) 대한소아내분비학회지 : 제 4 권제 호 9 원저 소아뇌종양수술후수분대사및전해질장애 연세대학교의과대학소아과학교실, 세브란스어린이병원 유하연 채현욱 김호성 김덕희 Water and Electrolyte Disturbances in Children after Surgery for Brain Tumors Ha Yeon Yoo, M.D., Hyun Wook Chae, M.D., Ho-Seong Kim, M.D. and Duk Hee Kim, M.D., Ph.D. Department of Pediatrics, Yonsei University College of Medicine, Severance Children s Hospital, Seoul, Korea Purpose : One of the most challenging problems associated with brain tumor surgery is the occurrence of water and electrolyte disturbances (WEDs) due to antidiuretic hormone (ADH) imbalance. This study was performed to investigate the incidence, risk factors and natural history of WEDs occurring after brain tumor surgery. Methods : We analyzed the clinical course and laboratory records of children who showed WEDs after brain tumor operation at Severance Children s Hospital between February 4 and February 9. Results : Fifty-two of 5 (.%) patients with WEDs (total, 65 cases) were diagnosed with diabetes insipidus (DI), and patient was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Eighteen patients had preoperative DI, which developed into a permanent condition. In another group of 4 patients, 7 had transient DI, while the remaining 7 patients, including 6 children with hyponatremia, showed progression to permanent DI. Among patients with craniopharyngioma, 7 developed preoperative DI;, transient DI; and 5, postoperative permanent DI. Among 4 patients with germinoma, 8 showed preoperative DI;, transient DI; and 4, postoperative permanent DI. In addition, among 7 patients with pituitary adenoma, developed transient DI and others developed postoperative permanent DI. The incidence of WEDs was high (5.5%) in patients with the abovementioned tumors, especially among those with suprasellar or hypothalamic lesions. Conclusion : Careful postoperative monitoring for WEDs is necessary for patients who have been preoperatively diagnosed with DI or suprasellar or hypothalamic lesions. Further, we recommend that postsurgical reassessment for DI should be performed in patients showing symptoms of DI. (J Korean Soc Pediatr Endocrinol 9;4:4- ) Key Words : Diabetes insipidus, Child, Brain neoplasms 서 소아에서뇌종양수술이후동반되는수분대사및전해질 장애 (water and electrolyte disturbances, WEDs) 는약 5.4-45.6% 에이르며, 이러한 WEDs 는주로뇌하수체, 시상하부주 Received : 5 September, 9, Revised : 9 October, 9 Accepted : 9 November, 9 Address for correspondence : Duk Hee Kim, M.D., Ph.D. Department of Pediatrics, Yonsei University College of Medicine, Severance Children s Hospital, 4 Shinchon-dong, Seodaemun-gu, Seoul, -75, Korea Tel : +8.-58-5, Fax : +8.-9-98 E-mail : dhkim@yuhs.ac.kr This study was presented at the 59 th fall meeting The Korean Pediatric Society, 9 론 위의병소에있는종양과관련되어발생한다 -). 이는항이뇨호르몬 (antidiuretic hormone, ADH) 혹은바소프레신 (arginine vasopressin, AVP) 이합성, 분비되는경로의손상과밀접한관계가있다. 항이뇨호르몬은시상상핵 (supraoptic nuclei) 과방실핵 (paraventricular nuclei) 의큰세포그물뉴론 (magnocellular neuron) 에서합성되어뇌하수체경 (pituitary stalk) 을타고뇌하수체후엽에저장되었다가분비되는데이경로에손상을주는대뇌병변이나, 혈관손상, 뇌부종등은중추성요붕증 (central diabetes insipidus, CDI) 혹은항이뇨호르몬부적절분비증후군 (syndrome of inappropriate antidiuretic hormone secretion, SIADH) 을일으킨다 4). 뇌종양수술후나타나는 WEDs는중추성요붕증과저나트륨혈증으로나타나는 SIADH와대뇌염분허비증후군 (cere- 4 대한소아내분비학회지 : 제 4 권제 호 9 년
bral salt wasting syndrome, CSWS) 으로구분되며전해질불균형때문에급성경련, 의식장애, 장기적인합병증등을가져올수있어고위험군을선별하여집중적으로감시하는것이필요하다. 국내에서뇌종양과방사선조사후동반되는소아의저신장, 범뇌하수체기능저하증, 비만에대한연구는많이보고되었으나수술후발생하는수분대사장애에대한보고는거의없는실정이다 5). 따라서본연구는단일기관에서최근 5년동안시행되었던소아뇌종양수술과관련중추성요붕증및 SIADH, CSWS의발생빈도와임상양상을고찰하고자하였다. 대상및방법 중반응마지막단계는 8-9% 이상의신경세포손상으로항이뇨호르몬결핍이나타나는시기로하였다 4). SIADH의진단은혈중나트륨농도가 5 mmol/l 이하, 혈중저삼투압농도, 혈장량의증가, 시간당.5 ml/kg 이하의핍뇨, 요중고삼투압농도소견을보이는환아로정의하였고수액이나신부전등의원인이있는경우는제외하였다 6). CSWS의진단은혈중나트륨농도가 mmol/l 이하이고, 혈중저삼투압농도, 혈장량의감소, 탈수, 시간당 cc/kg 이상의다뇨, 고나트륨뇨소견을보이는경우로하였다 7). 통계학적분석은 SPSS for Window (version., SPSS Inc., Chicago, IL, USA) 사용하여연속변수의분석은 Student s t-test, 비연속변수의분석은 Chi-square test를사용하였으며 P.5인경우통계적으로유의하다고판정했다. 4년 월부터 9년 월까지세브란스어린이병원소아신경외과에서뇌종양으로수술받은 세에서 9세에이르는소아청소년환자를대상으로하였다. 각환아의입원기록을후향적으로조사하여종양의위치와병리조직, 수술방법, 종양크기, 마취및투약기록과수술전후의수분섭취및배설량, 혈액과소변의전해질및삼투압농도, 요비중등을분석하였다. 수술과관련하여 주이내에발생한혈청나트륨의불균형이있을시이에대한경과와종양의병리학적분류를기록하였다. 외래기록을통해최근의임상경과와검사소견및약물사용의지속여부를확인하였다. 중추성요붕증의진단은혈중나트륨농도가 45 mmol/l 이상이고혈중삼투압이증가하고요비중이.5 미만이거나요중삼투압농도가 mosm/l 미만이며시간당 ml/ kg 이상의다뇨를보이면서바소프레신 (vasopressin, Han lim pharm. Korea) 혹은경구용 desmopressin (desmopressin acetate, minirin, Ferring parm. Korea) 을사용했을때다뇨증의호전을보이는경우로정의했다 6). 요붕증환아의혈중나트륨이 55 mmol/l 이상일때는중증고나트륨혈증이라하였다. 요붕증을진단할때고혈당, 신부전, 부신부전, 심부전의증거가없는환아만을포함하였으며임상소견및혈액소변의검사만으로진단을내리고혈중항이뇨호르몬검사및수분제한검사는시행하지않았다. 또한, 항이뇨호르몬치료지속여부에따라중추성요붕증을일과성요붕증, 영구적요붕증, 삼중반응 (triphasic pattern) 으로나누어분류하였다. 일과성요붕증이나삼중반응의첫단계는수술후 4-48시간이내에다뇨소견을보이다가 5-7 일이내에증세가스스로호전될때, 삼중반응의두번째단계는뇌하수체후엽세포의파괴로수술 -4일후호르몬이과다방출되어 SIADH의증상이나타날때, 영구적요붕증및삼. 대상환아의특성 Table. Number of Brain Tumor Cases Evaluated to Determine the Occurrence of Water and Electrolyte Disturbances Tumors 결 5 년동안뇌종양으로개두술을시행한 67 명의환아중뇌 종양으로진단받은환아는 65 명으로 명은 Rathke 열낭종이 었다. 65 례의종양을 7 년 WHO 에서권고한뇌종양분류 에의해나누어보면원발성종양 6 례, 전이성종양 4 례가 Tumors of neuroepithelial tissue Astrocytic tumors Neuronal and mixed neuronal-glial tumors Embryonal tumor Ependymal tumors Tumors of the pineal region Oligodendroglial tumors Choroid plexus tumors Oligoastrocytic tumors Other neuroepithelial tumors Tumors of the sellar region Craniopharyngioma Pituitary adenoma Germ cell tumors Germinoma Nongerminomatous germ cell tumors Tumors of the meninges Metastatic tumors Tumors of cranial and paraspinal nerves Lymphomas and hematopoietic neoplasms Total No. of cases (%) 5 (56.6) 6 5 4 47 (7.7) 7 4 (5.4) 4 7 (7.5) 4 (.5) (.) (.) 65 (.) Categorized by WHO 7 Classification of tumors of the central nervous system 과 소아뇌종양수술후수분대사및전해질장애 5
있었고단일종양중가장많은것은성상세포종 (astrocytoma) 으로 6례 (.6%) 였다. 그외종자세포종 (germ cell tumor) 4례 (5.4%), 두개인두종 (craniopharyngeoma) 례 (.%), 수모세포종 (medulloblastoma) 5례 (9.4%), 뇌하수체샘종 (pituitary adenoma) 7례 (6.4%) 의빈도를보였다 (Table ). 남, 여성비는.:로남아에서많았다. 발병연령의평균값은.9세 ±5.6세 (개월-9 세 개월 ), 평균추적관찰기간은 8.±7.7개월이었다 (Table ).. 수술전후발생한수분대사및전해질장애대상환아중수술전후로수분대사및전해질장애를보인환아는모두 5례 (.%) 로중추성요붕증이 5례, SIADH가 례있었다. 중추성요붕증환아 5례에서수술전요붕증소견을보였던환아는 8례 (6.8%) 였고이들은모두수술후영구적요붕증으로진행하였다 (Table ). 수술후요붕증소견을보인환아는 4례 (.8%) 로일시적으로저나트륨혈증을보인환아는 6명이었으며 명은 CSWS, 명은삼중반응의경과로 SIADH를나타냈다. 또한수술후 SIADH 소견을보이고정상으로회복된환아 례가있었다.. 종양의조직학적특성에따른수분대사및전해질장애수술전발생한요붕증환아 8례중배아종 (germinoma) 의요붕증발생률이.% 로가장높았다 (Table ). 두개인두종은수술전 7례 (.%) 에서요붕증소견을보였으며그외비전형기형 / 횡문근양종양 (atypical teratoid/rhabdoid tumor, ATRT), 수모세포종, 성상세포종등이수술전요붕증소견을보였다. 나머지 4명의요붕증환아는수술후에증상이나타났으며이중 7례는일시적인요붕증소견을보였고 7례는영구적요붕증으로나타났다. 두개인두종은모두 례가있었는데이중 7례에서수술후요붕증소견을보였으며 례는일시적경과를보이고호전되었고 5례는영구적요붕증으로진행하였다. 5례의영구적요붕증환아중 례에서요붕증과 SIADH가연이어나타나는삼중반응의경과가있었다. 배아종은모두 4례가있었는데이중 5례에서수술후요붕증을보였고 례에서수술후 SIADH를나타냈다. 수술후요붕증이발생한 5례중 례는일시적경과를보이고호전되었으며나머지 4례는영구적요붕증으로진행하였으며삼중반응의경과를보인배아종은없었다. 뇌하수체샘종은모두 7례가 Table. Clinical Characteristics of 65 Children with Brain Tumors Tumors of neuroepithelial tissue Tumors of the sellar region Germ cell tumors Tumors of the meninges Metastatic tumors Tumors of cranial and paraspinal nerves Lymphomas and hematopoietic neoplasms Total No. of cases (%) Mean Age (years) Sex (M/F) Mean Tumor size (cm) Mean FU (month) 5 (56.6) 47 (7.7) 4 (5.5) (7.5) 4 (.5) (.) (.) 65 () Abbreviation : FU, follow up duration after tumor surgery.±5.6.4±5.4.9±4.6.6±6. 6.8±. 9.± 6.8±6..9±5.6 7/77 7/ 6/5 4/6 / / / 46/9 4.±. 4.±.8.7±. 4.±.9.6±. 5.7.±. 4.±.6 8.7±6.4 6.±6.5 7.4±7.4.4±7..±.4.6 44.7±.5 8.±7.7 Table. Water and Electrolyte Disturbance Profile in Children with Brain Tumors Astrocytoma (n=6) Germ cell tumor (n=4) Germinoma (n=4) NGCT (n=7) Craniopharyngioma (n=) Medulloblastoma (n=5) Pituitary adenoma (n=7) Etc. (n=9) Total (n=65) Preoperative DI * (%) (.7) 8 (.) 7 (.) (4.) (.) 8 (6.8) Postoperative TDI SIADH PDI (%) 7 (.7) 4 (6.6) (5.9) 5 (5) (7.6) (.) 7 (.) WEDs (%) (.) 4 (58.) (5.9) 4 (8.) (8.) 6 (5.) 4 (4.) 5 (.) * The all of preoperative DI patients developed permanent DI after surgery There are cases of craniopharyngioma which combined with cerebral salt wasting syndrome followed by permanent DI after surgery glioblastoma, oligodendroglioma, neuroblastoma Abbrevations : DI, diabetes insipidus; Etc., et cetera; NGCT, nongerminomatous germ cell tumor; SIADH, syndrome of inappropriate secretion of antidiuretic hormone; TDI, transient diabetes insipidus; PDI, permanent diabetes insipidus; WEDs, water and electrolyte disturbances 6 대한소아내분비학회지 : 제 4 권제 호 9 년
있었고이중 6례에서수술후요붕증소견을보였으며 례는일시적인경과를보이고호전되었고나머지 례는영구적요붕증으로진행하였다. 기타희돌기교종 (oligodendroglioma) 례, 교모세포종 (glioblastoma) 례, 신경모세포종 (neuroblastoma) 례에서수술후요붕증소견을보였고모두영구적요붕증으로진행하였다. CSWS를보인종양은 례로모두두개인두종에해당했고수술후 시간내에저나트륨혈증, 다뇨, 탈수등을동반한증상을보이다가결국영구적요붕증으로진행하였다. 4. 종양의수술방법과위치에따른수분대사및전해질장애수술전수분대사및전해질장애를나타낸환아 8명을제외한 47명을수술방법에따라분류하여보면 78례에서전적출 (gross total removal) 을시행하였고 8례에서수분대사 및전해질장애가나타났으며전적출중 7례의경접형동접근법 (trans-sphenoidal approach, TSA) 환아중 6례에서수분대사및전해질장애가나타났다. 또한 8례의아전적출 (subtotal removal) 중 7례, 4례의정위조직검사 (sterotatic biopsy) 중 5례에서수분대사및전해질장애가나타났다. 뇌종양의최대직경의평균값은 4.±.6 cm로직경의범위는.-8. cm였고수분대사및전해질장애와종양크기와의상관관계는없었다 (P=.49). 종양을위치상으로분류했을때천막상종양이 례 (76.6%), 천막하종양이 6례 (.%) 였고천막상종양중에서도시상하부, 뇌하수체에있었던종양은모두 85례 (.%) 였다. 시상하부와뇌하수체등안상에있었던종양의수분대사및전해질장애발생률은 5.5%(4/85례 ) 로다른부위의종양에비해상대적으로높았다 (Table 4, P.5). Table 4. Incidences of Water and Electrolyte Disturbances with Respect to Tumor Location (65 patients) Supratentorial,hemisphere (n=) Pilocytic astrocytoma Glioblastoma Mestastasis Oliogodendroglioma Others Suprasellar (n=85) Craniopharyngioma Germ cell tumor Germinoma NGCT Pituitary adenoma Others Pineal gland tumor (n=5) Germ cell tumor Germinoma NGCT Others Infratentorial (n=6) Medulloblastoma Others Total No. of patients TDI SIADH PDI WEDs (%) 4 5 4 77 9 7 7 5 7 5 7 65 7 45 5 (4.9) 4 (5.5) 4 6 (.) (4.8) 5 (.) Abbrevations : NGCT, nongerminomatous germ cell tumor; PDI, permanent diabetes insipidus including preoperative DI; SIADH, syndrome of inappropriate antidiuretic hormone; TDI, transient diabetes insipidus; WEDs, water and electrolyte disturbances Table 5. Plasma Sodium (mmol/l) Levels in Symptomatic Subjects Preoperative Within days Within -7days After 7days Normal 5 Na 45 47 5 4 5 SIADH /CSWS Na 5/Na / / / / Mild DI 45 Na 55 6 5 6 4 Severe DI Na 55 Abbrevations : DI, diabetes insipidus; SIADH, syndrome of inappropriate antidiuretic hormone; Na, plasma sodium; CSWS, cerebral salt wasting syndrome 4 4 9 Total 65 65 65 65 소아뇌종양수술후수분대사및전해질장애 7
5. 수분대사및전해질장애발생시기및임상경과수분대사및전해질장애환아들의혈중나트륨은 4-79 mmol/l에이르는범위를보였고수술후경과를관찰했을때혈중나트륨이 55 mmol/l 이상의중증고나트륨혈증을보인환아는모두 6명이었다. 수분대사및전해질장애환아의수술후경과시간에따른혈중나트륨을살펴보면수술후 일이내고나트륨혈증의빈도수가 9례로가장많고 SIADH 와 CSWS에서보이는저나트륨혈증은수술 -7일에가장많았다 (Table 5). 수술전요붕증이있었던 8례중 4례 (77.7%) 는수술을시행하고 4시간이내에다시전형적인요붕증소견을보였고, 수술후요붕증이발생한 4례중 례 (9.4%) 는증상을 시간이내에, 6례 (76.4%) 는증상을 4시간이내에, 례 (88. %) 는증상을 48시간이내에보였다. 5명요붕증환아의평균외래추적기간은.8±5.개월이었으며이중 4명이사망하였고 명은추적할수없었다. 남은 46명환아중에서 7명은일주일내에요붕증치료를중단할수있어일시적요붕증이라할수있었고, 영구적요붕증환아중 명이 가지이상의뇌하수체호르몬을투약하며외래에서경과관찰하고있었다. 추적관찰중요붕증증상이호전되어투약을중단한경우는 4례로평균투약기간은.5±.5개월이었다. 고찰소아에서뇌종양은수술자체의어려움과종양주변조직의손상과관련된후유증때문에근치적제거가불가능한경우방사선치료를병행하고있다. 뇌종양수술후에동반되는저신장, 갑상선기능저하증, 비만등의내분비합병증은약 4% 에이르며 8), 특히방사선치료를추가로시행하거나뇌하수체, 시상하부주변에있는종양을제거하는수술일경우에는내분비합병증이더많이보고되고있다 9-). 뇌종양수술이나방사선치료후발생하는저신장, 뇌하수체기능저하등에대한연구는있었으나, 수술후소아에서발생하는수분대사및전해질장애특히요붕증에관한보고는거의없는실정이었다 5, 8, 9, -4). 따라서저자들은이번연구를통해뇌종양수술후발생하는수분대사및전해질장애의빈도와양상을파악하여고위험군에대한적절한평가와감시를하고자했다. 65명의수술환아중수분대사및전해질장애를보인환아는모두 5명이었고발생률은.% 였다. 중추성요붕증은 5명으로수분대사및전해질장애의 98.% 를차지하는주된 합병증이었는데이중 8례가수술전요붕증소견을보였으며수술후동반된요붕증은 4례로대부분 48시간내에증상을나타냈다. 소아뇌종양중안상 (suprasellar) 에서발생하는종양은약 % 에달하며내분비학적이상이빈번히동반된다고알려져있다 5). 본연구에서안상에위치하는두개인두종, 배아종, 뇌하수체샘종은전체종양의.% (85/65례) 에달했고수분대사및전해질장애 5례중 4례를차지했다. 985년부터 6 년간본원뇌종양환아를대상으로한연구를참고하면본연구의천막상종양이천막하종양보다매우높은것을알수있는데이는연구대상에청소년기를포함했기때문이다 6). 중추성요붕증은소아에게매우드문질환이지만시상하부나뇌하수체주변에서발생하는후천성뇌신경질환특히두개내종양에의해발생한다고알려져있다, 7). 이는종양을수술적조작할때주변혈관손상되거나병변자체나주변부위부종에의해삼투압에대한항이뇨호르몬분비가원활하게일어나지못하기때문이다. 요농축능력저하의정도와기간은병소의위치와연관이많아시상상핵및방실핵을침범하거나정중융기 (median eminence) 를지나는뇌하수체경이신경세포에가깝게절단될수록요붕증이잘발생한다고되어있으며뉴런이 8-9% 이상파괴될때는영구적요붕증으로진행한다 4). 개두술이후동반되는저나트륨혈증은경미한경과를보이지만일부에서는치명적인합병증을일으키며부신피질자극호르몬 (adrenocorticotropic hormone, ACTH) 을분비하는종양은약 6% 에서수술후저나트륨혈증을보인다 8). 시상하부, 뇌하수체주변의종양은경접형동접근법을통해제거하면약.8-5% 에서저나트륨혈증이동반되며이는성별, 종양의크기, 조직학소견에따라빈도에차이가있다 9). 이러한저나트륨혈증은대부분 SIADH나삼중반응의두번째단계혹은 CSWS로구분하여설명할수있다. 소아뇌종양수술후동반되는저나트륨혈증에서 CSWS의빈도수는약./, 례정도이며이번연구에서는 /65례 (.%) 로나타났지만, 아직소아에서정확한빈도를보고한연구는없다 7, ). 수분대사및전해질장애의출현이반드시시상하부뇌하수체주변부의수술에만국한되는것은아니다. 드물긴하지만시상하부와뇌하수체외다른부위종양수술후에도수분대사및전해질장애는나타날수있으며두개인두종, 종자세포종, 뇌하수체샘종외에도시상하부에있는성상세포종에서수술후요붕증과 SIADH가무려 9% 나보고되었다는연구도있다, ). 또한, 안상에위치한종양이라도수막종 (meningioma) 의경우에는요붕증발병이적다는것은흥미로운사실이다 ). 8 대한소아내분비학회지 : 제 4 권제 호 9 년
두개인두종은소아에서.5-례 /,명/ 년의발생률을보이는소아에서세번째로흔하게보고되는뇌종양으로약 6-9% 에이른다 -4). 발생학적으로라트케낭 (rathke s pouch) 의잔여상피조직에서유래하는양성종양이나시상하부, 뇌하수체, 시신경교차, 내경동맥, 뇌실에근접한안상주변 (parasellar) 에서발생하고누두경 (infundibular stalk) 과시상하부등의구조물을압박하여특징적인내분비증상을유발한다. 뇌신경과주요혈관들이종양의표면을가리고있어완전한적출이어려우며발견당시호르몬이상이 8-9% 에서동반되어있다 5). 이중뇌하수체전엽호르몬의불균형이가장흔하다고알려졌으며수술전뇌하수체후엽의불균형은적지만수술후약 7% 에서항이뇨호르몬결핍이나타나게되며근치적수술에서더잘발생한다. 중추성요붕증은수술전약 9-8% 에서수술후 76-94% 까지증가하여나타난다 4, 6-9). 본연구에서두개인두종의요붕증은수술전 7례 (.%) 에서수술후 4례 (8.%) 로증가하였으며이중 례는일시적요붕증소견을보였다. 두개인두종은종양의크기가클수록요붕증과함께목마름에대한지각능력도함께저하된다 ). 종자세포종은동양인과남아에서흔하게나타나고원발성두개내종양으로발생하는경우안상과송과체에주로발생한다. 소아뇌종양의 4-5% 를차지하며한국은약.% 정도로높은빈도를보인다 6). 종자세포종은시상하부전방, 송과체등의정중부에서흔히발생하며약 86% 에서요붕증을동반한다 -). 이중에서도배아종은남아와청소년기에가장많이나타나며두개내원발성종자세포종의 65% 를차지한다고알려졌다. 시상하부, 뇌하수체등안상에위치하는배아종은진단당시거의모든환아가요붕증을동반한다 5). 이는신경뇌하수체침범이빈번하기때문이다. 본연구에서보고된종자세포종은총 4례 (5.4%) 로 6례가안상에위치하였으며배아종은 9례있었다. 안상의종자세포종중요붕증을보인 례는모두배아종이었다. 본연구에서수술전요붕증을동반한배아종이.% 에불과했지만, 이는진단이의무기록을검토하는작업을통해후향적으로이루어졌기때문이라여겨지며수술전충분한병력청취가시행되었다면수술전요붕증을보이는환아가더많았을것이다. 뇌하수체종양은소아뇌종양의.% 를차지하는종양으로뇌하수체샘종의수술을시행한경우요붕증이나저나트륨혈증이약 5% 에서동반된다 ). 이러한수분대사및전해질장애의발현은수술방법에따라차이가있는데뇌하수체종양에서개두술을시행한경우약 75% 에서특히 TSA의경우에는 -44% 에서요붕증이동반된다 4,, 4). 그러나영구적으로요붕증증세가오는경우는.5-5% 로알려졌다 5). 종양의 크기와요붕증발현의상관관계는여러가지상반된보고들이있지만본연구에서종양의크기와수분대사장애발생의관련은없는것으로나타났다 6). 본연구의한계로는수분제한검사를시행하지못하고임상적인기록을통해요붕증을진단했던점, 임상증상이경미한요붕증환아를구분하는것이불가능했다는점, 재원일이비교적짧았던환아에게서수술 주일후의전해질변화를조사하지못하여일시적요붕증에대한판단이곤란했던점등이있다. 결론적으로뇌종양수술전이미요붕증이나타난환아는수술후에도영구적요붕증을보일가능성이크며시상하부, 뇌하수체상부를침범하는종양을진단받은환아는수술후수분대사및전해질장애의빈도가증가하므로철저한전해질과소변량의감시를통하여전해질불균형때문에발생하는합병증을막아야한다. 또한, 앞으로 CSWS의발병기전에관한연구와역학적조사가이루어져야할것이다. 요약목적 : 항이뇨호르몬은뇌종양수술후전해질불균형을가져오는중요한원인중하나로항이뇨호르몬과관련된수분대사및전해질장애의빈도, 경과및위험인자를분석하였다. 방법 : 4년 월에서 9년 월까지세브란스어린이병원에서뇌종양수술을시행한소아의기록을후향적으로조사하였으며수분대사및전해질장애와관련된검사결과와기록을참고하였다. 결과 : 총 65명환아중중추성요붕증을보인 5명과항이뇨호르몬부적절분비증후군 명을포함하여 5명 (.%) 이수술전, 후수분대사및전해질장애를보였다. 수술전부터요붕증소견을보인환아는 8명 (6.8%) 이었으며수술후에는모두영구적요붕증으로진행하였다. 수술후요붕증이발생한환아는모두 4명이었는데이중 7명은일시적요붕증소견을보이고나머지 7명은영구적요붕증으로진행하였다. 7명중저나트륨혈증의경과를동반한환아는 6명이었다. 례의두개인두종에는수술전요붕증을보인 7례와수술후일시적요붕증이나타난 례, 수술후영구적인요붕증경과를나타낸 5례가있었다. 4례의배아종에는수술전요붕증을보인 8례와수술후일시적요붕증이나타난 례, 수술후영구적인요붕증경과를나타낸 4례가있었다. 7례의뇌하수체샘종에는수술전요붕증을보인환아는없었고수술후에일시적요붕증나타난 례, 수술후영구적인요붕증이나타난 례가있었다. 수분대사및전해질장애는안상과시 소아뇌종양수술후수분대사및전해질장애 9
상하부에위치한위종양들에서높은빈도로발생했다 (5.5%). 결론 : 수술전이미요붕증이있거나안상과시상하부에 있는종양은수술전, 후수분대사및전해질장애에대한집 중관찰이필요하며요붕증소견을보였던환아들은수술후 일시적요붕증에대한재평가가필요하다. References ) Blumberg DL, Sklar CA, Wisoff J, David R. Abnormalities of water metabolism in children and adolescents following craniotomy for a brain tumor. Childs Nerv Syst 994;:55-8. ) Hiranrat P, Katavetin P, Supornsilchai V, Wacharasindhu S, Srivuthana S. Water and sodium disorders in children undergoing surgical treatment of brain tumors. J Med Assoc Thai ;86 Suppl :S5-9. ) Segura Matute S, Balaguer Gargallo M, Cambra Lasaosa FJ, Zambudio Sert S, Martin Rodrigo JM, Palomeque Rico A. Fluid and electrolyte disorders following surgery for brain tumors. An Pediatr (Barc) 7;67:5-. 4) Loh JA, Verbalis JG. Disorders of water and salt metabolism associated with pituitary disease. Endocrinol Metab Clin North Am 8;7:-4. 5) Song SM, Park EJ, Kim JS, Koo HH, Lee MH, Shin HJ, et al. Central diabetes insipidus in children related to craniotomy for a brain tumor. J Korean Pediatr Soc 999;4:7-. 6) Lin JJ, Lin KL, Hsia SH, Wu CT, Wang HS. Combined central diabetes insipidus and cerebral salt wasting syndrome in children. Pediatr Neurol 9;4:84-7. 7) Jimenez R, Casado-Flores J, Nieto M, Garcia-Teresa MA. Cerebral salt wasting syndrome in children with acute central nervous system injury. Pediatr Neurol 6;5:6-. 8) Gurney JG, Kadan-Lottick NS, Packer RJ, Neglia JP, Sklar CA, Punyko JA, et al. Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer ;97:66-7. 9) Darzy KH, Shalet SM. Hypopituitarism as a consequence of brain tumours and radiotherapy. Pituitary 5;8:-. ) Daaboul J, Steinbok P. Abnormalities of water metabolism after surgery for optic/chiasmatic astrocytomas in children. Pediatr Neurosurg 998;8:8-5. ) Hensen J, Henig A, Fahlbusch R, Meyer M, Boehnert M, Buchfelder M. Prevalence, predictors and patterns of postoperative polyuria and hyponatraemia in the immediate course after transsphenoidal surgery for pituitary adenomas. Clin Endocrinol (Oxf) 999;5:4-9. ) Gurney JG, Ness KK, Stovall M, Wolden S, Punyko JA, Neglia JP, et al. Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study. J Clin Endocrinol Metab ;88:47-9. ) Matarazzo P, Genitori L, Lala R, Andreo M, Grossetti R, de Sanctis C. Endocrine function and water metabolism in children and adolescents with surgically treated intra/parasellar tumors. J Pediatr Endocrinol Metab 4;7:487-95. 4) Meacham LR, Ghim TT, Crocker IR, O'Brien MS, Petronio J, Davis P, et al. Systematic approach for detection of endocrine disorders in children treated for brain tumors. Med Pediatr Oncol 997;9:86-9. 5) Aida T, Abe H, Fujieda K, Matsuura N. Endocrine functions in children with suprasellar germinoma. Neurol Med Chir (Tokyo) 99;:5-7. 6) Cho KT, Wang KC, Kim SK, Shin SH, Chi JG, Cho BK. Pediatric brain tumors: statistics of SNUH, Korea (959-). Childs Nerv Syst ;8:-7. 7) Maghnie M, Cosi G, Genovese E, Manca-Bitti ML, Cohen A, Zecca S, et al. Central diabetes insipidus in children and young adults. N Engl J Med ;4:998-7. 8) Sane T, Rantakari K, Poranen A, Tahtela R, Valimaki M, Pelkonen R. Hyponatremia after transsphenoidal surgery for pituitary tumors. J Clin Endocrinol Metab 994;79:95-8. 9) Sata A, Hizuka N, Kawamata T, Hori T, Takano K. Hyponatremia after transsphenoidal surgery for hypothalamo-pituitary tumors. Neuroendocrinology 6;8:7-. ) Dusick JR, Fatemi N, Mattozo C, McArthur D, Cohan P, Wang C, et al. Pituitary function after endonasal surgery for nonadenomatous parasellar tumors: Rathke's cleft cysts, craniopharyngiomas, and meningiomas. Surg Neurol 8; 7:48-9. ) Schneider HJ, Rovere S, Corneli G, Croce CG, Gasco V, Ruda R, et al. Endocrine dysfunction in patients operated on for non-pituitary intracranial tumors. Eur J Endocrinol 6;55: 559-66. ) Rickert CH, Paulus W. Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification. Childs Nerv Syst ;7:5-. ) Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM. The descriptive epidemiology of craniopharyngioma. J Neurosurg 998;89:547-5. 4) Kalina MA, Skala-Zamorowska E, Kalina-Faska B, Malecka- Tendera E, Mandera M. Practical approach to childhood craniopharyngioma: a role of an endocrinologist and a general paediatrician. Childs Nerv Syst 9;5:5-6. 5) Ohmori K, Collins J, Fukushima T. Craniopharyngiomas in children. Pediatr Neurosurg 7;4:65-78. 6) Caldarelli M, Massimi L, Tamburrini G, Cappa M, Di Rocco C. Long-term results of the surgical treatment of craniopharyngioma: the experience at the Policlinico Gemelli, Catholic University, Rome. Childs Nerv Syst 5;:747-57. 7) Karavitaki N, Brufani C, Warner JT, Adams CB, Richards P, Ansorge O, et al. Craniopharyngiomas in children and adults: systematic analysis of cases with long-term follow-up. Clin Endocrinol (Oxf) 5;6:97-49. 8) Sosa IJ, Krieger MD, McComb JG. Craniopharyngiomas of childhood: the CHLA experience. Childs Nerv Syst 5;: 대한소아내분비학회지 : 제 4 권제 호 9 년
785-9. 9) Halac I, Zimmerman D. Endocrine manifestations of craniopharyngioma. Childs Nerv Syst 5;:64-8. ) Ball SG. Vasopressin and disorders of water balance: the physiology and pathophysiology of vasopressin. Ann Clin Biochem 7;44:47-. ) Goodwin TL, Sainani K, Fisher PG. Incidence patterns of central nervous system germ cell tumors: a SEER Study. J Pediatr Hematol Oncol 9;:54-4. ) Janmohamed S, Grossman AB, Metcalfe K, Lowe DG, Wood DF, Chew SL, et al. Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen. Clin Endocrinol (Oxf) ;57:487-5. ) Ono N, Kohga H, Zama A, Inoue HK, Tamura M. A comparison of children with suprasellar germ cell tumors and craniopharyngiomas: final height, weight, endocrine, and visual sequelae after treatment. Surg Neurol 996;46:7-7. 4) Wise-Faberowski L, Soriano SG, Ferrari L, McManus ML, Wolfsdorf JI, Majzoub J, et al. Perioperative management of diabetes insipidus in children [corrected]. J Neurosurg Anesthesiol 4;6:4-9. 5) Paek SH, Oh CW, Chung YS, Yang HJ, Han DH, Cho BK, et al. The Clinical Behavior and Outcome of Operative Treatment of Craniopharyngiomas: Analysis of Cases [Journal Article]. J Korean Neurosurg Soc 997;6:989-94. 6) Smith D, Finucane F, Phillips J, Baylis PH, Finucane J, Tormey W, et al. Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma. Clin Endocrinol (Oxf) 4;6:7-9. 소아뇌종양수술후수분대사및전해질장애