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IGF-1 水平正常化后肢端肥大症相关甲状腺肿大的减少:一项前瞻性观察和体外研究。

DECREASE IN ACROMEGALY-ASSOCIATED THYROID ENLARGEMENT AFTER NORMALIZATION OF IGF-1 LEVELS: A PROSPECTIVE OBSERVATION AND IN VITRO STUDY.

出版信息

Endocr Pract. 2020 Apr;26(4):369-377. doi: 10.4158/EP-2019-0353. Epub 2019 Dec 20.

Abstract

Goiter occurs at high frequency in acromegaly patients. Whether normalization of insulin-like growth factor 1 (IGF-1) levels could decrease goiter and thyroid volume remains unclear. Thyroid hormone levels and ultrasound measurements were assessed in 101 acromegaly patients, compared with 108 patients with nonfunctioning pituitary adenoma (NFPA) and 55 healthy controls. Thirty-four acromegaly patients underwent repeat evaluation 1 year post-transsphenoidal surgery. The effect of IGF-1 on thyroid cell proliferation, cell cycle, and apoptosis was evaluated in vitro. Acromegaly patients showed larger thyroid volume than those with NFPAs (18.32 mL vs. 9.91 mL; <.001) and healthy controls (18.32 mL vs. 9.63 mL; <.001). Duration of acromegaly was shown to be independently associated with thyroid volume enlargement (B = 0.259; 95% confidence interval, 0.162 to 0.357) in multivariate analysis. At follow-up, the median thyroid volume decreased from 22.74 to 17.87 mL in the cured group (n = 20; = .003), but the number of nodular goiters showed no significant change. Serum free thyroxine levels decreased from 13.76 to 10.08 pmol/L in the cured group ( = .006) but increased from 9.28 to 12.09 pmol/L in the active group ( = .013). Change in thyroid volume was significantly correlated with IGF-1 level ( = 0.37; = .029). In vitro, IGF-1 time- and dose-dependently promoted proliferation and secretory function of thyroid cells by enhancing cell cycle shift from the G1/S to G2/M phase and suppressing apoptosis. Acromegaly-associated thyroid volume increase, but not nodular goiter, could be reversed in cured acromegaly. IGF-1 time- and dose-dependently promoted the proliferation and secretory function of thyroid cells. = Cell Counting Kit-8; = free triiodothyronine; = free thyroxine; = growth hormone; = insulin-like growth factor 1; = magnetic resonance imaging; = nonfunctioning pituitary adenoma; = quantitative real-time-polymerase chain reaction; = thyroid-stimulating hormone.

摘要

肢端肥大症患者中甲状腺肿的发生率很高。胰岛素样生长因子 1(IGF-1)水平的正常化是否能减少甲状腺肿和甲状腺体积尚不清楚。评估了 101 例肢端肥大症患者的甲状腺激素水平和超声测量值,并与 108 例无功能垂体腺瘤(NFPA)患者和 55 例健康对照者进行了比较。34 例肢端肥大症患者在经蝶窦手术后 1 年进行了重复评估。在体外评估了 IGF-1 对甲状腺细胞增殖、细胞周期和细胞凋亡的影响。肢端肥大症患者的甲状腺体积大于 NFPA 患者(18.32 mL 比 9.91 mL;<.001)和健康对照组(18.32 mL 比 9.63 mL;<.001)。多变量分析显示,肢端肥大症的持续时间与甲状腺体积增大独立相关(B = 0.259;95%置信区间,0.162 至 0.357)。在随访中,治愈组的中位数甲状腺体积从 22.74 降至 17.87 mL(n = 20;=.003),但结节性甲状腺肿的数量没有明显变化。在治愈组中,血清游离甲状腺素水平从 13.76 降至 10.08 pmol/L(=.006),但在活跃组中从 9.28 增加至 12.09 pmol/L(=.013)。甲状腺体积的变化与 IGF-1 水平显著相关(= 0.37;=.029)。在体外,IGF-1 时间和剂量依赖性地通过增强细胞周期从 G1/S 向 G2/M 期的转变和抑制细胞凋亡来促进甲状腺细胞的增殖和分泌功能。=细胞计数试剂盒-8;=游离三碘甲状腺原氨酸;=游离甲状腺素;=生长激素;=胰岛素样生长因子 1;=磁共振成像;=无功能垂体腺瘤;=实时定量聚合酶链反应;=促甲状腺激素。

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