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1 ORIGINAL ARTICLE ISSN: X Clin Exp Thyroidol 2014 November 7(2): 방사성요오드치료전단기간갑상선기능저하상태가혈청지질인자및심혈관계위험인자에미치는영향 부산대학교의학전문대학원내과학교실 여혜주, 조아라, 이혜원, 이동원, 강양호, 손석만 Effect of Short-Term Hypothyroid State on Lipid Profile and Cardiovascular Risk Markers in Subjects Preparing Radioactive Iodine Therapy Hye Ju Yeo, A Ra Jo, Hye Won Lee, Dong Won Yi, Yang Ho Kang and Seok Man Son Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Korea Background and Objectives: The relationship between short-term hypothyroidism due to levothyroxine (LT4) withdrawal for radioactive iodine (RI) therapy in patients with differentiated thyroid cancer (DTC) and risk of cardiovascular disease is not clear. In this study, we evaluated the impact of short-term overt hypothyroidism on lipid profiles and cardiovascular parameters in patients with DTC. Materials and Methods: We recruited 195 patients with DTC who were preparing RI therapy from March 2008 to February We analyzed the effect of thyroid stimulating hormone (TSH) level on the clinical, biochemical, and cardiovascular risk markers at the end of LT4 withdrawal protocol (P2). Results: After LT4 withdrawal (P2), TSH and total cholesterol (TC) levels were significantly increased (p<0.005). After adjustment for multiple factors such as age, sex, body mass index (BMI), hypertension and diabetes mellitus (DM), the positive relationship between TSH and TC remained significant (p=0.04). Mean levels of homocysteine, low density lipoprotein-cholesterol, triglyceride were increased. However, levels of high density lipoprotein-cholesterol, cystatin C, C-reactive protein, apolipoprotein B (ApoB), apolipoprotein A1 (Apo A1), lipoprotein (a) (Lp[a]), aspartate transaminase, alanine aminotransferase, total bilirubin, uric acid remained within normal range. Splitting the whole cohort into the three different age groups, serum Apo B, Lp(a) levels and BMI increased with increasing age (p<0.05). And splitting into three different TSH level groups (1st group; <79 μiu/ml, 2nd group; μiu/ml, 3rd group; >121 μiu/ml), all values did not have a statistical significant meaning except Apo A1. Conclusion: Short-term hypothyroidism induced worsening of lipid metabolic parameters, but not enough to induce the cardiovascular risk in patients with thyroid cancer. Key Words: Short-term hypothyroidism, Thyroid cancer, Cardiovascular risk markers, Radioactive iodine therapy Received August 10, 2014 / Revised October 24, 2014 / Accepted November 8, 2014 Correspondence: Seok Man Son, MD, PhD, Department of Internal Medicine, Pusan National University School of Medicine, 49 Busandaehak-ro, Mulgeum-up, Yangsan , Korea Tel: , Fax: , sonsm@pusan.ac.kr This study was supported for two years by Pusan National University Research Grant. Copyright c 2014, the Korean Thyroid Association. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 172

2 Short-Tem Hypothyroid State and Cardiovascular Risk 서론 대상및방법 갑상선분화암은전세계적으로발생이증가하고있으며, 2010년보건복지부통계에따르면연령표준화발생률이 10만명당 52.7명으로우리나라암발생 1위를차지하고있다. 1) 갑상선분화암의치료는수술과잔여갑상선및남은갑상선암을제거하기위한방사성요오드치료로이루어진다. 2) 효과적인방사성요오드치료를위해서는혈청갑상선자극호르몬 (thyroid stimulating hormone, TSH) 농도를적어도 30 μiu/ml 이상으로상승시켜야한다. 이를위해서갑상선호르몬의투여중단을통해단기간갑상선기능저하상태를유도하거나, 인간재조합갑상선자극호르몬을투여할수있다. 임상에서는전자가일반적으로행해지고있으며, 그에따라대부분환자들은불현성갑상선기능저하증부터심한급성갑상선기능저하증까지다양한상태를경험하게된다. 3) 갑상선기능저하증은동맥경화발생의잘알려진위험인자로서, 총콜레스테롤과저밀도지단백- 콜레스테롤 (low-density lipoprotein-cholesterol, LDLc) 수치를높이며, 이완기고혈압발생, 내피세포기능이상을동반한대혈관의강직도증가와혈전생성증가로심혈관질환의위험도를증가시킨다. 4,5) 단기간갑상선기능저하상태에서도이와관련된몇몇보고가있었지만, 6-11) 그관련성은분명하지않다. 따라서지속적인방사성요오드치료를받아야하는환자의경우심혈관계위험성이증가될가능성을배제할수없다. 본연구에서는방사성요오드치료를위해갑상선호르몬투여를중단하여발생된단기간갑상선기능저하상태가 TSH 농도에따라혈청지질인자및심혈관위험인자들에미치는영향을알아보고자하였다. 연구대상 2008년 3월부터 2012년 2월까지갑상선분화암으로갑상선전절제술을시행받고, 잔류갑상선조직과잔존암의방사성요오드치료를위해입원한 195명 ( 남자 29 명, 여자 166명, 평균연령 47.38±12세 ) 을대상으로후향적으로의무기록을분석하였다. 간질환, 신질환등의의미있는병력이있거나갑상선기능에영향을줄수있는약물을복용하는사람과흡연자는제외하였다. 잘조절된당뇨병은지질인자변화에중대한영향을미치지않음을전제로하여, 등록시점에지질강하제를복용하지않았고, 최근 3개월동안당화혈색소 7% 이하로조절이되었던당뇨병환자들 (15명) 과, 최근 6개월동안약물로혈압조절이잘되었던고혈압환자들 (45명) 이포함되었다. 방법방사성요오드치료의전처치로갑상선호르몬의복용을 4주간중지하여, TSH를 30 μiu/ml 이상상승시켰다. 대상자들은각각갑상선호르몬투여중단직전 (P1), 갑상선호르몬투여중단 4주후 (P2) 병원을방문하였고, 매방문시마다신체검사및혈액검사를시행하였고 (Fig. 1), TSH값에따라세군 (1군; <79 μiu/ml, 2군 ; μiu/ml, 3군 ; >121 μiu/ml) 으로분류하여단기간갑상선기능저하상태에따른혈청지질인자및심혈관위험인자들의수치를비교하였다. 모든대상자에서키, 몸무게, 수축기, 이완기혈압을측정하였으며혈압측정은최소 5분이상안정을취한후표준혈압계를사용하여상완에서수동으로측정하였다. 체질량지수 (body mass index, BMI) 는공식 (kg/m 2 ) Fig. 1. Study protocols for evaluation of effect of shortterm hypothyroid state on lipid and cardiovascular risk markers in subjects with thyroid cancer preparing radioiodine therapy. 173 Clin Exp Thyroidol

3 Hye Ju Yeo, et al 에의해계산하였다. 매방문시모든대상자에서 10시간공복후채혈하여, 갑상선자극호르몬및 T3, 유리 T4, 총콜레스테롤, 중성지방, 저밀도지단백-콜레스테롤, 고밀도지단백- 콜레스테롤 (high-density lipoprotein cholesterol, HDLc) 수치를측정하였다. 또한, 단기간갑상선기능저하상태 (P2) 에서 10시간공복후호모시스테인 (homocysteine), cystatin C, 아포지단백 B (apolipoprotein B, apob), 아포지단백 A1 (apolipoprotein A1, apoa1), aspartate aminotransferase (AST), alanine aminotransferase (ALT), 총빌리루빈 (total bilirubin), 요산, 리포지단백 (a) (lipoprotein[a], Lp[a]), 고감도 C-반응성단백질 (high sensitivity C-reactive protein, hscrp) 을측정하였다. 혈청 T3 ( 정상범위, ng/ml), 유리 T4 ( 정상범위, ng/dl), TSH ( 정상범위, μiu/ml) 농도는화학발광면역측정법 (Archotect i4000sr, Abbott, Chicago, IL, USA) 으로측정하였다. Anti-TG antibody 는화학발광면역측정법 (Lumipulse G1200, Fujirebio, Tokyo, Japan) 으로측정하였다. 콜레스테롤측정은효소비색법으로측정하였으며고밀도지단백-콜레스테롤과저밀도지단백- 콜레스테롤은직접측정법을, 중성지방은글리세롤소거법 (TBA-200 FR NEO, Toshiba, Tokyo, Japan) 으로측정하였다. 아포지단백 A1과아포지단백 B는비탁계면역분석법 (Cobas 6000ce, Roche, Chicago, IL, USA) 을사용하였으며호모시스테인은효소법 (TBA-200 FR NEO, Toshiba, Tokyo, Japan) 으로측정하였다. Cystatin C와 hscrp는라텍스응집면역비탁법 (TBA-200 FR NEO, Toshiba, Tokyo, Japan) 을사용하였으며, AST와 ALT는 JSCC법 (TBA-200 FR NEO, Toshiba, Tokyo, Japan) 을, 총빌리루빈은 Vanadate 산화법 (TBA-200 FR NEO, Toshiba, Tokyo, Japan) 을, 요산은 uricase 비색효소법 (TBA-200 FR NEO, Toshiba, Tokyo, Japan) 을사용하여측정하였다. 통계분석통계학적분석은 SPSS 18판 (PWSA Statistics 18; SPSS Inc., Chicago, IL, USA) 을이용하였다. 연속변수의비교분석을위해 Pearson correlation coefficients를이용하였고, 명목변수의비교분석을위해 Chi-square test를사용하였다. 측정치는빈도와백분율, 평균 ± 표준편차로나타내었고, 평균분석은 t-test, 빈도분석은 χ 2 -test, Fisher s exact test를사용하였다. 결과는단기간갑상선기능저하상태에서갑상선기능및지질, 임상화학적지표들의평균값을제시하였다. 갑상선호르 몬및총콜레스테롤의변화를살펴보기위해 paired t-test와 unpaired t-test를사용하였다. LT4 중단전후의총콜레스테롤델타값과이에미치는인자들과의관계를알아보고자다중로지스틱회귀분석을사용하였다. 또한나이 (1군, <40세 ; 2군, 40 50세 ; 3군, >50세 ) 에따른각군의평균치비교는 analysis of variance (ANOVA) 를사용하였다. TSH값에따라 3분위수로나누어세군으로분류하였으며 (1군, <79 μiu/ml; 2 군, μiu/ml; 3군, >121 μiu/ml), 각군의평균치비교는 ANOVA를사용하였고, post hoc 분석은 Scheffe 방법을사용하였다. p값이 0.05 미만인경우통계적으로유의한관계가있는것으로정의하였다. 대상군의임상특징 Table 1. Basal characteristics of subjects Age, years Female, % BMI, kg/m 2 SBP, mmhg DBP, mmhg Hypertension, % Diabetes, % FBS, mg/dl 결과 대상군 195명은남자 29명과여자 166명으로평균연령은 47.6±12.4세였다. 대상군의평균 BMI는 24.7± 3.7이었다. 수축기혈압은 118.7±14.8 mmhg, 이완기혈압은 75.9±11.3 mmhg였고고혈압환자는 45명 (23%) 이포함되었다. 당뇨병환자는 14명 (7%) 이었으며당뇨병환자의평균공복혈당은 90.8 mg/dl 였다 (Table 1). 갑상선호르몬중단전후갑상선기능검사및총콜레스테롤수치의변화 갑상선호르몬중단 4주후 (P2) 평균 TSH 수치는중단전 (P1) 과비교하여 3.9 μiu/ml에서 μiu/ml 로유의하게증가하였고, 평균 T3는 1.3 ng/ml에서 0.4 ng/ml, 평균 FT4는 1.2 ng/dl에서 0.5 ng/dl로유의한감소를보여갑상선기능저하상태에합당한소견을보였다. 혈청평균총콜레스테롤은 198 mg/dl에서 262 Mean±SD 47.6± (n=166) 24.7± ± ± (n=45) 7.1 (n=14) 90.8±18.2 BMI: body mass index, DBP: diastolic blood pressure, FBS: fasting blood sugar, SBP: systolic blood pressure Vol. 7, No. 2,

4 Short-Tem Hypothyroid State and Cardiovascular Risk Table 2. Changes in parameters during follow-up P1 P2 p value TSH, μiu/ml T3, ng/ml FT4, ng/dl TC, mg/dl LDLc, mg/dl HDLc, mg/dl TG, mg/dl SBP, mmhg DBP, mmhg BMI, kg/m 2 3.9± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± BMI: body mass index, DBP: diastolic blood pressure, P1: the last day on levothyroxine (LT4) at their usual TSH-suppressive doses, P2: 4 weeks after withdrawal of LT4, SBP: systolic blood pressure Table 3. Delta correlation of total cholesterol associated with variables R Total cholesterol p value Mean BP Body mass index T3 FT4 TSH BP: blood pressure, FT4: free T4, TSH: thyroid stimulating hormone mg/dl로유의하게증가하였다 (p<0.05). 단기간갑상선기능저하시기에는수축기혈압은감소하고 (p=0.017), 이완기혈압은증가하였으며 (p=0.015) 갑상선기능변화와의미있는상관관계를보였다. 그러나 BMI의변화는유의하지않았다 (Table 2). 총콜레스테롤과 TSH 와의델타상관관계 단기간갑상선기능저하상태에서총콜레스테롤의델타값은 TSH 델타값과의미있는상관관계를보였지만, T3와 FT4 델타값과는통계적으로유의한상관관계는없었다. 이외에도총콜레스테롤에영향을미칠수있는체질량지수와혈압과의관계를살펴보았을때유의한상관관계를보이지않았다 (Table 3). 단기간갑상선기능저하상태에서혈청지질검사를포함한심혈관질환위험인자 갑상선호르몬중단 4주후 (P2) 단기간갑상선기능저하상태에서호모시스테인 (15.4±7.1), 저밀도지단백-콜레스테롤 (169.7±50.3), 중성지방 (212.0±128.1), 총콜레스테롤 (262.1±56.7) 은정상보다높은수치를보였으나, 그외값들은정상범위를보였다 (Table 4). Table 4. Biochemical findings during hypothyroid states (P2) TG, mg/dl LDLc, mg/dl HDLc, mg/dl Homocysteine, μmol/l Cystatin C, mg/l hscrp, mg/dl ApoB, mg/dl Apo A1, mg/dl Lipoprotein(a), mg/dl AST, IU/L ALT, IU/L Total Bilirubin, mg/dl Uric Acid, mg/dl Mean±SD 212.0± ± ± ± ± ± ± ± ± ± ± ± ±1.42 Reference ranges Apo A1: apolipoprotein A1, Apo B: apolipoprotein B, ALT: alanine aminotransferase, AST: aspartate aminotransferase, HDLc: high-density lipoprotein cholesterol, hscrp: C-reactive protein, LDLc: low-density lipoprotein cholesterol, TG: triglycerides 단기간갑상선기능저하상태에서나이에따른지질인자및심혈관위험인자들의값 나이에따라세군 (1군, <40세 ; 2군, 40-50세 ; 3군, >50세 ) 으로나누어단기간갑상선기능저하상태에따른혈청지질및심혈관위험인자들의수치를비교하였다. 세군간성별차이는없었으며 (p=0.100), 고혈압 (p) 및당뇨병 (p=0.001) 과 BMI (p=0.009) 는나이가증가함에따라증가하였다. Cystatin C (p) 와아포지단백 B (p=0.013), Lp(a) (p) 는나이에따라증가하는양상을보였다. 반면그외값들은유의한차이가없었다 (Table 5). 175 Clin Exp Thyroidol

5 Hye Ju Yeo, et al Table 5. Clinical and biochemical parameters (P2) in the three different age groups 1st group (n=54) 2nd group (n=68) 3rd group (n=73) p value Post hoc Scheffe Sex, % female BMI, kg/m 2 DM, % Tg Ab, % SBP, mm/hg DBP, mm/hg LDLc, mg/dl HDLc, mg/dl TG, mg/dl Homocysteine, μmol/l Cystatin C, mg/l hscrp, mg/dl Apo B, mg/dl Apo A1, mg/dl Lipoprotein(a), mg/dl Thyroglobulin, mg/dl Total bilirubin, mg/dl AST, IU/L ALT, IU/L Uric acid, mg/dl 87.0% 23.4± % 13.0% 114.0± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± % 24.9± % 5.9% 117.4± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± % 25.4± % 13.7% 123.4± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± , 2:3, 2:3 Age groups were defined as: 1st group; <39 years, 2nd group; years, 3rd group; >50 years Apo A1: apolipoprotein A1, Apo B: apolipoprotein B, ALT: alanine aminotransferase, AST: aspartate aminotransferase, BMI: body mass index, DBP: diastolic blood pressure, HDLc: high-density lipoprotein cholesterol, hscrp: C-reactive protein, LDLc: low-density lipoprotein cholesterol, SBP: systolic blood pressure, TG: triglycerides 단기간갑상선기능저하상태에서 TSH에따른지질인자및심혈관위험인자들의값 TSH값에따라세군 (1군, <79 μiu/ml; 2군, μiu/ml; 3군, >121 μiu/ml) 으로분류하여단기간갑상선기능저하상태에따른혈청지질및심혈관위험인자들의수치를비교하였다. 혈청아포지단백 A1 (p=0.019) 및나이 (p=0.031) 는 TSH 농도변화와유의한상관관계가있었다. 그러나다른지질인자및간기능수치, Lp(a) 등다른심혈관위험인자들은유의한차이가없었다 (Table 6). 고찰 본연구는갑상선분화암환자에서단기간갑상선기능저하상태에서 TSH의변화가지질및심혈관계질환인자들에미치는영향을알아보고자하였다. 갑상선호르몬을중단하였을때전체대상군에서단기간갑상선기능저하상태 ( 평균값 : TSH μiu/ml, FT4 0.5 ng/dl, T3 0.4 ng/ml) 가유발되었으며, TSH 농도의증가는총콜레스테롤수치변화를증가시켰다. 총 콜레스테롤은나이, 성별, 체질량지수, 혈압, 당뇨병등의인자와비교하였을때유의한관계를보이지않아서, 성별, 연령및체격의변화에따른영향을받지않고 TSH에따라증가하는양상을보였다. 갑상선기능저하증의경우고콜레스테롤혈증과함께초저밀도지질단백질, 저밀도지단백콜레스테롤, 중성지방, 아포지단백 A1, 아포지단백 B, Lp(a) 등이증가될수있으며, 고밀도지단백콜레스테롤은감소혹은증가되는등다양한양상을보인다. 4,5) 그러나단기간갑상선기능저하상태의경우혈청지질농도의변화는보고자들마다차이가있으며, 이러한지질성분의변화와심혈관질환의위험성증가와의관련성은확실치않다. 6,7,12,13) 지금까지단기간갑상선기능저하상태에서심혈관계에미치는영향에관한여러연구가있었으나대부분심전도변화나혈압변화, 심초음파를통한수축력이나이완기기능평가등에국한되어있었다 ) 일부는본연구와같이지질성분변화와심혈관질환과의관계에대해연구하였으나, 8,9) 아직까지확실한결론이없는실정이다. 이는단기간갑상선기능저하상태가심혈관계에미치는영향을평가하는것이어렵기때문이다. Vol. 7, No. 2,

6 Short-Tem Hypothyroid State and Cardiovascular Risk Table 6. Clinical and biochemical features of the whole cohort according to three different TSH level groups 1st group (n=65) 2nd group (n=66) 3rd group (n=64) p value Post hoc Scheffe Sex, % female Age, years BMI, kg/m 2 DM, % Tg Ab, % Systolic BP, mm/hg DiastolicBP, mm/hg LDLc, mg/dl HDLc, mg/dl TG, mg/dl Homocysteine, μmol/l Cystatin C, mg/l hscrp, mg/dl Apo B, mg/dl Apo A1, mg/dl Lipoprotein(a), mg/dl Thyroglobulin, mg/dl T3, ng/ml FT4, mg/dl Total bilirubin, mg/dl AST, IU/L ALT, IU/L Uric acid, mg/dl 80% (n=52) 50.4± ± % (n=5) 7.6% (n=5) 118.7± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±1.5 84% (n=56) 44.7± ± % (n=5) 7.6% (n=5) 119.4± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± % (n=58) 47.7± ± % (n=4) 17.2% (n=11) 117.8± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± :2 1:2 TSH groups were defined as: 1st group; <79 μiu/ml, 2nd group; μiu/ml, 3rd group; <121 μiu/ml Apo A1: apolipoprotein A1, Apo B: apolipoprotein B, ALT: alanine aminotransferase, AST: aspartate aminotransferase, BMI: body mass index, DBP: diastolic blood pressure, HDLc: high-density lipoprotein cholesterol, hscrp: C-reactive protein, LDLc: low-density lipoprotein cholesterol, SBP: systolic bloodpressure, TG: triglycerides 갑상선기능저하증에서심혈관질환은주로동맥경화성변화에의해일어나며, 이는지질성분의변화뿐만아니라, 인슐린저항성, 혈압의증가, 동맥벽의강도증가등내피세포의기능이상및염증과정을통해가속화된다. 4,6,7) 이러한내피세포의기능은간접적으로 hscrp, 호모시스테인, cystatin C 등을통해평가할수있다. 단기간갑상선기능저하상태에서지질성분및내피세포기능인자들의평균값을살펴보았을때, 혈청총콜레스테롤, 저밀도지단백-콜레스테롤, 중성지방, 호모시스테인이증가하였다. 이는기존의연구결과들 8,9) 과일치하였으며, 고밀도지단백-콜레스테롤은높지않아기존연구들 8-10) 과는다른결과를보였다. 또한관상동맥질환의존재를예측하는독립적인인자인아포지단백 A1, 아포지단백 B 및 hscrp, Cystatin C, Lp(a) 는증가하지않았고, 호모시스테인은증가하였으나 TSH와유의한상관관계는없었다. Catargi 등 18) 이갑상선기능저하에서호모시스테인의증가및 TSH와의유의한관계를보고한것과는대조된다. 본연구에앞서 Erbil 등 11) 은단기간갑상선기능저하에서지질인자 의악화가내피세포의기능이상및심혈관질환위험증가와관련된다고보고하였다. 그러나본연구에서는앞서언급한것처럼콜레스테롤과저밀도지단백콜레스테롤은증가하였으나, TSH와콜레스테롤외다른인자들과는의미있는상관관계는없었다. 갑상선기능저하증에서아포지단백 A와 B의증가를보고한것 19) 과는달리단기간갑상선기능저하상태에서아포지단백 A1과아포지단백 B 모두정상범위였다. Lp(a) 또한죽상동맥경화증과관상동맥질환의독립적인위험인자로알려진지단백으로, 갑상선기능저하증에서높았던혈청 Lp(a) 농도가갑상선호르몬투여후감소함이보고되었으며, 20) 이와달리변화가없다는보고도있으나, 21) 단기간갑상선기능저하상태에서이에대한연구는없다. 혈청 Lp(a) 농도는성별, 연령의변화및 BMI 의영향을받지않으나간질환및신질환에영향을받을수있어본연구에서는이들을연구대상에서제외하였고, 21) Lp(a) 농도는정상범위를보였다. hscrp 농도는많은연구에서죽상동맥경화증과의관련성이밝혀지고있으나, 22-26) 갑상선기능저하증과의관련성에 177 Clin Exp Thyroidol

7 Hye Ju Yeo, et al 대해서는논란이있다. Miller 등 22) 에의하면 hscrp는염증인자로서심혈관위험의강력한예측인자로사용되지만현성갑상선기능저하증에서 CRP는상반된결과를보였다. 일부는갑상선기능저하증에서 hscrp가높음을보고하였으나, 23-25) Erbil 등 11) 과 Lee 등 26) 은차이가없음을보고하였다. 본연구결과에서도정상값을보였다. 갑상선기능저하상태에서는지질검사외에도여러가지임상화학검사결과에변화가생기는데간기능중특히담즙의배출지연을가져오며지방성분의축적과정과간기능유지에필요한효소의활성화가낮아져 AST, ALT, 포합형빌리루빈등화학적지표들의수치가상승될수있다. 8,26,27) 앞서 Jeong 등 28) 은중증갑상선기능저하증에서총빌리루빈수치의증가및상대적으로비포합형빌리루빈수치가높음을보고하였으나, 본연구에서는 AST, ALT 및총빌리루빈수치는정상값을보였다. 본연구의제한점으로대상군이남성에비해여성이많이포함되고연령군분포에차이가있으며, 단일병원의적은수를대상으로한연구이므로일반화하기는어렵다. 또한, 환자를추적관찰하지않았기때문에실제갑상선호르몬의변화가심혈관질환의위험인자가될가능성을배제할수없는단면연구로서의제한점을가진다. 결론 본연구결과갑상선암환자에서수술후방사성요오드치료를위해유발된단기간갑상선기능저하상태에서 TSH 범위에따라 (1군, <79 miu/ml; 2군, miu/ml; 3군, >121 miu/ml) 심혈관계질환의위험도에관한혈액지표들 ( 아포지단백, Lp(a), homocysteine, cystatin C, hscrp) 을비교하였을때의미있는차이가없었다. 하지만갑상선암환자에서방사성요오드치료기간동안갑상선호르몬제제를중단하는기간과 TSH 농도의변화에따른심혈관질환발생의위험성에대해서는더많은연구가필요할것으로생각된다. 중심단어 : 단기간갑상선기능저하, 갑상선암, 심혈관계위험인자, 방사성요오드치료. References 1) Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Cancer statistics in Korea: incidence, mortality, survival and prevalence in Cancer Res Treat 2013;45(1): ) American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19(11): ) Hilts SV, Hellman D, Anderson J, Woolfenden J, Van Antwerp J, Patton D. Serial TSH determination after T3 withdrawal or thyroidectomy in the therapy of thyroid carcinoma. J Nucl Med 1979;20(9): ) Peppa M, Betsi G, Dimitriadis G. Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. J Lipids 2011;2011: ) Kutluturk F, Yuce S, Tasliyurt T, Yelken BM, Aytan P, Ozturk B, et al. Changes in metabolic and cardiovascular risk factors before and after treatment in overt hypothyroidism. Med Glas (Zenica) 2013;10(2): ) Regalbuto C, Alagona C, Maiorana R, Di Paola R, Cianci M, Alagona G, et al. Acute changes in clinical parameters and thyroid function peripheral markers following L-T4 withdrawal in patients totally thyroidectomized for thyroid cancer. J Endocrinol Invest 2006;29(1): ) Duntas LH, Biondi B. Short-term hypothyroidism after Levothyroxine-withdrawal in patients with differentiated thyroid cancer: clinical and quality of life consequences. Eur J Endocrinol 2007;156(1): ) Lien EA, Nedrebo BG, Varhaug JE, Nygard O, Aakvaag A, Ueland PM. Plasma total homocysteine levels during short-term iatrogenic hypothyroidism. J Clin Endocrinol Metab 2000;85(3): ) Bicikova M, Hampl R, Hill M, Stanicka S, Tallova J, Vondra K. Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation. Clin Chem Lab Med 2003; 41(3): ) Chrisoulidou A, Pazaitou-Panayiotou K, Kaprara A, Platoyiannis D, Lafaras C, Boudina M, et al. Effects of thyroxine withdrawal in biochemical parameters and cardiac function and structure in patients with differentiated thyroid cancer. Minerva Endocrinol 2006;31(2): ) Erbil Y, Ozbey N, Giris M, Salmaslioglu A, Ozarmagan S, Tezelman S. Effects of thyroxine replacement on lipid profile and endothelial function after thyroidectomy. Br J Surg 2007;94(12): ) Chang HJ, Kim KW, Choi SH, Lim S, Park KU, Park do J, et al. Endothelial function is not changed during short-term withdrawal of thyroxine in patients with differentiated thyroid cancer and low cardiovascular risk. Yonsei Med J 2010;51(4): ) Botella-Carretero JI, Alvarez-Blasco F, Sancho J, Escobar- Morreale HF. Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal. Thyroid 2006;16(4): Vol. 7, No. 2,

8 Short-Tem Hypothyroid State and Cardiovascular Risk 14) Mazzaferri EL, Massoll N. Management of papillary and follicular (differentiated) thyroid cancer: new paradigms using recombinant human thyrotropin. Endocr Relat Cancer 2002; 9(4): ) Botella-Carretero JI, Gomez-Bueno M, Barrios V, Caballero C, Garcia-Robles R, Sancho J, et al. Chronic thyrotropinsuppressive therapy with levothyroxine and short-term overt hypothyroidism after thyroxine withdrawal are associated with undesirable cardiovascular effects in patients with differentiated thyroid carcinoma. Endocr Relat Cancer 2004;11(2): ) Di Paola R, Alagona C, Pezzino V, Mangiameli S, Regalbuto C. Left ventricular function in acute hypothyroidism: a Doppler echocardiography study. Ital Heart J 2004;5(11): ) Fommei E, Iervasi G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab 2002;87(5): ) Catargi B, Parrot-Roulaud F, Cochet C, Ducassou D, Roger P, Tabarin A. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid 1999;9(12): ) Shong YK, Ryu JS, Lee KU, Kim GS, Lee M. Serum lipids and apolipoproteins in subclinical and overt hypothyroidism and their changes with thyroxine therapy. J Korean Soc Endocrinol 1992;7(1): ) Engler H, Riesen WF. Effect of thyroid hormones on Lp(a) and lipid metabolism. Clin Chem Lab Med 1998;36(9): ) Sharma AK, Arya R, Mehta R, Sharma R, Sharma AK. Hypothyroidism and cardiovascular disease: factors, mechanism and future perspectives. Curr Med Chem 2013;20(35): ) Miller VM, Redfield MM, McConnell JP. Use of BNP and CRP as biomarkers in assessing cardiovascular disease: diagnosis versus risk. Curr Vasc Pharmacol 2007;5(1): ) Christ-Crain M, Meier C, Guglielmetti M, Huber PR, Riesen W, Staub JJ, et al. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A crosssectional and a double-blind, placebo-controlled trial. Atherosclerosis 2003;166(2): ) Jublanc C, Bruckert E, Giral P, Chapman MJ, Leenhardt L, Carreau V, et al. Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hscrp. Atherosclerosis 2004;172(1): ) Nagasaki T, Inaba M, Shirakawa K, Hiura Y, Tahara H, Kumeda Y, et al. Increased levels of C-reactive protein in hypothyroid patients and its correlation with arterial stiffness in the common carotid artery. Biomed Pharmacother 2007;61(2-3): ) Lee WY, Suh JY, Rhee EJ, Park JS, Sung KC, Kim SW. Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lpa levels according to thyroid function status. Arch Med Res 2004;35(6): ) Bayraktar M, Van Thiel DH. Abnormalities in measures of liver function and injury in thyroid disorders. Hepatogastroenterology 1997;44(18): ) Jeong HJ, Kim CG, Lee KM, Jeong SJ, Song HC, Bom HS. Reversible changes of clinical chemical tests in severe hypothyroid patients with differentiated thyroid cancer who were admitted for radioiodine therapy. J Korean Surg Soc 2004;66(1): Clin Exp Thyroidol

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) 전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) - i - - ii - - iii - - iv - - v - - vi - - vii - - viii - - ix - -