Determinants of Early Atherosclerotic Changes in Adults with Growth Hormone Deficiency Receiving Replacement Therapy: A Cross-sectional Analysis of Intima-media Thickness and Endothelial Function

Background: Patients with adult growth hormone deficiency (AGHD) show accelerated atherosclerosis. While growth hormone replacement therapy (GHRT) may help mitigate this process, the mechanisms driving atherosclerosis progression in GHRT-treated patients with AGHD remain unclear. Methods: Thirty-one patients with AGHD on daily GHRT for ≥5 years were assessed in this crosssectional study. Carotid intima-media thickness (cIMT) was evaluated by ultrasound. Reactive hyperemia index (RHI) was measured using peripheral arterial tonometry. Associations between vascular measures and clinical, pituitary, treatment, body composition, and laboratory parameters were evaluated. Results: cIMT correlated with body mass index (r=0.584, p=0.001) and visceral adipose tissue area (r=0.791, p<0.001), while demonstrating nominally significant associations with triglyceride levels, insulin resistance index, smoking history, and arterial hypertension. Neither the current nor the 5-year mean insulin-like growth factor 1 standard deviation score directly correlated with vascular parameters. Median cIMT was higher in adult-onset compared with child-onset AGHD (0.70 vs. 0.58 mm; p=0.020), while median RHI was lower in genetic than structural etiology (1.58 vs. 2.18; p=0.010); however, both associations were nominally significant. Discussion: Several of the identified cardiovascular risk factors associated with cIMT are unlikely to be sufficiently controlled through GHRT. Pituitary disease characteristics may play a role in atherogenesis; however, the subgroups defined by disease onset timing and etiology were small and not fully comparable. Conclusion: In long-term GHRT-treated patients, cIMT is linked to well-established cardiovascular risk factors rather than features of the pituitary disorder and its management, highlighting the need for targeted cardiovascular risk management alongside GHRT in AGHD.