Pincelli A I, Bragato R, Scacchi M, Branzi G, Osculati G, Viarengo R, Leonetti G, Cavagnini F
University of Milan, IRCCS San Luca Hospital, Italian Auxologic Institute, Milan, Italy.
J Endocrinol Invest. 2003 May;26(5):420-8. doi: 10.1007/BF03345197.
GH replacement therapy given 3 times weekly (TWI) and adjusted to allow serum IGF-I concentrations in the mid-normal range for sex and age has been shown to be as effective as the daily regimen in improving lipid profile, body composition, bone mass and turnover in adult GH deficient (GHD) patients. Only one study has investigated so far the short-term (6 months) effect of a fixed weight-based TWI dosing schedule on heart structure and function in childhood onset (CO) GHD patients, whereas such a schedule in adult onset (AO) GHD patients has not been studied as yet. Aim of this study was to investigate whether a 1-yr low-dose titrated TWI GH-replacement regimen aimed at achieving and maintaining IGF-I levels within the low normal limits for age and sex is able to affect cardiovascular and heart parameters in a group of AO GHD patients. Eight adult patients (4 women and 4 men, age 35.8 +/- 3.37 yr, body mass index, BMI, 28.7 +/- 2.62 kg/m2) with AO GHD were included in the study, along with 10 healthy subjects, matched for age, sex, BMI and physical activity (6 women and 4 men, age 35.2 +/- 4.05 yr, BMI 28.4 +/- 2.34 kg/m2). M- and B- mode ecocardiography and pulsed doppler examination of transmitral flow were performed in GHD patients at baseline and after 3 and 12 months of GH therapy (mean GH dose 6.7 +/- 0.8 microg/kg/day given thrice a week), while normal subjects were studied once. Treatment with GH for 1 yr induced a significant increase in left ventricular (LV) diastolic and systolic volumes (+11.1 and +16.5%, respectively). Systolic LV posterior wall thickness and LV mass were increased (+10.2 and +7.7%, respectively) by GH administration. Systemic vascular resistance was significantly decreased by 1-yr GH therapy (-13.8% after 1 yr), while stroke volume, cardiac output and cardiac index were increased (+9.4, +11.6 and + 11.9%, respectively). LV end-systolic stress was decreased at the end of GH therapy (-11.2%). E and A wave, significantly reduced at baseline, were increased by 1 yr of GH therapy (+23.3% and +28.1%, respectively); likewise, the abnormally high E peak deceleration time was partially reversed by GH administration (-10.7%). Our study, though conducted in a small sample size, demonstrates that a TWI GH treatment schedule is able to reverse the cardiovascular abnormalities in AO GHD patients and to improve body composition and lipid profile. The maintenance of circulating IGF-I concentrations within the low normal range allows to avoid most of the side-effects reported with higher GH doses while being cost-effective and improving the patient's compliance.
对于成年生长激素缺乏（GHD）患者，每周三次（TWI）给予生长激素（GH）替代治疗并进行调整，以使血清胰岛素样生长因子-I（IGF-I）浓度处于与年龄和性别相应的正常范围中间值，已被证明在改善脂质谱、身体组成、骨量和骨转换方面与每日治疗方案同样有效。到目前为止，仅有一项研究调查了基于固定体重的TWI给药方案对儿童期起病（CO）GHD患者心脏结构和功能的短期（6个月）影响，而对于成年期起病（AO）GHD患者的此类给药方案尚未进行研究。本研究的目的是调查一种为期1年的低剂量滴定TWI GH替代方案，该方案旨在使IGF-I水平达到并维持在与年龄和性别相应的低正常范围内，是否能够影响一组AO GHD患者的心血管和心脏参数。本研究纳入了8例AO GHD成年患者（4例女性和4例男性，年龄35.8±3.37岁，体重指数，BMI为28.7±2.62kg/m²），以及10名年龄、性别、BMI和体力活动相匹配的健康受试者（6例女性和4例男性，年龄35.2±4.05岁，BMI为28.4±2.34kg/m²）。对GHD患者在基线时以及GH治疗3个月和12个月后（平均GH剂量为6.7±0.8μg/kg/天，每周三次给药）进行M型和B型超声心动图检查以及二尖瓣血流脉冲多普勒检查，而对正常受试者仅进行一次检查。GH治疗1年导致左心室（LV）舒张末期和收缩末期容积显著增加（分别增加11.1%和16.5%）。给予GH后，LV后壁收缩期厚度和LV质量增加（分别增加10.2%和7.7%）。1年的GH治疗使全身血管阻力显著降低（1年后降低13.8%），而每搏输出量、心输出量和心脏指数增加（分别增加9.4%、11.6%和11.9%）。GH治疗结束时LV收缩末期应力降低（降低11.2%）。在基线时显著降低的E波和A波，经过1年的GH治疗后增加（分别增加23.3%和28.1%）；同样，异常高的E峰减速时间通过给予GH部分得到逆转（降低10.7%）。我们的研究虽然样本量较小，但表明TWI GH治疗方案能够逆转AO GHD患者的心血管异常，并改善身体组成和脂质谱。将循环IGF-I浓度维持在低正常范围内能够避免高剂量GH报道的大多数副作用，同时具有成本效益并提高患者的依从性。
