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 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 microg/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 microg/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 microg/l measured by RIA (probably <1 microg/l measured by modern sensitive immunoassay) and normal serum IGF-I values, to restore the elevated mortality of the condition to normal levels.