In recent years, despite the rapid availability of diagnostic tools in emergency units, no significant progress has been observed in the rate of misdiagnosis of appendicitis. The negative rate of laparotomy remains approximately 20% after a decision based on clinical symptoms. A delay in the diagnosis of acute appendicitis is associated with an increased risk of perforation and may lead to peritonitis or abscess formation (11, 12). Symptoms of appendicitis significantly overlap with other clinical conditions, including gastroenteritis, urinary tract infection, and pelvic inflammatory disease (12). Many attempts have been made to determine the reduction in the negative appendectomy rate, but there is still no diagnostic test that can accurately diagnose appendicitis in all cases. The appendix is rich in enterochromaffin cells that synthesize and store serotonin or 5-hydroxytryptamine (5-HT). The digestive system contains about 95% of serotonin in the whole body (13, 14).
Recent studies have shown that in an inflammatory process of the appendix, blood serotonin levels increase. In the liver, 5-HT is rapidly metabolized to 5-HIAA by the monoamine oxidase system and then excreted in the urine (15). Several studies have evaluated plasma serotonin concentration in the diagnosis of acute appendicitis. Kalra et al., as well as Singh et al., found that measurement of plasma serotonin levels is a reliable marker for early acute appendicitis in which physical symptoms are ambiguous and serotonin does not help much in the diagnosis of gangrenous appendicitis. These findings indicate that the source of 5-HT decreases with the progress of the inflammatory process towards severe mucosal necrosis and cell destruction (16, 17).
In this study, it was shown that the difference between HIAA-5 in two groups of acute and perforated appendicitis was significant and based on statistical analysis, sensitivity, specificity, positive predictive value, negative predictive value were 82, 62, 75 and 77% respectively. Ilkhanizadeh et al showed that the level of U-5-HIAA increases significantly in appendicitis with high sensitivity (98%) and specificity (100%) (15). Bolandparvaz et al reported that 20 nmol/L was the best diagnostic cut-off point for early detection of acute appendicitis, and at this stage, the specificity was (96%), but the sensitivity was (88%) (18). In the study of Versic et al. in 2015 in Croatia, the specificity of 5-HIAA for the diagnosis of acute appendicitis was calculated to be 49% and its sensitivity to be 60% (8). In a study conducted by Zuhair et al. in Iraq in 2017, the specificity of 5-HIAA for diagnosing mild acute appendicitis was calculated as 100% and its sensitivity as 94%. Also, the diagnostic accuracy of 5-HIAA in mild appendicitis was measured at 97%. On the other hand, the sensitivity of 5-HIAA for the diagnosis of severe and complicated acute appendicitis was calculated to be about 37%. Also, the diagnostic accuracy of 5-HIAA in severe and complicated appendicitis was measured at 68%. The results of these studies were different from our study, and the reason for this difference could be the number of patient samples, the severity of the disease, and the stage of appendicitis in which the patient was examined (10). In the study of Mentes et al in 2009 in Turkey, the amount of urinary 5-HIAA was evaluated in acute appendicitis. The amount of 5-HIAA increased in all groups of appendectomy rabbits within 24 hours after the operation, and this increase was more in group 3 of appendectomy 12 hours after ligation of the cecum, and the diagnostic accuracy of 5-HIAA in this study was estimated to be about 76%, which It was almost similar to our study (3).
This study had some limitations. The collection of samples for this study was interrupted due to the conditions of the Covid-19 epidemic, and these conditions caused the final sample size to decrease compared to the sample size that was calculated at the beginning of the work. This was a pioneering study in our country and no similar study has been conducted so far. It is suggested that future studies can be conducted in a larger community and on other patients such as children and other causes of acute abdomen. Also, studies should be done to accurately determine the cut off number for complicated appendicitis.