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A meta-analysis of the effect of lowering serum levels of growth hormone and insulin-like growth-factor-I on mortality in acromegaly

I Holdaway, Dept of Endocrinology, Greenlane Clinical Centre, Auckland, 1142, New Zealand
M Bolland, Bone Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand
G Gamble, Medicine, Auckland University School of Medicine, Auckland, New Zealand

Correspondence: Im Holdaway, Email: ian{at}adhb.govt.nz

Abstract

Abstract:

Objective:

Studies of acromegaly have found increased mortality from the disorder, although reduction of serum levels of growth hormone (GH) and insulin-like growth factor-I (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 <2.5ug/l following treatment, mostly measured by standard radioimmunoassay, had mortality close to expected levels (SMR 1.1, 95% CI 0.9-1.4) compared with a SMR of 1.9 (95% CI 1.5-2.4) for those with final GH >2.5ug/l. Similarly, a normal serum IGF-I for age and sex at last follow-up after treatment was associated with SMR 1.1 (95% CI 0.9-1.4) compared with a 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.

Conclusions:

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