Endocrine Abstracts (2004) 7 P130

Possible factors determining individual sensitivity to GH replacement therapy; a KIMS database analysis

J Monson1, M Lundberg2, PMG Bouloux3, JS Bevan4, J Svensson5, M Koltowska-Haggstrom2 & N Finer6

1Department of Endocrinology, St Bartholomew's Hospital, London, UK; 2KIGS/KIMS Outcomes Research, Pharmacia AB, Stockholm, Sweden; 3Royal Free Hospital School of Medicine, London, UK; 4Aberdeen Royal Infirmary, Aberdeen, UK; 5Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Gothenburg, Sweden; 6Wellcome Trust CRF, Addenbrooke's Hospital, Cambridge, UK.

Large databases facilitate the examination of those factors, which may determine response to treatment, potentially to develop prediction models. We have used KIMS (Pfizer's international metabolic database of GH-treated adults), to examine parameters that might predict clinical response to GH therapy in hypopituitary adults.

Patients/methods: Patients with non-functioning pituitary adenoma on GH titrated to maintain serum IGF-I between minus 2 and 2 SDS, and with appropriate replacement of other hormone deficiencies were selected from the database (n-326). Potential response-predictors (gender, age at GH start, GH peak at diagnosis, type of tumour treatment, GH starting dose, duration of GHD, baseline: IGF-I SDS, LDL-cholesterol, and QoL-AGHDA) were correlated against changes in waist circumference, waist/hip ratio (WHR), LDL-cholesterol and QoL-AGHDA score after 1 year of treatment. Potential effects of regression to the mean were explored.

Results: Significant inverse correlation was found between QoL at baseline vs change in QoL (r= minus 0.54) and between LDL cholesterol vs change in LDL cholesterol (r= minus 0.44). The correlation between gender vs. change in QoL was also statistically significant (r= 0.17 p < 0.01)

Conclusions: Males are more responsive to GH than females although the significance is low consistent with inter-individual variation. Baseline LDL-cholesterol (n=326) and QoL-AGHDA score (n=217) predict LDL and QoL responses respectively to GH treatment. Thus patients with worse QoL (higher QoL-AGHDA score) and/or higher LDL-cholesterol values improve most. The effect of regression to the mean accounted for some of the change in LDL-C. However, the limited ability to predict treatment response, as shown by small R values suggests that all GH-deficient patients should be considered for GH therapy and continue according to individual clinical response.

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