| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Letters to the Editor |
Department of Medicine University Hospital of Wales CF4 4XW Cardiff, United Kingdom
We read with interest the recent paper by Pfeifer et al. (1) examining the effect of GH treatment on endothelial function and its ability to reverse atherosclerotic changes in GH-deficient (GHD) adults. In this study, the noninvasive, ultrasonic measurement of flow-mediated endothelial-dependent dilatation (EDD) of the brachial artery was used to measure endothelial function before and after GH treatment. An impaired EDD response was documented in GHD adults, which improved after GH treatment. It was, therefore, concluded that a state of endothelial dysfunction exists in GHD adults, which is reversible with GH replacement.
At our center we have had considerable experience with the measurement of endothelial function using the technique of EDD (2, 3). The findings of the study by Pfeifer et al. (1) are consistent with our own observations (4). However, some of the EDD data from the study by Pfeifer et al. (1) are surprising and at variance with our data. EDD itself relies on the stimulus of hyperemic blood flow. To permit valid comparisons of EDD between groups, increases in blood flow should be of similar magnitude. However, in this study, the results of brachial artery flow readings are inconsistent between groups, complicating the interpretation of the results. The authors demonstrated that the increase in brachial artery blood flow following cuff release was significantly lower in the pretreatment GHD group (362%) than in controls (509%). This result is not only at variance with our observations but also implies a diminished stimulus for the endothelial dependent release of nitric oxide. This may, therefore, account for the lower EDD measured in the pretreatment GHD group rather than it resulting from abnormal endothelial function as the authors conclude. We disagree with this conclusion, as the mechanisms responsible for producing increased flow following cuff release are not dependent on an intact endothelium or nitric oxide production. Instead, they are related to ischemic metabolites and other vasodilatory substances induced in the hand by cuff occlusion. Accordingly, similar increases in flow are observed in disease states associated with endothelial dysfunction as well as healthy controls (5).
There also may have been methodological problems accounting for anomalies in the results from the EDD data. It should be noted that this technique is highly operator dependent, although in the presence of skilled operators it can produce an accurate and reproducible measurement of endothelial function with a quoted intraoperator coefficient of variation of 1.8% (6). This degree of variation allows for the technique to determine the usually small differences in EDD responses (often between 4–8%) between disease states and normal controls. Pfeifer et al. have not published details of their reproducibility data but do quote that their intraoperator coefficient of variation was 8.3%. This is in excess of most other published EDD data (2, 3, 6) and casts doubt on their results. They observed an increase in brachial artery diameter at pretreatment of 7.93% increasing to a maximum of 12.16% after 18 months of GH treatment. This modest increase of about 4% could be entirely accounted for by operator error, given the high coefficient of variation. Similar factors are likely to account for the inexplicable and incongruous EDD decrease observed after 12 months of treatment. Concern has been expressed previously about the ultrasonographical measurement of brachial artery diameter with a 7.5 MHz transducer (7) principally because of inadequate resolution with this type of probe (usually >0.2 mm) in measuring small changes of less than 1 mm in artery diameter during reactive hyperemia. At our center we use a wall tracking system (Vadirec, Medical Systems, Arnhem, Holland) to follow changes in brachial artery diameter over a 10-sec period. This overcomes some of the methodological problems with limited resolution associated with the use of the 7.5-MHz transducer by relying less on the high quality images needed to visualize the borders between intima, media, and adventitia. In experienced hands, this method produces highly reproducible data with an interoperator coefficient of variation for baseline arterial diameter measurements of 1.6% (2).
We agree with the authors that endothelial dysfunction, an early event in the process of atherogenesis, does exist in GHD adults and that GH treatment could potentially reverse this dysfunction. The potential mechanisms accounting for this abnormality may, as the authors suggest, result from a direct insulin-like growth factor-I-mediated effect via increased production of nitric oxide. However, other mechanisms need to be considered. Although no quantitative changes in the serum lipids were observed in this study, qualitative alterations in lipoproteins have been described in GHD adults (8), resulting in the generation of an atherogenic lipoprotein phenotype, which would contribute to endothelial dysfunction. Furthermore, we have demonstrated the presence of increased oxidative stress in GHD adults, reduced by GH therapy (9). Since enhanced oxidative stress may be a factor in atherogenesis, the effect of GH therapy on endothelial dysfunction in GHD adults may be partly mediated by its effect on oxidative stress. Noninvasive measurements of endothelial function using flow-mediated dilatation provide an insight into the pathogenesis of vascular disease. However, certain caveats need to be considered when using this highly operator-dependent technique to ensure that accurate and reproducible data are obtained.
Footnotes
Received March 12, 1999. Accepted March 24, 1999. Address correspondence to: Jamie C. Smith, Research Registrar, A7 Office, Department of Medicine, University of Wales, Heath Park, CF4 4XW Cardiff, United Kingdom.
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
