Dose of growth hormone (GH) and not IGFI level at treatment start influences treatment outcome in GH deficient adults (GHDA): Data from the NordiNet International Outcome Study (IOS)
Jens Otto L Jørgensen1, Matthias M Weber2, Charlotte Höybye3, Birgitte T Pedersen4, Viatcheslav Rakov5 & Jens Sandahl Christiansen1
Background: Serum IGFI measurements are used during GH replacement in GHDA for titration of the GH dose, to monitor compliance and to avoid overdosing, but it is uncertain if pretreatment IGFI is a determinant of the GH dose or the response to GH treatment.
Methods: Data from the NordiNet IOS have been analyzed to determine pretreatment serum IGFI concentrations in GHDA and to analyze if they influence the GH starting dose and/or the therapeutic response after one year. The patients were divided in two groups: A) with a normal IGFI level before GH treatment start (>−1 SDS), and B) with a low IGFI level at treatment start (<−1 SDS).
Results: Two hundred and seventeen patients (98 females/119 males) with IGFI measurements at treatment start and after one year of treatment were included in this analysis. Mean±S.D. IGFI was 158±87 ug/l in group A and 68±38 ug/l in group B. This corresponds with 0.1± 1.0 SDS and −2.0±1.0 SDS for IGFI levels respectively. Baseline characteristics were slightly different in groups A and B. Mean age was higher in group A than in group B. Patients in group A also had a higher weight and a higher BMI which may have been influenced by age. Starting mean GH dose was 0.26±0.19 mg/day in group A and 0.24±0.19 mg/day in group B. After one year of treatment the GH dose increased more in patients from group B. Serum IGFI levels changed accordingly and increased more in group B achieving normal range: −0.2±1.6 SDS, comparing to 0.8±1.2 SDS in group A. We observed a significant decrease in mean LDL level in group B together with a more pronounced reduction in waist circumference. However, multivariate analysis revealed that only the GH dose was a significant predictor of the change in waist circumference during treatment (P<0.05).
Conclusion: 1) GHDA patients with low IGFI levels prior to treatment were younger and less obese as compared to patients with normal IGFI levels, 2) Pretreatment IGFI levels did not seem to determine the starting dose of GH treatment, but the increase in GH dose after one year of treatment was higher in patients with low pretreatment levels of IGFI, 3) The observation that GH dose was the main predictor of the therapeutic response does not obviate the use of serum IGFI measurements to avoid overdosing with GH.
Table Changes from baseline to first year follow up under GH treatment in GHD adults dependent on serum level of IGFI at baseline.
|Group A||Group B|
|Weight kg||62||− 1.23||0.17||75||0.14||0.9|
|Total cholesterol mmol/l||37||−0.1||0.52||38||−0.3||0.07|
|Absolute GH dose (mg/day)||103||0.06||<0.0001||114||0.12||<0.0001|
|aSilgnificance level in comparison to baseline measurement.|