Keywords
Basal acid output
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chronic diarrhea
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Zollinger–Ellison syndrome
Introduction
Chronic diarrhea can sometimes be difficult to diagnose, especially for the primary
care physician. Of the varied causes of diarrhea, Zollinger–Ellison syndrome (ZES)
is a frequently underdiagnosed condition.[1],[2] Although many advances have been made in diagnosing ZES, measurement of basal acid
output (BAO) still holds an important place, especially in a resource-limited setting.
Case Report
A 54-year-old man working in cooperatives came to our hospital in May 2016 with 5
months of watery diarrhea moving his bowels 15–20 times/day with nocturnal episodes
and not associated with tenesmus, blood, or mucus in stool. He experienced severe,
colicky constant upper abdominal pain that prevented him from eating. Despite fasting,
he continued to pass watery stools and had lost 15 kg over 5 months. He did not report
to have fever, skin rashes, tremors, or joint pain.
Three months before this admission, he received a diagnosis of fistula-in-ano by a
primary care physician, for which he underwent fistulectomy and was treated with antibiotics.
A colonoscopy done at that time showed a normal study up to the cecum except for a
fistulous opening in the anal canal. He had no other medical or surgical comorbidities
in the past.
On admission, he was visibly distressed due to pain and was severely dehydrated. His
physical examination was remarkable for an intensely tender upper abdomen and a healed
perianal scar.
Investigations
Blood work showed leukocytosis, predominant neutrophils, and prerenal azotemia. His
stool examination and culture were negative. Esophagogastroduodenoscopy (EGD) revealed
severe esophagitis and multiple ulcers with necrotic base in the duodenum and upper
jejunum from which biopsies revealed nonspecific inflammation [Figure 1]. A small fundic polyp was noted, biopsy of which showed oxyntic gland hyperplasia.
Considering a possibility of ZES, we took the patient off proton-pump inhibitor (PPI)
and and H2 receptor antagonists and measured basal acid output.[3] BAO was elevated (11.4 mmol/h). The gastric pH was <2. Subsequent serum fasting
gastrin levels measured were also high (404 pg/ml). A contrast-enhanced computed tomography
of the abdomen was unremarkable except for prominent rugal folds. EUS showed a submucosal
nodule in the first part of duodenum with an inconclusive fine-needle aspiration cytology.68
Ga-DOTA-NOC scan revealed avid uptake in the medial wall of pylorus of the stomach,
highly suggestive of neuroendocrine tumor (NET) [Figure 2].
Figure 1 Endoscopy showing multiple duodenal ulcers
Figure 2 DOTA scan showing prominent uptake in the region of the pylorus
Treatment
Initially, he was hydrated intravenously, after which renal parameters normalized.
The patient was started on high-dose PPIs (omeprazole 120 mg/day) with which he had
immediate resolution of abdominal pain and diarrhea. Ten days after PPI therapy, we
repeated EGD which showed complete resolution of the esophagitis and ulcers in the
duodenum and jejunum [Figure 3]. The patient later underwent pyloroduodenotomy, and a thorough examination of the
pylorus and duodenum was undertaken. The pylorus was normal, and the first part of
the duodenum had a submucosal nodule which was excised [Figure 4]. Pathologists reported it as NET showing insular and trabecular architecture. Unfortunately,
due to various reasons, we could not do immunohistochemistry staining.
Figure 3 Complete healing of ulcers in the duodenum after proton-pump inhibitor therapy
Figure 4 Resected tumor
Follow-up
Postsurgery, the patient recovered well and is on regular follow-up. He remains asymptomatic
till date.
Discussion
ZES is caused by ectopic secretion of gastrin by a NET (gastrinoma), which causes
excessive gastric acid secretion, characteristically causing peptic disease (often
severe) and/or gastroesophageal reflux disease with an incidence of 0.1–3 persons/million/year.
About 60% to 90% are malignant. More than half of them are in the duodenum. In our
case, the DOTA scan revealed uptake in the medial wall of the pylorus, but it was
actually located in the first part of the duodenum which was confirmed on surgery.
Serum fasting gastrin levels are typically> 1000 pg/dl. Sometimes, one cannot solely
rely on serum fasting gastrin alone.[3] If levels are only modestly increased, as in our case, a combination of tests can
be used to establish the diagnosis. In a country like India, where secretin is not
widely available, the measurement of BAO is a useful and easy test to do.[4]
Histologically, most gastrinomas are well differentiated and show a trabecular and
pseudoglandular pattern. Their proliferative activity (i.e., the Ki67 index) varies
between 2% and 10% but is mostly close to 2%. Immunohistochemically, almost all gastrinomas
stain for gastrin.
Tumor-localizing methods are many, of which somatostatin receptor scintigraphy, EUS,
and intraoperative ultrasound are more yielding. Pharmacological control of acid secretion
can be achieved with twice-daily PPI (starting from 60 mg/day for omeprazole) or H2-receptor
antagonists. Most authorities recommend surgical exploration of ZES patients for a
possible curative resection as long as diffuse metastatic disease to the liver is
absent and the patient does not have Multiple Endocrine Neoplasia –Type I. In advanced
cases, chemotherapy and somatostatin analogs/peptide receptor radionuclide therapy
have been used.[5]
Learning points
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ZES, though uncommon, should be considered in all patients with painful watery diarrhea
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BAO measurement and pH measurement are simple, cost-effective tests that can be collected
at bedside and can guide higher investigations.
Declaration of patient consent
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In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
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