Secretin stimulation test and early diagnosis of gastrinoma in MEN1 syndrome: Survey on the MEN1 Florentine database

Context Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrine cancer syndrome. Multiple gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) affect 30-80% of MEN1 patients, with the most common functioning GEP-NET being gastrinoma. Biochemical identification of hypergastrinemia may help to recognize the presence of gastrinomas before they are detectable by instrumental screening, enabling early diagnosis and start of therapy, preferably before tumor progression and metastases occurrence. Objective Evaluate the effectiveness of secretin stimulation test to precociously diagnose the presence of gastrin-secreting tumors. Design Results of secretin stimulation tests, performed between 1991 and February 2020, were retrospectively analyzed, as aggregate, in a cohort of MEN1 patients with GEP-NETs. Setting Data were extracted from the MEN1 Florentine database. Patients The study included 72 MEN1 patients with GEP-NETs who underwent a secretin stimulation test for the evaluation of gastrin secretion. Outcomes A positive secretin stimulation test was assumed with a difference between basal fasting serum gastrin (FSG) and the maximum stimulated value of gastrin over 120 pg/ml. Results The secretin stimulation test showed a secretin-induced hypergastrinemia in 27.8% (20/72) of patients with GEP-NETs, and a positive test in 18 cases. The test allowed the identification of a positively stimulated hypergastrinemia in 75.0% (3/4) of patients who presented a basal FSG within the normal range. Conclusions Diagnosis of gastrinoma is complex, difficult and controversial. Results of this study confirm that a positive secretin stimulation test allows early diagnosis of gastrinomas, even in the presence of borderline or normal levels of non-stimulated FSG.

Gastrin and the Moderate Hypergastrinemias

The antral hormone gastrin potently regulates gastric acid secretion and fundic mucosal growth. Consequently, appropriate gastrin secretion and plasma concentrations are important for the early phases of digestion. This review describes as the first premise the normal biogenesis of gastrin in the antral mucosa, but also mentions the extraantral expression. Subsequently, the molecular nature and concentration levels of gastrin in serum or plasma are overviewed. Third, assays for accurate measurements of plasma or serum concentrations are commented. Finally, the problem of moderate hypergastrinemia due to Helicobacter pylori infections and/or treatment with proton-pump inhibitors (PPI) is discussed. The review concludes that accurate measurement of the true concentrations of bioactive gastrins in plasma is important. Moreover, it suggests that moderate hypergastrinemias are also essential health issues that require serious attention.

Stomach gastrin is regulated by sodium via PPAR-α and dopamine D1 receptor

Gastrin, secreted by stomach G cells in response to ingested sodium, stimulates the renal cholecystokinin B receptor (CCKBR) to increase renal sodium excretion. It is not known how dietary sodium, independent of food, can increase gastrin secretion in human G cells. However, fenofibrate (FFB), a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, increases gastrin secretion in rodents and several human gastrin-secreting cells, via a gastrin transcriptional promoter. We tested the following hypotheses: (1.) the sodium sensor in G cells plays a critical role in the sodium-mediated increase in gastrin expression/secretion, and (2.) dopamine, via the D1R and PPAR-α, is involved. Intact human stomach antrum and G cells were compared with human gastrin-secreting gastric and ovarian adenocarcinoma cells. When extra- or intracellular sodium was increased in human antrum, human G cells, and adenocarcinoma cells, gastrin mRNA and protein expression/secretion were increased. In human G cells, the PPAR-α agonist FFB increased gastrin protein expression that was blocked by GW6471, a PPAR-α antagonist, and LE300, a D1-like receptor antagonist. LE300 prevented the ability of FFB to increase gastrin protein expression in human G cells via the D1R, because the D5R, the other D1-like receptor, is not expressed in human G cells. Human G cells also express tyrosine hydroxylase and DOPA decarboxylase, enzymes needed to synthesize dopamine. G cells in the stomach may be the sodium sensor that stimulates gastrin secretion, which enables the kidney to eliminate acutely an oral sodium load. Dopamine, via the D1R, by interacting with PPAR-α, is involved in this process.

Inhibitory Effects of Deoxynivalenol on Gastric Secretion in Rats

Deoxynivalenol (DON) is a common mycotoxin produced by Fusarium sp. in cereals and foods. Ingestion of contaminated foodstuffs can cause digestive disorders in various animals. Many researchers focus on its toxicity and the pathological damage and absorptive function in the intestines. However, the effect of DON on gastric function is still unclear. The objective of the current study was to evaluate the impact of DON on gastric secretion. Rats were gavaged with DON at the dose of 0, 1, 5, and 25 mg/kg of body weight (bw). Gastric fluids were gathered by pylorus ligation 0.5 h after DON exposure. The results indicate that the volume of gastric fluid decreased by 25, 51, and 61% compared with the control, respectively. The pH increased to 3.2, 3.81, and 6.65 in the 1, 5, and 25 mg/kg bw DON group, compared with the control (1.9). To examine the mucosal injuries, the stomach tissues were made into hematoxylin and eosin slides. Histopathology observations suggest that no mucosal lesions were observed until DON exposure at 25 mg/kg bw. Additionally, the gastrin secretion in the fluids and mRNA expression in tissues were determined by the radioimmunoassay and real-time PCR assay, respectively. The results indicated that both significantly decreased in DON-exposed rats compared with the control. Taken together, DON exposure reduced gastric secretion in rats. Low gastrin secretion and mRNA expression play a major role, unless mucosal lesions by high DON exposure are present.