C A S E REPORT ISSN: 2005-162X Clin Exp Thyroidol 2015 May 8(1): 98-102 http://dx.doi.org/10.11106/cet.2015.8.1.98 중독성선종으로방사성요오드치료후발생한그레이브스병 1 예 원자력병원내과 윤석영, 신기철, 조애리, 김민주 Radioactive Iodine-Induced Graves Disease in a Patient with Toxic Adenoma Seokyoung Yoon, Kichul Shin, Eirie Cho and Min Joo Kim Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea We report a rare case of radioactive iodine (RAI)-induced Graves disease in a patient with toxic adenoma. A 42-year-old woman presented with neck masses. A hot nodule was detected on a thyroid scan, which suggested toxic adenoma. She was treated with RAI. Three months after the treatment, she complained of thyrotoxic symptoms such as weight loss, palpitation, diarrhea, and menstrual irregularity. A new thyroid scan showed diffuse increased uptake, while the toxic adenoma previously detected was now a cold nodule. Moreover, an increased level of antibodies against the thyroid-stimulating hormone receptor was detected. These findings indicated Graves disease. Hence she was treated with anti-thyroid drug. This case serves as a reminder for physicians to consider RAI-induced Graves disease if thyrotoxicosis is noted after RAI treatment. Key Words: Graves disease, Radioisotopes, Thyroid nodule, Thyrotoxicosis 서론 갑상선중독증은혈액과말초조직에갑상선호르몬이과다하여나타나는모든증상을일컫는데, 여러가지원인이있을수있다. 우리나라에서갑상선중독증의가장흔한원인은그레이브스병 (82.7%) 이고, 그다음은무통성갑상선염 (13.3%) 과아급성갑상선염 (3.5%) 이며, 중독성선종이원인인경우는 0.5% 에불과하다. 1) 중독성선종의빈도는요오드섭취량과밀접한관련이있는데, 요오드섭취가적은유럽이나남미지역에서는중독성선종이갑상선중독증의 20-30% 를차지하는반면, 요오드섭취량이충분한미국이나영국에서는 2-4% 에불과하다. 2) 우리나라또한요오드섭취량이충분한지역으로중독성선종이차지하는비율이낮다. 중독성선종을진단하기위해서는갑상선스캔검사를시행해야하며, 스캔에서중독성선종은열결절로나타난다. 그러나우리나라에서는갑상선중독증인경우에갑상선스캔을시행하는비율은 61% 에불과하기때문에 3) 중독성선종을간과하기쉽다. 중독성선종은방사성요오드나수술로치료해야하고, 항갑상선제는효과가없다. 방사성요오드치료는중독성선종뿐만아니라그레이브스병에도효과적인치료이다. 드물게중독성선종에대하여방사성요오드치료후그레이브스병이나타나는경우가외국에서보고된바가있으나 4-7) 아직국 Received April 1, 2014 / Revised August 13, 2014 / Accepted September 1, 2014 Correspondence: Min Joo Kim, MD, PhD, Department of Internal Medicine, Korea Cancer Center Hospital, 75 Nowon-ro, Nowon-gu, Seoul 139-706, Korea Tel: 82-2-970-1215, Fax: 82-2-970-2410, E-mail: chorong24@gmail.com Copyright c 2015, 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 (http:// creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 98
Radioactive Iodine-Induced Graves Disease 내에는 보고된 바가 없다. 저자들은 최근 중독성 선종 압 120/80 mmhg, 맥박 90회/분이었으며, 갑상선 촉진 에 대해 방사성요오드 치료 이후에 발생한 그레이브스 상 오른쪽에 2 cm, 왼쪽에 1 cm의 종괴가 만져졌다. 안 병을 경험하였기에 보고하는 바이다. 구돌출 등의 그레이브스 안병증 소견은 없었다. 흉부 및 복부, 신경학적 검사상 특이 소견은 없었다. 검사실 증 례 소견상 갑상선자극호르몬(thyroid stimulating hormone, TSH) 0.007 μiu/ml (정상범위, 0.27-4.20), 유리티록 42세 여자가 한 달 전부터 만져진 양측 갑상선결절 신(free thyroxine, ft4) 2.78 ng/dl (정상범위, 0.93-1.71), 로 내원하였다. 환자는 10년 전 첫 아이를 출산한 이후 삼요오드티로닌(triiodothyronine, T3) 2.06 ng/dl(정상 갑상선기능에 이상이 있어 잠시 약물을 복용한 적이 범위, 0.85-2.02), 제2세대 측정법을 이용한 갑상선수용 있었고, 몇 년 전 공황장애로 신경정신과 약물을 복용 체항체(TSH receptor antibody) 1.78 IU/L (정상범위, 한 적이 있었다. 가족력상 아버지가 갑상선암으로 치 1.72)이었다. 갑상선스캔(Fig. 1A)에서는 오른쪽 갑상 료받았고, 어머니가 갑상선기능 이상으로 약물을 복용 선에서 열결절 소견 보이고, 갑상선 초음파(Fig. 2A)에 중이었다. 이학적 소견상 신장 160 cm, 체중 50 kg, 혈 서는 오른쪽에 2.9 cm, 왼쪽에 1.3 cm의 결절이 발견되 Fig. 1. Change in the Tc99m thyroid scan. (A) Before radioactive iodine therapy, a hot nodule was noted in the right upper part of the thyroid. (B) After radioactive iodine therapy, diffuse uptake in both thyroid lobes was observed, except in the region in which toxic adenoma was previously noted. Fig. 2. Ultrasonography imaging and fine-needle aspiration cytology of the thyroid nodule. (A) Ultrasonography showed a 2.9 cm cystic heterogeneous nodule. (B) Fine-needle aspiration cytology of the thyroid nodule showed cystic goiter (magnification 200). 99 Clin Exp Thyroidol
Seokyoung Yoon, et al 었다. 갑상선결절의에코는불균일하였고일부에서낭성변화를보였다. 오른쪽갑상선결절에대하여세포흡인검사를시행하였고, 결과는양성 (cystic goiter) 이었다 (Fig. 2B). 이상의소견을종합하여갑상선중독성선종으로진단하고, 5주후에방사성요오드치료 (10 mci) 를시행하였다. 치료 3주후유리티록신 1.34 ng/dl로호전되었으나환자는가슴이두근거리고답답한증상을호소하였다. 치료 7주후에시행한검사에서유리티록신은 1.42 ng/dl으로유지되었다 (Fig. 3). 치료 12주후환자는가슴이두근거리고답답한증상뿐만아니라심한피로감과체중감소, 설사, 묽은변, 생리불순을호소하였다. 안구돌출등의그레이브스안병증소견은없었다. 혈액검사결과갑상선자극호르몬 0.05 μiu/ml, 유리티록신 >7.77 ng/dl, 삼요오드티로닌 3.76 ng/dl 으로갑상선중독증의재발소견을보였다. 그러나이전과달리갑상선수용체항체가 18.70 IU/L로높고, 갑상선스캔 (Fig. 1B) 에서이전의오른쪽중독성선종부위는냉결절로나타났으나다른부위에서는미만성섭취증가소견을보여그레이브스병으로진단하였다. 메티마졸 (methimazole) 을하루 30 mg 복용하기시작하였고, 약물복용 8주후환자의증상은호전되고유리티록신 0.903 ng/dl으로감소하였다. 이에메티마졸용량을감량하여복용하면서외래에서추적관찰중이다. 고찰 중독성선종과그레이브스병은발생기전과자연경 Fig. 3. Change in thyroid function after radioactive iodine (RAI) treatment. ft4: free thyroxine, T3: triiodothyronine, TSH: thyroid stimulating hormone. 과를고려할때전혀다른질병이다. 중독성선종은갑상선결절의자율성때문에생기는반면, 그레이브스병은자가면역질환으로갑상선수용체항체가갑상선세포를자극하기때문에발생한다. 2) 본증례에서는한환자에서중독성선종과그레이브스병이순차적으로발생하였다. 그레이브스병과중독성결절이함께동반되는 Marine-Lenhart 증후군을의심해볼수도있으나 8) 본증례의갑상선스캔에서단일열결절이명확하였기때문에 Marine-Lenhart 증후군이라기보다는방사성요오드치료에의한그레이브스병으로판단된다. 방사성요오드치료에의한그레이브스병에대한국내보고는아직없으나외국에서는중독성선종 4-7) 또는비중독성결절성갑상선종으로 9,10) 방사성요오드치료를받은후그레이브스병이발생한증례가여러차례보고된바있다. 유럽에서중독성선종또는비중독성결절성갑상선종으로방사성요오드치료를받았던환자들을후향적으로관찰한연구들에서그레이브스병은 1-9% 에서발생하였다. 11-15) 대부분방사성요오드치료후 3-6 개월에주로발병하였고, 늦게는 1년후에발병한경우도있었다. 본증례에서도방사성요오드치료 3개월후에그레이브스병이발생하였다. 중독성선종이나중독성다결절성갑상선종에서방사성요오드치료를한경우주로갑상선기능이정상화되었다가그레이브스병이발생하나, 드물게갑상선기능이정상화된적이없이계속갑상선중독증상태인경우도있다. 4,11) 본증례에서도방사성요오드치료후유리티록신은정상화되었으나갑상선자극호르몬은정상화되지않은채그레이브스병이발생하였다. 방사성요오드치료후갑상선세포가파괴되면서갑상선항원물질들이쏟아져나오고이에대한면역반응으로갑상선수용체항체가만들어졌다고추정된다. 16,17) 수술이나감염과같은다른원인에의해서갑상선세포가파괴되는경우에도갑상선수용체항체와그레이브스병이유발될수있음이이를뒷받침한다. 2) 방사성요오드치료후 3-6개월에갑상선수용체항체가증가하였다가이후에점차감소하며, 갑상선수용체항체가증가하더라도일부에서는그레이브스병이발생하지않고갑상선기능은정상으로유지되기도한다. 12) 환자의유전적인소인이나자가면역적인소인도관여한다. 18) 방사성요오드치료전갑상선과산화효소항체 (thyroid peroxidase antibody) 를가지고있는환자에서방사성요오드치료에의한그레이브스병이보다많이발생하였다. 4,12,13,15,19,20) 치료전갑상선과산화효소항체가양성인경우그레이브스병이 10-22% 에서발생 Vol. 8, No. 1, 2015 100
Radioactive Iodine-Induced Graves Disease 하였고, 이러한환자들은갑상선과산화효소항체가없는환자들에비해그레이브스병이 10배나많이발생한것이다. 12,15) 본증례의경우방사성요오드치료전갑상선과산화효소항체검사를시행하지는못하였지만이전에출산후갑상선질환을앓은병력과갑상선질환의가족력으로미루어보아자가면역성갑상선질환의소인을가지고있었을가능성이높다. 또한본증례에서는방사성요오드치료전에갑상선수용체항체가약간높았기때문에그레이브스병의소인을가지고있다가방사성요오드치료로발현되었다고생각할수도있다. 파종갑상선자율성 (disseminated thyroid autonomy) 도방사성요오드유발그레이브스병의위험인자로생각된다. 중독성선종중에서는단일중독성선종보다는중독성다결절성갑상선종 (toxic multinodular goiter) 에서보다많이발생하는것으로보고된바있다. 13,19) 방사성요오드치료후갑상선중독증이나타나는경우, 방사선갑상선염으로인하여발생한일시적인갑상선중독증인경우가많지만, 드물게본증례와같이방사성요오드치료에의한그레이브스병이발생할수있다. 따라서방사성요오드치료후 3-6개월뒤에갑상선중독증이발생한다면그레이브스병을배제하기위해갑상선스캔과갑상선수용체항체검사를시행해볼필요가있다. 특히, 치료전갑상선과산화효소항체가높은환자나자가면역질환의소인이있는환자는방사성요오드치료에의한그레이브스병의가능성을염두에두고주의깊게관찰해야하겠다. 중심단어 : 갑상선항진증, 그레이브스병, 방사성요오드, 중독성선종. References 1) Cho BY. Clinical thyroidology. 3rd ed. Seoul, Korea: Korea Medical Book Publisher; 2010. 2) Braverman LE, Cooper DS. Werner & Ingbar's the thyroid, a fundamental and clinical text. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. 3) Yi KH, Moon JH, Kim IJ, Bom HS, Lee J, Chung WY, et al. The diagnosis and management of hyperthyroidism consensus - report of the Korean Thyroid Association. J Korean Thyroid Assoc 2013;6(1):1-11. 4) Chiovato L, Santini F, Vitti P, Bendinelli G, Pinchera A. Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre. Clin Endocrinol (Oxf) 1994;40(6):803-6. 5) van Leussen JJ, Edelbroek MA, Talsma MA, de Heide LJ. Graves' disease induced by Na(131)I therapy for toxic multinodular goitre. Neth J Med 2000;57(5):194-7. 6) Regalbuto C, Salamone S, Scollo C, Vigneri R, Pezzino V. Appearance of anti TSH-receptor antibodies and clinical Graves' disease after radioiodine therapy for hyperfunctioning thyroid adenoma. J Endocrinol Invest 1999;22(2):147-50. 7) Orsolon P, Lupi A, De Antoni Migliorati G, Vianello Dri A. Appearance of Graves'-like disease following regression of autonomously functioning thyroid nodules. Two case reports. Minerva Endocrinol 1998;23(2):53-6. 8) Nishikawa M, Yoshimura M, Yoshikawa N, Toyoda N, Yonemoto T, Ogawa Y, et al. Coexistence of an autonomously functioning thyroid nodule in a patient with Graves' disease: an unusual presentation of Marine-Lenhart syndrome. Endocr J 1997;44(4):571-4. 9) Nygaard B, Metcalfe RA, Phipps J, Weetman AP, Hegedus L. Graves' disease and thyroid associated ophthalmopathy triggered by 131I treatment of non-toxic goiter. J Endocrinol Invest 1999;22(6):481-5. 10) Huysmans AK, Hermus RM, Edelbroek MA, Tjabbes T, Oostdijk, Ross HA, et al. Autoimmune hyperthyroidism occurring late after radioiodine treatment for volume reduction of large multinodular goiters. Thyroid 1997;7(4):535-9. 11)Nygaard B, Faber J, Veje A, Hegedus L, Hansen JM. Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy. Thyroid 1999;9(5):477-81. 12) Nygaard B, Knudsen JH, Hegedus L, Scient AV, Hansen JE. Thyrotropin receptor antibodies and Graves' disease, a side-effect of 131I treatment in patients with nontoxic goiter. J Clin Endocrinol Metab 1997;82(9):2926-30. 13) Meller J, Siefker U, Hamann A, Hufner M. Incidence of radioiodine induced Graves' disease in patients with multinodular toxic goiter. Exp Clin Endocrinol Diabetes 2006;114(5):235-9. 14) Custro N, Ganci A, Scafidi V. Relapses of hyperthyroidism in patients treated with radioiodine for nodular toxic goiter: relation to thyroid autoimmunity. J Endocrinol Invest 2003;26(2):106-10. 15) Schmidt M, Gorbauch E, Dietlein M, Faust M, Stutzer H, Eschner W, et al. Incidence of postradioiodine immunogenic hyperthyroidism/graves' disease in relation to a temporary increase in thyrotropin receptor antibodies after radioiodine therapy for autonomous thyroid disease. Thyroid 2006;16(3): 281-8. 16) Bech K. Immunological aspects of Graves' disease and importance of thyroid stimulating immunoglobulins. Acta Endocrinol Suppl (Copenh) 1983;254:3-38. 17) Feldt-Rasmussen U, Bech K, Date J, Petersen PH, Johansen K. A prospective study of the differential changes in serum thyroglobulin and its autoantibodies during propylthiouracil or radioiodine therapy of patients with Graves' disease. Acta Endocrinol (Copenh) 1982;99(3):379-85. 18) Kay TW, Heyma P, Harrison LC, Martin FI. Graves disease induced by radioactive iodine. Ann Intern Med 1987;107(6): 857-8. 19) Wallaschofski H, Muller D, Georgi P, Paschke R. Induction of TSH-receptor antibodies in patients with toxic multinodular goitre by radioiodine treatment. Horm Metab Res 2002;34(1): 36-9. 20) Dunkelmann S, Wolf R, Koch A, Kittner C, Groth P, Schue- 101 Clin Exp Thyroidol
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