Extended Octreotide Supression Test To Determine Hormone Responsiveness in a Patient with Multiple Gastric Carcinoid Tumors

Abstract

Purpose: Type I gastric carcinoid tumors arise from enterochromaffin-like (ECL) cells of gastric fundus under the trophic effect of hypergastrenemia. Histidine decarboxylase (HDC), the enzyme responsible for histamine production in these cells, is regulated by gastrin. Lesions less than 1 cm and fewer than 3–5 in number are typically managed by endoscopic resection. Management of tumors that are larger than 1 cm or more than 5 in number is controversial. Antrectomy has been reported to result in complete regression of tumors. However, in some cases the tumors may become autonomous and no longer gastrin dependent. This has led some authorities to recommend total gastrectomy for tumors that are large or multiple. Methods: A 62 year old asymptomatic male referred for mild anemia, was found to have at least 12 gastric carcinoids 3–10 mm in size in the setting of chronic atrophic gastritis. Biopsies of the intervening mucosa revealed microcarcinoidosis. There was no evidence of local extension or metastasis. We decided to do an extended octreotide supression test to determine if the tumors are still gastrin dependent and would likely regress after antrectomy. The patient was started on octreotide infusion at 12.5–25 mcg/hr for 86 hours after obtaining an informed consent and then started on octreotide depot injections every 4 weeks for five months. Serum fasting gastrin levels and chromogranin A (CGA) levels were measured and an endoscopy with biopsies was performed immediately before and after the infusion and at five months. RNA was extracted from the biopsy specimens and comparative quantitation of HDC mRNA was performed using real-time PCR with FAM-labeled LUX primers after generation of cDNA. Results: Serum fasting gastrin levels decreased from 306 pg/ml pre-treatment to 31 pg/ml at the end of infusion and 112 pg/ml at 5 months. CGA levels decreased from 4–6 times the upper limit of normal to within the normal range at the end of infusion and stayed normal at 5 months. Tissue HDC mRNA decreased 54 fold at the end of infusion and decreased further at five months. There was a decrease in size and number of tumors at five months. Conclusions: Long term octreotide treatment resulted in effective supression of serum gastrin, serum CGA, and tissue HDC mRNA associated with partial tumor regression. These results demonstrate that the carcinoid tumors in this patient are still gastrin dependent and expected to regress after antrectomy.