, we conclude that it is very likely macroamylasemia. Definitive laboratory diagnosis by electrophoresis or polyethylene glycol precipitation test was not available to us and the patient was not motivated for additional diagnostics. (macrogol) as needed. The patient was examined after two months (December 25, 2019). He was without problems, the clinical findings were orderly. Serum amylase levels were 210 IU / L, urine amylase 45 IU / L. Due to the patient's advanced age, lower digestive endoscopy was suggested, which the patient refused. A clinical control with new laboratory findings and an ultrasound examination of the abdomen is scheduled for 6 months. As the patient is older than 50, we anticipate monitoring the patient for another 1-2 years in order to definitely declare hypermilasemia benign.

DISCUSSION:
Amylase is an enzyme responsible for the breakdown of amylase and other starches during digestion. It exists as three subtypes, where α-amylase is found in animals, including humans, and it is the only one of clinical importance [6]. Although hyperamylasemia is particularly associated with pancreatitis, there are other conditions and diseases that can occur with hyperamylasemia, including sialadenitis, lung disease, ovarian cysts, ruptured ectopic pregnancy, abdominal trauma, mesenteric infarction, perforated peptic ulcer, appendicitis. renal failure, mumps, and some malignancies, all of which would require additional testing, unlike macroamylasemia [1,2,6,8,12].

Although macroamylasemia is mostly asymptomatic, diagnosis of this condition often begins with abdominal pain, including determination of serum and urine amylase. However, abdominal pain is not a symptom of macroamylasemia. It is usually just a coincidence, and amylase testing is often required when patients complain. to abdominal pain. According to one hypothesis, which has no confirmation, abdominal pain and macroamylasemia are detected together due to the deposition of macroamylase molecules in the pancreas [13], hematological malignancies [19,20] of systemic lupus erythematosus [21], rheumatoid arthritis [22] or celiac disease [23,24,25]. Several cases of celiac disease with macroamylasemia have been reported in which amylasemia has returned to normal after treatment with [26] Induced macroamylasemia has also been described, as shown by a study in which a group of subjects received infusions with a solution of hydroxyethyl starch (HES), a volemic colloid used in the treatment of hypovolaemia. with HES solution Hyperamylasemia has been shown to be due to macroamylase amylase complex and HES). As HES molecules disintegrated, hyperamylasemia or macroamylasemia resolved on their own. This study demonstrated that macroamylasemia may also have iatrogenic induction [13].

Other cases of asymptomatic hyperamylasemia have been reported in the literature, including chronic nonpathological hyperamylasemia of pancreatic origin, ethnic hyperemylasemia, and familial hyperemylasemia [27].

The theory of the formation of macro molecules of amylase is based on the "dysregulation" of immune tolerance, which can occur in immune disorders [28]. Cross-reactivity to either gluten or other antigens is thought to lead to the formation of autoantibodies against pancreatic serum amylase at the intestinal level. In this way, antibodies are formed, in most cases immunoglobulin A, rarely immunoglobulin G, which react with amylazoam to form immune complexes [29].

Almost all patients who have hyperemylasemia undergo expensive, long, difficult and often unnecessarily repeated diagnostic procedures. In one study that followed patients for 4 years, 60.7% of patients were diagnosed with chronic pancreatitis, 24.5% with recurrent pancreatitis and 13.7% had no specific diagnosis. After detailed clinical processing (serum Ca19-9 level, ultrasound) abdomen, computed tomography and magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography) in 35.2% of these patients it was concluded that it was macroamylasemia [30].

To avoid irrational diagnosis of elevated serum amylase in patients without clinical symptoms and symptoms, without elevated urinary amylase and normal serum lipase levels, renal function should be examined and renal amylase clearance calculated relative to creatinine clearance - ACCR at the beginning of the diagnostic program and assess the need for additional diagnostics. In that sense, the diagnostic algorithm of macroamylasemia, which dates back to 1989, is very practical. proposed by David LeVine and David Parrish [7].

Conclusion: In our patient, based on the clinical picture, performed diagnostics and calculated ACCR, we conclude that it is most likely macroamylasemia. These simple and inexpensive laboratory tests and calculations confirmed the diagnosis despite the lack of a confirmatory laboratory test (Definitive diagnosis by electrophoresis or polyethylene glycol precipitation test was not available to us and the patient was not motivated for additional diagnosis). With the recommended diet and therapy, the patient was without any problems. Due to age, a colonoscopy was suggested, which the patient refused. A control clinical examination and ultrasound examination of the abdomen are scheduled for 6 months.

The diagnosis of macroamylasemia should be considered in the differential diagnosis of patients who have permanently elevated serum amylase, but do not show any characteristics of pancreatitis or inflammation of the salivary glands. ACCR can be a quick and inexpensive screening test to prevent unnecessary diagnosis and therapy.

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