Glucagon-like peptides (
GLP) 1 and 2 are
hormones derived from the post-translational processing of
proglucagon in the intestinal L cells that influence intestinal motility and small bowel growth, respectively. We describe a patient with a
neuroendocrine tumor of unknown primary origin with
peritoneal carcinomatosis and diffuse liver
metastases, who presented with
constipation and nocturnal
itching for over 3 years. Small bowel follow-through showed decreased small intestinal motility and marked intestinal
hypertrophy. Biopsies from mesenterial lymph nodes showed, histologically, a well-differentiated
neuroendocrine tumor (G1), with positive immunostaining for
chromogranin A,
GLP-1, GLP-2 and
polypeptide YY (PYY). Jejunal biopsy demonstrated marked intestinal mucosal
hypertrophy. HPLC analysis combined with RIA of
tumor and serum extracts revealed that the
tumor was producing and releasing 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,
tumor growth was not inhibited by
octreotide,
interferon or
dacarbazine therapy and the patient died 8 months later. This is the first case report demonstrating the overproduction of
GLP-1, GLP-2 and PYY from an
neuroendocrine tumor, in a patient with intestinal
hypertrophy and delayed intestinal transit time.