Institute of Internal Medicine, University of Bologna, S. Orsola Hospital. Bologna, Italy
Received: December 6th, 2005
Amylases; Hyperamylasemia; Lipase; Pancreas, Exocrine
I read the recent paper by Frulloni et al.  on pancreatic hyperenzymemia with interest. These investigators undertook a review of many papers published on this topic, discussing the clinical significance of both pancreatic and extrapancreatic hyperenzymemia. They also discussed the condition of pancreatic hyperenzymemia without apparent causes. However, in this context, they cited my paper on familial pancreatic hyperenzymemia  but not my previous study on sporadic pancreatic hyperenzymemia . I believe that this second paper should have been mentioned in a review of the literature on pancreatic hyperenzymemia, above all, because this was the first study on benign pancreatic hyperenzymemia. In this study, I demonstrated that healthy subjects, without any pancreatic disease, with clinical, laboratory and pancreatic function tests, ultrasound, computed tomography and retrograde cholangiopancreatography all absolutely normal, can have pancreatic hyperenzymemia, which generally presents considerable fluctuations, including periods of normalization. Most of these subjects were followed by me for many years and they continued to have pancreatic hyperenzymemia and continued to be without any pancreatic disease.
This letter reported a group of 30 healthy subjects, of whom 16 had hyperamylasemia alone and the remaining 14 hyperamylasemia and hyperlipasemia; in addition, 13 of these 30 subjects also had hypercholesterolemia and/or hypertriglyceridemia. They concluded that the abnormal increase of serum pancreatic enzymes in these subjects was due to pancreatic steatosis caused by the dyslipidemia. The diagnosis of pancreatic steatosis was made by these investigators on the basis of the ultrasonographic finding of a hyperechogenic pancreas. This conclusion is, however, unacceptable, first, because there is no proof that pancreatic steatosis actually exists in humans and, second, because there are no studies which indicate with certainty that the ultrasound finding of a hyperechogenic pancreas is an expression of steatosis or of pancreatic fat infiltration. Moreover, even if the dyslipidemia could actually cause pancreatic steatosis or pancreatic fat infiltration and consequently hyperenzymemia, this would only have occurred in the 13 of the 30 subjects with pancreatic hyperenzymemia that they described, i.e. the 13 who had the dyslipidemia. In the remaining 17 patients in whom there was no dyslipidemia and no other possible cause of pancreatic hyperenzymemia, what was it due to?
They also reported that 24 of the 30 subjects with hyperenzymemia had a hyperechogenic pancreas at ultrasound; 13 of these 24 had dyslipidemia which, in their opinion, was the cause of the hyperechogenic pancreas, but why did the remaining 11 who did not have dyslipidemia have a hyperechogenic pancreas? Perhaps, had these 11 subjects pancreatic steatosis also which was the cause of their hyperenzymemia? If so, what was the cause of the pancreatic steatosis?
Many of the subjects described by these authors (16 out of 30) only had hyperamylasemia; if there was really steatosis of the pancreatic cells, i.e. “an accumulation of fat inside the pancreatic acinar cell, disturbing exocytosis” as Frulloni et al. write in their article , should there not also have been an increase in the other pancreatic enzymes, at least in some of them?
In my first paper on pancreatic hyperenzymemia , only 3 of the 18 subjects with this anomaly had hypercholesterolemia and, on the basis of this work and of all my subsequent experience on this topic, I believe that the dyslipidemia does not have any role in the serum increase of the pancreatic enzymes, at least not in this syndrome which I described.
In addition, I have just completed a study in which I used magnetic resonance to assess whether the pancreas of healthy subjects with dyslipidemia and with pancreatic hyperenzymemia is a fatty pancreas, as the abovementioned authors claim, but I found no signs of fatty infiltration of the pancreas in any of them.
To see whether alterations in the Wirsung duct could explain the hyperenzymemia, we recently evaluated the effect of secretin on the duct in subjects with this benign form of pancreatic hyperenzymemia , and we found no alterations in the caliber of the Wirsung duct which could explain the enzymatic alteration.
In another recent study , we assessed whether mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may have a role in the etiology of this form of hyperenzymemia. We found that the frequencies of the mutations detected in subjects with pancreatic hyperenzymemia were similar to those in the general Italian population which excludes a role of this gene in the etiology of this hyperenzymemia.
I have seen and continue to see several healthy subjects with sporadic or familial benign pancreatic hyperenzymemia. I believe that this is a new syndrome which I am the first to have described. The pathogenesis of this anomaly remains to be clarified.