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活动期肢端肥大症患者促甲状腺激素分泌减少且不规则,但昼夜节律仍保留。

Diminished and irregular thyrotropin secretion with preserved diurnal rhythm in patients with active acromegaly.

作者信息

Roelfsema Ferdinand, Biermasz Nienke R, Frolich Marijke, Keenan Daniel M, Veldhuis Johannes D, Romijn Johannes A

机构信息

Leiden University Medical Center, Department of Endocrinology and Metabolic Diseases, P.O. Box 9600, Leiden 2300 RC, The Netherlands.

出版信息

J Clin Endocrinol Metab. 2009 Jun;94(6):1945-50. doi: 10.1210/jc.2009-0174. Epub 2009 Mar 31.

Abstract

CONTEXT

The hypothalamo-pituitary-thyroid axis in acromegaly may be altered. Previous studies report diminished serum TSH concentrations in patients with active acromegaly and decreased response to TRH. On the other hand, most patients have normal thyroid hormone concentrations.

OBJECTIVE

Our aim was to analyze serum TSH profiles in relation to GH profiles in patients with untreated acromegaly, in order to delineate aberrations in the hypothalamo-pituitary-thyroid system.

INTERVENTION

Twenty-one patients with active acromegaly and matched controls underwent a 24-h, 10-min blood sampling study. GH and TSH data were analyzed with a newly developed automated deconvolution program, approximate entropy, and cosinor regression.

RESULTS

Basal (10.4 +/- 2.0 vs. 13.8 +/- 1.4 mU/liter . 24 h; P = 0.02) and pulsatile (11.4 +/- 1.7 vs. 18.6 +/- 1.6 mU/liter . 24 h; P = 0.002) TSH secretion was decreased in patients. TSH secretory regularity was diminished with loss of pattern synchrony between TSH and GH. Total TSH secretion correlated with TSH increase after TRH (R = 0.75; P = 0.0001), negatively with the log-transformed GH secretion rate (R = -0.52; P = 0.001), but not with adenoma size. The diurnal TSH rhythm was preserved. Total and free T4 concentrations were similar in patients and controls.

CONCLUSION

Basal and pulsatile TSH secretion is decreased in active acromegaly, although T4 levels are unaffected. Diminished TSH secretion is compatible with enhanced restraint by tumoral GH feedback-driven somatostatin outflow, explaining also the reduced regularity of TSH secretion. Unchanged T4 concentrations might reflect decreased sympathetic function in GH excess states, heightening responsiveness of the thyroid gland to TSH.

摘要

背景

肢端肥大症患者的下丘脑 - 垂体 - 甲状腺轴可能发生改变。既往研究报道,活动期肢端肥大症患者血清促甲状腺激素(TSH)浓度降低,对促甲状腺激素释放激素(TRH)的反应减弱。另一方面,大多数患者甲状腺激素浓度正常。

目的

我们的目的是分析未经治疗的肢端肥大症患者血清TSH谱与生长激素(GH)谱的关系,以明确下丘脑 - 垂体 - 甲状腺系统的异常。

干预措施

21例活动期肢端肥大症患者及匹配的对照组接受了一项为期24小时、每10分钟采集一次血样的研究。采用新开发的自动去卷积程序、近似熵和余弦节律回归分析GH和TSH数据。

结果

患者的基础TSH分泌(10.4±2.0 vs. 13.8±1.4 mU/升·24小时;P = 0.02)和脉冲式TSH分泌(11.4±1.7 vs. 18.6±1.6 mU/升·24小时;P = 0.002)均降低。TSH分泌的规律性减弱,TSH与GH之间的模式同步性丧失。总TSH分泌与TRH刺激后TSH升高相关(R = 0.75;P = 0.0001),与对数转换后的GH分泌率呈负相关(R = -0.52;P = 0.001),但与腺瘤大小无关。TSH的昼夜节律得以保留。患者和对照组的总甲状腺素(T4)和游离T4浓度相似。

结论

活动期肢端肥大症患者的基础和脉冲式TSH分泌减少,尽管T4水平未受影响。TSH分泌减少与肿瘤性GH反馈驱动的生长抑素流出增强的抑制作用相符,这也解释了TSH分泌规律性降低的原因。T4浓度不变可能反映了GH过多状态下交感神经功能降低,增强了甲状腺对TSH的反应性。

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