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Mortality and Cancer Incidence in Acromegaly: A Retrospective Cohort Study¹

Department of Endocrinology (S.M.O., P.E.B.), The General Infirmary at Leeds, The Leukemia Research Fund (R.J.Q.M., R.A.C.), Center for Clinical Epidemiology, University of Leeds, Leeds, United Kingdom

Address all correspondence and requests for reprints to: Dr. S. M. Orme, Department of Endocrinology, The General Infirmary at Leeds, Great George Street, Leeds, United Kingdom LS1 3EX.

Patients with acromegaly have a reduced life expectancy, with the accepted causes for premature death being vascular and respiratory disease. Increased mortality from malignant disease has also been reported. We, therefore, performed a multicenter retrospective cohort study of 1362 patients with acromegaly and investigated the relationships of mortality and cancer incidence with GH levels, duration of disease, and age at diagnosis.

The overall cancer incidence rate [standardized incidence ratio, 0.76; 95% confidence interval (CI), 0.60–0.95] was lower than that in the general population of the United Kingdom, and there was no significant increase in site-specific cancer incidence rates. The overall cancer mortality rate was not increased, but the colon cancer mortality rate (standardized mortality ratio, 2.47; 95% CI, 1.31–4.22) was higher than expected. Mortality rates due to colon cancer, all malignant disease, cardiovascular disease and overall mortality were increased with higher posttreatment GH levels (P for trends, <0.02, <0.05, <0.02, and <0.0001). The overall mortality rate in patients with acromegaly with posttreatment GH levels less than 2.5 ng/mL (5 mU/L) was comparable to that in the general population of the United Kingdom (standardized mortality ratio, 1.10; 95% CI, 0.89–1.35).

We conclude that high posttreatment GH levels are associated with an increased overall mortality rate and increased mortality rates due to colon cancer, cardiovascular disease, and all malignant disease. Posttreatment GH levels less than 2.5 ng/mL (5 mU/L) result in an overall mortality rate similar to that in the general population.

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				R. N. Clayton Cardiovascular Function in Acromegaly Endocr. Rev., June 1, 2003; 24(3): 272 - 277. [Abstract] [Full Text] [PDF]

				J. C. Smith, H. Lane, N. Davies, L. M. Evans, J. Cockcroft, M. F. Scanlon, and J. S. Davies The Effects of Depot Long-Acting Somatostatin Analog on Central Aortic Pressure and Arterial Stiffness in Acromegaly J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2556 - 2561. [Abstract] [Full Text] [PDF]

				D. Komninou, A. Ayonote, J. P. Richie Jr., and B. Rigas Insulin Resistance and Its Contribution to Colon Carcinogenesis Experimental Biology and Medicine, April 1, 2003; 228(4): 396 - 405. [Abstract] [Full Text] [PDF]

				A. Ben-Shlomo and S. Melmed The Role of Pharmacotherapy in Perioperative Management of Patients with Acromegaly J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 963 - 968. [Full Text] [PDF]

				V. D. Longo and C. E. Finch Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians? Science, February 28, 2003; 299(5611): 1342 - 1346. [Abstract] [Full Text] [PDF]

				S. R. Rose Studies Reveal Minimal Cancer Risks with Growth Hormone Therapy AAP Grand Rounds, November 1, 2002; 8(5): 49 - 50. [Full Text] [PDF]

				E. M. Erfurth, B. Bulow, G. Svahn-Tapper, B. Norrving, K. Odh, Z. Mikoczy, J. Bjork, and L. Hagmar Risk Factors for Cerebrovascular Deaths in Patients Operated and Irradiated for Pituitary Tumors J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4892 - 4899. [Abstract] [Full Text] [PDF]

				J. J. Kopchick, C. Parkinson, E. C. Stevens, and P. J. Trainer Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly Endocr. Rev., October 1, 2002; 23(5): 623 - 646. [Abstract] [Full Text] [PDF]

				J. S. Bevan, S. L. Atkin, A. B. Atkinson, P.-M. Bouloux, F. Hanna, P. E. Harris, R. A. James, M. McConnell, G. A. Roberts, M. F. Scanlon, et al. Primary Medical Therapy for Acromegaly: An Open, Prospective, Multicenter Study of the Effects of Subcutaneous and Intramuscular Slow-Release Octreotide on Growth Hormone, Insulin-Like Growth Factor-I, and Tumor Size J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4554 - 4563. [Abstract] [Full Text] [PDF]

				P J Jenkins and P D Fairclough Screening guidelines for colorectal cancer and polyps in patients with acromegaly Gut, October 1, 2002; 51(90005): v13 - 14. [Full Text] [PDF]

				J. Ayuk, S. E. Stewart, P. M. Stewart, and M. C. Sheppard Long-Term Safety and Efficacy of Depot Long-Acting Somatostatin Analogs for the Treatment of Acromegaly J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4142 - 4146. [Abstract] [Full Text] [PDF]

				D. M. Cook Shouldn't Adults with Growth Hormone Deficiency Be Offered Growth Hormone Replacement Therapy? Ann Intern Med, August 6, 2002; 137(3): 197 - 201. [Abstract] [Full Text] [PDF]

				L. A. Frohman Controversy about Treatment of Growth Hormone-Deficient Adults: A Commentary Ann Intern Med, August 6, 2002; 137(3): 202 - 204. [Full Text] [PDF]

				P. J. Trainer Acromegaly--Consensus, What Consensus? J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3534 - 3536. [Full Text] [PDF]

				M. S. Sandhu, D. B. Dunger, and E. L. Giovannucci Insulin, Insulin-Like Growth Factor-I (IGF-I), IGF Binding Proteins, Their Biologic Interactions, and Colorectal Cancer J Natl Cancer Inst, July 3, 2002; 94(13): 972 - 980. [Abstract] [Full Text] [PDF]

				C. A. Sklar, A. C. Mertens, P. Mitby, G. Occhiogrosso, J. Qin, G. Heller, Y. Yasui, and L. L. Robison Risk of Disease Recurrence and Second Neoplasms in Survivors of Childhood Cancer Treated with Growth Hormone: A Report from the Childhood Cancer Survivor Study J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3136 - 3141. [Abstract] [Full Text] [PDF]

				G. Brevetti, P. Marzullo, A. Silvestro, R. Pivonello, G. Oliva, C. di Somma, G. Lombardi, and A. Colao Early Vascular Alterations in Acromegaly J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3174 - 3179. [Abstract] [Full Text] [PDF]

				R. J. Irving, M. N. Carson, D. J. Webb, and B. R. Walker Peripheral Vascular Structure and Function in Men with Contrasting GH Levels J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3309 - 3314. [Abstract] [Full Text] [PDF]

				R Palmqvist, G Hallmans, S Rinaldi, C Biessy, R Stenling, E Riboli, and R Kaaks Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden Gut, May 1, 2002; 50(5): 642 - 646. [Abstract] [Full Text] [PDF]

				T. Shioi, J. R. McMullen, P. M. Kang, P. S. Douglas, T. Obata, T. F. Franke, L. C. Cantley, and S. Izumo Akt/Protein Kinase B Promotes Organ Growth in Transgenic Mice Mol. Cell. Biol., April 15, 2002; 22(8): 2799 - 2809. [Abstract] [Full Text] [PDF]

				C. Parkinson, W. M. Drake, M. E. Roberts, K. Meeran, G. M. Besser, and P. J. Trainer A Comparison of the Effects of Pegvisomant and Octreotide on Glucose, Insulin, Gastrin, Cholecystokinin, and Pancreatic Polypeptide Responses to Oral Glucose and a Standard Mixed Meal J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1797 - 1804. [Abstract] [Full Text] [PDF]

				A. G. Renehan and S. M. Shalet Acromegaly and Colorectal Cancer: Risk Assessment Should Be Based on Population-Based Studies J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1909 - 1909. [Full Text] [PDF]

				L. Le Marchand, T. Donlon, A. Seifried, R. Kaaks, S. Rinaldi, and L. R. Wilkens Association of a Common Polymorphism in the Human GH1 Gene with Colorectal Neoplasia J Natl Cancer Inst, March 20, 2002; 94(6): 454 - 460. [Abstract] [Full Text] [PDF]

				C. Parkinson, W. D. J. Ryder, and P. J. Trainer The Relationship between Serum GH and Serum IGF-I in Acromegaly Is Gender-Specific J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5240 - 5244. [Abstract] [Full Text] [PDF]

				E. Giovannucci Insulin, Insulin-Like Growth Factors and Colon Cancer: A Review of the Evidence J. Nutr., November 1, 2001; 131(11): 3109S - 3120. [Abstract] [Full Text] [PDF]

				J. Ma, E. Giovannucci, M. Pollak, J. M. Chan, J. M. Gaziano, W. Willett, and M. J. Stampfer Milk Intake, Circulating Levels of Insulin-Like Growth Factor-I, and Risk of Colorectal Cancer in Men J Natl Cancer Inst, September 5, 2001; 93(17): 1330 - 1336. [Abstract] [Full Text] [PDF]