Morcos M, Fohr B, Tafel J, Pfisterer F, Hamann A, Humpert P, Bode H, Schwenger V, Zeier M, Becker C, Kasperk C, Schilling T, Hammes H P, Bierhaus A, Nawroth P P
University of Heidelberg, Department of Internal Medicine, Endocrinology, Metabolism and Clinical Chemistry Heidelberg, Germany.
Exp Clin Endocrinol Diabetes. 2007 May;115(5):292-7. doi: 10.1055/s-2007-970162.
Central Cushing's syndrome is not always curable by surgery or radiation of the pituitary. Medical treatment is often not possible or effective. Some studies revealed beneficial effects of the PPARgamma (Peroxisome-Proliferator-Activator- Receptor-gamma)-agonist rosiglitazone (RG) in in vitro studies, animal models and short term clinical studies.
of this study was to observe the long-term effects of RG-treatment on cortisol- and ACTH -secretion, clinical outcomes and morphological changes of the pituitary in patients with persistent ACTH-overproduction despite previous operation and radiation.
DESIGN, SETTING AND PATIENTS: 14 patients with persistent central ACTH -production were included and monitored over a period up to 12 months. RG was administered daily and increased to a maximum dosage of 24 mg daily, according to the response of ACTH and cortisol secretion. ACTH and cortisol were measured at least every 4 weeks during RG treatment.
Patients were treated between 4 and 12 months with RG (mean 6.8 months). Compared to baseline, ACTH- and cortisol levels dropped significantly (p<0.01) after 12, 16, 20, 24 and 28 weeks but thereafter rose again during the study period, despite continuous RG- treatment and dose increase up to the maximum dosage. This was paralleled by reocurrence of clinical symptoms. MRI-scans were performed in 6 patients because of persisting visible adenoma, but showed no morphological changes.
RG seems not to be a long-term treatment option for patients with persistent central ACTH-evcess. Though, in order to reduce perioperative complications, short term treatment of patients could be an alternative.
中枢性库欣综合征并非总能通过垂体手术或放疗治愈。药物治疗往往不可行或无效。一些研究在体外研究、动物模型和短期临床研究中揭示了过氧化物酶体增殖物激活受体γ（PPARγ）激动剂罗格列酮（RG）的有益作用。
本研究旨在观察RG治疗对尽管先前已接受手术和放疗但仍持续存在促肾上腺皮质激素（ACTH）过度分泌的患者的皮质醇和ACTH分泌、临床结局及垂体形态学变化的长期影响。
设计、地点和患者：纳入14例持续存在中枢性ACTH分泌的患者，并对其进行长达12个月的监测。根据ACTH和皮质醇分泌的反应，每天给予RG，并将剂量增加至最大每日24 mg。在RG治疗期间，至少每4周测量一次ACTH和皮质醇。
患者接受RG治疗4至12个月（平均6.8个月）。与基线相比，在第12、16、20、24和28周后，ACTH和皮质醇水平显著下降（p<0.01），但在研究期间此后又再次上升，尽管持续进行RG治疗且剂量增加至最大剂量。这与临床症状的复发同时出现。6例患者因持续可见腺瘤进行了磁共振成像（MRI）扫描，但未显示形态学变化。
对于持续存在中枢性ACTH分泌过多的患者，RG似乎不是一种长期治疗选择。不过，为了减少围手术期并发症，对患者进行短期治疗可能是一种替代方法。
