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垂体腺瘤的激素分泌特点是无序性和峰值增加,但脉冲更规律。

Hormone secretion by pituitary adenomas is characterized by increased disorderliness and spikiness but more regular pulsing.

作者信息

Roelfsema Ferdinand, Pereira Alberto M, Biermasz Nienke R, Veldhuis Johannes D

机构信息

Department of Endocrinology and Metabolic Diseases (F.R., A.M.P., N.R.B.), Leiden University Medical Center, 2333ZA Leiden, The Netherlands; and Endocrine Research Unit (J.D.V.), Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota 55901.

出版信息

J Clin Endocrinol Metab. 2014 Oct;99(10):3836-44. doi: 10.1210/jc.2014-2363. Epub 2014 Jul 11.

Abstract

CONTEXT

Hormone secretion by functioning pituitary tumors is characterized by increased basal (nonpulsatile) secretion, enhanced pulse frequency, amplified pulse mass, and increased disorderliness.

OBJECTIVE

The objective of the study was to quantify (subtle) abnormalities of hormone secretion by pituitary adenomas and the influence of selective pituitary surgery and suppressive medications on these parameters.

METHODS

Approximate entropy (ApEn) was quantified with a refined algorithm, spikiness by a new method to evaluate sudden short-lived increases in hormone levels, and pulsing regularity, determined with a fully automated deconvolution program. These 3 distinct measures of secretory disruption were compared in untreated and treated patients with acromegaly, prolactinoma, and Cushing's disease together with matching profiles in healthy controls.

RESULTS

ApEn and spikiness were markedly increased in all untreated patient groups and normalized after pituitary surgery in acromegaly and hypercortisolism. In contrast, hormone-suppressive medical treatment in acromegaly and prolactinoma did not normalize ApEn. Spikiness normalized in acromegalic patients but not in prolactinoma. GH and cortisol pulsing regularity was elevated in acromegaly and Cushing's disease, respectively, and normalized after surgery. Medical treatment caused normalization of pulsing regularity in acromegaly but not in prolactinoma patients.

CONCLUSION

This study extends the understanding of disorganized hormone secretion by hyperfunctioning pituitary adenomas. The new findings are increased spikiness in all 3 tumor groups and increased pulsing regularity in GH- and ACTH-secreting adenomas. The mechanisms behind the marked pattern irregularity and the selective normalization by surgical and medical therapies are not established yet but may include diminished feedback signaling in addition to the anatomical and functional disorganization of intrapituitary cell networks.

摘要

背景

功能性垂体瘤的激素分泌特点是基础(非脉冲式)分泌增加、脉冲频率增强、脉冲量增大以及紊乱性增加。

目的

本研究的目的是量化垂体腺瘤激素分泌的(细微)异常情况,以及选择性垂体手术和抑制性药物对这些参数的影响。

方法

采用一种改进算法对近似熵(ApEn)进行量化,用一种新方法评估激素水平突然短暂升高来衡量峰值,通过一个全自动反卷积程序确定脉冲规律性。在未经治疗和接受治疗的肢端肥大症、泌乳素瘤和库欣病患者中比较这三种不同的分泌紊乱指标,并与健康对照的匹配情况进行对比。

结果

在所有未经治疗的患者组中,ApEn和峰值均显著增加,在肢端肥大症和皮质醇增多症患者接受垂体手术后恢复正常。相比之下,肢端肥大症和泌乳素瘤患者接受激素抑制药物治疗后,ApEn未恢复正常。肢端肥大症患者的峰值恢复正常,而泌乳素瘤患者未恢复正常。肢端肥大症患者的生长激素(GH)和库欣病患者的皮质醇脉冲规律性分别升高,手术后恢复正常。药物治疗使肢端肥大症患者的脉冲规律性恢复正常,但泌乳素瘤患者未恢复正常。

结论

本研究扩展了对功能亢进性垂体腺瘤激素分泌紊乱的认识。新发现是所有三个肿瘤组的峰值均增加,以及分泌GH和促肾上腺皮质激素(ACTH)的腺瘤的脉冲规律性增加。显著的模式不规则以及手术和药物治疗选择性恢复正常背后的机制尚未明确,但可能除了垂体细胞网络的解剖和功能紊乱外,还包括反馈信号减弱。

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本文引用的文献

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Anterior pituitary cell networks.垂体前叶细胞网络。
Front Neuroendocrinol. 2012 Aug;33(3):252-66. doi: 10.1016/j.yfrne.2012.08.002. Epub 2012 Sep 7.
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A tridimensional view of pituitary development and function.垂体发育和功能的三维视图。
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