Seehofer Daniel, Steinmueller Thomas, Graef Klaus-Juergen, Rayes Nada, Wiegand Wolfgang, Tullius Stefan G, Settmacher Utz, Neuhaus Peter
Department of General-, Visceral- and Transplant Surgery, Charité Campus Virchow, Humboldt University of Berlin.
Ann Transplant. 2002;7(2):32-7.
Hormonal alterations caused by chronic liver disease are well described. In contrast, the reversibility of peripheral hormonal changes after orthotopic liver transplantation (OLT) has only partially been analyzed since the establishment of OLT as treatment of chronic hepatic failure. In addition it is not finally verified if chronic liver failure and especially hepatic encephalopathy also affect pituitary function. We therefore performed extensive endocrine studies including a global pituitary stimulation test before and after liver transplantation.
22 patients with chronic alcoholic and non alcoholic liver failure were included in this prospective study. Basal hormone values (ACTH, cortisol, FSH, GH, IGF-I, LH, oestradiol, PRL, thyroid hormones and testosterone) were measured before and up to 5 years after OLT. Furthermore all patients underwent pituitary function tests with application of GRF, TRH, GnRH, and CRF before, 3 weeks and 3 months after OLT.
Estradiol, LH and FSH increased significantly in postmenopausal and only slightly in premenopausal female patients after OLT. Total testosterone revealed no marked changes and was normal before and up to five years after OLT in male patients. After stimulation with GnRH the LH response in females and the FSH response in males was significantly higher three months after OLT than pretransplant. LH response in males and FSH response in females was only slightly higher after OLT. Peripheral IGF-I was low and growth hormone was elevated in all patients prior OLT. Growth hormone declined significantly three months afterwards. The response to GRF was highest prior OLT and decreased afterwards. Prolactin values were normal prior and post OLT. After stimulation with TRH prolactin values in male patients were significantly higher before OLT than afterwards.
In the observed relatively small number of patients gross pituitary function in chronic liver failure remained intact, whereas slight alterations in several axis were found. These pituitary alterations are presumably only partially caused by feedback mechanisms. Both a normalisation of peripheral endocrine parameters and pituitary function were achieved by OLT despite significant alterations pretransplant.
慢性肝病所致的激素改变已有充分描述。相比之下，自原位肝移植（OLT）作为慢性肝衰竭的治疗方法确立以来，外周激素变化在OLT后的可逆性仅得到部分分析。此外，慢性肝衰竭尤其是肝性脑病是否也影响垂体功能尚未得到最终证实。因此，我们进行了广泛的内分泌研究，包括肝移植前后的全面垂体刺激试验。
本前瞻性研究纳入了22例慢性酒精性和非酒精性肝衰竭患者。在OLT前及OLT后长达5年的时间里测量基础激素值（促肾上腺皮质激素、皮质醇、促卵泡激素、生长激素、胰岛素样生长因子-I、促黄体生成素、雌二醇、催乳素、甲状腺激素和睾酮）。此外，所有患者在OLT前、OLT后3周和3个月接受了应用生长激素释放因子（GRF）、促甲状腺激素释放激素（TRH）、促性腺激素释放激素（GnRH）和促肾上腺皮质激素释放因子（CRF）的垂体功能测试。
绝经后女性患者OLT后雌二醇、促黄体生成素和促卵泡激素显著升高，绝经前女性患者仅略有升高。男性患者总睾酮无明显变化，OLT前及OLT后长达5年均正常。用GnRH刺激后，女性的促黄体生成素反应和男性的促卵泡激素反应在OLT后3个月显著高于移植前。OLT后男性的促黄体生成素反应和女性的促卵泡激素反应仅略有升高。所有患者OLT前外周胰岛素样生长因子-I水平低而生长激素水平升高。3个月后生长激素显著下降。对GRF的反应在OLT前最高，之后下降。OLT前后催乳素值均正常。用TRH刺激后，男性患者OLT前的催乳素值显著高于之后。
在观察到的相对少数患者中，慢性肝衰竭时垂体的总体功能保持完整，而在几个轴上发现了轻微改变。这些垂体改变可能仅部分由反馈机制引起。尽管移植前有显著改变，但OLT实现了外周内分泌参数和垂体功能的正常化。
