Increased epithelial cell proliferation in the colon of patients with acromegaly.
To gain insight into the possible physiological mechanisms responsible for the increased incidence of colonic neoplasms in patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly. Seven patients had newly diagnosed acromegaly and 23 were studied during follow-up. Serum growth hormone and insulin-like growth factor-1 (IGF-1) were determined on two separate occasions. During diagnostic endoscopy, mucosal biopsies were obtained for immunohistochemical determination of sigmoidal epithelial cell proliferation, expressed as labeling index (LI). Duodenal and fecal bile acid analyses were performed using gas-liquid chromatography. Results were compared with normal ranges of the laboratory. An increased overall LI was found in 54% of the patients. Increased LI of the luminal, middle, and basal crypt compartments was found in 11, 64, and 28%, respectively. Similarly, comparisons of the mean +/- SEM of the overall LI and the LI of the middle and basal compartments between acromegalic patients and a control group showed overall LI 10.0 +/- 0.8% versus 5.7 +/- 0.6% (P < 0.001), middle LI 12.1 +/- 1.2% versus 5.0 +/- 0.6% (P < 0.001), and basal LI 17.1 +/- 1.3% versus 10.8 +/- 1.3% (P < 0.01). Duodenal and fecal bile acid proportions were within the normal ranges of the laboratory. There was a positive correlation between growth hormone and overall LI (r = 0.55, P < 0.01) by least square regression analysis. There was no correlation between duodenal bile acid composition and hormone levels. The proportion of secondary bile acids in feces correlated with growth hormone (r = 0.55, P < 0.05) as well as with IGF-1 (r = 0.59, P < 0.05). With multiple regression analyses, only a relation between overall LI and IGF-1 (P = 0.007) remained to hold true. Increased epithelial cell proliferation, most probably due to a direct stimulatory effect of especially IGF-1, contributes to the increased risk of colonic neoplasms in acromegaly.
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Division of Medical Oncology, University Hospital, Groningen, The Netherlands.
Dullaart
R P
RP
Kleibeuker
J H
JH
Kuipers
F
F
Sluiter
W J
WJ
Hardonk
M J
MJ
de Vries
E G
EG
D000172:Acromegaly / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D015331:Cohort Studies; D003106:Colon / Q000166:cytology*; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D004386:Duodenum / Q000378:metabolism; D004847:Epithelial Cells; D005069:Evaluation Studies as Topic; D005243:Feces / Q000737:chemistry; D005260:Female; D005500:Follow-Up Studies; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D015994:Incidence; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D001647:Bile Acids and Salts; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone