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1 대한내과학회지 : 제 81 권제 5 호 F-FDG PET 상관찰되는미만성갑상선섭취의임상적의의 전남대학교의과대학내과학교실 김희경 윤지희 김수정 강호철 Clinical Meaning of Diffuse 18 F-FDG PET Thyroid Uptake Hee Kyung Kim, Jee Hee Yoon, Soo Jeong Kim, and Ho-Cheol Kang Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea Background/Aims: Thyroid abnormalities are frequently detected in patients undergoing 18 F-fludeoxyglucose positron emission tomography (FDG-PET). The clinical importance of diffuse thyroid FDG uptake (DU) has been controversial, although focal thyroid FDG uptake (FU) indicates a high probability for thyroid cancer. Methods: In total, 3,303 subjects underwent PET for cancer staging (n = 1,744) or a health screening (n = 1,559) between August 2004 and March Fifty-six (1.7%) subjects showed FU (n = 34) or DU (n = 22). Serum thyroid simulating hormone (TSH) and thyroid autoantibodies were measured with high-resolution thyroid ultrasonography (US). US-guided fine-needle aspiration cytology was performed when a nodular lesion was found. Results: Twelve of 34 (35.3%) patients with FU and 3 of 22 (13.6%) patients with DU had a malignancy. This difference in malignancy frequency was not significant between the two groups (p = 0.07). The US findings were consistent with chronic thyroiditis in 17 of 22 (77.3%) patients with DU. Three cases of DU had an apparently normal thyroid gland. In the three patients diagnosed with a malignancy in the DU group, the tumors included one papillary thyroid cancer, one primary thyroid lymphoma, and one metastatic squamous cell carcinoma from lung cancer. No correlation between TSH and SUV max (p = 0.086) was observed in the DU group, and the SUV max in patients with a malignancy was not different from that in the benign group. Conclusions: Most patients with DU had chronic autoimmune thyroiditis, but the frequency of malignancy was not different from that of the FU group. Further clinical examinations, including thyroid function tests, thyroid autoantibodies, and thyroid US are needed to diagnose chronic autoimmune thyroiditis and possible thyroid malignancy in subjects with DU. (Korean J Med 2011;81: ) Keywords: Cancer; 18 F-FDG; Nodule; Thyroid; Ultrasonography Received: Revised: Accepted: Correspondence to Ho-Cheol Kang, M.D., Ph.D. Department of Internal Medicine, Chonnam National University Medical School, 160 Ilsim-ri, Hwasun , Korea Tel: , Fax: , drkang@chonnam.ac.kr * This study was financially supported by Chonnam National University ( )

2 - The Korean Journal of Medicine: Vol. 81, No. 5, 서론 18 F-FDG (fluoro-deoxyglucose) 양전자방출단층촬영술 (positron emission tomography, PET) 은다양한암의진단, 병기결정및추적관찰을할수있는비침습적인검사로임상적이용이급증하고있다 [1]. 그결과암의진단혹은건강검진목적의 18 F-FDG PET/CT (FDG PET) 검사에서갑상선의 FDG 섭취가발견되는것은드물지않으며, 국소적 (focal) FDG 섭취를보이는경우악성가능성이 26-50% 정도로보고되어추가적인갑상선초음파검사및갑상선미세침흡인세포검사가권고된다 [2-6]. 정상갑상선세포의주영양소는유리지방산으로정상갑상선세포에서는 18 F-FDG의섭취가없어 PET 영상에서갑상선은관찰되지않는다 [7]. PET 검사에서국소적 FDG 섭취를보이는갑상선우연종에서갑상선암의빈도가증가되어있다는다양한보고들에비해미만성 (diffuse) 섭취에대한연구는드물며정상적인현상 [8,9] 이라는의견과자가면역갑상선질환과관련되었다는의견으로양분되어있다 [5,10-13]. 이에저자들은 FDG PET 검사에서미만성 FDG 섭취를보였던환자에서갑상선기능검사, 자가항체검사및갑상선초음파검사를시행하여그임상적의의를알아보자하였다. 대상및방법연구대상 2004년 8월부터 2006년 3월까지화순전남대학교병원에서 18 F-FDG PET/CT (PET trace, GE Medical Systems, Wisconsin, USA) 를시행한총 3,303명을대상으로하였다. 건강검진목적으로 1,559명, 기존암에대한병기평가를위해 1,744명에서 PET/CT가시행되었다. 연구대상의평균나이는 57.5 ± 15.4세였으며, 남자는 1,746명 (52.9%), 여자는 1,557명 (47.1%) 이었다. 방법 18 F FDG PET/CT 소견 FDG 섭취증가양상을국소적, 미만성으로분류하였고, maximum standard uptake values (SUV max) 로 FDG 섭취증가정도를평가하였다. 갑상선초음파검사 FDG 섭취증가를보인모든환자에서갑상선초음파검사를시행하여갑상선의크기, 실질에코변화등으로하시모토갑상선염과같은미만성갑상선질환유무를확인하였고결절이관찰되는경우초음파유도미세침흡인세포검사를시행하였다. 미세침흡인세포검사초음파유도하에 25-27G 바늘과비흡인법을이용하여한결절당적어도 3회의검사를시행하여얻어진검체는도말후즉시 99% 에탄올에담가고정하였고 Papanicolaou 염색을시행하였다. 선종양갑상선종 (adenomatous goiter) 과갑상선염 (thyroiditis) 을양성으로정의하고갑상선유두암 (thyroid papillary carcinoma) 등의암이관찰되면악성으로정의하였다. 미세침흡인세포검사결과가악성인경우전이성암과림프종을제외하고모든환자에서갑상선절제술을시행하였다. 혈액검사갑상선기능과자가면역기전을확인하기위해혈청에서 TSH ( 정상범위 µiu/ml) 와 anti-tpo antibody ( 정상범위 0-8 U/mL) 를측정하였다. 통계분석모든결과는평균 ± 표준편차로나타내었고, 통계처리는 SPSS for Windows 19.0을이용하였다. 대상비교는 Unpaired sample t-test와 Chi-square analysis를시행하였고, TSH 및 TPO antibody와 SUV의상관관계는선형회귀분석을통해분석하였다. 모든자료는 p value가 0.05 미만일때유의하다고판정하였다. 결과갑상선의 FDG 섭취는흔하지않았으며국소적섭취가더많았다. 3,303명에서시행된 18 F-FDG PET/CT 검사중 56명 (1.7%) 에서갑상선에 FDG 섭취를보였으며, 그양상은 34명 (60.7%) 에서국소적섭취였고, 22명 (39.3%) 에서미만적섭취로국소적인섭취가더많았다 (Table 1). FDG 섭취를보인대상환자의평균나이는 55.9 ± 10.1세

3 - Hee Kyung Kim, et al. Diffuse 18 F-FDG thyroid uptake - Table 1. Frequency of malignancy and SUV max in the focal and diffuse fludeoxyglucose (FDG) uptake groups Focal (n = 34) Diffuse (n = 22) p value Age 57.7 ± ± Sex (M/F) 10/24 3/ SUV max 7.5 ± ± Malignancy 12 (35.3%) 3 (13.6%) 0.07 % of thyroid papillary carcinoma 12/12 (100%) 1/3 (33.3%) - 였고, 남자 13명 (23.2%), 여자 43명 (76.8%) 으로여자에서더흔했다. 검사의목적은건강검진이 41명 (73.2%) 으로더흔했고암에대한병기평가목적으로 15명 (26.8%) 에서 FDG PET이시행되었다. 악성의빈도는국소적 FDG 섭취군에서높았으나미만섭취군과통계학적차이는없었다. 국소적 FDG 섭취군에서 12명 (35.3%) 이악성이었고, 모두갑상선유두암이었다. 미만성 FDG 섭취군중 3명 (13.6%) 에서암이진단되었고 1명이갑상선유두암이었다. 갑상선유두암의경우 SUV max 2.4의미만성갑상선섭취와함께갑상선유두암부위에 SUVmax 3.0의국소섭취증가가함께관찰되었다. 국소섭취군에서악성의빈도가더높았으나양군간에악성의빈도는차이가없었다 (p = 0.07). 미만성 FDG 섭취군은대부분자가면역갑상선질환을동반하고있었고 TSH 증가정도와 SUV max 는상관관계가없었다. 갑상선기능검사, 자가항체및갑상선초음파소견을근거로미만성 FDG 섭취를보인 22예중 17예 (77.3%) 에서자가면역갑상선질환 (16명: 하시모토갑상선염, 1명 : 그레이브스병 ) 이진단되었으며하시모토갑상선염환자중 1예에서원발성갑상선림프종이진단되었다 (Table 2). 3예에서기능과형태학적으로정상소견을보였으며, 폐암에대한평기결정을위해시행되었던 1예에서갑상선초음파상양엽의미만성종대가관찰되었으며미세침흡인세포검사에서전이성폐암으로진단되었다. 갑상선초음파에서우엽의결절성병변이보인 1예에서갑상선유두암이진단되었으며, 수술후시행한조직학적검사에서갑상선유두암외기저만성갑상선염소견은관찰되지않았다. 여성의빈도는자가면역갑상선질환의경우 88.2% (15/17), 양성의경우 94.7% (18/19) 였으며악성 의경우 33.3% (1/3) 에서여성이었다. 미만섭취군에서 TSH 증가정도와 SUV max 와의상관관계는 TSH가증가할수록 SUV max 가증가하는경향을보였으나통계학적유의성은관찰되지않았다 (R 2 = 0.140, p = 0.086, Fig. 1A). 갑상선자가항체 (anti-tpo antibody) 가측정된환자 19예에서항체의역가가증가할수록 SUV max 가증가되는경향은보였지만역시통계학적유의성은보이지않았다 (R 2 = 0.197, p = 0.057, Fig. 1B). SUV max 는악성군에서 10.2 ± 6.9로양성갑상선질환군의 4.4 ± 2.4에비해악성군에서높았으나통계학적유의성은없었다 (p = 0.282, Fig. 2). 고찰건강검진또는암의병기평가를위해 18 F-FDG PET/CT 이시행된 3,303예중에서 56예 (1.7%) 에서갑상선의 18 F-FDG 섭취가관찰되었으며 34예 (60.7%) 에서국소섭취를 22예 (39.3%) 에서미만섭취가확인되었다. 미만섭취를보이는경우추가적인갑상선초음파검사및미세침흡인세포검사를시행하여 17예 (77.3%) 에서갑상선실질의에코가감소되는만성갑상선염소견이관찰되었으며, 3예 (13.6 %) 에서악성종양이진단되었다. SUV max 와 TSH 및 anti-tpo antibody 역가간의상관관계는보이지않았으며악성군과양성군사이 SUV max 의통계학적차이는없었다. 갑상선암진단에있어 FDG PET 의민감도는 60-80%, 특이도 66-91% 로보고되고있는데 [14,15], 암의선별검사로서의유용성보다는분화갑상선암수술후추적관찰중혈청갑상선글로불린 (thyroglobulin) 이높아재발이나전이가의심되나방사성요오드스캔에서병소가확인되지않는경우매우유용한검사로알려져있다 [16]. 양전자방사성동위원소인 18 F가포도당과구조적유사체인 FDG에결합하여갑상선세포막의포도당수송체를통해갑상선세포내로유입되어

4 - 대한내과학회지 : 제 81 권제 5 호통권제 615 호

5 - 김희경외 3 인. 18 F-FDG PET 에서미만성갑상선섭취 - A B Figure 1. (A) Plot of serum thyroid stimulating hormone (TSH) vs. SUV max in 22 patients with diffuse fludeoxyglucose (FDG) thyroid uptake. (B) Plot of serum anti-tpo antibody vs. SUV max in 19 patients with diffuse FDG thyroid uptake. Figure 2. Comparison of SUVmax between the malignant and non-malignant groups in patients with diffuse thyroid uptake of fludeoxyglucose (FDG). No statistical difference was found. hexokinase 1에의해 18 FDG-6-PO 4 로인산화후세포내에축적되면영상학적으로갑상선섭취를보이게된다 [16]. 정상갑상선세포는주영양소가포도당보다는유리지방산으로정상적으로는섭취가관찰되지않지만 [7], 일부갑상선암에서 glucose transporter 1 (GLUT1) 유전자의발현과 hexokinase 1의발현이증가되어세포내포도당축적이늘어나면 18 F-FDG 의섭취가증가된다 [17,18]. 하시모토갑상선염, 그레이브스병등자가면역갑상선질환에서보이는갑상선의미만성 FDG 섭취기전에대해서는명확하지않지만, 유육종증 [19], 선림프종 (Warthin s tumor)[20] 및반응성림프선염 [21] 에서 FDG 섭취가관찰되는것과같이림프구의갑상선침윤에의한것으로알려져있다 [10]. 본연구에서도 22예중 17예 (77.3%) 에서하시모토갑상선염 (16예) 과그레이브스병 (1예) 으로진단되어다른연구와유사한소견을보였다 [2,10]. FDG PET 에서국소성갑상선섭취를보이는경우악성의빈도가 26-50% 로보고되었으며 [2,3,22,23], 공격적인임상경과를보이는것으로알려져있어 [24], FDG PET 에서발견된갑상선우연종은갑상선암의고위험군으로 5 mm 이상인경우미세침흡인세포검사를시행할것이권고되고있다 [25]. 본연구에서도국소적섭취를보이는경우악성의빈도가 35.3% (12/34) 로기존의보고와유사하였으며, 미만섭취를보이는경우악성의빈도가 13.6% (3/22) 로국소적섭취에비해낮은악성빈도를보였지만통계학적으로차이는없었다. 다른연구에서도국소적섭취에비해서미만섭취의경우갑상선암의빈도가낮은것으로보고되었으나 [2] 조직학적확인이이루어지지않은제한점이있다. 본연구에서는세포학적으로원발성갑상선림프종과폐암의갑상선전이로진단된경우를제외하고악성이의심되는경우모든환자에서수술을통해병리학적으로악성을확인하였다. 갑상선의악성종양중가장흔한것은분화갑상선암이며 [26] 본연구에서국소섭취를보이는악성종양 12예모두에서는분화갑상선암인갑상선유두암이진단된반면, 미만섭취를보인 3예의악성종양중 1예에서만갑상선유두암이었고, 이경우에서도유두암부위에서더높은국소적섭취가관찰되었다. 일부연구에서갑상선에국소또는미만섭취를보이는경우 SUV max 가양성군에비해통계학적으로유의하게높고종양의크기및공격성과연관되며 [2,15], SUV max 3.5 이상인경우악성의민감도 80.0%, 특이도 66.1% 인것으로보고되

6 - The Korean Journal of Medicine: Vol. 81, No. 5, 었다. 하지만일부보고에서는악성과양성간에 SUV max 의차이가없다 [3,24] 는결과를보여논란이있는실정이다. 본연구에서미만섭취를보이는경우악성군에서 SUV max 가 10.2 ± 6.9로양성갑상선질환군의 4.4 ± 2.4에비해높았지만통계학적으로의의있는차이를보이지않았다. 하지만갑상선유두암 ( 미만성섭취 SUV max 2.4, 국소섭취 SUV max 3.0) 을제외한악성종양의경우원발성갑상선림프종에서 SUV max 12.7, 전이상폐암에서는 15.6으로 10 이상의높은 SUV max 를확인할수있었다. 본연구를통해미만성갑상선섭취를보이는경우분화갑상선암은비교적흔하지않으며, 높은 SUV max 를보이는경우분화갑상선암외의다른갑상선의악성질환을고려하여추가적인검사를시행해야할것으로생각한다. 또한미만성갑상선섭취를보이는경우자가면역갑상선질환이주원인으로여성의빈도 86.4% (19/22) 가높았지만, 3명의남성에서 2명이악성으로진단되어남성의경우특히세밀한검사가필요할것으로생각한다. 본연구의제한점으로는후향적연구로서적은수의환자군을대상으로연구가진행되어악성환자에서 SUV max 에따른공격성및예후에대한연구가불충분한점이있다. 또한미만섭취를보이는경우 22예에서남성의수가 3예로적어실제적으로성별에따른차이가있는지여부는향후추가적인전향적연구를통해확인이필요하다. 결론적으로, FDG PET 에서갑상선미만섭취는대부분 [77.3% (17/22)] 자가면역갑상선질환이었으나일부환자에서 (13.6%) 악성질환이진단되었다. SUV max 는 TSH 및 anti-tpo antibody 역가와관련성이없었으며양성과악성간의통계학적차이도없어 FDG PET 만으로명확한진단에이르지못하였다. 그러므로갑상선에 FDG의미만섭취가발견되는모든환자에서는자가면역성갑상선질환과갑상선암을배제하기위한면밀한혈청학적검사, 갑상선초음파및미세침흡인세포검사 ( 결절이발견되는경우 ) 가필요할것으로생각한다. 요약목적 : 다양한암의진단및병기결정을위해 18 F-FDG PET/CT (FDG PET) 의이용이급증하면서우연히갑상선에 FDG 섭취증가가발견되는경우가증가하고있다. 갑상선의국소적 FDG 섭취증가는갑상선암의위험이높다는사실이알려져있으나미만성 FDG 섭취증가의임상적의미는불 분명하다. 방법 : 2004년 8월부터 2006년 3월까지암에대한병기평가 (1,744예) 및건강검진 (1,559예) 을목적으로 FDG PET을시행한총 3,303예중갑상선에비정상적인섭취증가를보인 56예 (1.7%, 남 13, 여 53; 나이 55.9 ± 10.1) 를대상으로하였다. FDG 섭취정도는 SUV max 로평가하였다. 대상환자에서혈청 TSH, anti-tpo Ab와갑상선초음파검사를시행했으며결절이보이는경우미세침흡인세포검사를시행하였다. 결과 : FDG PET 에서갑상선 FDG 섭취증가는국소섭취가더흔했으며 (34 vs. 22) 악성의빈도는국소섭취군에서더흔했으나미만섭취군과유의한차이는없었다 (12예[35.3%] vs. 3예 [13.6%], p = 0.07). 미만섭취군 22명중 17예 (77.3%) 에서자가면역갑상선질환이있었고 ( 원발성갑상선림프종 1명포함 ), 3명은정상갑상선, 그리고갑상선유두암과전이성폐암이각각 1예씩확인되었다. 미만섭취군에서 TSH 증가정도및 anti-tpo Ab 역가와 SUV max 간에상관관계는없었으며 (p = 0.086, p = 0.057) 악성소견을보인 3예의 SUV max 는높았으나양성군에비교하여통계학적차이는없었다. 결론 : FDG PET 에서미만성갑상선섭취는대부분자가면역성갑상선질환을시사했으나암의빈도에있어국소섭취와차이가없었고 FDG PET만으로는암을감별할수없었다. 갑상선에미만성 FDG 섭취를보이는환자에서는자가면역갑상선질환을진단하기위한혈액검사뿐만아니라암을배제하기위한갑상선초음파검사및미세침흡인세포검사가필요할것으로생각한다. 중심단어 : 갑상선 ; 결절 ; 암 ; 18 F-FDG PET/CT; 초음파 REFERENCES 1. Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med 2006;354: Kang KW, Kim SK, Kang HS, et al. Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography for metastasis evaluation and cancer screening in healthy subjects. J Clin Endocrinol Metab 2003;88: Kim TY, Kim WB, Ryu JS, Gong G, Hong SJ, Shong YK. 18F-fluorodeoxyglucose uptake in thyroid from positron emission tomogram (PET) for evaluation in cancer patients: high prevalence of malignancy in thyroid PET incidentaloma. Laryngoscope 2005;115: Kwak JY, Kim EK, Yun M, et al. Thyroid incidentalomas

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untitled 대한내분비외과학회지 : 제9권제3호 Vol. 9, No. 3, September 2009 원저 PET-CT 에서우연히발견된국소적갑상선결절의특징및중요성 경상대학교의학전문대학원외과학교실, 1 내분비내과학교실 김주연ㆍ문형곤ㆍ정은정ㆍ정태식 1 ㆍ정순일 1 ㆍ정상호ㆍ정치영ㆍ주영태ㆍ이영준ㆍ홍순찬ㆍ최상경하우송ㆍ박순태 The Characteristics and Significances