Hypopituitary patients receiving conventional hormonal therapy, excluding Growth Hormone, have an increased risk of vascular mortality. Significant endothelial dysfunction with impaired aortic distensibility has been demonstrated in these patients with some improvement in arterial stiffness after GH therapy. Inflammation is central in the pathophysiology of atherosclerosis and C-reactive protein is a validated marker for predicting cardiovascular risk.
For the first time we examined the effects of 6 months GH therapy on 24 hour ambulatory blood pressure, large artery compliance, resistance artery function and CRP in the same cohort of hypopituitary patients.
16 hypopituitary patients with severe GH deficiency were recruited. Patients were randomised to a twelve month study using a cross-over design to either 6 months of GH therapy or no treatment; then allocated to the opposite team. At baseline, 6 and 12 months, blood samples were obtained for CRP along with measurement of pulse wave velocity, 24 hour ambulatory blood pressure and resistance artery function using small vessel myography.
IGF-1 increased significantly from 67.7 ± 7.2 to 166.7 ± 16.2 micrograms per litre (p<0.001), with GH therapy, and CRP reduced significantly from 3.78 to 1.99 milligrams per litre (p=0.007). 24 hour mean arterial BP fell significantly from 91.3 to 89.3 mmHg (p=0.006). PWV was significantly reduced from 8.1 +/- 0.4 to 6.7 +/-0.5 m/s (p<0.05). No significant differences could be found in vascular responses of resistance arteries to endothelial, non-endothelial dependent agents or following incubation with IGF-1.
Growth hormone replacement induces significant discernable alterations in the vasculature such as reduction in blood pressure and large artery compliance. This is not associated with increased vasodilatation in the smaller arteries and may represent a differential effect of GH on large vessels /small arteries. It is possible that by reducing inflammation GH modulates the atherosclerotic process and may reduce cardiovascular risk.
22 - 24 Mar 2004
British Endocrine Societies