手術治療後のクッシング病患者の脳血流の可逆性について

Reversibility of cerebral blood flow in patients with Cushing's disease after surgery treatment.

• Hewei Cheng
• Lu Gao
• Bo Hou
• Feng Feng
• Xiaopeng Guo
• Zihao Wang
• Ming Feng
• Bing Xing
• Yong Fan

抄録

背景と目的:

クッシング病（CD）患者は、内因性コルチゾールの過剰な曝露により脳の代謝異常を呈する。しかし、治療後のCD患者の脳代謝の可逆性はほとんど不明のままである。

BACKGROUND AND OBJECTIVES: Cushing's disease (CD) patients have metabolic abnormalities in the brain caused by excessive exposure to endogenous cortisol. However, the reversibility of brain metabolism of CD patients after treatment remains largely unknown.

方法:

本研究では、治療を希望する50人のCD患者と34人の正常対照者（NC）を募集した。患者には蝶形骨経絡膜腺摘出術（TSA）を行い、3ヵ月後に再検査を行った。治療前と3ヶ月後の追跡調査では、3D pseudo-continuous arterial spin labelling（PCASL）画像を用いて患者の脳血流（CBF）を評価し、全脳ボクセルワイズ群間比較法を用いてNC群のCBFと比較した。寛解した患者については、CBF測定値と副腎皮質刺激ホルモン（ACTH）、24時間尿中遊離コルチゾール（24hUFC）、血清コルチゾールを含むホルモンレベル測定値を治療前後で比較した。最後に、再発CD患者のCBFの変化とホルモンレベルの測定値との関係を探るために相関分析を行った。

METHODS: This study recruited 50 CD patients seeking treatment and 34 matched normal controls (NCs). The patients were treated with Transsphenoidal Adenomectomy (TSA) and reexamined 3 months later. Cerebral blood flow (CBF) of the patients was assessed using 3D pseudo-continuous arterial spin labelling (PCASL) imaging before the treatment and at the 3-month follow-up and were compared with CBF measure of the NCs using a whole-brain voxelwise group comparison method. For remitted patients, their CBF measures and hormone level measures, including adrenocorticotropic hormone (ACTH), 24-hour urinary free cortisol (24hUFC) and serum cortisol, were compared before and after the treatment. Finally, a correlation analysis was carried out to explore the relationship between changes of CBF and hormone level measures of the remitted CD patients.

結果:

治療後、45人の患者が寛解に達した。治療前のCD患者は、NC患者と比較して、後頭葉、頭頂葉、上中下側頭回、上中下前頭回、眼窩前頭前皮質を含む皮質領域のCBFが有意に低下していた。また、尾状部、掌蹠部、口蓋骨、四肢葉、海馬傍回、海馬、視床、扁桃体を含む皮質下層のCBFが有意に増加した(p<)。0.01、偽発見率補正済み）。)寛解した患者では，治療前後のCBFの変化は治療前のNC患者とCD患者の差と同様の空間パターンを示し，治療後のNC患者と寛解したCD患者のCBFには有意差は認められなかった．また，24hUFCの変化は，寛解患者の皮質下領域における平均CBFの変化と有意な相関を示した（p=0.01）．

RESULTS: After the treatment, 45 patients reached remission. Compared with the NCs, the CD patients before the treatment exhibited significantly reduced CBF in cortical regions, including occipital lobe, parietal lobe, superior/middle/inferior temporal gyrus, superior/middle/inferior frontal gyrus, orbitofrontal cortex, precentral gyrus, middle/posterior cingulate gyrus, and rolandic operculum, as well as significantly increased CBF in subcortical structures, including caudate, pallidum, putamen, limbic lobe, parahippocampal gyrus, hippocampus, thalamus, and amygdala (p < 0.01, false discovery rate corrected). For the remitted patients, the change in CBF before and after the treatment displayed a spatial pattern similar to the difference between the NCs and the CD patients before the treatment, and no significant difference in CBF was observed between the NCs and the remitted CD patients after the treatment. The changes of 24hUFC were significantly correlated with the changes of averaged CBF within the subcortical region in the remitted patients (p = 0.01).

結論:

我々の知見は、CD患者の脳代謝異常は、手術治療後にホルモンレベルが正常に変化すると可逆的であることを示している。

CONCLUSIONS: Our findings demonstrate that the brain metabolic abnormalities of CD patients are reversible when their hormone level changes towards normal after surgery treatment.

Copyright © 2019 Elsevier Inc. All rights reserved.