OBJECTIVE: To assess central arterial stiffness in thyrotoxicosis using the technique of pulse wave analysis. DESIGN: Case control study designed to determine the effect of thyrotoxicosis on central arterial stiffness and at 6 months after radioiodine treatment. PATIENTS: Twenty (18 women and 2 men) thyrotoxic patients and 20 age- and sex-matched controls were studied at baseline. Thyrotoxic patients were re-studied at 6 months following treatment of thyrotoxicosis with 555 MBq (131)I with no additional therapy for the six-month period. MEASUREMENTS: Using the sphygmocor apparatus, peripheral pressure waveforms were recorded non-invasively from the radial artery and central pressure waveforms were generated from these. Indices of arterial stiffness, central augmentation index (AI), augmentation of central arterial pressure (AG) and central blood pressures were derived. AI corrected for heart rate (AIc) was calculated. RESULTS: Thyrotoxic patients recorded a significantly lower AI (means+/-s.e.m.) compared with controls (15.0+/-2.1 vs 28.0+/-2.1%; P<0.0005) even when corrected for differences in heart rate AIc (20.0+/-2.1 vs 28.0+/-2.1%; P<0.005) as well as AG (6.0+/-0.8 vs 10.0+/-1.1 mmHg; P<0.002) but higher pulse pressure (58.0+/-3.5 vs 47.0+/-2.0 mmHg; P<0.02). At 6 months following treatment, a significant rise in AIc (27.0+/-1.8 vs 20.0+/-2.1%; P<0.005) and AG (11.0+/-1.0 vs 6.0+/-0.8 mmHg; P<0.005) was noted. Lipid profiles were comparable between the groups. CONCLUSIONS: These data suggested that subjects with untreated thyrotoxicosis have a decreased augmentation of central arterial pressure or lowered central arterial stiffness that would not appear to contribute to any excess cardiovascular risk in that condition.
K Obuobie, J Smith, R John, JS Davies and JH Lazarus
LM Evans, JS Davies, RA Anderson, GR Ellis, SK Jackson, MJ Lewis, MP Frenneaux, A Rees and MF Scanlon
OBJECTIVES: Controversy persists with regard to the atherogenic risk associated with adult growth hormone deficiency (GHD). Endothelial dysfunction and enhanced oxidative stress are early features of atherogenesis. Therefore, we have studied the effect of three months of low dose GH replacement therapy (0.03IU/kg/day) on these parameters in GHD adults. SUBJECTS AND METHODS: Eight hypopituitary GHD adults (4 male, 4 female), who were receiving conventional hormone replacement therapy, were studied before and after 3 months of GH replacement (0.03IU/kg/day). All observations obtained were compared with similar measurements made in 8 matched control subjects. All study subjects were non-smokers, normotensive and gave no personal or family history of premature vascular disease. Endothelial function was assessed using a specialised vessel wall tracking system to measure endothelium-dependent, flow-mediated, brachial artery dilatation (FMD). Measurements were repeated following glyceryl-trinitrate (GTN) (endothelium-independent dilatation). Oxidative stress was assessed by directly measuring lipid-derived free radicals in venous blood by electron paramagnetic resonance spectroscopy. Fasting lipids, insulin, plasma glucose and IGF-I were also measured at baseline and following GH replacement. RESULTS: FMD, expressed as a percentage change from resting base-line diameter, was significantly impaired in the pre-treatment GHD patients compared with controls (3.1+/-2.1% vs 6.1+/-0.9%, P<0. 001; means+/-s.d.) indicating endothelial dysfunction. Significant increase in FMD was noted following GH therapy (3.1+/-2.1% vs 6. 5+/-1.9%, P<0.001). Free radicals (arbitrary units) were elevated in the pre-treatment GHD patients compared with controls (0.36+/-0.09 vs 0.11+/-0.12, P<0.05) and fell significantly following GH therapy (0.23+/-0.03 vs 0.36+/-0.09, P<0.05), although they remained elevated compared with controls. Fasting insulin was significantly higher (25.9+/-18.8 vs 13.9+/-6.7mu/l, P<0.05) and IGF-I concentrations lower (10.8+/-4.7 vs 20.2+/-6.3nmol/l, P<0.05) in the pre-treatment GHD subjects. After treatment there were no changes in insulin concentration, although IGF-I levels were normalised (10. 8+/-2.3 vs 23.6+/-11.4nmol/l, P<0.05). CONCLUSIONS: Endothelial dysfunction and enhanced oxidative stress are features of adult GHD. This study suggests plausible mechanisms underlying any proatherogenic tendency in adult GHD and demonstrates improvement of these factors following GH replacement.