GH Dosing in GHD Adults: Investigating IGF-I's U-shaped Association with Cardiovascular Risk Factors

Abnormally low and high levels of Insulin-like Growth Factor-I (IGF-I), a key mediator of Growth Hormone (GH) action, are both associated with increased metabolic risk. A U-shaped association of IGF-I, even within the normal range, has been observed with cardiovascular risk factors and disease in the general population. For adults with Growth Hormone Deficiency (GHD) receiving GH replacement therapy, the optimal IGF-I target within the normal range for minimizing cardiovascular risk remains undefined. This study aims to address this critical gap, providing evidence for endocrinologists to refine GH dosing strategies and potentially improve long-term patient outcomes.

This open-label randomized trial will enroll at least 32 adult men and women (20-65 years) with childhood or adult-onset Growth Hormone Deficiency (GHD), already on GH treatment for over a year. Participants with baseline IGF-I of 0-1 SD score (SDS) will be randomized to receive either a decreased GH dose (targeting -2 to -1 SDS IGF-I) or an increased GH dose (targeting 1-2 SDS IGF-I). The adjusted dosing will continue for at least 24 weeks. Primary endpoints include changes in body composition and lipid profile, with secondary endpoints evaluating glucose metabolism, physical performance, and neuropsychological functioning.