Possible Gastrinoma


Question

A physician writes in to say that he has a problem case and would like some help. He has a female patient who is 48 years old. Since 1996 she was diagnosed with gastric ulcer - for the next 5 years , multiple episodes and different ulcers , patient states she had the acid test at that time and was told that she produces too much acid . test not available . she is a heavy smoker and she currently smokes 1 to 3 ppd .

she takes about 10 excedrin a day. Her BMI is 15 ( unable to gain weight )

she takes misoprostol and zegerid .

when she does not take those medication she is not able to tolerate the pain

she was refer for gastrectomy and since her gastrin level was 198 was refer to me .

I stopped her medication and gave her proper instructions to measure her gastrin level again and was over 200 .

I gave her instructions about smoking cessation and no t to use excedrin .

I requested secretin stimulation test , I was told that secretin is not available .

what is your advise with this patient .

Is secretin available ??

she is refusing to do the acid test again and an attempt to get prior results had been unsuccessful. No records of it .

Thank you

I will appreciate your recommendations Dr MM

Response

You do have a problem case indeed . With this background of a +10 year of gastric ulcer disease superimposed on heavy smoking, anorexia, low body weight and the excessive use of aspirin, a prostaglandin analog and a proton pump inhibitor it is not easy to make the diagnosis with the information available.

Firstly, we need to distinguish an elevated gastrin due to a tumor from secondary causes of hypergastrinemeia. Under the circumstances it would be mandatory to obtain a gastric pH. She is thin, smokes heavily, uses aspirin, prostaglandin and a proton pump inhibitor all of which contrive to produce a pseudo gastrinoma syndrome with reduction of gastric output, loss of the restraint on gastrin secretion and therefore an increase of gastrin leading one to make the tentative diagnosis of a gastrinoma. Misoprostol is approved for use in the prevention of NSAID -induced gastric ulcers. It acts upon gastric parietal cells , inhibiting the secretion of gastric acid via G-protein coupled receptor -mediated inhibition of adenylate cyclase , which leads to decreased intracellular cyclic AMP levels and decreased proton pump activity at the apical surface of the parietal cell. Because other classes of drugs, especially H2-receptor antagonists and proton pump inhibitors , are more effective for the treatment of acute peptic ulcers, Misoprostol is only indicated for use by people who are both taking NSAIDs and are at high risk for NSAID-induced ulcers, including the elderly and people with ulcer complications. Misoprostol is sometimes co-prescribed with NSAIDs to prevent their common adverse effect of gastric ulceration (e.g. with Diclofenac in Arthrotec )..It can also induce proliferation of gastric mucosal folds and induce a resemblance to the rugae found in gastrinoma syndrome. The ph would be <2 in contrast to gastrinoma in which case it would be >2. The situation is similar for the PPIs and one would have to have stopped both drugs for at least a week or longer and obtained a repeat gastrin level-preferably with an acid measurement to be confident that the parietal cells had been unbridled. With he asthenia one might also consider other factors and antibodies to gastric parietal mucosa and a B12 level would exclude pernicious anemia. Incidentally with the difficulty in weight gain, if antibodies were found one ought to check her thyroid function.

Now say we thought that she did have a gastrinoma. It would have been helpful to know the family history as well as know the Pth, ionized calcium and prolactin and pancreatic polypeptide values since they would point in the direction of MEN syndrome in which case the treatment would still be conservative (<10% are malignant). And then to the final question would it be useful to do a secretin test. Yes if all these other variables are controlled for. Secretin is available again ( a different company) so it can be done-but the drugs being used and the possibilities of alternate diagnoses raise the issue of a false positive secretin test!!

Now for a few words of prognostication. This has gone for 10 years with pure medical therapy so it does not seem to be behaving in an aggressive manner. I would measure her Chromogranin A ( again after stopping the medications), pancreastatin and NeurokininA. , the first as an indicator of the general presence of a neuroendocrine tumor and the latter as indicators of prognosis and the need to be aggressive or conservative in management. Hope this helps.

Aaron Vinik MD PhD, FCP, MACP

Professor Internal Medicine, Pathology/Neurobiology

Director Research