Endocrine Abstracts (2008) 15 P261

Effect of radiotherapy and pituitary dysfunction on mortality in patients with acromegaly

Mark Sherlock1, Aurora Aragon Alonso1, Raoul C Reulen2, John Ayuk1, Richard N Clayton3, Michael C Sheppard1, Mike Hawkins2, Andy Bates4 & Paul M Stewart1

1Division of Medical Sciences, Department of Medicine and 2Department of Public Health and Epidemiology, Centre for Childhood Cancer Survivor Studies, University of Birmingham, Birmingham, UK; 3Department of Postgraduate Medicine, University of Keele, Stoke-on-Trent, UK; 4Birmingham Heartlands and Solihull NHS Trust, Birmingham, UK.

Acromegaly is associated with increased morbidity and premature mortality which has been demonstrated in a number of retrospective studies reporting a standardised mortality ratio (SMR) between 1.3 and 3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or surgery and/or radiotherapy. Hypopituitarism is also associated with an increased SMR (1.2–2.17).

Using the West Midlands Acromegaly database (n=501, 275 female) we assessed the influence of prior radiotherapy and hypopituitarism on mortality in patients with acromegaly. About 128 patients had surgery alone, 32 radiotherapy alone, 43 medical therapy alone, 143 surgery and radiotherapy, 68 surgery and medical therapy, 162 had radiotherapy and medical therapy and 104 received all 3. Median duration of follow up was 13.9 years (interquartile range 7.9–21 years).

On external analysis (compared to the general population) prior radiotherapy, ACTH and gonadotrophin deficiency were significantly associated with an elevated SMR. Radiotherapy (SMR 2.1; 1.7–2.6), P=0.006; ACTH deficiency (SMR 2.5; 1.9–3.2), P<0.0005; gonadotrophin deficiency (SMR 2.1; 1.6–2.7), P=0.037; TSH deficiency (SMR 2.1; 1.5–2.9), P=0.15.

On internal analysis within the acromegaly cohort the relative risk of mortality was 1.4 (1.04–2.02) in the radiotherapy group (P=0.03), 1.7 (1.2–2.4) in the ACTH deficiency group (P=0.01), 1.2 (0.8–1.9) in the gonadotrophin deficient group (P=0.37) and 1.0 (0.7–1.5) in the TSH deficiency group (P=0.91).

Radiotherapy and ACTH deficiency (one component of hypopituitarism) are significantly associated with increased mortality in patients with acromegaly. Further work is needed to assess how much of the excess mortality reported in acromegaly is due to these factors compared with long-term exposure to elevated GH and IGF-I concentrations.

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