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

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 or 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 its a standardized mortality ratio (SMR). Results: Patients with random serum GH < 2.5 mu g/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 mu g/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 0.91-1.4) 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 mu g,/l Measured by RIA (probably < 1 mu g/l measured by modern sensitive immunoassay) and normal serum lGF-I values. to restore the elevated mortality of the condition to normal levels.