Acromegaly colonoscopy findings12/24/2023 ( 17) reported that patients with acromegaly had an increased proliferation index of colonic epithelium proportional to their circulating IGF-1 levels. IGF-1 can stimulate growth of CRC cells in vitro, whereas the blockade of its effect by the alpha IR3, a neutralizing monoclonal antibody against the human IGF-1 receptor, inhibits cell growth in the same model ( 15, 16). IGF-1 receptors, as well as IGF-1 mRNA, have been identified in human CRC cell lines ( 15). Any imbalance in the tight control between epithelial cell turn-over and cell death could result in epithelial hyperproliferation, promoting the formation of hyperplastic polyps and colorectal adenomas ( 14). Plasma GH triggers the production of IGF-1 from the liver, which in turn stimulates the growth of organs and tissues, through its known mitogenic and antiapoptotic properties. Some authors have described increased risk for benign and malignant tumors in digestive tract in acromegalics, and they found that the odds ratio for the presence of hyperplastic polyps was 8.3, for adenomas 4.2 and for colon carcinomas 9.8, showing an association with higher serum GH levels ( 12).Ī recent study performed in a cohort of Japanese acromegalic patients has shown that increased mean area under the curve (AUC) for GH was associated with an increased risk for colon adenocarcinomas ( 13).Īn attractive explanation for the increased risk of CRC in acromegaly has been the link to IGF-1. Overall and cancer mortality in acromegaly have been shown to correlate with the degree of GH control ( 2, 6, 7). Chronic exposure to high IGF-1 levels seems to be the most important. Several hypothesis have been investigated and they may be related to sustained increase of GH and insulin-like growth factor 1 (IGF-1) levels, metabolic disorders, and genetic factors ( 7, 8, 12) ( Figure 1).įigure 1 Potential factors involved in the pathogenesis of colorectal carcinoma (CRC) in acromegaly. The mechanisms involved in cancer initiation in acromegalic patients remain unclear. Pathogenesis of colorectal cancer (CRC) in acromegaly The main objective of the current article is to review the most relevant aspects concerning prevalence, pathogenesis and screening of CRC in acromegalic patients. Data from registry-based cohorts in Europe showed increased risks for digestive system cancers [standardized incidence ratio (SIR) =2.1, 95% CI, 1.6-2.7), notably of the small intestine (SIR =6.0, 95% CI, 1.2-17.4), colon (SIR =2.6, 95% CI, 1.6-3.8), and rectum (SIR =2.5, 95% CI, 1.3-4.2) ( 10).ĬRC is one of the most prevalent malignancy worldwide ( 11) and among patients with acromegaly ( 7- 10), in whom it implies a mortality rate higher than that expected for the general population ( 6). Prospective studies using colonoscopy showed a three times higher prevalence of intestinal polyps and up to four times increased presence of colorectal cancer (CRC) in acromegaly than in normal controls, independently of sex, age, duration of disease and clinical status of the patients ( 8). Several studies have suggested increased risk of colon cancer and polyps in acromegalic patients ( 6- 9). Overall and cancer mortality in acromegaly have been shown to correlate with the degree of GH control. The disease has a subclinical course, and the delay on diagnosis is associated with high morbidity and with premature mortality related to increased cardiovascular risk, sleep apnea, metabolic comorbidities, and cancer ( 3- 5). Accepted for publication Aug 26, 2014.Īcromegalic patients are exposed to chronic growth hormone (GH) hypersecretion mostly associated to pituitary adenomas ( 1, 2). Keywords: Acromegaly growth hormone (GH) insulin-like growth factor 1 (IGF-1) colorectal cancer (CRC) colonoscopy screening
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