Wexler Tamara L, Durst Ronen, McCarty David, Picard Michael H, Gunnell Lindsay, Omer Zehra, Fazeli Pouneh, Miller Karen K, Klibanski Anne
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Growth Horm IGF Res. 2010 Oct;20(5):333-7. doi: 10.1016/j.ghir.2010.05.003. Epub 2010 Jul 3.
Growth hormone excess and growth hormone deficiency (GHD) are both associated with increased cardiovascular morbidity. A specific acromegaly-related cardiomyopathy has been described, characterized in part by increased left ventricular mass (LVM). Growth hormone deficiency is associated with reduced LVM. Following cure of acromegaly with surgery or radiation therapy, GHD may develop; however, its effects on cardiac morphology and function in this population are not established.
We hypothesized that the development of GHD in patients with prior acromegaly would be associated with cardiac morphologic and functional changes that differ from those in patients who are GH sufficient following cure of acromegaly.
A cross-sectional study was conducted in a Clinical Research Center. Study participants consisted of three groups of subjects (n=34): I. Cured acromegaly with GHD (n=15), II. Cured acromegaly with GH sufficiency (n=8), and III. Active acromegaly (n=11). Main outcome measures included cardiac morphology and function, using echocardiography parameters.
Mean age and BMI, 44.6 ± 2.3 years (SEM) and 30.7 ± 1.3 kg/m², respectively, were not different among the three groups. Mean peak GH values were: I. 2.8 ± 0.4 ng/ml; II. 30.1 ± 9.1 ng/ml (p=0.0002.) In group I, left ventricular mass, indexed to body surface area (LVMi), was within the normal range in all patients; moreover, left ventricular (LV) geometry was normal. At least 50% of patients in groups II and III had elevated LVMi, and in 50% of patients, LV geometry was abnormal, indicating pathologic hypertrophy. Ejection fraction was similar between all three groups. There were no significant differences in diastolic function.
Patients who develop GHD following cure of acromegaly do not demonstrate elevated LV mass, in contrast to patients with a history of acromegaly but normal GH levels or to patients with active acromegaly. This suggests that GH status after treatment of acromegaly correlates with LV mass, and that, in GH sufficient patients, reversal of remodeling may be slower than previously thought. These data suggest that it will be important to determine whether GH replacement alters left ventricular morphology over time.
生长激素分泌过多和生长激素缺乏(GHD)均与心血管疾病发病率增加有关。一种特定的肢端肥大症相关心肌病已被描述,其部分特征是左心室质量(LVM)增加。生长激素缺乏与LVM降低有关。在通过手术或放射治疗治愈肢端肥大症后,可能会发生GHD;然而,其对该人群心脏形态和功能的影响尚未明确。
我们假设既往患有肢端肥大症的患者发生GHD会伴有心脏形态和功能的改变,这些改变与肢端肥大症治愈后生长激素充足的患者不同。
在临床研究中心进行了一项横断面研究。研究参与者由三组受试者组成(n = 34):I. 治愈的肢端肥大症伴GHD(n = 15),II. 治愈的肢端肥大症且生长激素充足(n = 8),以及III. 活动期肢端肥大症(n = 11)。主要结局指标包括使用超声心动图参数评估心脏形态和功能。
三组的平均年龄和体重指数分别为44.6±2.3岁(标准误)和30.7±1.3kg/m²,无差异。平均生长激素峰值分别为:I组2.8±0.4ng/ml;II组30.1±9.1ng/ml(p = 0.0002)。在I组中,所有患者的左心室质量指数(LVMi)均在正常范围内;此外,左心室(LV)几何形态正常。II组和III组中至少50%的患者LVMi升高,且50%的患者LV几何形态异常,提示病理性肥厚。三组的射血分数相似。舒张功能无显著差异。
与有肢端肥大症病史但生长激素水平正常的患者或活动期肢端肥大症患者相比,肢端肥大症治愈后发生GHD的患者未表现出左心室质量升高。这表明肢端肥大症治疗后的生长激素状态与左心室质量相关,并且在生长激素充足的患者中,重构的逆转可能比先前认为的要慢。这些数据表明,确定生长激素替代治疗是否会随时间改变左心室形态将很重要。