Endocrine Abstracts

IGF-1 generation tests (IGF-1GT) have been used extensively in children to investigate growth hormone (GH) responsiveness. To help understand differences in the GH/IGF-1 axis in health and disease in adulthood interest has turned to the use of the IGF-1GT in adults. Different designs of IGF-1GT have been used with no clear evidence delineating which is the most sensitive to describe subtle changes in GH responsiveness. In order to design an IGF-1GT we have performed the first dose response (DR) profile to an acute bolus of GH in healthy men and women using an extensive range of doses.

22 healthy volunteers (11male) received 6 different doses of sc GH (0.8, 2, 4, 6, 12 and 21IU) at monthly intervals in random order (females were examined in the early follicular phase of the menstrual cycle). IGF1, IGFBP3 and acid labile subunit (ALS) were measured at baseline and 18 and 24 hours after each GH dose.

Baseline IGF-1 levels were lower in females than males (340.5+/-79.6ng/ml vs 423.3+/-70.6ng/ml (FvsM); p=0.02). There was no gender difference in basal levels of mean IGFBP3 or mean ALS. Using a 3 way nested ANOVA there was a DR in the increment of IGF-1 (p<0.001) and ALS (p<0.05) levels but not IGFBP3. The effect of gender was not significant in the DR of IGF-1 and IGFBP3 but almost reached significance with ALS, females exhibiting a greater response than males (p=0.06). Converting the doses into weight-based doses (IU/kg) also revealed no gender difference in IGF-1 response using a fitted log equation. Using Duncan's Multiple Range Test in the whole cohort a plateau in IGF-1 DR occurred between GH doses 4IU and 6IU.

We have now defined an IGF-1 DR plateau for an acute bolus of GH. To design an IGF-1GT we suggest that a GH dose is chosen from both the linear and plateau sections of the IGF-1 DR curve to characterise tissue responsiveness to GH.