• Partial Growth Hormone Deficiency is Associated With an Adverse Cardiovascular Risk Profile and Increased Carotid Intima-Medial Thickness.

      Murray, Robert D; Wieringa, Gilbert E; Lawrance, Jeremy A L; Adams, Judith E; Shalet, Stephen M; Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK. (2009-12-18)
      Abstract. Objective: To quantify the relative prevalence of surrogate markers of vascular risk in adults with partial GHD (GH-insufficiency; GHI) Context: Hypopituitary adults with untreated GHD have an excess vascular mortality and demonstrate clustering of adverse vascular risk factors. The vascular risk profile of GHI adults have yet to be comprehensively studied. Design: A cross-sectional case controlled study. Patients: 30 GHD adults, 24 GHI, and 30 age and sex-matched controls. GHI adults were defined biochemically using two GH stimulation tests (peak GH 3-7mug/l). Measurements: Serum lipids and apolipoproteins, PAI-I, CRP, Lp(a), fibrinogen, blood pressure and carotid IMT. Results: IGF-I levels of GHI adults were lower than controls (373+/-123 vs. 295+/-104mug/l; P<0.001). TC, LDL-C, and TG values were consistently between those of, but not significantly different from, GHD and control subjects. GHI adults showed significantly elevated PAI-I levels (80 [13-98] vs. 50.5 [3-98]ng/ml; P=0.01), though no difference in CRP, Lp(a), and fibrinogen levels compared with control subjects. No differences in systolic or diastolic BP were shown between study groups. In parallel with the increased vascular risk profile of GH-insufficient adults, carotid IMT was significantly increased (0.503+/-0.08 vs. 0.578+/-0.130mm; P=0.02). TC, LDL-C, WHR, truncal FM, and IMT correlated with IGF-I levels and GH status. TG, K(ITT), and PAI-I additionally correlated with GH status, but not IGF-I levels. Conclusion: GHI adults are at elevated vascular risk, reflected by adverse surrogate markers and increased carotid IMT. The surrogate risk marker profile parallels GHD adults, but is less divergent from that observed in healthy individuals. No data are yet available as to whether these anomalies will be reflected in an increased vascular mortality in GHI adults.
    • Serum vascular endothelial growth factor (VEGF) is elevated in GH deficient adults.

      Murray, Robert D; Randeva, Harpal S; Lewandowski, Krzysztof C; Komorowski, Jan; Lawrance, Jeremy A L; Adams, Judith E; Shalet, Stephen M; Department of Endocrinology, Christie Hospital, Manchester, UK. Robert.Murray@leedsth.nhs.uk (2011-04)
      GHD adults exhibit a number of adverse surrogate markers of vascular risk culminating in excess vascular morbidity and mortality. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of a number of vascular morbidities. Furthermore, serum levels decrease following GH replacement in GHD adults, though it remains unclear if levels are significantly elevated in untreated individuals.