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A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly

Department of Endocrinology, Greenlane Clinical Centre and Auckland City Hospital, PO Box 92 189, Auckland 1142, New Zealand¹ Department of Medicine, Auckland School of Medicine, University of Auckland, Auckland, New Zealand

(Correspondence should be addressed to I M Holdaway; Email: ian{at}adhb.govt.nz)

Objective: Formal studies of acromegaly have found increased mortality associated with the disorder, although reduction of serum levels of GH and IGF-I by treatment appears to improve survival. A meta-analysis of mortality studies in acromegaly has thus been performed to assess the effect of lowering serum GH and IGF-I on survival.

Design and methods: Medline was searched for studies under ‘acromegaly’, ‘mortality’ and ‘cause of death’ (1965–2008), and abstracts of recent meetings of the US Endocrine Society were hand searched. Studies were restricted to those presenting mortality data according to serum GH and IGF-I at last follow-up, and with mortality expressed as a standardized mortality ratio (SMR).

Results: Patients with random serum GH <2.5 µg/l following treatment, mostly measured by standard RIA, had mortality close to expected levels (SMR 1.1, 95% confidence interval (CI) 0.9–1.4) compared with an SMR of 1.9 (95% CI 1.5–2.4) for those with final GH >2.5 µg/l. Similarly, a normal serum IGF-I for age and sex at last follow-up after treatment was associated with an SMR of 1.1 (95% CI 0.9–1.4) compared with an SMR of 2.5 (95% CI 1.6–4.0) for those with continued IGF-I elevation. There was a significant trend for reduced mortality in series reporting frequent use of somatostatin analogues and in studies reporting high (>70%) rates of biochemical remission after treatment.

Conclusions: Clinicians treating acromegalic patients should aim for random serum GH <2.5 µg/l measured by RIA (probably <1 µg/l measured by modern sensitive immunoassay) and normal serum IGF-I values, to restore the elevated mortality of the condition to normal levels.