Endocrine Abstracts (2008) 15 P258

Monitoring acromegaly disease activity with growth hormone and insulin like growth factor-I in 501 patients

Mark Sherlock1, Aurora Aragon Alonso1, John Ayuk1, Richard N Clayton2, Michael C Sheppard1, Andy Bates3 & Paul Stewart1

1Department of Medicine, Division of Medical Sciences, University of Birmingham, Birmingham, UK; 2Department of Postgraduate Medicine, University of Keele, Stoke-on-Trent, UK; 3Birmingham Heartlands and Solihull NHS Trust, Birmingham, UK.

The aim of treatment in patients with acromegaly is to achieve serum GH/ IGF-I concentrations associated with cure or normalisation of mortality. Using the West Midlands acromegaly database (n=501) we assessed a number of parameters in the follow up of patients with acromegaly including the reliability of basal fasting GH in predicting nadir or mean GH during oral glucose tolerance test (OGTT) or growth hormone day curve (GHDC) respectively, the degree of discordance between disease activity as measured by GH and IGF-I and the effect of radiotherapy on the above relationships. In total there were 773 OGGT (421 IGF-I) and 507 GHDC (223 IGF-I) performed.

Basal fasting GH was strongly correlated with nadir/mean GH on OGTT/GHDC (r=+0.87, P<0.0001, r=+0.9040, P<0.0001, respectively). A basal GH <2 μg/l was associated with a nadir/ mean GH during OGTT/GHDC <2 μg/l in 96.7% and 87% of cases, respectively.

Elevated IGF-I was seen in 32.4% and 43.8% of patients with GH nadir values on OGTT <1 and <2 μg/l, respectively, and in 21.2% and 44.3% of GHDC with mean GH <1 and <2 μg/l, respectively. When nadir/mean GH >2 μg/l IGF-I was normal in 15.8% OGTT and 20% GHDC. Radiotherapy had minimal effect on the association between basal fasting and nadir/mean GH during OGTT/GHDC however it did increase the discordance between disease activity as assessed by GH compared with IGF-I at GH levels <2 μg/l (elevated IGF-I values when nadir GH during OGTT <2 μg/l: radiotherapy 53.2% versus no radiotherapy 34.1%, P=0.002).

In summary, there is a close association between basal fasting GH <2 μg/l and nadir/mean GH<2 μg/l during OGTT/GHDC. There is a large discordance between disease activity when assessed by GH and IGF-I, which is further aggravated by radiotherapy. These observations illustrate the challenge of defining appropriate biochemical endpoints to achieve control of disease and normalization of mortality in acromegaly.

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