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Growth Hormone and Pituitary Radiotherapy, But Not Serum Insulin-Like Growth Factor-I Concentrations, Predict Excess Mortality in Patients with Acromegaly

Division of Medical Sciences (J.A., M.C.S., P.M.S.), University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, United Kingdom; Department of Postgraduate Medicine (R.N.C.), University of Keele, Hartshill, Stoke-on-Trent, ST4 7QB, United Kingdom; Department of Diabetes and Endocrinology (A.S.B.), Birmingham Heartlands and Solihull National Health Service (NHS) Trust, B9 5SS, United Kingdom; and Regional Endocrine Laboratory (G.H.), Department of Clinical Biochemistry, University Hospital Birmingham NHS Trust, B29 6JD, United Kingdom

Address all correspondence and requests for reprints to: Professor P. M. Stewart, Division of Medical Sciences, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom. E-mail: p.m.stewart{at}bham.ac.uk.

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF-I remain uncertain. The West Midlands Pituitary database contains details of 419 patients (241 female) with acromegaly. Serum IGF-I data from the Regional Endocrine Laboratory were available for 360 patients (86%). At diagnosis, mean age was 47 yr (range, 12–84) and mean duration of follow-up was 13 yr (0.5–48). Sixty-one percent were treated by surgery and 39% by nonsurgical means. Radiotherapy was used alone or as adjuvant therapy in 50%. All patients were registered with the Office of National Statistics to obtain information on deaths. At the date of analysis (31 December 2001), 95 of the 419 patients had died (43 males), giving a standardized mortality ratio of 1.26 [confidence interval (CI), 1.03–1.54; P = 0.046]. After controlling for age and sex, data indicated that mortality was increased in subjects with posttreatment GH levels more than 2 µg/liter, compared with those with levels less than 2 µg/liter [ratio of mortality rates (RR), 1.55 (range, 0.97–2.50); P = 0.068]. By contrast, a much smaller increase was observed for subjects with elevated posttreatment IGF-I levels compared with those with normal levels [RR, 1.20 (range, 0.71–2.03); P = 0.50]. Treatment with radiotherapy was associated with increased mortality [RR, 1.67 (range, 1.09–2.56); P = 0.018], with cerebrovascular disease the predominant cause of death [standardized mortality ratio, 4.42 (range, 2.71–7.22); P = 0.005]. These results confirm the increased mortality in acromegaly and suggest that reduction of GH levels to less than 2 µg/liter is beneficial in terms of improving long-term outcome. The sole use of IGF-I as a marker for effective treatment of acromegaly is not justified by this data. This study also highlights the potential deleterious effect of radiotherapy.

Ipsen Ltd. and Novartis Pharmaceuticals have supported the West Midlands Acromegaly Database.

The following additional investigators contributed patients to the West Midlands Acromegaly Database: D. A. Heath, J. A. Franklyn, R. Walsh, R. Mitchell, A. Johnson (Queen Elizabeth and Selly Oak Hospitals, Birmingham); H. Connor (County Hospital, Hereford); P. Dodson (Heartlands Hospital, Birmingham); P. R. Daggert (Staffordshire District General Hospital); K. Taylor, R. Ryder, S. Jones (City Hospital, Birmingham); E. Hillhouse, F. Vince (Coventry and Warwick Hospital); D. Jenkins (Worcester Royal Infirmary); S. Walford, D. Singh (New Cross Hospital, Wolverhampton); C. Carter (Alexandra Hospital, Redditch); J. Benn (Burton District Hospital); D. Robertson, P. Davies (Sandwell Hospital); T. West (Telford District General Hospital); T. Harvey, A. D. Wright (Manor Hospital, Walsall); and A. Zalin (Wordesley Hospital).

Abbreviations: CI, Confidence interval; CV, coefficient of variation; OGTT, oral glucose tolerance test; RR, ratio of mortality rates; SMR, standardized mortality ratio.

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