Hána V, Prázný M, Marek J, Skrha J, Justová V
Third Department of Internal Medicine, Faculty of Medicine I, Charles University, Prague, Czech Republic.
Eur J Endocrinol. 2002 Sep;147(3):333-7. doi: 10.1530/eje.0.1470333.
An increased cardiovascular risk and mortality in hypopituitary patients receiving conventional hormonal treatment without GH replacement have been shown in several studies. Various atherogenic risk factors including endothelial dysfunction - an early event in the atherogenesis - are more expressed in adults with GH-deficiency (GHD). Changes in microcirculation and vascular reactivity could represent an early marker of developing vascular changes.
To evaluate the microcirculation and vascular reactivity in a GHD state before and during GH replacement. SUBJECTS, METHODS AND DESIGN: Thirteen adult patients (ten men, mean age 40+/-9 years) with severe GHD were studied. The skin microvascular perfusion and reactivity were measured by laser-Doppler flowmetry on the forearm. Two dynamic tests for vascular perfusion and reactivity were used - postocclusive reactive hyperemia (PORH) and thermal hyperemia (TH) at 44 degrees C. Measurements were performed before and after 6 and 12 months on GH replacement with a dose of GH that normalized IGF-I serum levels. The parameters of tissue perfusion and vascular reactivity measured in GHD were compared with values during GH treatment and with the results of the control group.
Peak flow during TH in GHD patients was significantly reduced before GH treatment when compared with healthy subjects (means+/-s.e.m., 68+/-6.6 vs 111+/-8.3 perfusion units (PU), P<0.001) and normalized on GH treatment (109+/-12.7 PU). The velocity of perfusion increase during TH before treatment was significantly reduced in GHD as well (0.84+/-0.07 vs 1.53+/-0.19 PU/s, P<0.03) and normalized on GH treatment (1.38+/-0.24 PU/s). The PORH was also significantly reduced in GHD compared with controls (PORH(max) 414+/-63 vs 528+/-58%, P<0.05) and during GH treatment was restored to values not different from controls (642+/-86%, P=NS).
Skin microcirculation and vascular reactivity measured by laser-Doppler flowmetry is significantly reduced in GHD adults and is restored during GH replacement therapy. Reduced tissue perfusion and reactivity probably reflect the endothelial dysfunction in the GHD state. Reduced nitric oxide production and bioavailability and also other factors like increased sympathetic activity and reduced conversion of thyroxine to triiodothyronine in the GHD state can contribute to changes in microcirculation. Restoration of vascular reactivity by GH replacement might have favorable clinical consequences on the increased vascular morbidity of GHD patients. Reduced skin microvascular perfusion and reactivity in GHD probably contribute to the impaired thermoregulation - a clinical symptom of GHD.
多项研究表明，接受常规激素治疗但未补充生长激素（GH）的垂体功能减退患者心血管风险和死亡率增加。包括内皮功能障碍（动脉粥样硬化发生的早期事件）在内的各种致动脉粥样硬化危险因素在生长激素缺乏（GHD）的成年人中表现更为明显。微循环和血管反应性的变化可能是血管变化发展的早期标志物。
评估GH替代治疗前和治疗期间GHD状态下的微循环和血管反应性。
受试者、方法和设计：对13例严重GHD的成年患者（10例男性，平均年龄40±9岁）进行研究。通过激光多普勒血流仪测量前臂皮肤微血管灌注和反应性。采用两种血管灌注和反应性动态试验——闭塞后反应性充血（PORH）和44℃热充血（TH）。在使用使IGF-I血清水平正常化的GH剂量进行GH替代治疗前、治疗6个月和12个月后进行测量。将GHD状态下测量的组织灌注和血管反应性参数与GH治疗期间的值以及对照组的结果进行比较。
与健康受试者相比，GHD患者在GH治疗前TH期间的峰值血流显著降低（平均值±标准误，68±6.6 vs 111±8.3灌注单位（PU），P<0.001），GH治疗后恢复正常（109±12.7 PU）。治疗前TH期间灌注增加的速度在GHD患者中也显著降低（0.84±0.07 vs 1.53±0.19 PU/s，P<0.03），GH治疗后恢复正常（1.38±0.24 PU/s）。与对照组相比，GHD患者的PORH也显著降低（PORH(max) 414±63 vs 528±58%，P<0.05），GH治疗期间恢复到与对照组无差异的值（642±86%，P=无显著性差异）。
通过激光多普勒血流仪测量的GHD成年患者皮肤微循环和血管反应性显著降低，GH替代治疗期间恢复。组织灌注和反应性降低可能反映了GHD状态下的内皮功能障碍。GHD状态下一氧化氮产生和生物利用度降低以及其他因素，如交感神经活性增加和甲状腺素向三碘甲状腺原氨酸转化减少，可能导致微循环变化。GH替代治疗恢复血管反应性可能对GHD患者血管发病率增加产生有利的临床后果。GHD患者皮肤微血管灌注和反应性降低可能导致体温调节受损——GHD的一种临床症状。
