Hormone secretion by pituitary adenomas is characterized by increased disorderliness and spikiness but more regular pulsing.
Hormone secretion by pituitary adenomas is characterized by increased disorderliness and spikiness but more regular pulsing.
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DOI：
10.1210/jc.2014-2363
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发表时间：
2014-07
期刊：
影响因子：
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通讯作者：
F. Roelfsema;A. Pereira;N. Biermasz;J. Veldhuis
中科院分区：
文献类型：
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作者：
F. Roelfsema;A. Pereira;N. Biermasz;J. Veldhuis
功能性垂体瘤的激素分泌以基础（非搏动性）分泌增加、脉冲频率增强、脉冲质量增大和紊乱性增加为特征。目的：本研究的目的是量化垂体腺瘤激素分泌的（细微）异常，以及选择性垂体手术和抑制性药物对这些参数的影响。方法近似熵（ApEn）量化与一个完善的算法，尖峰的一种新的方法来评估突然短暂的激素水平的增加，和脉冲规律性，确定与一个全自动的去卷积程序。在未治疗和治疗的肢端肥大症、催乳素瘤和库欣病患者中比较这3种不同的分泌中断指标，并在健康对照组中进行匹配。结果：在所有未治疗的患者组中，ApEn和尖峰显著增加，在肢端肥大症和皮质醇增多症患者中，垂体手术后恢复正常。相反，肢端肥大症和催乳素瘤的抑制性药物治疗不能使ApEn正常化。尖突在肢端肥大症患者中正常化，但在泌乳素瘤中不正常。肢端肥大症和库欣病的GH和皮质醇脉冲规律性分别升高，并在手术后恢复正常。药物治疗使肢端肥大症患者的脉搏规律性正常化，但催乳素瘤患者则不然。结论本研究扩大了对功能亢进垂体腺瘤激素分泌紊乱的认识。新的发现是所有3个肿瘤组的棘状突起增加，GH和ACTH分泌腺瘤的脉冲规律性增加。标记模式不规则性和通过手术和药物治疗选择性正常化背后的机制尚未建立，但可能包括除了垂体内细胞网络的解剖和功能紊乱之外，反馈信号减少。
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.