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.

Effects of Proton Pump Inhibitor Therapy, H. pylori Infection and Gastric Preneoplastic Pathology on Fasting Serum Gastrin Concentrations

BackgroundHypergastrinaemia occasionally indicates the presence of a gastrinoma. However it is much more commonly associated with various benign causes including proton pump inhibitor (PPI) use, Helicobacter pylori infection and/or atrophic gastritis. The extent to which these factors interact to influence fasting serum gastrin concentrations remains incompletely understood.Materials and MethodsFasting serum gastrin concentrations were measured by radioimmunoassay in 1,400 patients attending for diagnostic oesophagogastro-duodenoscopy. After exclusions, 982 patients were divided into four groups and their results analysed. We compared gastrin concentrations in normal patients (no H. pylori infection, no PPI use and no histological evidence of gastric preneoplasia (n=233)), with those in patients who were taking regular PPIs (H. pylori negative with no gastric preneoplasia (n=301)), patients who had active H. pylori infection but no gastric preneoplasia (n=164) and patients with histologically confirmed gastric preneoplasia (n=284).ResultsMedian fasting gastrin concentration in the normal group was 20pM and was significantly increased in PPI users (46pM, p<0.0001), patients with active H. pylori infection (27pM, p<0.0001), and patients with antral (25pM, p<0.01) or corpus (48pM, p<0.0001) gastric preneoplasia. PPI use resulted in further significant increases in fasting serum gastrin concentrations in patients who were infected with H. pylori (50pM, n=56) or who had antral gastric preneoplasia (53pM, n=87), but did not significantly alter serum gastrin concentrations in patients with corpus preneoplasia (90pM, n=66).ConclusionsPPI use, H. pylori infection and atrophic gastritis all caused significant elevations of median fasting gastrin concentrations. However, several patients who had potential risk factors for hypergastrinaemia still demonstrated fasting serum gastrin concentrations within the normal range.

Progressive Imbalance and Visual Impairment in a Patient With Diabetes

A 72-year-old man with hypothyroidism and type 2 diabetes sought care for a 3-year history of slowly progressive, ascending lower limb paresthesias and imbalance. Three months earlier, he noted subacute onset of finger numbness and substantial worsening of imbalance with infrequent falls. He also had a 1-year history of progressive visual decline that persisted despite cataract surgery. Additional symptoms included intermittent light-headedness and confusion. Laboratory evaluations showed a decreased hemoglobin value and an increased mean corpuscular volume. Macrocytic red blood cells were noted on a peripheral blood smear. Serum vitamin B12 level was less than 70 ng/L. Levels of plasma homocysteine and serum methylmalonic acid were markedly increased to 375 µmol/L and 143 nmol/L, respectively. Serum copper level was normal. Serum parietal cell antibodies were increased to 46 U, and intrinsic factor antibodies were absent. Serum gastrin was markedly increased. The clinical presentation in this patient suggested a myeloneuropathy. His vitamin B12 level was undetectable and accompanied by a macrocytic anemia and increased methylmalonic acid and homocysteine levels. Even though intrinsic factor antibodies were negative, the clinical picture was supportive of subacute combined degeneration in the setting of pernicious anemia. The patient was started on vitamin B12 replacement. At 6-month follow-up he had striking improvement in gait and vision. The light-headedness and confusion were no longer present. His examination was remarkable only for mild impairment, with tandem gait and a slightly positive Romberg sign. The lower limb reflexes were reduced. Impaired position perception at the toes persisted, but vibration perception in the lower limbs improved. Laboratory investigations showed normalization of the hemoglobin, vitamin B12, methylmalonic acid, and homocysteine levels. The serum gastrin level had improved but was still increased at 742 pg/mL. The best-characterized neurologic manifestations of vitamin B12 deficiency include myelopathy and myeloneuropathy. Autonomic neuropathy, optic neuropathy, and neuropsychiatric manifestations have also been reported. Neurologic manifestations may occur without evidence of the characteristic hematologic derangement, megaloblastic anemia. Macrocytosis or hypersegmented neutrophils on peripheral blood smear may be clues.

GASTRIN IN SERUM AND MORPHOLOGICAL STATE OF GASTRIN-SECRETING CELLS IN PATIENTS WITH GASTRIC POLYPOSIS

Objective. Numerous studies regarding gastric hormones and their regulation have been performed until now. However, the effect of the hormones on the formation and malignisation of gastric polyps still remains not clear. Our aim was to identify the relation between the level of gastrin in the blood, gastric mucosa, polyp tissue, gastric juice and pathogenesis of gastric polyposis. Materials and methods. A thorough investigation of gastrointestinal hormones in serum and gastric juice, in polyp’s tissue and mucosa, gastrin-secreting cells and proteolytic activity of gastric juice was carried out in 40 patients with gastric polyps. These patients were divided into groups, depending on the location, number, and malignancy of the polyps. As a control group, 10 healthy individuals were used to determine the normal values of the studied indicators. Results: A significant increase (more than two times) in the gastrinemia level before the surgery was noted in patients with polyp recurrence, and gastrin level increased to more significant digits of 227.0+37.4 pg/ml (p<0.05) in one year after polypectomy. Conclusion. Gastrin is apparently involved in the process of polyp formation since polyp’s growth is accompanied by elevation of serum gastrin. This is confirmed by a response of gastrin in the blood to a test meal in individuals with different duration of the disease: a marked increase in gastrinemia appears in patients suffering from gastric polyposis for more than three years. Therefore, evaluation of gastrin level in the patients’ blood can be used to predict a recurrence potential of polyps. This is evidenced by more pronounced hypergastrinemia before polypectomy in patients who had a further recurrence of the disease within one year after the surgery

Gastric mucosal function in portal hypertensive gastropathy secondary to schistosomal hepatic fibrosis: effect of sclerotherapy

Gastric mucosal function in portal hypertensive gastropathy secondary to schistosomal hepatic fibrosis [SHF] was evaluated. Group I comprised 20 patients with no bleeding;10 had portal hypertensive gastropathy [PHG]. Group II comprised 20 patients with bleeding. Free acidity, total acidity, basal acid output, serum pepsinogen I, gastric mucosal blood flow [GMBF] and gastrin were significantly lower in group II, whereas serum gastrin and somatostatin staining were significantly higher. No histopathological changes were noted between both groups, In conclusion, bleeding caused by SHF results in hypoacidity, hypergastrinaemia and hypopepsinogenaemia. Estimated GMBF distinguishes patients with PHG and those who are bleeders