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肢端肥大症性心肌病可逆吗?生长激素和胰岛素样生长因子I水平5年恢复正常对心脏功能的影响。

Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance.

作者信息

Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Della Morte A M, Pivonello R, Salvatore M, Lombardi G

机构信息

Department of Molecular and Clinical Endocrinology, Federico II University of Naples, 80131 Naples, Italy.

出版信息

J Clin Endocrinol Metab. 2001 Apr;86(4):1551-7. doi: 10.1210/jcem.86.4.7376.

Abstract

Acromegalic patients are considered to be exposed to a doubled mortality rate, mostly for cardiovascular diseases. This open prospective study was designed to evaluate whether the impairment of cardiac performance could be reversed by the long-term suppression of GH and insulin-like growth factor I (IGF-I) levels. Eighteen patients with active acromegaly were studied before and 5 yr after surgery, followed by sc octreotide in 11 patients. Disease control (GH levels < or =1 microg/L after glucose load or < or =2.5 microg/L after fasting, respectively, together with normalized IGF-I levels for age) was achieved in seven patients after surgery and in six patients after 0.3--0.6 mg/day sc octreotide. Five patients were not controlled during the 5-yr follow-up. Cardiac performance at rest and at peak exercise was assessed by equilibrium radionuclide angiography at study entry and 5 yr after surgery alone or plus octreotide. Thirty-six sex- and age-matched healthy subjects served as controls. At study entry, patients had a lower left ventricular ejection fraction (LVEF) at peak exercise and LVEF exercise-induced changes, exercise duration, and capacity than controls (P < 0.001). After 5 yr of treatment, a significant decrease of resting heart rate (P = 0.03) and a significant increase of LVEF at peak exercise (P = 0.003) was found in patients achieving disease control. LVEF response at peak exercise worsened in none of the patients with controlled disease and in three patients with uncontrolled disease (60%) (chi(2) = 5.5; P = 0.02). Diastolic filling, exercise duration, and workload did not significantly change during the 5-yr follow-up. No difference was found between patients controlled by surgery alone or by surgery plus octreotide. This 5-yr prospective study demonstrated that the LVEF response at peak exercise improved in all patients achieving disease control, while it was worsened in 60% of uncontrolled ones. These results strengthen the need of a stable suppression of GH and IGF-I hypersecretion to restore a normal cardiac performance in acromegaly.

摘要

肢端肥大症患者的死亡率被认为会翻倍,主要是心血管疾病导致的。这项开放性前瞻性研究旨在评估长期抑制生长激素(GH)和胰岛素样生长因子I(IGF-I)水平是否能逆转心脏功能损害。对18例活动期肢端肥大症患者在手术前及术后5年进行了研究,其中11例患者术后接受皮下注射奥曲肽治疗。7例患者术后、6例患者接受0.3 - 0.6mg/天皮下注射奥曲肽后实现了疾病控制(葡萄糖负荷后GH水平≤1μg/L或空腹后≤2.5μg/L,同时IGF-I水平恢复至年龄匹配的正常范围)。5例患者在5年随访期间未得到控制。在研究开始时以及术后5年单独或联合奥曲肽治疗后,通过平衡放射性核素血管造影评估静息和运动峰值时的心脏功能。36例性别和年龄匹配的健康受试者作为对照。研究开始时,患者在运动峰值时的左心室射血分数(LVEF)、LVEF运动诱发变化、运动持续时间和运动能力均低于对照组(P < 0.001)。经过5年治疗,疾病得到控制的患者静息心率显著降低(P = 0.03),运动峰值时LVEF显著升高(P = 0.003)。疾病得到控制的患者中,运动峰值时LVEF反应均未恶化,3例疾病未得到控制的患者(60%)中LVEF反应恶化(χ² = 5.5;P = 0.02)。在5年随访期间,舒张期充盈、运动持续时间和工作量均无显著变化。单纯手术控制的患者与手术加奥曲肽控制的患者之间未发现差异。这项为期5年的前瞻性研究表明,所有疾病得到控制的患者运动峰值时的LVEF反应均得到改善,而60%疾病未得到控制的患者LVEF反应恶化。这些结果强化了稳定抑制GH和IGF-I分泌过多以恢复肢端肥大症患者正常心脏功能的必要性。

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