1、時間：二O二一年七月二十九日甲狀腺功能亢進與肝損害之馬矢奏春創(chuàng)作時間：二O二一年七月二十九日甲狀腺功能亢進癥（甲亢）所引起的肝臟損害在臨床上相當罕 見.據(jù)Gurlek A （1）等觀察,60.5 %的甲亢病人在確診原發(fā)病時被 發(fā)現(xiàn)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(guān)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發(fā)生一定的影響.植物試驗證實（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，具增加肝臟氧耗量的作

2、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甘肽-S-轉(zhuǎn)移酶活性，從而改變肝內(nèi)相關(guān)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(nèi)膽固醇的發(fā)生，增進肝內(nèi)膽固醇從膽道排泄或轉(zhuǎn)化為膽汁酸，從而使血清膽固醇降低干擾膽汁酸代謝.另外，甲狀腺激素還能影響膽汁中膽汁酸鹽的組 成.研究發(fā)現(xiàn)，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大都呈亞臨床狀態(tài).不外，少數(shù)病人也可呈現(xiàn)黃疸、腹水、凝血酶原明顯延長、肝硬化等嚴重情況.這

3、一情況多發(fā)生于甲亢控制欠安或有心衰、嚴重感染等患者.至于甲亢嚴重度與肝損是否存在正相關(guān)，目前還有所爭論.在血生化檢查方面，甲亢肝臟損害患者主要暗示為 ALT、AST ALR 丫 -GT和膽紅素升高，血清白卵白下降（1,2 ）.其中，以ALP 升高最為明顯，ALT次之.白卵白的下降與基礎(chǔ)代謝率和病程相關(guān).不外，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不單僅來自肝臟，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(jié)合卵白濃度 的明顯改變，總T4水平其實不能如實反映甲狀腺功能狀態(tài)

4、，此時，應監(jiān)測游離T4和甲狀腺安慰素（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(jù)尸檢結(jié)果，年夜 體上可分為三年夜類：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罕見.Beaver等人的研究標明，甲 亢患者呈現(xiàn)肝臟脂肪浸潤的比例可高達 87.8 % .在病理切片上，可 呈現(xiàn)肝細胞氣球樣改變，肝細胞壞死，殘余肝細胞膽色素顆粒冷靜， 肝小葉中央灶性壞死，結(jié)締組織增生，新生毛細血管呈現(xiàn)，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(fā)病機制肝臟在甲狀腺激

5、素的轉(zhuǎn)運、代謝、貯存、分泌以及活性的發(fā)揮過程中都起著重要的作用，而甲狀腺激素水平對維持肝臟正常功能 及膽汁正常代謝也是不成缺少的.雖然甲亢引起肝臟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(fā)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(chǔ)代謝率.它使內(nèi)臟組織耗氧 量增加，而與此同時，內(nèi)臟動脈血流其實不增加，造成相對缺氧狀態(tài) 尤其是肝小葉中央?yún)^(qū)域細胞供氧相對缺乏引起該區(qū)域壞死，使谷丙轉(zhuǎn)氨酶（ALT）升高，這與臨床上甲亢肝損病人肝穿刺活檢結(jié)果相一 致（8） . （2）由于甲狀腺激素年夜量分泌，分解代謝亢進，肝糖原 耗

6、損，必需氨基酸和維生素消耗過多，造成負氮平衡，卵白質(zhì)缺乏，營養(yǎng)不良而使肝細胞變性，造成肝內(nèi)膽汁瘀積而引起 丫 -GT和堿性 磷酸酶（AL?升高.植物試驗證實（12）,甲狀腺激素除可引起與 劑量有依賴關(guān)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(zhì)激素受體（GCR數(shù)目增多,Gurlek等的研究進一步證 實，甲亢患者ALP和丫-GT升高的比例分別高達 44.2 %和14%,不 外由于甲亢患者骨代謝異常也可引起ALP升高，一定水平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(zhuǎn)移酶，使膽紅素和葡萄糖醛酸結(jié)合障礙，進而影響膽紅素從膽汁中排泄，

7、招致血中膽紅素升高（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位置日 益引起人們的關(guān)注.目前認為，甲狀腺疾病與肝臟疾病有著共同的 發(fā)病基礎(chǔ)，即自身免疫.研究發(fā)現(xiàn)，丙肝病毒感染、干擾素治療等都可誘發(fā)甲亢(13,14,15 ).甲亢病人往往存在特異性免疫調(diào)節(jié)缺陷 ， 其抑制性T細胞功能減弱，B細胞和巨噬細胞數(shù)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水平平行發(fā)展，經(jīng)抗甲狀腺藥物治療后好轉(zhuǎn)(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

8、性，比如，目前已經(jīng)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水平與甲亢引起的其它并發(fā)癥也有密 切關(guān)系，如心功能不全，休克等.通過病例分析，F(xiàn)ong TL等人(20) 發(fā)現(xiàn)，甲亢和/或甲亢合并CHF患者都可呈現(xiàn)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，呈現(xiàn)肝功能異常 的比例遠比無并發(fā)癥的甲亢病人多.國內(nèi)資料也證實了這一點(21).另外，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(zhuǎn)

9、 移酶活性的顯著下降有關(guān)(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容易區(qū)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(guān)，相互自力存在.這一類情況最為多見；(2)病毒性肝炎引起甲亢.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(fā)病基礎(chǔ)，尤其是丙肝病毒感染.流 行病學觀察發(fā)現(xiàn)(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(fā)生率正相關(guān)，其中甲狀腺機能亢進占了相當年夜的 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，仍有可能呈現(xiàn)甲亢癥狀 (10,11 ),兩者的鑒別

10、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(guī)抗甲狀腺藥物治療或呈現(xiàn)各 種并發(fā)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(tǒng)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、甲亢合并病毒性肝炎患者血清中肝炎病毒標識表記 標幟物陽性，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.另一需要鑒另外是甲亢治療過程中呈現(xiàn)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(fā)生，往往呈一過性；肝損癥狀也比力輕微，但常合并呈現(xiàn)皮膚搔癢、

11、皮疹等過敏現(xiàn)象；血生化檢查除酶學異常外，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(fā).由于誤診其實不是少見，尤其是甲亢肝損與甲亢合并病毒性肝 炎這兩種情況，而它們在治療上年夜不相同，因此，臨床醫(yī)生在下診 斷前必需對病史作綜合分析.治療與預后由于體內(nèi)甲狀腺激素分泌過多是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(guān)鍵.臨床上以內(nèi)科藥物治療為主.慣例治療方案：（1）注意休息，攝入足夠的營養(yǎng). （2）停用一切肝損藥物.（3）抗甲狀腺藥物.經(jīng)常使用者為硫月尿類 中的甲基及丙基硫氧喀咤和咪口坐類中的他巴口坐及甲亢平.丙基硫氧喀咤是甲亢合并肝臟損害的首選藥物，開始可用10

12、0150mg，每8小時一次，一旦病情獲得控制，宜逐漸減少劑量，摸索一個合適的維持 量.（4） （3-受體阻滯劑.B -受體阻滯劑如心得安能阻抑T4轉(zhuǎn)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(jīng)興奮癥狀 但不影響病程.劑量可用1020mg, 一日三次.暫不宜硫月尿類藥物治 療的病人，可先用此類藥物控制癥狀，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(fā)病也起了重要作用，因此，對較為嚴重的肝損病人，也可短時間應用糖皮質(zhì)激素治療（18）,至于輕中度肝損患者，是否應用糖皮質(zhì)激素尚有爭論.（6）嚴格控制心衰、感 染等

13、并發(fā)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(guī)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(zhì)性肺炎：咳嗽、勞力性呼吸困難、低氧血癥發(fā)生于一 Graves'病患者PTU （300 mg/day）治療6月后和 另一 Graves'病患者PTU （300 mg/day ）治療3周后,胸片和 時間：二O二一年七月二十九日支氣管鏡下肺活檢顯示彌漫的間質(zhì)性肺炎 .植物血凝素轉(zhuǎn)化 淋巴細胞受PTU高度安慰.停用PTU予以強的松龍治療后癥 狀和體征獲得改善.Propylthiou

14、racil-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, Livingston SF. 1947 Agranulocytosis and hepatocellular jaundice. JAMA. 135:422- 425.2 Characteristics of patients w

15、ithpropylthiouracil-associated hepatotoxicityAll cases (nSurvivors (n Fatalities (n=28)= 21)= 7)27.9 17.124.7 15.537.3 19.225/319/24/1426 ±199424 立00433 蟲163.6 3.53.7 3.23.6 4.52 (7.1)2 (9.5)0 (0)5 (17.9)4 (19.0)1 (14.3)21 (75.0)15 (71.4)6 (85.7)Age, yr (mean S D)Females/males (no.)Propylthiour

16、acil dose at presentation with hepatotoxicity, mg/day (mean SD) ±Months of continuous propylthiouracil therapy before hepatotoxicity (mean SD) ±Baseline liver function tests, no. of cases (%)NormalAbnormalNot reporteds exact te st.Table 4. Prevalence of thyroid function test abnormalities

17、and management of hyperthyroidism at presentation with propylthiouracil hepatotoxicitySurvivors (n = 22)Fatalities (n = 7)Thyroid function 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, Patients

18、may have received more than one form of therapy.2P < 0.05 compared to fatalities, by Fisher no. of cases (%)Radioactive iodine12 (54.5)No patient who died received 131I. The timing of 131Iranged from 1 - 15 weeks (mean, 32 士 8 days) afterpresentation with hepatotoxicity. Ten of the 12 patients wh

19、o received 131I0 (0)Propranolol10 (45.5)4 (57.1)Methimazole3 (13.6)0 (0)Oral iodide4 (18.2)1 (14.3)Thyroidectomy1 (4.5)0 (0)Not reported7 (31.8)3 (42.9)therapy were treated before the hepatic function test abnormalitiesresolved.據(jù)估計ATD相關(guān)的肝毒性發(fā)生率小于 0.5%; PTU相關(guān)的肝毒性發(fā)生 于各個年齡；女性居多；發(fā)生肝毒性的PTU劑量與療程范圍甚廣；肝活檢示非特

20、異的肝細胞壞死；ATD致肝毒性的機制尚不明了 ，部份是由于機體對PTU發(fā)生免疫反應.在迸發(fā)性肝功能衰竭中，一些早期預后因素與生存率低（20%有 關(guān)，其包括病人年齡（11和40 yr）、腦病發(fā)生前黃疸延續(xù)時間 （7 days）、血清膽紅素濃度（300"mol/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(chǔ)上（因為停用PTU后肝功能衰竭仍可發(fā)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晦氣.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 締造時機.因TT4受甲狀腺激素結(jié)合卵白、血清膽紅素（降低 T

21、4與甲狀腺激 素結(jié)合卵白的親和）、甲狀腺功能正常性病變綜合征的影響，所以檢測FT4才華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(fā)生嚴重的肝毒性.治療應在做腹部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.肝毒性呈現(xiàn)后可獨自使用碘化物.在大都病人,114 mg碘化物在7- 14天內(nèi)對甲狀腺激素的發(fā)生最年夜的抑制，作用繼續(xù)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%者至少陪伴1個肝酶指標 的升高.以AKP升高最罕見，轉(zhuǎn)

22、氨酶升高是由于甲狀腺毒癥招致的 肝臟的氧耗增加，而肝血流代償缺乏.已報道MMI所致肝毒性21例，死亡3例（14% ,死亡率與PTU比力 無顯著不同.MMI所致肝毒性患者的肝活檢更多暗示為膽汁淤積.Table 5. Summary of recommendations for management of propylthiouracil hepatotoxicity1 .盡管肝酶研究無法預測哪些病人將發(fā)生肝毒性，但肝酶基值的測定可作為治療過程中發(fā)生月干臟疾病的參考 . Although liver enzyme studies may not predict which patients wil

23、l develop hepatotoxicity, baseline studies may serve as a reference value if signs of liver disease develop during the course of therapy.2 .治療過程中呈現(xiàn)明顯的肝酶異常時，需停用PTU,并尋找引起肝并的潛在因 H .Significant liver enzyme abnormalities detected during the course of therapy require prompt discontinuation of propylthiou

24、racil 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 re

25、cognition of the need for livertransplantation may improve survival.5 .甲狀腺狀態(tài)的判斷需結(jié)合臨床檢查和FT4水平，因為高膽紅素血癥可負向干擾 TT4水平.Thyroidal status must be determined by a combination of clinical examination and free T 4 levels because hyperbilirubinemia can adversely affect the interpretation of total T 4 levels.6 .

26、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 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賦 性.Propylthiouracil should not be reinstituted even after

27、 the resolution of liver enzyme abnormalities due to the possible autoimmune nature of its hepatotoxicity.甲亢相關(guān)的肝功能基值的異常沒有需要成為運用ATD的禁忌癥，現(xiàn)有的資料無法證實肝功能基值異常的病人更易發(fā)生PTU所致的肝毒性.由于自身免疫因素介入PTU所致的肝毒性、肝毒性情況在再次用PTU后又呈現(xiàn)，所以肝毒性治療后和肝移植后仍不能用PTU.fFifty Years of Experience with Propylthiouracil-AssociatedHepatotoxicity:

28、 What Have We Learned?1Katherine V. Williams, Sunil Nayak, Dorothy Becker, JorgeReyes and Lynn A. BurmeisterThe Journal of Clinical Endocrinology & Metabolism Vol. 82,No. 6 1727-17333.Toxic hepatitis (primarily with propylthiouracil) and cholestatic jaundice (primarily with methimazole) are fort

29、unately uncommon.150 Toxic hepatitis can be severe or fatal, but the incidence of serious liver complications 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 dysfunctioni

30、n 3 to 14%of all treatedpatients with chronic hepatitis C, leading to hypothyroidism, hyperthyroidism, 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)

31、:165-9.Related Articles,Links國 The incidence and clinical characteristics of symptomatic propylthiouracil-induced hepatic injury in patients with hyperthyroidism:a single-centerretrospective study.Kim HJ, Kim BH, Han YS, Yang I, Kim KJ, Dong SH, Kim HJ, Chang YW, Lee JI, Chang R.Department of Intern

32、al Medicine, Kyung Hee University College of Medicine,搜索引擎優(yōu)化 ul, Korea.OBJECTIVES: Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. Wetried to evaluate its incidence in a si

33、ngle center and its clinical course.METHODS: Medical records of 912 hyperthyroid patients 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 developme

34、nt of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function 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

35、yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALPincreased in five, four, and six patients, respectively (293 +/-288 micromol/L, 143 +/- 111 U/L, and

36、265 +/- 81 U/L;normal, < 117 U/L).The type of hepatic injurywascholestatic in three,hepatocellular in one, and mixedin 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 w

37、ithout hepatic injury. LFT normalized in all patients between 16 and 145 (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

38、drug is withdrawn. However, it may be difficult to predict its development, 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,LinksaAbnormal results of liver function tests in patie

39、nts with Graves' disease.Biscoveanu M, Hasinski S.Division of Endocrinology and Metabolism, Department of Medicine, HahnemannUniversity Hospital, Philadelphia, 時間：二O二一年七月二十九日Pennsylvania 19102, USA.OBJECTIVE: To determine the frequency of liver dysfunction in patients with hyperthyroidism. METHO

40、DS: We analyzed the clinical records of 30 consecutive patients with Graves' disease to identify thespectrumof abnormal results of liver function tests. The values for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma -glutamyltransferase (GGT), a

41、nd total bilirubin were examined. RESULTS: The frequencies of increased levels 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 fun

42、ction test. All 30 patients in the study had determinations of AP (not fractionated), 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 de

43、terminations of ALT had increased values that ranged from 45 to 157 U/L. Of the25 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 in

44、dicate that abnormal results of liver function tests are common in patients 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,LinksLessons to be learned

45、: a case study approach: severe hyponatraemia induced by primary hypothyroidism and associated with possible increased hepatic sensitivity to thyroxine WordStrment.Olukoga A, Horsman G, Stewart F.Department of Clinical Biochemistry, Hope Hospital, Salford, Manchester. AOlukogaThe case is presented o

46、f a 74 year-old woman who was admitted with severe hypo-osmolar hyponatraemia 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 th

47、yroid hormone WordStrment. Low dose thyroxine therapy led to rapid but 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 'hyperthyr

48、oidism' and in this case, the fact that they occurred acutely at 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,LinksLiver volume, portal vein flow, and clearance of indocyanine gree

49、n and antipyrine in hyperthyroidism before and after antithyroid treatment.Andersen V, Sonne J, Court-Payen M, Sletting S, Prip A, Molholm Hansen J.Dept. of Endocrinology and Internal Medicine, HerlevHospital, Denmark.BACKGROUND: The aim of the study was to examine livervolume, portal vein flow, and

50、 indocyanine green (ICG) and antipyrine clearance in hyperthyroidism before and after antithyroid drug treatment. METHODSLiver volume and blood flow in the portal vein were investigated in nine fasting patients with hyperthyroidism bymeans ofcomputed tomography scan and Doppler ultrasound, respectiv

51、ely. ICG clearance was estimated by bolus injection of ICG (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 fo

52、r statistical analysis. RESULTSThe median liver volume increased 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)

53、. The relation between liver volume and body weight increased 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). CONCLU

54、SIONS: The liver volume increased by 19% in nine hyperthyroid 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 differe

55、ntial regulation of liver volume and oxidative metabolic capacity in hyperthyroidism was seen.參考文獻：1: Gurlek A, Cobankara V, Bayraktar M. Liver tests in hyperthyroidism:effect of antithyroid therapy.J ClinGastroenterol 1997 Apr;24(3):180-32: Huang MJ, Li KL, Wei JS, Wu SS, Fan KD, Liaw YF. Sequentia

56、l liver and bone biochemical changes in hyperthyroidism: 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

57、Gastroenterol 1984 May;79(5):421-35: Smith AC, Berman ML, James RC, Harbison RD.Characterization of hyperthyroidism enhancement of halothane-induced hepatotoxicity.Biochem Pharmacol 1983 Dec 1;32(23):3531-96: Videla LA, SmokG, Troncoso P, Simon KA, Junqueira VB, Fernandez V. Influence of hyperthyroi

58、dism on lindane-induced hepatotoxicity in the rat.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 with autoimmune hepatitis and mixed connective tissue disease.Endocr J 1999 Feb;46(1):