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肢端肥大症中甲状腺毒症的心脏效应。

Cardiac effect of thyrotoxicosis in acromegaly.

作者信息

Marzullo P, Cuocolo A, Ferone D, Pivonello R, Salvatore M, Lombardi G, Colao A

机构信息

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

出版信息

J Clin Endocrinol Metab. 2000 Apr;85(4):1426-32. doi: 10.1210/jcem.85.4.6510.

Abstract

Cardiac structure and function are affected both by acromegaly and hyperthyroidism. Whereas the former is mainly characterized by ventricular hypertrophy as well as diastolic and systolic impairment, the latter frequently leads to increased heart rate and enhancement of contractility and cardiac output. To further investigate this issue, we designed this two-arm study. In the first cross-sectional study, we compared echocardiography and radionuclide angiography results obtained in eight hyperthyroid acromegalic patients, eight hyperthyroid nonacromegalic patients, and eight healthy subjects. All acromegalic patients were receiving treatment for acromegaly at the onset of hyperthyroidism. In the second longitudinal study, performed in the group of acromegalic patients, we compared the cardiovascular results obtained during hyperthyroidism with the retrospective data obtained at the initial diagnosis of acromegaly and after 1-yr treatment for this disease and those prospective data obtained during the remission of hyperthyroidism. In the cross-sectional study, hyperthyroid acromegalic patients showed an increase in the left ventricular (LV) mass index (LVMi) compared to healthy and hyperthyroid controls (P < 0.05), with evidence of LVMi hypertrophy in five of them (62.5%). A significant correlation was found between LVMi and GH levels (r = 0.785; P < 0.05). The LV ejection fraction (LVEF) at rest was higher in the control hyperthyroid population than in healthy controls (P < 0.05), whereas the LVEF response to exercise was reduced in acromegalic patients (P < 0.05 vs. healthy controls). In acromegalics, the exercise-induced change in LVEF was significantly reduced compared to that in healthy controls (P < 0.001), but not to that in hyperthyroid controls (P < 0.07), being abnormal (<5% increase vs. baseline values) in six patients. Four of these six patients (66%) had elevated GH and insulin-like growth factor I levels during the treatment of acromegaly. An inverse correlation between GH and LVEF at rest (r = -0.896;P < 0.05) and at peak exercise (r = -0.950; P < 0.001) was recorded. The peak filling rate was reduced in hyperthyroid acromegalic patients compared to those in both control populations (P < 0.05). In the longitudinal study, acromegalic patients showed an increased LVMi during hyperthyroidism compared to that observed after successful treatment of acromegaly (P < 0.05); resting LVEF was increased compared to both basal (P < 0.001) and posttreatment values (P < 0.05). However, the exercise-induced change in LVEF was reduced (P < 0.05 vs. previous follow-up values). Remission of hyperthyroidism led to significant reduction of LVMi (P < 0.05) and resting LVEF (P < 0.05) and an increase in exercise-induced LVEF (P < 0.05). In light of these findings, hyperthyroidism produces a detrimental effect on the cardiovascular system of acromegalic patients, particularly in those with uncontrolled disease. Thus, control of GH and insulin-like growth factor I should be a major objective, as cardiovascular risk persists in patients with ineffective hormonal suppression, and constant endocrine and cardiovascular surveillance remain crucial steps in patient follow-up.

摘要

肢端肥大症和甲状腺功能亢进均会影响心脏结构和功能。前者主要表现为心室肥厚以及舒张和收缩功能受损,而后者则常导致心率加快、收缩力增强和心输出量增加。为进一步研究此问题,我们设计了这项双臂研究。在第一项横断面研究中,我们比较了8例甲状腺功能亢进的肢端肥大症患者、8例甲状腺功能亢进的非肢端肥大症患者和8例健康受试者的超声心动图和放射性核素血管造影结果。所有肢端肥大症患者在甲状腺功能亢进发作时均正在接受肢端肥大症治疗。在第二项纵向研究中,我们对肢端肥大症患者组进行了研究,比较了甲状腺功能亢进期间获得的心血管结果与肢端肥大症初诊时及该病治疗1年后获得的回顾性数据,以及甲状腺功能亢进缓解期获得的前瞻性数据。在横断面研究中,与健康对照组和甲状腺功能亢进对照组相比,甲状腺功能亢进的肢端肥大症患者左心室(LV)质量指数(LVMi)升高(P < 0.05),其中5例(62.5%)有LVMi肥大证据。发现LVMi与生长激素(GH)水平之间存在显著相关性(r = 0.785;P < 0.05)。静息时,甲状腺功能亢进对照组的左心室射血分数(LVEF)高于健康对照组(P < 0.05),而肢端肥大症患者运动时的LVEF反应降低(与健康对照组相比,P < 0.05)。在肢端肥大症患者中,与健康对照组相比,运动诱导的LVEF变化显著降低(P < 0.001),但与甲状腺功能亢进对照组相比无显著差异(P < 0.07),6例患者异常(与基线值相比增加<5%)。这6例患者中有4例(66%)在肢端肥大症治疗期间GH和胰岛素样生长因子I水平升高。记录到静息时(r = -0.896;P < 0.05)和运动峰值时(r = -0.950;P < 0.001)GH与LVEF呈负相关。与两个对照组相比,甲状腺功能亢进的肢端肥大症患者的峰值充盈率降低(P < 0.05)。在纵向研究中,与肢端肥大症成功治疗后相比,肢端肥大症患者在甲状腺功能亢进期间LVMi升高(P < 0.05);静息LVEF与基础值(P < 0.001)和治疗后值相比均升高(P < 0.05)。然而,运动诱导的LVEF变化降低(与先前的随访值相比,P < 0.05)。甲状腺功能亢进的缓解导致LVMi(P < 0.05)和静息LVEF(P < 0.05)显著降低,运动诱导的LVEF增加(P < 0.05)。鉴于这些发现,甲状腺功能亢进对肢端肥大症患者的心血管系统产生有害影响,尤其是在疾病未得到控制的患者中。因此,控制GH和胰岛素样生长因子I应是主要目标,因为激素抑制无效的患者心血管风险仍然存在,持续的内分泌和心血管监测仍是患者随访的关键步骤。

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