Intestinal proliferation and delayed intestinal transit in a patient with a GLP-1-, GLP-2- and PYY-producing neuroendocrine carcinoma

Glucagon-like peptides (GLP) 1 and 2 are hormones derived from the post-tra nslational processing of proglucagon in the intestinal L cells that influen ce intestinal motility and small bowel growth, respectively. We describe a patient with a neuroendocrine tumor of unknown primary origin with peritone al carcinomatosis and diffuse liver metastases, who presented with constipa tion and nocturnal itching for over 3 yea rs. Small bowel follow-through sh owed decreased small intestinal motility and marked intestinal hypertrophy. Biopsies from mesenterial lymph nodes showed, histologically, a well-diffe rentiated neuroendocrine tumor (G1), with positive immunostaining for chrom ogranin A, GLP-1, GLP-2 and polypeptide YY (PYY). Jejunal biopsy demonstrat ed marked intestinal mucosal hypertrophy. HPLC analysis combined with RIA o f tumor and serum extracts revealed that the tumor was producing and releas ing fasting levels of GLP-1 of 738+/-20.7 pg/ml (normal levels (nl) <100 pg /ml), GLP-2 of 3,150+/-9 pg/ml (nl <100 pg/ml) as well as PYY 550 pg/ml (nl <100 pg/ml). Octreotide administration decreased levels of GLP-1 and GLP-2 and reduced small intestinal transit time from 150 to 50 min. However, tum or growth was not inhibited by octreotide, interferon or dacarbazine therap y and the patient died 8 months later. This is the first case report demons trating the overproduction of GLP-1, GLP-2 and PYY from an neuroendocrine t umor, in a patient with intestinal hypertrophy and delayed intestinal trans it time. Copyright (C) 2001 S. Karger AG, Basel.