Gastroenterology · Gastrinoma

The Diagnostic Journey: Proving and Locating a Gastrinoma

At a Glance

Pancreatic gastrinoma is confirmed by combining fasting gastrin with gastric pH; secretin testing can help when results are unclear. DOTATATE PET/CT and endoscopic ultrasound help locate small tumors, while Ki-67 and mitotic count show how quickly the tumor may grow.

Confirming a diagnosis of Zollinger-Ellison Syndrome (ZES) requires more than a single blood test. Because high levels of the hormone gastrin can be caused by many different things—including the very medications used to treat reflux—doctors must follow a specific sequence of tests to prove a tumor is responsible ^[1]^[2].

The First Step: Gastrin and Acid

The diagnostic process usually begins with two tests performed at the same time:

Fasting Serum Gastrin (FSG): A blood test to measure how much gastrin your body is producing ^[3].
Gastric pH: A test to measure how much acid is actually in your stomach ^[1].

The Diagnostic Threshold: A gastrin level above 1,000 pg/mL combined with a gastric pH of less than 2.0 is considered diagnostic for ZES when measured under appropriate conditions ^[1]^[2]. However, testing must be interpreted carefully. If your gastrin is high but your stomach is not acidic (pH above 4.0), it does not automatically rule out ZES if you are taking a PPI; it simply means the medication is working. If you are off medications, high gastrin with a pH above 4.0 means your body might be making gastrin to compensate for a lack of acid, a condition called atrophic gastritis ^[2]^[4]. Kidney insufficiency and H. pylori can also raise gastrin.

The Secretin Stimulation Test

If your gastrin is elevated but hasn’t reached the 1,000 pg/mL mark, or if your acid levels are borderline, your doctor may order a secretin stimulation test ^[1].

How it works: Secretin is a hormone that normally stops gastrin production in healthy cells. However, in gastrinoma tumor cells, secretin actually triggers a massive release of gastrin ^[5].
The Result: If your gastrin levels rise significantly (often defined as an assay-dependent jump of more than 120 pg/mL or 200 pg/mL) after receiving secretin, it strongly points to a gastrinoma ^[6]^[5].

The Dangers of Stopping PPIs

To get accurate results, patients were historically told to stop taking Proton Pump Inhibitors (PPIs) like omeprazole for at least one week before testing ^[1]. Warning: Do not stop these medications on your own. Abruptly stopping PPIs in a patient with an undiagnosed gastrinoma can cause a “rebound” of massive acid production, leading to emergency ulcers or perforation ^[1]^[7]. Some recent research suggests that the secretin test can be performed safely while still on PPIs, but this must be managed by a specialist ^[8].

Imaging: Finding the “Hidden” Tumor

Once the bloodwork confirms ZES, the next challenge is finding the tumor, which can be as small as a pea ^[9].

DOTATATE PET/CT: This is the most sensitive scan available. It uses a radioactive tracer that sticks to somatostatin receptors on the surface of neuroendocrine tumors ^[10].
The “Pancreas Head” Trap: A common pitfall of this scan is that the head of the pancreas often shows “physiologic uptake”—meaning it naturally glows on the scan even when no tumor is present ^[10]^[11]. Radiologists must carefully compare this with a CT or MRI to see if there is an actual physical lump ^[12].
Endoscopic Ultrasound (EUS): A tiny ultrasound probe is passed down your throat to look at the pancreas and duodenum from the inside, which is excellent for finding very small tumors that other scans miss ^[13].

Reading Your Pathology Report

If a piece of the tumor is removed or biopsied, a pathologist will assign it a WHO Grade based on its differentiation, its Ki-67 index, and its mitotic count ^[14]. The Ki-67 index measures what percentage of the tumor cells are currently dividing (growing) ^[15]. A small biopsy can sometimes under-sample a faster-growing “hotspot.”

WHO Grade	Ki-67 Index	Meaning
Well-Differentiated Grade 1 (G1)	Less than 3%	Very slow-growing ^[16].
Well-Differentiated Grade 2 (G2)	3% to 20%	Moderately slow-growing ^[16].
Well-Differentiated Grade 3 (G3)	Greater than 20%	Faster-growing, but still well-differentiated; distinct from poorly differentiated neuroendocrine carcinoma (NEC) ^[16].

Knowing your grade helps your doctor predict how the tumor will behave over time and determine how often you need follow-up scans ^[17].

Common questions in this guide

How is a pancreatic gastrinoma diagnosed?

Doctors usually measure fasting serum gastrin and gastric pH together. A gastrin level above 1,000 pg/mL with a stomach pH below 2.0 is considered diagnostic for Zollinger-Ellison syndrome when testing is performed under appropriate conditions. Medicines and other conditions can change gastrin results, so a specialist must interpret them.

What happens during a secretin stimulation test for gastrinoma?

After secretin is given, clinicians measure gastrin again at set times. Secretin normally lowers gastrin, but gastrinoma cells may release much more of it. A rise above the laboratory’s threshold, often more than 120 or 200 pg/mL, supports the diagnosis.

Can I stop my PPI before gastrinoma testing?

Do not stop a proton pump inhibitor on your own. In someone with an undiagnosed gastrinoma, stopping acid suppression abruptly can cause a dangerous rebound in stomach acid, ulcers, or perforation. A specialist may adjust the medicine or perform selected testing while it is continued.

Which scans can find a small pancreatic gastrinoma?

DOTATATE PET/CT is highly sensitive because its tracer can bind to receptors commonly found on neuroendocrine tumors. Endoscopic ultrasound can examine the pancreas and duodenum from inside the body and may find very small tumors. CT or MRI helps confirm whether an area seen in the pancreatic head is a real mass.

Does activity in the head of the pancreas on a DOTATATE scan always mean a tumor?

No. The head of the pancreas can normally take up the tracer, a finding called physiologic uptake. Radiologists compare the PET result with CT or MRI and look for a distinct physical mass before deciding whether it represents a gastrinoma.

What do Ki-67 and mitotic count mean on a gastrinoma pathology report?

Ki-67 estimates the percentage of tumor cells that are dividing, while mitotic count records dividing cells under the microscope. In a well-differentiated neuroendocrine tumor, Ki-67 below 3% is grade 1, 3% to 20% is grade 2, and above 20% is grade 3. A small biopsy can miss a faster-growing area, so the sample size and hotspot matter. These grades apply to well-differentiated tumors and are not the same as a poorly differentiated neuroendocrine carcinoma.

Can something other than a gastrinoma cause a high gastrin level?

Yes. Proton pump inhibitors, atrophic gastritis, kidney insufficiency, and H. pylori infection can all raise gastrin. Doctors interpret the result alongside gastric pH, medication use, and other test findings rather than relying on the blood level alone.

Get notified when new evidence is published on pancreatic gastrinoma.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References (17)

1
All you need to know about gastrinoma today | Gastrinoma and Zollinger-Ellison syndrome: A thorough update.
Chatzipanagiotou O, Schizas D, Vailas M, et al.
Journal of neuroendocrinology 2023; (35(4)):e13267 doi:10.1111/jne.13267.
PMID: 37042078
2
Gastric Hypersecretory States: Investigation and Management.
Phan J, Benhammou JN, Pisegna JR
Current treatment options in gastroenterology 2015; (13(4)):386-97 doi:10.1007/s11938-015-0065-8.
PMID: 26342486
3
Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies.
Rossi RE, Elvevi A, Citterio D, et al.
World journal of gastroenterology 2021; (27(35)):5890-5907 doi:10.3748/wjg.v27.i35.5890.
PMID: 34629807
4
Diarrhea, Weight Loss, and an Elevated Gastrin: A Case Report.
Alexander RG, Cheville JC, Thompson GB, Alexander GL
Case reports in gastroenterology 2025; (19(1)):428-433 doi:10.1159/000545714.
PMID: 40503451
5
Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger-Ellison Syndrome.
Mendelson AH, Donowitz M
Digestive diseases and sciences 2017; (62(9)):2258-2265 doi:10.1007/s10620-017-4695-7.
PMID: 28776139
6
Secretin Stimulation Test and Early Diagnosis of Gastrinoma in MEN1 Syndrome: Survey on the MEN1 Florentine Database.
Giusti F, Cioppi F, Fossi C, et al.
The Journal of clinical endocrinology and metabolism 2022; (107(5)):e2110-e2123 doi:10.1210/clinem/dgab903.
PMID: 34922358
7
Assessing for Multiple Endocrine Neoplasia Type 1 in Patients Evaluated for Zollinger-Ellison Syndrome-Clues to a Safer Diagnostic Process.
Singh Ospina N, Donegan D, Rodriguez-Gutierrez R, et al.
The American journal of medicine 2017; (130(5)):603-605 doi:10.1016/j.amjmed.2016.11.035.
PMID: 28011308
8
Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome.
Bhattacharya S, Blau JE, Cochran C, et al.
The American journal of gastroenterology 2021; (116(11)):2216-2221 doi:10.14309/ajg.0000000000001487.
PMID: 34515664
9
[Comparison of clinical characteristics between sporadic gastrinoma and multiple endocrine neoplasia type 1-related gastrinoma].
Guo Y, Chen LH, Liu M, et al.
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 2021; (24(10)):875-882 doi:10.3760/cma.j.cn.441530-20210719-00291.
PMID: 34674462
10
Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation.
Hofman MS, Lau WF, Hicks RJ
Radiographics : a review publication of the Radiological Society of North America, Inc 2015; (35(2)):500-16 doi:10.1148/rg.352140164.
PMID: 25763733
11
Current Concepts in 68Ga-DOTATATE Imaging of Neuroendocrine Neoplasms: Interpretation, Biodistribution, Dosimetry, and Molecular Strategies.
Bodei L, Ambrosini V, Herrmann K, Modlin I
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2017; (58(11)):1718-1726 doi:10.2967/jnumed.116.186361.
PMID: 28818983
12
Autoimmune Pancreatitis Mimicking a Pancreatic Neuroendocrine Tumor: A Case Report with a Literature Review.
Franchina M, Dell'Oro L, Massironi S
International journal of molecular sciences 2025; (26(4)) doi:10.3390/ijms26041536.
PMID: 40004001
13
Endoscopic ultrasound-guided side-fenestrated needle biopsy sampling is sensitive for pancreatic neuroendocrine tumors but inadequate for tumor grading: a prospective study.
Appelstrand A, Bergstedt F, Elf AK, et al.
Scientific reports 2022; (12(1)):5971 doi:10.1038/s41598-022-09923-1.
PMID: 35396490
14
Digital image analysis of Ki67 hotspot detection and index counting in gastroenteropancreatic neuroendocrine neoplasms.
Saetiew K, Angkathunyakul N, Hunnangkul S, Pongpaibul A
Annals of diagnostic pathology 2024; (71()):152295 doi:10.1016/j.anndiagpath.2024.152295.
PMID: 38547761
15
Comparison of Three Ki-67 Index Quantification Methods and Clinical Significance in Pancreatic Neuroendocrine Tumors.
Kroneman TN, Voss JS, Lohse CM, et al.
Endocrine pathology 2015; (26(3)):255-62 doi:10.1007/s12022-015-9379-2.
PMID: 26072124
16
Surgery in Patients with Gastro-Entero-Pancreatic Neuroendocrine Carcinomas, Neuroendocrine Tumors G3 and High Grade Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.
Holmager P, Langer SW, Kjaer A, et al.
Current treatment options in oncology 2022; (23(6)):806-817 doi:10.1007/s11864-022-00969-x.
PMID: 35362798
17
Grading Using Ki-67 Index and Mitotic Rate Increases the Prognostic Accuracy of Pancreatic Neuroendocrine Tumors.
Philips P, Kooby DA, Maithel S, et al.
Pancreas 2018; (47(3)):326-331 doi:10.1097/MPA.0000000000000990.
PMID: 29351120

This page is for informational purposes only and does not constitute medical advice about a suspected pancreatic gastrinoma. Do not change or stop a PPI or other acid-suppressing medicine without guidance from your healthcare team.

Guide Contents