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.

SAT-121 Secretin Stimulation Test in a Patient Receiving Proton PUMP Inhibitor Therapy- to Do or Not to Do?

Introduction: Complications of gastrinoma cause increase in mortality in patients with MEN syndrome. There are concerns that secretin stimulation test (SST) can produce false positive results in the setting of proton pump inhibitor (PPI) use. However, withholding the PPI treatment in a patient with severe peptic ulcer disease can be potentially unsafe. There is also a theoretical concern that abrupt withdrawal of PPI will cause a surge in gastrin. Here we discuss a case where SST yielded impressive results despite the use of PPI. Case report: 78 y.o. Caucasian male presented in December 2018 with chronic nausea, vomiting, diarrhea of 5-year duration. Further evaluation showed severe esophagitis with strictures, multiple gastric and duodenal ulcers and he was initiated on PPI. He also had h/o hyperparathyroidism diagnosed 2 years ago s/p parathyroidectomy (2 of 4 parathyroid glands removed) and one kidney stone in his late 20s and early 70s. He had no family history of any endocrine issues. Physical examination was unremarkable. Labs were significant for gastrin levels (nl <100 pg/mL) of 375 pg/mL in 6/2016 and 219 pg/mL in 11/2018. SST was performed on 12/22/2018 which showed gastrin levels as follows: -10 min=405 pg/mL, - 5 min=404 pg/mL, + 2 min=3201 pg/mL, + 5 min=3439 pg/m, +10 min=2445 pg/mL, +20 min=1218 pg/mL, +30 min=578 pg/mL. He was diagnosed with gastrinoma based on the SST results. Genetic testing did not show any pathogenic sequence variants or deletions/duplications identified in MEN-1; CASR; CDC73; CDKN1B or RET. Given history of hyperparathyroidism and gastrinoma, he was clinically diagnosed with MEN1 syndrome. Ga-68 DOTATATE scan in May 2019 revealed focal radiotracer avidity in the tail the pancreas suspicious for neuroendocrine tumor and multiple radiotracer avid retroperitoneal and abdominal lymph nodes. Focal radiotracer avid lesion was also noted in the sacrum suspicious for osseous metastatic disease. He was started on lantreotide monthly injections in July 2019. Gastrin level decreased to 94 pg/mL 1 week after first injection, however later increased to 304 pg/ml 1 week after third dose of lantreotide. Surgical options are also being explored. Conclusion: An increase in more than 120pg/mL over basal gastrin level within 10 min in SST is consistent with a diagnosis of gastrinoma. Our patient demonstrated an impressive increase in gastrin level with SST while on PPI therapy. Pertinent diagnostic information was successfully obtained without increasing the risk of complications that can occur by withdrawal of PPI therapy.