1、甲狀腺功能亢進與肝損害甲狀腺功能亢進癥(甲亢)所引起的肝臟損害在臨床上相當常見。據Gurlek A（1）等觀察，60.5的甲亢病人在確診原發病時被發現至少有一項肝功能異常，而在臺灣進行的一項前瞻性研究（Huang. MJ等）中，這個比例更是高達75.8（2）。本文就甲亢合并肝臟損害作一綜述。甲狀腺激素對肝臟的影響甲狀腺激素和肝臟之間關系密切。血清甲狀腺激素濃度增高，對肝臟功能和膽汁代謝都可產生一定的影響。動物試驗證實(3，4)，甲狀腺激素可使肝臟重量減輕，肝糖原含量下降，氧耗量增加，其增加肝臟氧耗量的作用僅次于對心臟和橫膈膜。血清中過多的甲狀腺激素可顯著降低細胞色素P450、谷胱甘肽水平及谷胱

2、甘肽-S-轉移酶活性，從而改變肝內相關酶的活性（5，6）。T4能使-磷酸甘油脫氫酶(GPD)的活力增強。甲狀腺激素可抑制肝內膽固醇的產生，促進肝內膽固醇從膽道排泄或轉化為膽汁酸，從而使血清膽固醇降低，干擾膽汁酸代謝。此外，甲狀腺激素還能影響膽汁中膽汁酸鹽的組成。研究發現，正常鼠膽汁中的牛磺膽汁酸占膽汁酸的30左右，給予甲狀腺素后，牛磺膽汁酸所占的比例可上升至60-80。甲亢時肝臟的改變甲亢引起的肝臟損害多數呈亞臨床狀態。不過，少數病人也可出現黃疸、腹水、凝血酶原明顯延長、肝硬化等嚴重情況。這一情況多發生于甲亢控制不佳或有心衰、嚴重感染等患者。至于甲亢嚴重度與肝損是否存在正相關，目前還有所爭論。

3、在血生化檢查方面，甲亢肝臟損害患者主要表現為ALT、AST、ALP、-GT和膽紅素升高，血清白蛋白下降（1，2）。其中，以ALP升高最為明顯，ALT次之。白蛋白的下降與基礎代謝率和病程相關。不過，鑒于甲亢患者往往骨代謝旺盛，成骨細胞和破骨細胞活性增加，且體外試驗證實甲狀腺激素有直接使骨吸收的作用，因此，升高的ALP不僅僅來自肝臟，也來自骨骼，它對肝臟的評價意義可能不如ALT。在嚴重肝臟損害時，由于病人血中甲狀腺激素結合蛋白濃度的明顯改變，總T4水平并不能如實反映甲狀腺功能狀態，此時，應監測游離T4和甲狀腺刺激素（TSH）以正確評估甲狀腺功能（7）。甲亢病人肝臟損害的病理改變多種多樣，根據尸檢結

4、果，大體上可分為三大類：1、急性退行性肝損害如顯著脂肪變性，中心性或局灶性肝壞死；2、局部或彌漫性萎縮；3、硬變。這三種改變可同時存在。其中以脂肪浸潤最為常見。Beaver等人的研究表明，甲亢患者出現肝臟脂肪浸潤的比例可高達87.8。在病理切片上，可出現肝細胞氣球樣改變，肝細胞壞死，殘存肝細胞膽色素顆粒沉著，肝小葉中央灶性壞死，結締組織增生，新生毛細血管出現，局部淋巴細胞、單核細胞浸潤，毛細膽管及Kupffer細胞增生等（8）。發病機制肝臟在甲狀腺激素的轉運、代謝、儲存、分泌以及活性的發揮過程中都起著重要的作用，而甲狀腺激素水平對于維持肝臟正常功能及膽汁正常代謝也是不可缺少的。雖然甲亢引起肝臟

5、損害的機制目前仍不是很清楚，但高水平的甲狀腺激素在肝臟損害的發病中所起的作用是毋庸置疑的（7）。甲亢患者高甲狀腺激素（T3、T4）通過以下可能途徑影響肝功能：（1）高基礎代謝率。它使內臟組織耗氧量增加，而與此同時，內臟動脈血流并不增加，造成相對缺氧狀態，尤其是肝小葉中央區域細胞供氧相對不足引起該區域壞死，使谷丙轉氨酶（ALT）升高，這與臨床上甲亢肝損病人肝穿刺活檢結果相一致（8）。（2）由于甲狀腺激素大量分泌，分解代謝亢進，肝糖原耗損，必需氨基酸和維生素消耗過多，造成負氮平衡，蛋白質缺乏，營養不良而使肝細胞變性，造成肝內膽汁瘀積而引起-GT和堿性磷酸酶（ALP）升高。動物試驗證實（12），甲狀

6、腺激素除可引起與劑量有依賴關系的肝糖原含量降低外，還同時引起劑量依賴性的肝胞液糖皮質激素受體（GCR）數目增多，Gurlek等的研究進一步證實，甲亢患者ALP和-GT升高的比例分別高達44.2和14，不過由于甲亢患者骨代謝異常也可引起ALP升高，一定程度上削弱了評價肝損的可靠性（2）。（3）甲狀腺激素直接作用于肝臟，包括抑制肝臟中葡萄糖醛酸基轉移酶，使膽紅素和葡萄糖醛酸結合障礙，進而影響膽紅素從膽汁中排泄，導致血中膽紅素升高（2，7）。隨著免疫學的飛速進展，自身免疫機制在甲亢肝損中的地位日益引起人們的關注。目前認為，甲狀腺疾病與肝臟疾病有著共同的發病基礎，即自身免疫。研究發現，丙肝病毒感染、干

7、擾素治療等都可誘發甲亢（13，14，15）。甲亢病人往往存在特異性免疫調節缺陷，其抑制性T細胞功能減弱，B細胞和巨噬細胞數目增多（16，17）。95年，Cathebras PJ等報道了第1例甲亢引起的肉芽腫性肝炎，后者的進展與甲亢的嚴重程度平行發展，經抗甲狀腺藥物治療后好轉（18）。從分子水平來看，Graves病等甲狀腺疾病和肝炎都存在著細胞因子的異常，它們反應了特定人群對某種疾病的易感性，比如，目前已經證實，HLA-A11和HLA-DR4陽性的病人，甲亢合并肝損的比例可能更高（8,19）。這為將來甲亢肝損易感人群的防治提供了新的思路。甲亢引起肝損及其嚴重程度與甲亢引起的其它并發癥也有密切關系

8、，如心功能不全，休克等。通過病例分析，Fong TL等人（20）發現，甲亢和/或甲亢合并CHF患者都可出現嚴重的肝功能異常，包括重度黃疸、凝血酶原時間延長等。而合并心衰者，出現肝功能異常的比例遠比無并發癥的甲亢病人多。國內資料也證實了這一點（21）。此外，甲亢可加劇其它肝損藥物的毒性作用，包括酒精、氟烷等。這可能與甲亢引起細胞色素P450、谷胱甘肽水平及谷胱甘肽-S-轉移酶活性的顯著下降有關（5，6）。診斷甲亢肝損有時與甲亢合并病毒性肝炎、抗甲狀腺藥物引起的藥物性肝炎不易區分。甲亢合并病毒性肝炎主要有以下幾種情況：（1）病毒性肝炎和甲亢無關，相互獨立存在。這一類情況最為多見；（2）病毒性肝炎引

9、起甲亢。這是因為病毒性肝炎主要通過免疫機制攻擊人體，與甲亢存在著共同的發病基礎，尤其是丙肝病毒感染。流行病學觀察發現（9），慢性丙肝病毒感染的女性患者與甲狀腺自身免疫性疾病的發生率正相關，其中甲狀腺機能亢進占了相當大的比例（7）；（3）干擾素治療的肝炎患者。由于干擾素使機體免疫功能紊亂，即使停藥后，仍有可能出現甲亢癥狀（10，11）。兩者的鑒別要點：1、甲亢合并病毒性肝炎患者多有明確的流行病學史，如輸血等；甲亢所致的肝損多見于未進行正規抗甲狀腺藥物治療或出現各種并發癥的患者。2、甲亢合并病毒性肝炎患者除甲亢的癥狀外，消化系統食欲不振、厭食油膩等肝炎癥狀明顯，而甲亢患者肝損癥狀一般較輕微。3、甲

10、亢合并病毒性肝炎患者血清中肝炎病毒標志物陽性，具有確診價值；同時，這一類患者肝功能血清酶滴度也明顯比甲亢肝損患者高。4、治療上，一為保肝藥物為主，一為抗甲狀腺藥物為主。另一需要鑒別的是甲亢治療過程中出現的藥物性肝損。后者多有明確的抗甲狀腺藥物服用史，一般在治療一個月后發生，往往呈一過性；肝損癥狀也比較輕微，但常合并出現皮膚搔癢、皮疹等過敏現象；血生化檢查除了酶學異常外，還可見嗜酸粒細胞升高；停藥后肝功能可恢復正常，再用再發。由于誤診并非少見，尤其是甲亢肝損與甲亢合并病毒性肝炎這兩種情況，而它們在治療上大不相同，因此，臨床醫生在下診斷前必須對病史作綜合分析。治療與預后由于體內甲狀腺激素分泌過多是

11、肝臟損害的主要原因，因此，有效地控制甲狀腺功能亢進是預防、治療肝損的關鍵。臨床上以內科藥物治療為主。常規治療方案：（1）注意休息，攝入足夠的營養。（2）停用一切肝損藥物。（3）抗甲狀腺藥物。常用者為硫脲類中的甲基及丙基硫氧嘧啶和咪唑類中的他巴唑及甲亢平。丙基硫氧嘧啶是甲亢合并肝臟損害的首選藥物，開始可用100150mg，每8小時一次，一旦病情得到控制，宜逐漸減少劑量，摸索一個合適的維持量。（4）-受體阻滯劑。-受體阻滯劑如心得安能阻抑T4轉化為T3，減少氧耗量與負氮平衡，同時減慢心率，減輕交感神經興奮癥狀，但不影響病程。劑量可用1020mg，一日三次。暫不宜硫脲類藥物治療的病人，可先用此類藥物

12、控制癥狀，待病情控制后再選用其它手段治療。（5）保肝治療。可同時服用維生素B族和維生素C族。（6）由于免疫因素在甲亢肝損的發病也起了重要作用，因此，對于較為嚴重的肝損病人，也可短期應用糖皮質激素治療（18），至于輕中度肝損患者，是否應用糖皮質激素尚有爭論。（6）嚴格控制心衰、感染等并發癥。甲亢肝損患者若診斷及時，治療積極，預后良好。一般在正規抗甲狀腺治療36個月后，肝功能全部恢復正常。Arch Intern Med. 1984 Sep;144(9):1764-5. PTU致彌漫的間質性肺炎：咳嗽、勞力性呼吸困難、低氧血癥發生于一Graves'病患者PTU（300 mg/day）治療6月

13、后和另一Graves'病患者PTU（300 mg/day）治療3周后，胸片和支氣管鏡下肺活檢顯示彌漫的間質性肺炎。植物血凝素轉化淋巴細胞受PTU高度刺激。停用PTU、予以強的松龍治療后癥狀和體征得到改善。Propylthiouracil-induced diffuse interstitial pneumonitis.Miyazono K, Okazaki T, Uchida S, Totsuka Y, Matsumoto T, Ogata E, Terakawa K, Kurihara N, Takeda T.1. 1947年，首次報道PTU的肝毒性副作用。Livingston HJ

14、, Livingston SF. 1947 Agranulocytosis and hepatocellular jaundice. JAMA. 135:422425. 2 Characteristics of patients with propylthiouracil-associated hepatotoxicity All cases (n = 28)Survivors (n = 21)Fatalities (n = 7)Age, yr (mean± SD)27.9 ± 17.124.7 ± 15.537.3 ± 19.2Females/male

15、s (no.)25/319/24/1Propylthiouracil dose at presentation with hepatotoxicity, mg/day (mean± SD)426 ± 199424 ± 200433 ± 216Months of continuous propylthiouracil therapy before hepatotoxicity (mean± SD)3.6 ± 3.53.7 ± 3.23.6 ± 4.5Baseline liver function tests, no.

16、 of cases (%)Normal2 (7.1)2 (9.5)0 (0)Abnormal5 (17.9)4 (19.0)1 (14.3)Not reported21 (75.0)15 (71.4)6 (85.7)Table 4. Prevalence of thyroid function test abnormalities and management of hyperthyroidism at presentation with propylthiouracil hepatotoxicity Survivors (n = 22)Fatalities (n = 7)Thyroid fu

17、nction tests, no. of cases (%)Hyperthyroid5 (19)2 (28.6)Normal8 (38.1)1 (14.3)Hypothyroid1 (4.8)0 (0)Not reported8 (38.1)4 (57.1)Treatment of hyperthyroidism,1 no. of cases (%)Radioactive iodine12 (54.5)20 (0)Propranolol10 (45.5)4 (57.1)Methimazole3 (13.6)0 (0)Oral iodide4 (18.2)1 (14.3)Thyroidectom

18、y1 (4.5)0 (0)Not reported7 (31.8)3 (42.9)1 Patients may have received more than one form of therapy. 2 P < 0.05 compared to fatalities, by Fishers exact test. No patient who died received 131I. The timing of 131I ranged from 115 weeks (mean, 32 ± 8 days) after presentation with hepatotoxicit

19、y. Ten of the 12 patients who received 131I therapy were treated before the hepatic function test abnormalities resolved.據估計ATD相關的肝毒性發生率小于0.5%；PTU相關的肝毒性發生于各個年齡；女性居多；發生肝毒性的PTU劑量與療程范圍甚廣；肝活檢示非特異的肝細胞壞死；ATD致肝毒性的機制尚不明了，部分是由于機體對PTU產生免疫反應。在暴發性肝功能衰竭中，一些早期預后因素與生存率低（<20%）有關，其包括病人年齡(<11 和 >40 yr)、腦病發生前

20、黃疸延續時間(>7 days)、血清膽紅素濃度(>300 µmol/L)、凝血酶原時間(>50 s)。在對PTU所致肝毒性病人進行嚴密的臨床和實驗室觀察的基礎上（因為停用PTU后肝功能衰竭仍可發展），應考慮肝移植。腦病、低凝血酶原血癥、肝腎綜合征對肝移植不利。血漿置換、用血流灌注法血透可有效地糾正凝血障礙和腦病，為恢復肝功能或進行肝移植創造時機。因TT4受甲狀腺激素結合蛋白、血清膽紅素（降低T4與甲狀腺激素結合蛋白的親和）、甲狀腺功能正常性病變綜合征的影響，所以檢測FT4才能真正反映患者甲狀腺功能狀況。病人接受131I 治療比未接受治療者較少發生嚴重的肝毒性。治療應

21、在做腹部CT（如果需要碘造影劑）或因甲狀腺毒癥需碘化物治療前進行。碘化物可在131I治療1周后服。心得安可用于控制甲亢癥狀；肝酶正常后也可使用MMI。肝毒性出現后可單獨使用碘化物。在多數病人，114 mg碘化物在 714天內對甲狀腺激素的產生最大的抑制，作用持續150天。但通常與ATD合用，碘化物也可加重甲狀腺毒癥狀況。繼往肝功能正常的甲亢病人中，高達72%者至少伴有1個肝酶指標的升高。以AKP升高最常見，轉氨酶升高是由于甲狀腺毒癥導致的肝臟的氧耗增加，而肝血流代償不足。已報道MMI所致肝毒性21例，死亡3例（14%），死亡率與PTU比較無顯著差異。MMI所致肝毒性患者的肝活檢更多表現為膽汁淤

22、積。Table 5. Summary of recommendations for management of propylthiouracil hepatotoxicity 1. 盡管肝酶研究無法預測哪些病人將發生肝毒性，但肝酶基值的測定可作為治療過程中發生肝臟疾病的參考。Although liver enzyme studies may not predict which patients will develop hepatotoxicity, baseline studies may serve as a reference value if signs of liver diseas

23、e develop during the course of therapy.2. 治療過程中出現明顯的肝酶異常時，需停用PTU，并尋找引起肝并的潛在因素。Significant liver enzyme abnormalities detected during the course of therapy require prompt discontinuation of propylthiouracil as well as a search for any other potential sources of liver disease.3. 懷疑有肝毒性的病人需密切隨訪，因為肝功能障礙

24、在停用PTU后仍有進展。Patients with suspected hepatotoxicity require close clinical follow-up because liver dysfunction can progress despite discontinuation of propylthiouracil.4. 對是否需要肝移植的早期認識可能提高生存。Early recognition of the need for liver transplantation may improve survival.5. 甲狀腺狀態的判斷需結合臨床檢查和FT4水平，因為高膽紅素血癥

25、可負向干擾TT4水平。Thyroidal status must be determined by a combination of clinical examination and free T4 levels because hyperbilirubinemia can adversely affect the interpretation of total T4 levels.6. 進一步用放射性碘治療甲亢，隨后配以碘化物可能緩解甲亢的惡化。Prompt treatment of the underlying thyroid disease with radioactive iodine

26、 followed by iodide may diminish the chance of clinical deterioration from persistent hyperthyroidism.7. 即使肝酶恢復正常仍不能再次用PTU，因為它的肝毒性存在自身免疫的本性。Propylthiouracil should not be reinstituted even after the resolution of liver enzyme abnormalities due to the possible autoimmune nature of its hepatotoxicity.

27、甲亢相關的肝功能基值的異常沒有必要成為運用ATD的禁忌癥，現有的資料無法證實肝功能基值異常的病人更易發生PTU所致的肝毒性。由于自身免疫因素參與PTU所致的肝毒性、肝毒性情況在再次用PTU后又出現，所以肝毒性治療后和肝移植后仍不能用PTU。fFifty Years of Experience with Propylthiouracil-Associated Hepatotoxicity: What Have We Learned?1 Katherine V. Williams, Sunil Nayak, Dorothy Becker, Jorge Reyes and Lynn A. Burme

28、isterThe Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 6 1727-173332.Toxic hepatitis (primarily with propylthiouracil) and cholestatic jaundice (primarily with methimazole) are fortunately uncommon.150 Toxic hepatitis can be severe or fatal, but the incidence of serious liver compl

29、ications is so low that routine monitoring of function tests has not been advised.151,152 Liver transplantation has been used with success in several patients 152.1.IFN-a induces thyroid dysfunction in 3 to 14% of all treated patients with chronic hepatitis C, leading to hypothyroidism, hyperthyroid

30、ism, or thyroiditis. In a few patients, thyroid disease will develop in the absence of antithyroid antibodies, a scenario that suggests a nonimmune-mediated mechanism.: Am J Gastroenterol. 2001 Jan;96(1):165-9. Related Articles, Links   The incidence and clinical characteristics of symptomatic

31、propylthiouracil-induced hepatic injury in patients with hyperthyroidism: a single-center retrospective study.Kim HJ, Kim BH, Han YS, Yang I, Kim KJ, Dong SH, Kim HJ, Chang YW, Lee JI, Chang R.Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea.OBJECTIVES: Althoug

32、h symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course. METHODS: Medical records of 912 hyperthyroid patient

33、s who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function

34、 tests (LFT) without other causes. RESULTS: Four hundred ninety-seven patients (age 42.6 +/- 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 +/- 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundi

35、ce and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 +/- 288 micromol/L, 143 +/- 111 U/L, and 265 +/- 81 U/L; normal, < 117 U/L). The type of hepatic injury was cholestatic

36、 in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (

37、72.8 +/- 46.4) days after the PTU withdrawal. CONCLUSIONS: Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its developme

38、nt, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.70: Endocr Pract. 2000 Sep-Oct;6(5):367-9. Related Articles, Links   Abnormal results of liver function tests in patients with Graves' disease.Biscoveanu M, Hasinski S.Division

39、of Endocrinology and Metabolism, Department of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania 19102, USA.OBJECTIVE: To determine the frequency of liver dysfunction in patients with hyperthyroidism. METHODS: We analyzed the clinical records of 30 consecutive patients with Graves&

40、#39; disease to identify the spectrum of abnormal results of liver function tests. The values for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma -glutamyltransferase (GGT), and total bilirubin were examined. RESULTS: The frequencies of increased le

41、vels of AP, AST, ALT, GGT, and bilirubin in the current study group were similar to but somewhat lower than those reported in previous studies. Of the 30 study patients, 11 (37%) had at least one abnormal result of a liver function test. All 30 patients in the study had determinations of AP (not fra

42、ctionated), of which 10 values (33%) were above normal (range, 124 to 283 U/L). Of the 30 patients who had determinations of AST, 5 (17%) had increased values that ranged from 36 to 71 U/L. Six of the 23 patients (26%) with determinations of ALT had increased values that ranged from 45 to 157 U/L. O

43、f the 25 patients who had measurements of GGT, 6 had above normal results (range, 69 to 331 U/L). In addition, 2 of the 24 patients (8%) with determinations of total bilirubin had increased levels. CONCLUSION: These findings indicate that abnormal results of liver function tests are common in patien

44、ts with hyperthyroidism and make the diagnosis of concomitant, unrelated liver disease difficult until the euthyroid state has been established.: J R Soc Health. 1999 Jun;119(2):117-20. Related Articles, Links Lessons to be learned: a case study approach: severe hyponatraemia induced by primary hypo

45、thyroidism and associated with possible increased hepatic sensitivity to thyroxine replacement.Olukoga A, Horsman G, Stewart F.Department of Clinical Biochemistry, Hope Hospital, Salford, Manchester. AOlukogaThe case is presented of a 74 year-old woman who was admitted with severe hypo-osmolar hypon

46、atraemia associated with inappropriately raised urinary osmolality, and who was subsequently discovered to have primary hypothyroidism. A normal serum sodium concentration was restored by means of judicious fluid restriction and thyroid hormone replacement. Low dose thyroxine therapy led to rapid bu

47、t modest increases in the serum activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP); both returned to normal over a period of three weeks. These sub-clinical enzyme changes may indicate tissue 'hyperthyroidism' and in this case, the fact that they occurred acutely at

48、only low doses of thyroxine possibly suggests an increased hepatic sensitivity to the hormone.104: Scand J Gastroenterol. 1999 Jun;34(6):618-22. Related Articles, Links Liver volume, portal vein flow, and clearance of indocyanine green and antipyrine in hyperthyroidism before and after antithyroid t

49、reatment.Andersen V, Sonne J, Court-Payen M, Sletting S, Prip A, Molholm Hansen J.Dept. of Endocrinology and Internal Medicine, Herlev Hospital, Denmark.BACKGROUND: The aim of the study was to examine liver volume, portal vein flow, and indocyanine green (ICG) and antipyrine clearance in hyperthyroi

50、dism before and after antithyroid drug treatment. METHODS: Liver volume and blood flow in the portal vein were investigated in nine fasting patients with hyperthyroidism by means of computed tomography scan and Doppler ultrasound, respectively. ICG clearance was estimated by bolus injection of ICG (

51、0.5 mg/kg body weight) and antipyrine clearance with a one-sample technique. All patients were investigated before and after 3 months of antithyroid treatment, when euthyroidism had been achieved. The Wilcoxon matched-pairs test was used for statistical analysis. RESULTS: The median liver volume inc

52、reased by 238 (155-289) ml (median, 95% confidence interval), corresponding to 19%, and the weight by 5.0 (0.0-8.0) kg (8%), and the antipyrine clearance decreased by 8 (3.1-34.4) ml/min (16%). These changes were all significant (P < 0.05). The relation between liver volume and body weight increa

53、sed from 19.9 (16.5-23.7) ml/kg to 21.4 (17.1-21.9) ml/kg (P = 0.11). The liver blood flow as estimated by ICG clearance and Doppler ultrasound was not altered significantly after the treatment period (P = 0.07 and 0.77, respectively). CONCLUSIONS: The liver volume increased by 19% in nine hyperthyr

54、oid patients during treatment with antithyroids. Antipyrine clearance was reduced by 16%, whereas liver blood flow, as estimated by ICG clearance and Doppler ultrasound examination of portal vein flow, was not significantly altered. A differential regulation of liver volume and oxidative metabolic c

55、apacity in hyperthyroidism was seen.參考文獻：1: Gurlek A, Cobankara V, Bayraktar M. Liver tests in hyperthyroidism: effect of antithyroid therapy. J Clin Gastroenterol 1997 Apr;24(3):180-32: Huang MJ, Li KL, Wei JS, Wu SS, Fan KD, Liaw YF. Sequential liver and bone biochemical changes in hyperthyroidism

56、: prospective controlled follow-up study. Am J Gastroenterol 1994 Jul;89(7):1071-63: Sheridan P . Thyroid hormones and the liver. Clin Gastroenterol 1983 Sep;12(3):797-8184: Babb RR . Associations between diseases of the thyroid and the liver. Am J Gastroenterol 1984 May;79(5):421-35: Smith AC, Berm

57、an ML, James RC, Harbison RD. Characterization of hyperthyroidism enhancement of halothane-induced hepatotoxicity. Biochem Pharmacol 1983 Dec 1;32(23):3531-96: Videla LA, Smok G, Troncoso P, Simon KA, Junqueira VB, Fernandez V. Influence of hyperthyroidism on lindane-induced hepatotoxicity in the ra

58、t. Biochem Pharmacol 1995 Nov 9;50(10):1557-657: Huang MJ, Liaw YF. Clinical associations between thyroid and liver diseases. J Gastroenterol Hepatol 1995 May-Jun;10(3):344-508: Inoue K, Okajima T, Tanaka E, Ando B, Takeshita M, Masuda A, Yamamoto M, Sakai K. A case of Graves' disease associated

59、 with autoimmune hepatitis and mixed connective tissue disease. Endocr J 1999 Feb;46(1):173-79. Huang MJ, Tsai SL, Huang BY, Sheen IS, Yeh CT, Liaw YF. Prevalence and significance of thyroid autoantibodies in patients with chronic hepatitis C virus infection: a prospective controlled study. Clin Endocrinol (Oxf) 1999 Apr;50(4):503-910: W