Skip to main content

Advertisement

SpringerLink
Log in

The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Purpose

Colorectal neoplasms are well known to be a complication in cases of acromegaly; however, data on the prevalence of colorectal neoplasms in Asian patients with acromegaly are limited. Further, the factors associated with colorectal neoplasms in cases of acromegaly are controversial. Therefore, we aimed to clarify the prevalence of and factors associated with colorectal neoplasms in Japanese patients with acromegaly in a single center.

Methods

We analyzed consecutive 57 patients who had undergone full-length colonoscopy at the time of diagnosis at Kobe University Hospital between 1986 and 2012.

Results

Of the 57 patients, 22 (38.6 %), 18 (31.6 %) and 3 (5.3 %) patients were diagnosed with hyperplastic polyps, adenomas, and adenocarcinomas, respectively and the prevalence was significantly higher than in a historical control group, Chinese patients with irritable bowel syndrome (The odds ratio was 4.0, 8.7, and 17.5, respectively). The prevalence of adenocarcinomas was also significantly higher in these patients than in the general Japanese population (odds ratio 14.5). Patients with acromegaly who had colorectal neoplasms had longer disease duration than those without colorectal neoplasms. Of note, the area under the growth hormone (GH) concentration–time curve (GH AUC) during the oral glucose tolerance test was significantly higher in patients with adenocarcinomas than in those with no colonic lesion or those with hyperplastic polyps.

Conclusion

Japanese patients with acromegaly exhibited an increased risk of colorectal neoplasms, especially colorectal adenocarcinomas. An increased GH AUC was associated with an increased risk for colon adenocarcinomas in patients with acromegaly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Colao A, Ferone D, Marzullo P, Lombardi G (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25(1):102–152

    Article  CAS  PubMed  Google Scholar 

  2. Orme SM, McNally RJ, Cartwright RA, Belchetz PE (1998) Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom acromegaly study group. J Clin Endocrinol Metab 83(8):2730–2734

    CAS  PubMed  Google Scholar 

  3. Jenkins PJ, Fairclough PD, Richards T, Lowe DG, Monson J, Grossman A, Wass JA, Besser M (1997) Acromegaly, colonic polyps and carcinoma. Clin Endocrinol (Oxf) 47(1):17–22

    Article  CAS  Google Scholar 

  4. Rokkas T, Pistiolas D, Sechopoulos P, Margantinis G, Koukoulis G (2008) Risk of colorectal neoplasm in patients with acromegaly: a meta-analysis. World J Gastroenterol 14(22):3484–3489

    Article  PubMed Central  PubMed  Google Scholar 

  5. Matano Y, Okada T, Suzuki A, Yoneda T, Takeda Y, Mabuchi H (2005) Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels. Am J Gastroenterol 100(5):1154–1160. doi:10.1111/j.1572-0241.2005.40808.x

    Article  CAS  PubMed  Google Scholar 

  6. Tanimoto K, Hizuka N, Fukuda I, Takano K, Hanafusa T (2008) The influence of age on the GH–IGF1 axis in patients with acromegaly. Eur J Endocrinol 159(4):375–379. doi:10.1530/eje-08-0243

    Article  CAS  PubMed  Google Scholar 

  7. Kurimoto M, Fukuda I, Hizuka N, Takano K (2008) The prevalence of benign and malignant tumors in patients with acromegaly at a single institute. Endocr J 55(1):67–71

    Article  PubMed  Google Scholar 

  8. Jenkins PJ, Frajese V, Jones AM, Camacho-Hubner C, Lowe DG, Fairclough PD, Chew SL, Grossman AB, Monson JP, Besser GM (2000) Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab 85(9):3218–3221

    CAS  PubMed  Google Scholar 

  9. Schoen RE, Weissfeld JL, Kuller LH, Thaete FL, Evans RW, Hayes RB, Rosen CJ (2005) Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps. Gastroenterology 129(2):464–475. doi:10.1016/j.gastro.2005.05.051

    Article  PubMed  Google Scholar 

  10. Colao A, Pivonello R, Auriemma RS, Galdiero M, Ferone D, Minuto F, Marzullo P, Lombardi G (2007) The association of fasting insulin concentrations and colonic neoplasms in acromegaly: a colonoscopy-based study in 210 patients. J Clin Endocrinol Metab 92(10):3854–3860. doi:10.1210/jc.2006-2551

    Article  CAS  PubMed  Google Scholar 

  11. Terzolo M, Reimondo G, Gasperi M, Cozzi R, Pivonello R, Vitale G, Scillitani A, Attanasio R, Cecconi E, Daffara F, Gaia E, Martino E, Lombardi G, Angeli A, Colao A (2005) Colonoscopic screening and follow-up in patients with acromegaly: a multicenter study in Italy. J Clin Endocrinol Metab 90(1):84–90. doi:10.1210/jc.2004-0240

    Article  CAS  PubMed  Google Scholar 

  12. Wolever TM (2004) Effect of blood sampling schedule and method of calculating the area under the curve on validity and precision of glycaemic index values. Br J Nutr 91(2):295–301

    Article  CAS  PubMed  Google Scholar 

  13. Okuno Y, Komada H, Sakaguchi K, Nakamura T, Hashimoto N, Hirota Y, Ogawa W, Seino S (2013) Postprandial serum C-peptide to plasma glucose concentration ratio correlates with oral glucose tolerance test- and glucose clamp-based disposition indexes. Metabolism 62(10):1470–1476. doi:10.1016/j.metabol.2013.05.022

    Article  CAS  PubMed  Google Scholar 

  14. Tanaka T, Tachibana K, Shimatsu A, Katsumata N, Tsushima T, Hizuka N, Fujieda K, Yokoya S, Irie M (2005) A nationwide attempt to standardize growth hormone assays. Horm Res 64(Suppl 2):6–11. doi:10.1159/000087746

    Article  CAS  PubMed  Google Scholar 

  15. Isojima T, Shimatsu A, Yokoya S, Chihara K, Tanaka T, Hizuka N, Teramoto A, Tatsumi KI, Tachibana K, Katsumata N, Horikawa R (2012) Standardized centile curves and reference intervals of serum insulin-like growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method. Endocr J 59(9):771–780

    Article  CAS  PubMed  Google Scholar 

  16. Gu HX, Zhang YL, Zhi FC, Jiang B, Huang Y (2011) Organic colonic lesions in 3,332 patients with suspected irritable bowel syndrome and lacking warning signs, a retrospective case–control study. Int J Colorectal Dis 26(7):935–940. doi:10.1007/s00384-011-1163-2

    Article  PubMed  Google Scholar 

  17. Wassenaar MJ, Cazemier M, Biermasz NR, Pereira AM, Roelfsema F, Smit JW, Hommes DW, Felt-Bersma RJ, Romijn JA (2010) Acromegaly is associated with an increased prevalence of colonic diverticula: a case–control study. J Clin Endocrinol Metab 95(5):2073–2079. doi:10.1210/jc.2009-1714

    Article  CAS  PubMed  Google Scholar 

  18. Renehan AG, Bhaskar P, Painter JE, O’Dwyer ST, Haboubi N, Varma J, Ball SG, Shalet SM (2000) The prevalence and characteristics of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab 85(9):3417–3424

    Article  CAS  PubMed  Google Scholar 

  19. Yamaji Y, Mitsushima T, Ikuma H, Watabe H, Okamoto M, Kawabe T, Wada R, Doi H, Omata M (2004) Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese. Gut 53(4):568–572

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Morikawa T, Kato J, Yamaji Y, Wada R, Mitsushima T, Shiratori Y (2005) A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population. Gastroenterology 129(2):422–428. doi:10.1016/j.gastro.2005.05.056

    Article  PubMed  Google Scholar 

  21. Matsuda T, Marugame T, Kamo K, Katanoda K, Ajiki W, Sobue T (2010) Cancer incidence and incidence rates in Japan in 2004: based on data from 14 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 40(12):1192–1200. doi:10.1093/jjco/hyq109

    Article  PubMed  Google Scholar 

  22. Terzolo M, Tappero G, Borretta G, Asnaghi G, Pia A, Reimondo G, Boccuzzi A, Cesario F, Rovero E, Paccotti P et al (1994) High prevalence of colonic polyps in patients with acromegaly. Influence of sex and age. Arch Intern Med 154(11):1272–1276

    Article  CAS  PubMed  Google Scholar 

  23. Nouraie M, Hosseinkhah F, Brim H, Zamanifekri B, Smoot DT, Ashktorab H (2010) Clinicopathological features of colon polyps from African–Americans. Dig Dis Sci 55(5):1442–1449. doi:10.1007/s10620-010-1133-5

    Article  PubMed Central  PubMed  Google Scholar 

  24. Yano T, Sano Y, Iwasaki J, Fu KI, Yoshino T, Kato S, Mera K, Ochiai A, Fujii T, Yoshida S (2005) Distribution and prevalence of colorectal hyperplastic polyps using magnifying pan-mucosal chromoendoscopy and its relationship with synchronous colorectal cancer: prospective study. J Gastroenterol Hepatol 20(10):1572–1577. doi:10.1111/j.1440-1746.2005.03970.x

    Article  PubMed  Google Scholar 

  25. Williams GT (1997) Metaplastic (hyperplastic) polyps of the large bowel: benign neoplasms after all? Gut 40(5):691–692

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Cats A, Dullaart RP, Kleibeuker JH, Kuipers F, Sluiter WJ, Hardonk MJ, de Vries EG (1996) Increased epithelial cell proliferation in the colon of patients with acromegaly. Cancer Res 56(3):523–526

    CAS  PubMed  Google Scholar 

  27. Jenkins PJ (2000) Acromegaly and colon cancer. Growth Horm IGF Res 10(Suppl A):S35–S36

    Article  PubMed  Google Scholar 

  28. Snover DC, Jass JR, Fenoglio-Preiser C, Batts KP (2005) Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept. Am J Clin Pathol 124(3):380–391. doi:10.1309/v2ep-tplj-rb3f-ghjl

    Article  PubMed  Google Scholar 

  29. Torlakovic E, Skovlund E, Snover DC, Torlakovic G, Nesland JM (2003) Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol 27(1):65–81

    Article  PubMed  Google Scholar 

  30. Jass JR, Whitehall VL, Young J, Leggett BA (2002) Emerging concepts in colorectal neoplasia. Gastroenterology 123(3):862–876

    Article  CAS  PubMed  Google Scholar 

  31. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319(9):525–532. doi:10.1056/nejm198809013190901

    Article  CAS  PubMed  Google Scholar 

  32. Dutta P, Bhansali A, Vaiphei K, Dutta U, Ravi Kumar P, Masoodi S, Mukherjee KK, Varma A, Kochhar R (2012) Colonic neoplasia in acromegaly: increased proliferation or deceased apoptosis? Pituitary 15(2):166–173. doi:10.1007/s11102-011-0300-9

    Article  CAS  PubMed  Google Scholar 

  33. Chi F, Wu R, Zeng YC, Xing R, Liu Y (2013) Circulation insulin-like growth factor peptides and colorectal cancer risk: an updated systematic review and meta-analysis. Mol Biol Rep 40(5):3583–3590. doi:10.1007/s11033-012-2432-z

    Article  CAS  PubMed  Google Scholar 

  34. Nevalainen MT, Xie J, Torhorst J, Bubendorf L, Haas P, Kononen J, Sauter G, Rui H (2004) Signal transducer and activator of transcription-5 activation and breast cancer prognosis. J Clin Oncol 22(11):2053–2060. doi:10.1200/jco.2004.11.046

    Article  CAS  PubMed  Google Scholar 

  35. Tan SH, Nevalainen MT (2008) Signal transducer and activator of transcription 5A/B in prostate and breast cancers. Endocr Relat Cancer 15(2):367–390. doi:10.1677/erc-08-0013

    Article  CAS  PubMed  Google Scholar 

  36. Ferbeyre G, Moriggl R (2011) The role of Stat5 transcription factors as tumor suppressors or oncogenes. Biochim Biophys Acta 1815(1):104–114. doi:10.1016/j.bbcan.2010.10.004

    CAS  PubMed  Google Scholar 

  37. Du W, Wang YC, Hong J, Su WY, Lin YW, Lu R, Xiong H, Fang JY (2012) STAT5 isoforms regulate colorectal cancer cell apoptosis via reduction of mitochondrial membrane potential and generation of reactive oxygen species. J Cell Physiol 227(6):2421–2429. doi:10.1002/jcp.22977

    Article  CAS  PubMed  Google Scholar 

  38. Mao YL, Li ZW, Lou CJ, Pang D, Zhang YQ (2011) Phospho-STAT5 expression is associated with poor prognosis of human colonic adenocarcinoma. Pathol Oncol Res 17(2):333–339. doi:10.1007/s12253-010-9321-3

    Article  CAS  PubMed  Google Scholar 

  39. Favre H, Benhamou A, Finidori J, Kelly PA, Edery M (1999) Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction. FEBS Lett 453(1–2):63–66

    Article  CAS  PubMed  Google Scholar 

  40. Michaylira CZ, Ramocki NM, Simmons JG, Tanner CK, McNaughton KK, Woosley JT, Greenhalgh CJ, Lund PK (2006) Haplotype insufficiency for suppressor of cytokine signaling-2 enhances intestinal growth and promotes polyp formation in growth hormone-transgenic mice. Endocrinology 147(4):1632–1641. doi:10.1210/en.2005-1241

    Article  CAS  PubMed  Google Scholar 

  41. Wassenaar MJ, Biermasz NR, Pereira AM, van der Klaauw AA, Smit JW, Roelfsema F, van der Straaten T, Cazemier M, Hommes DW, Kroon HM, Kloppenburg M, Guchelaar HJ, Romijn JA (2009) The exon-3 deleted growth hormone receptor polymorphism predisposes to long-term complications of acromegaly. J Clin Endocrinol Metab 94(12):4671–4678. doi:10.1210/jc.2009-1172

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Drs. K Chihara, H Kaji, Y Okimura for their support and discussion. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology 19591077 and 70301281 and in part by Grants-in-Aid for Scientific Research (research on hypothalamic-hypophyseal disorders) from the Japanese Ministry of Health, Labor, and Welfare.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

    Masaaki Yamamoto, Hidenori Fukuoka, Genzo Iguchi, Ryusaku Matsumoto, Michiko Takahashi, Hitoshi Nishizawa, Kentaro Suda, Hironori Bando & Yutaka Takahashi

Authors
  1. Masaaki Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hidenori Fukuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Genzo Iguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryusaku Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michiko Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hitoshi Nishizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kentaro Suda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hironori Bando
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yutaka Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yutaka Takahashi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamamoto, M., Fukuoka, H., Iguchi, G. et al. The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study. Pituitary 18, 343–351 (2015). https://doi.org/10.1007/s11102-014-0580-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-014-0580-y

Keywords

Search

Navigation