Comparison of low-normal and high-normal IGF-1 target levels during growth hormone replacement therapy: A randomized clinical trial in adult growth hormone deficiency.
BACKGROUND
Current guidelines state that the goals of growth hormone (GH) therapy in adults should be an appropriate clinical response, avoidance of side effects, and an IGF-1 value within the age-adjusted reference range. There are no published studies on the target level for IGF-1 that offer specific guidance in this regard.


OBJECTIVE
To compare low-normal and high-normal target levels of IGF-1 on efficacy and safety of GH treatment.


METHODS
A randomized, open-label, clinical trial including thirty-two adults from one university hospital receiving GH therapy for at least one year with a stable IGF-1 concentration between -1 and 1 SD score (SDS). Subjects were randomized to receive either a decrease (IGF-1 target level of -2 to -1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24weeks. The effect on cardiovascular risk factors and physical performance, next to tolerability, was compared.


RESULTS
Thirty subjects (65.6% men, mean age 46.6 (SD 9.9) years) could be analyzed. In subjects with a high-normal IGF-1 target level, waist circumference decreased (p=0.05), and overall they felt better (p=0.04), compared to subjects with a low-normal IGF-1 target level. However, increasing IGF-1 levels led to more myalgia, and decreasing IGF-1 levels to more fatigue. There was a gender-dependent difference in effect on HDL cholesterol.


CONCLUSIONS
Although increasing GH dose to IGF-1 levels between 1 and 2 SDS improved waist circumference and well-being, safety was not guaranteed with the demonstrated effect on HDL cholesterol in men, and reported myalgia.
Department of Internal Medicine, Section of Endocrinology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: c.vanbunderen@vumc.nl.
Christa C
CC
van Bunderen
Department of Internal Medicine, Section of Endocrinology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Paul
P
Lips
Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
Mark H
MH
Kramer
Department of Internal Medicine, Section of Endocrinology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Madeleine L
ML
Drent
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D005221:Fatigue / Q000209:etiology; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000209:etiology; D009426:Netherlands; D012016:Reference Values; D012307:Risk Factors; D012727:Sex Characteristics; D055105:Waist Circumference
D008076:Cholesterol, HDL; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
Clinical practice; Efficacy; Growth hormone deficiency; Growth hormone treatment; Insulin-like growth factor-1; Safety