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1 Osteoporosis Vol. 10 No. 2 August 2012 pp Case Report 말기신부전환자에서이차성부갑상선기능항진증과연관하여상악골에발생한갈색종의 7년간추적결과 1예 연세대학교의과대학내과학교실 1, 연세대학교의과대학내분비연구소 2 김원진 1 김다함 1 이수진 1 임승길 1,2 이유미 1,2 Seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure Wonjin Kim 1, Daham Kim 1, Su Jin Lee 1, Sung-Kil Lim 1,2, Yumie Rhee 1,2 1 Department of Internal Medicine, 2 Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD) as a result of prolonged hyperphosphatemia and hypocalcemia. Brown tumor is a rare bony complication of hyperparathyroidism as a result of increased osteoclastic activity and fibroblastic proliferation. Frequent sites of brown tumor are known as ribs, clavicles, mandible, and pelvic bone, but maxilla is very rare site. Twenty sevenyear-old woman with stage V CKD on hemodialysis presented with maxillary mass which had gradually increased in size for 3 years. It was painless, but tooth derangement occurred. Initial laboratory findings revealed hypercalcemia (11.0 mg/dl), hyperphosphatemia (6.9 mg/dl), high creatinine (7.5 mg/dl), and high serum PTH ( pg/ml). The bone mineral density was significantly low (lumbar spine Z-score: -4.1, femur neck Z-score: -4.5). Radiologically, there were resorptive lesions in the maxilla. We performed total parathyroidectomy with transplanting half of her parathyroid gland on her right forearm. After surgery, serum PTH was markedly decreased to normal level. Immediate post-operative hypocalcemia developed without any change in serum Pi, then calcium gradually normalized. Seven years after the parathyroid surgery, she finally underwent renal transplantation that lead her calcium, phosphate and creatinine corrected to normal range, and the size of brown tumor has decreased further more. We report a case of long term follow up on a brown tumor in the maxilla which is infrequent site finally recovered. Key Words: Brown tumor, Secondary hyperparathyroidism, Chronic kidney disease 이차성부갑상선기능항진증은만성신부전의흔한합병증으로, 고인산혈증과저칼슘혈증으로특징지어진다. 1-3 갈색종 (Brown tumor, osteitis fibrosa Received: April 30, 2012 Revised: August 2, 2012 Accepted: August 20, 2012 Corresponding Author: Yumie Rhee, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, , Korea Tel: , Fax: YUMIE@yuhs.ac cystica) 은파골세포의활성화및섬유세포의증식으로인해뼈에발생하게되는부갑상선기능항진증의드문합병증가운데하나로 4, 이는늑골, 쇄골, 하악골, 골반과같은부위에주로발생하고, 상악골이나경구개에서의발생은극히드문것으로알려져있다. 5 갈색종은이차성부갑상선기능항진증에서약 1.5~1.75%, 일차성부갑상선기능항진증에서약 3~4% 발생하는것으로알려져있다. 6 이들중상악 82

Wonjin Kim, et al:seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure A B C D Fig. 1. Initial radiologic findings.

2 Wonjin Kim, et al:seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure A B C D Fig. 1. Initial radiologic findings. (A) Panoramic view of maxilla and mandible: Multifocal bone demineralization is ed on both jaws. Generalized loss of lamina dura on whole dentition is also ed. (B) Lumbar-sacrum lateral x-ray: compression fracture of L1 (arrow). (C) and (D) Maxilla and mandible CT. (C) Axial soft tissue window setting image: Multifocal osteolytic lesions with bony expansion are ed on maxilla. (D) Coronal bone window setting image: Multifocal bone demineralization with bony expansion is ed on both mandiblar rami. 골에서 4.5~11.8% 정도로발생하는것으로알려져있다 년에처음국내에보고되었고, 5 최근까지 11개의증례가더보고되었다. 골반뼈 1예, 하악골 3예, 손목뼈 1예, 척추뼈 1예, 갈비뼈 1예, 대퇴골 1 예, 손가락뼈 1예 4,5,8-14 가있으며, 일차성부갑상선기능항진증에의해상악골에발생한 1예 5 와이차성부갑상선기능항진증에의해상악골에발생한갈색종 1예 15 가있다. 2008년부터 2011년까지국외에서는 18개의상악골갈색종 6,16-22 이보고되었고이들은대부분부갑상선절제술을통하여치료되었다. 저자들은혈액투석을받고있는만성신부전환자에서발생된이차성부갑상선기능항진증으로인한상악골의갈색종 1예를 7년간장기추적검사하여이에대해보고하는바이다. 증례보고환자 : 27세, 여자주소 : 지속적인크기증가를보이는상악골의종물및하부요통 현병력 : 내원 3년전부터상악골의종물이점점커지기시작하였으나이에대한특별한치료는받지않았다. 환자는입이잘다물어지지않아식사를할때에음식이바깥으로새어나왔으며, 치열이흐트러지면서잇몸에간헐적인출혈도동반되었다. 또한내원 1달전부터하부요통증상발생하여시행한검사에서골다공증에의한압박골절발생하여이에대한치료위해내분비내과로협의진료의뢰되었다. 과거력 : 1997년고혈압으로투약시작하였고, 만성신부전진단받고혈액투석중이었다. 2003년이차성부갑상선기능항진증진단받았으나치료받고있지않았다. 가족력 : 특이사항없었다. 진찰소견 : 급성병색을보였으며, 혈압 170/90 mmhg, 맥박 95회 / 분, 호흡 20회 / 분, 체온 36.8 o C이었고의식은명료하였다. 하부요통있었으나부종이나열감은관찰되지않았고, 상악골의종괴는치열이상을초래하였고이로인해치아사이가벌어지면서잇몸이파열되어이로인한통증이동반되었고, 또한입을잘다물어지지않았다 (Fig. 1A, 5A). 그외 83

Osteoporosis Vol. 10 No. 2 August 2012 pp. 82-89 Fig. 2. Parathyroid scan (MIBI).

lesion. Fig. 3. Neck ultrasonography: dense calcified or non-calcified rim lesions, suspicious of parathyroid gland.

3 Osteoporosis Vol. 10 No. 2 August 2012 pp Fig. 2. Parathyroid scan (MIBI). The inferior portion of bilateral thyroid lobe showed focal uptake of radioiodide and delayed washout, which indicates parathyroid lesion. Fig. 3. Neck ultrasonography: dense calcified or non-calcified rim lesions, suspicious of parathyroid gland. 에는신체진찰상다른이상소견은보이지않았다. 검사소견 : 혈청칼슘은 11.0 mg/dl ( 참고치 : 8.5~ 10.5) 로증가되어있었고, 인산염은 6.9 mg/dl ( 참고 치 : 2.5~4.5) 였으며, 부갑상선호르몬은 1,729.9 pg/ml ( 참고치 : 10~65) 였고, 크레아티닌은 7.5 mg/dl였다. 말초혈액검사에서백혈구 4,300/uL (%), 혈색소 84

Wonjin Kim, et al:seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure Fig. 4. Serial change of PTH. Fig. 5.

4 Wonjin Kim, et al:seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure Fig. 4. Serial change of PTH. Fig. 5. The features of brown tumor. (A) Before parathyroidectomy (B) 5-year postparathyroidectomy (C) 2-year post-renal transplantation. 9.0 g/dl, 혈소판 207,000 /ul였고, 생화학검사에서아스파르테이트아미노전이효소 (AST) 9 IU/L, 알라닌아미노전이효소 (ALT) 5 IU/L였으며, 알칼리인산분해효소는 456 IU/L ( 참고치 : 38~115), 총빌리루빈은 0.5 mg/dl였다. 혈청총콜레스테롤 149 mg/dl, BUN 33.2 mg/dl였다. 전해질검사에서 Na mmol/l, K mmol/l, Cl - 98 mmol/l, total CO 2 25 mmol/l였다. 25-수산화비타민 D는 5.33 ng/ml ( 참고치 : 9.6~37.6) 였다. 단순흉부엑스선검사에서경도의심장비대가있었고, 단순복부엑스선촬영에서요로결석은보이지않았다. 요추부엑스선검사상요추 1번의압박성골절이있었다 (Fig. 1B). 골밀도검사상요추부 Z-score -4.1, 대퇴부 -4.5로심한골다공증이확인되었고, 상악파노라마엑스선검사상양악골치조경선 (lamina dura) 의전반적인소실이관찰되었다 (Fig. 1A). 당시시행하였던부갑상선스캔 (MIBI) 에서갑상선양쪽하엽에서부분적조영증강이관찰되었고 (Fig. 2), 두경부초음파검사에서양측갑상선하부에석회화음영의유무가동반된병변이관찰되어 (Fig. 3), 부갑상선선종을의심할수있었다. 치료및경과 : 고칼슘혈증및부갑상선기능항진증에대해부갑상선전절제술을시행하였고우측상박에부갑상선자가이식을시행하였다. 수술후조직소견에서부갑상선비후가관찰되었다. 수술직후환자에서손발저림증상은관찰되지않았으며, 수술후 2일째혈청칼슘 6.7 mg/dl, 인산 2.6 mg/dl 소견보여염화칼슘 (calcium chloride) 1,200 mg을정주하였다. 혈청부갑상선호르몬은수술전 1,729.9 pg/ml에서수술후 5일째 pg/ml로감소되었다 (Fig. 4). 이후혈청칼슘이정상수치로회복되어수술후 22일째퇴원하였다. 이후외래에서추적관찰하였으며, 상악골의갈색종은지속적으로크 85

5 Osteoporosis Vol. 10 No. 2 August 2012 pp Fig. 6. Bone mineral density by dual x-ray absorptiometry, expressed by Z-score. 기감소되어입을다물수있게되었으며통증및출혈도없어졌다 (Fig. 5b). 환자는부갑상선절제술후 6년뒤신장이식술시행받았고, 혈청칼슘, 인산염, 크레아티닌모두정상범위로조절중이다. 진단당시동반되었던비타민 D 결핍증은칼시트리올 0.50 µg과콜레칼시페롤 1000 IU, 탄산칼슘 1,250 mg 복합제 (Dicamax R ) 를복용하면서정상범위로유지중이다. 부갑상선절제술후매년골밀도검사를시행하였고, 7년후시행한골밀도검사상에서도요추부 Z-score 0.7, 대퇴부 -0.2로정상화되고있으며 (Fig. 6), 갈색종의크기도더감소되었다. 고찰부갑상선기능항진증은혈청내의부갑상선호르몬농도증가로여러질환을유발하는병으로크게원발성, 이차성, 삼차성, 이소성으로분류한다. 원발성부갑상선기능항진증은부갑상선선종이나드물게부갑상선암에의하여발생하고, 이차성부갑상선기능항진증은비타민 D 결핍증이나만성신부전환자에서장기간의고인산혈증과이에따른저칼슘혈증에의하여발생한다. 오랜기간동안지속적인이차성부갑상선기능항진증으로부갑상선세포비후에서자가분비 (autonomous secretion) 하는선종으로변하게되면삼차 성부갑상선기능항진증이라한다. 9 만성신부전으로인한이차성부갑상선기능항진증은대부분약물및식이조절, 비타민 D 보충, 인산의섭취조절및인산결합제로치료한다. 최근에는칼슘유사물질 (calcimimetics) 도쓰는데투석중인환자에서만보험급여처리가되므로현재로서는제한적인사용만가능하다. 삼차성부갑상선기능항진증으로진행될경우부갑상선전또는아전절제술을시행한다. 갈색종즉, 낭성섬유성골염은부갑상선기능항진증의후기에나타나는고립성혹은다발성골병변이다. 5 대부분의갈색종은만성신부전에의한이차성부갑상선기능항진증으로인해발생하게된다. 23 이차성부갑상선기능항진증에서갈색종의발생률은약 1% 에서 13% 까지로추정된다 과거에는갈색종의원인이대부분일차성부갑상선기능항진증에서발생하였으나, 최근에는이차성부갑상선기능항진증에서의발생률이증가하고있다. 이것은투석을받고있는말기신부전환자들의생명연장과연관이있을것으로생각된다. 말기신부전에서갈색종, 골연화증, 골경화증, 그리고골다공증과같이여러가지골격계이상이발생하게된다. 23 갈색종은부갑상선기능항진증에의한광범위한골흡수과정의결과로알려져있다. 증가된부갑상선호르몬으로인해파골세포의작용이증가가되어 86

6 Wonjin Kim, et al:seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure Table 1. Case reports of brown tumor in Korea Authors, Year Sex/ Age Site of brown tumor Hyperparathyroidism Calcium (mg/dl) Phosphate (mg/dl) Creatinine (mg/dl) Park et al., F/56 left maxilla Secondary Kim et al., F/32 mandible Secondary Treatment Total parathyroidectomy & mass excision Total parathyroidectomy Postoperative follow-up period 12 months 6 months Mok et al., M/44 left pelvic bone Primary Total parathyroidectomy 12 months Chun et al., F/39 hard palate Primary 14.2 Left parathyroidectomy & mass excision 8 months Lee et al., F/50 maxilla, mandible Primary Park et al., F/35 lingual side of the mandible Secondary Park et al., F/70 right wrist Primary Choi et al., M/34 spine: L compression fracture Primary Parathyroidectomy Excision of the mandible lesion Total parathyroidectomy Right parathyroidectomy 12 months Mok et al., M/80 right 10th rib Primary Total parathyroidectomy Chon et al., M/52 femur shaft, phalanges Primary Parathyroidectomy Lee et al., M/18 right 5th phalanx Primary Total parathyroidectomy 8 months 골흡수가진행된다. 활성화된다핵파골세포들이뼈안에미세골절을생성하게되어출혈및그주위로혈철소를포함하는대식세포들이둘러싸게된다. 이것을신호로섬유모세포들이섬유주표면과골수에모이게되고섬유주의주변으로섬유화를촉진하게된다. 갈색종은이러한골흡수와섬유화의진행으로육안으로보이는낭종이발생한것이다. 23,26 이것은대부분서서히자라고통증을동반하는종괴의형태로나타난다. 주로늑골, 쇄골, 하악골, 골반에발생하고, 상악골이나경구개에서의발생은극히드물게발생한다. 5 본증례에서도내원 3년전부터상악골종괴의크기가서서히증가하였고종괴자체는통증을유발하지는않았지만주위압박으로인해잇몸이찢어지면서통증및출혈을동반하였다. 부갑상선기능항진증에의한갈색종에대한일반적인치료방법은부갑상선절제술로알려져있다. 그러나부갑상선절제술후의갈색종치료방법에대해서는이견이있다. Scott 등 27 은부갑상선호르몬의증가로인해갈색종은서서히소실되지만골파괴를동반한광범위한낭성변화가있는갈색종의경우는수술이필요하다고보고하였고, Daniel 등 28 은갈색종의자연소실이더디거나오히려크기가커지는경우, 기능적장애를초래하는경우에국소소파술이나외과적적출술을시행해야한다고보고하였다. 반면부갑상선절제술후갈색종이정상적인골로전환되면서골병변이소실된다는주장도있는데, Knevezic 등 29 은부갑상선절제술후젊은나이일경우에는골병변의소실이몇달사이에도일어날수 87

7 Osteoporosis Vol. 10 No. 2 August 2012 pp 있고, 나이가많은경우에는수년이걸릴수도있다고하였다. 즉, 환자의나이와골병변의크기에따라골병변이소실되는시간에차이가있을뿐골병변에대한수술은필요하지않다고하였다. 앞서기술한바와같이국내에서도 11개의증례보고가있었다 (Table 1). 8명의환자가일차성부갑상선기능항진증에의해갈색종이발생하였으며, 5,8,9,11-14,30 3명은이차성부갑상선기능항진증에의해발생하였다. 4,10,15 일차성부갑상선기능항진증이있는환자들에서혈청칼슘은 11.0~16.7 mg/dl로증가되어있었고, 이차성부갑상선기능항진증환자들은 9.9~ 10.4 mg/dl로정상범위내에있었다. 대부분의환자에서부갑상선절제술을시행하였고, 1예에서만갈색종적출술을시행하였다. 10 증례들에서는 1년정도의단기간추적관찰후에보고를하였다. 본증례는부갑상선절제술시행후 7년간의장기추적관찰중이며, 수술적인치료없이갈색종의종괴는지속적으로감소하고있다. 발생초기에있었던저작시불편감이나통증및출혈은없고, 현재칼시트리올 0.25 mcg을복용하면서매년시행하는골밀도검사에서골밀도가정상화되었다. 요약저자들은만성신부전으로인한부갑상선기능항진증의드문합병증인상악골의갈색종을진단하였고, 부갑상선절제술시행후갈색종의지속적인크기감소가관찰되었다. 이차성부갑상선기능항진증으로인한갈색종을수술적인치료없이 7년간의장기간추적관찰을통하여크기의감소와통증의소실등의호전을경험하였기에보고하는바이다. 참고문헌 1. Kronenberg HM. Hormones and disorders of mineral metabolism. 11th ed. Philadelphia: Saunders; Fraser WD. Hyperparathyroidism. Lancet 2009;374: JT P. Harrison's principles of internal medicine. 17th ed: McGraw-Hill Professional; Kim MS, Han DH, Lee CH. A Case of Brown Tumor of the Mandible Caused by Hyperparathyroidism. Korean J Otorhinolaryngol-Head Neck Surg AID 2010;53: Chun BJ, Lee MH, Noh HI, Park YJ. A Case of Brown Tumor of the Hard Palate in Association with Primary Hyperparathyroidism. Korean J Otorhinolaryngol-Head Neck Surg AID 2009;52: Di Daniele N, Condo S, Ferrannini M, Bertoli M, Rovella V, Di Renzo L, et al. Brown tumour in a patient with secondary hyperparathyroidism resistant to medical therapy: case report on successful treatment after subtotal parathyroidectomy. Int J Endocrinol 2009;2009: Triantafillidou K, Zouloumis L, Karakinaris G, Kalimeras E, Iordanidis F. Brown tumors of the jaws associated with primary or secondary hyperparathyroidism. A clinical study and review of the literature. Am J Otolaryngol 2006;27: Mok JO. A Case of Brown Tumor with Severe Hypercalcemia Caused by Parathyroid Adenoma. J Korean Soc Endocrinol 2003;18: Choi YW, Ok CS. Brown Tumor of The Spine with Compression Fracture: A Case Report. J Korean Radiol Soc 2006;54: Park JW, Choi BR, Gang TI, Huh KH, Yi WJ, Choi SC. Mandibular brown tumor in renal osteodystrophy. Korean J Oral Maxillofac Radiol 2008; 38: Park H, Kang GH, Kim SG, Kim JJ, Baek NN, Kim DM, et al. Brown Tumor of the Ulna and Radius: An Unusual Presentation of Primary Hyperparathyroidism. J Korean Endocr Soc AID /jkes [doi] 2008;23: Mok JY, Kim HY, Ter HC, Kim SO, Kim DK, Han JS, et al. A Case of Primary Hyperparathyroidism with Rapid Regression of a Brown Tumor after Parathyroidectomy. J Korean Endocr Soc AID /jkes [doi] 2010;25:

8 Wonjin Kim, et al:seven Year-follow-up of a Brown Tumor in the Maxilla Associated with Secondary Hyperparathyroidism in End-stage Renal Failure 13. Chon S, Kim YH, Park JY, Ko KP, Park CY, Kim DY, et al. A Case of Cystic Parathyroid Adenoma Presenting as Severe Bony Lesion. J Korean Soc Endocrinol 2003;18: Lee SK, Moon SD, Kim HS, Park EJ, Ahn SJ, Han JH, et al. A case of mediastinal parathyroid adenoma presenting as fracture of brown tumor. The korean Journal of Medicine 1999;56: Park DW, Lee CG, Lee JY, Kim HK. A case of brown tumor of the maxilla associated with secondary hyperparathyroidism. Korean J otorhinolaryngol Head Neck Surg 2011;54: LB. Fatma, S. Barbouch, BH. Fethi, BA. Imen, K. Karima, H. Imed, et al. Brown tumors in patients with chronic renal failure and secondary hyperparathyroidism: report of 12 cases. Saudi J Kidney Dis Transpl 2010;4: Nabi Z, Algailani M, Abdelsalam M, Asaad L, Albaqumi M. Regression of brown tumor of the maxilla in a patient with secondary hyperparathyroidism after a parathyroidectomy. Hemodial Int 2010;14: Marlene Corr Pinto, Scheila Maria Gabeta Sass, Cl dia Paragua Pupo Sampaio, Danielle Salvatti Campos. Brown tumor in a patient with hyperparathyroidism secondary to chronic renal failure. Braz J Otorhinolaryngol 2010;76: Sutbeyaz Y, Yoruk O, Bilen H, Gursan N. Primary hyperparathyroidism presenting as a palatal and mandibular brown tumor. J Craniofac Surg 2009; 20: Firat. Selvi, S. Cakarer, R. Tanakol, SD. Guler, C. Keskin. Brown tumour of the maxilla and mandible: a rare complication of tertiary hyperparathyroidism. Dentomaxillofacial radiology 2009;38: Proimos E, Chimona TS, Tamiolakis D, Tzanakakis MG, Papadakis CE. Brown tumor of the maxillary sinus in a patient with primary hyperparathyroidism: a case report. J Med Case Reports 2009; 3: Resendiz-Colosia JA, Rodriguez-Cuevas SA, Flores-Diaz R, Juan MH, Gallegos-Hernandez JF, Barroso-Bravo S, et al. Evolution of maxillofacial brown tumors after parathyroidectomy in primary hyperparathyroidism. Head Neck 2008;30: Fargen KM, Lin CS, Jeung JA, Yachnis AT, Jacob RP, Velat GJ. Vertebral Brown Tumors Causing Neurologic Compromise. World Neurosurg Griffiths HJ, Ennis JT, Bailey G. Skeletal changes following renal transplantation. Radiology 1974; 113: Kaya RA, Cavusoglu H, Tanik C, Kahyaoglu O, Dilbaz S, Tuncer C, et al. Spinal cord compression caused by a brown tumor at the cervicothoracic junction. Spine J 2007;7: Fineman I, Johnson JP, Di-Patre PL, Sandhu H. Chronic renal failure causing brown tumors and myelopathy. Case report and review of pathophysiology and treatment. J Neurosurg 1999;90: Scott SN, Graham SM, Sato Y, Robinson RA. Brown tumor of the palate in a patient with primary hyperparathyroidism. Ann Otol Rhinol Laryngol 1999;108: Daniels JS. Primary hyperparathyroidism presenting as a palatal brown tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98: Knezevic G, Uglesic V, Kobler P, Svajhler T, Bagatin M. Primary hyperparathyroidism: evaluation of different treatments of jaw lesions based on case reports. Br J Oral Maxillofac Surg 1991;29: Lee JK, Cho SD, Leem DH. A case report: brown tumor of the maxilla and mandible in association with primary hyperparathyroidism. J Korean Assoc Maxillofac Plat Reconstr Surg 2009;31:

05.Kaes001.hwp

05.Kaes001.hwp 혈액투석환자에서삼차성부갑상선기능항진증으로부갑상선절제술후발생한 Hungry Bone Syndrome 1 예 A Case of Hungry Bone Syndrome after Parathyroidectomy in Patient with Tertiary Hyperparathyroidism and Hemodialysis Patient Myoung Won Son, M.D.,