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지은 피
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1 대한내분비학회지 : 제 23권제 3 호 2008 증 례 /jkes 두개인두종치료후범뇌하수체기능저하증이발생한성인환자에서동반된대퇴골두골단분리증 1 예 전남대학교의과대학내과학교실 정진욱 홍세인 조동혁 정동진 정민영 A Case of Slipped Capital Femoral Epiphysis in Association with Panhypopituitarism after Treatment of Craniopharyngioma Jin Ook Chung, Se In Hong, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung Department of Internal Medicine, Chonnam National University Medical School ABSTRACT Craniopharyngioma accounts for 2~5% of all primary intracranial neoplasms. It may present with a variety of manifestations including neurological, visual, and/or hypothalamic-pituitary dysfunction. Treatment options include radical surgery or radiotherapy, or a combination of these modalities. Craniopharyngioma ablation results in anterior and/or posterior pituitary hormone deficits. Slipped capital femoral epiphysis (SCFE), in which the femoral head slips downward and backward on the femoral neck at the epiphyseal plate, most commonly occurs during the rapid growth phase of puberty. Its actual cause is unknown, but the clinical association between SCFE and endocrine disorders is well known. We report a case of an adult male patient who developed SCFE in association with panhypopituitarism after treatment of a craniopharyngioma. (J Korean Endocr Soc 23:193~198, 2008) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ Key Words: craniopharyngioma, hypopituitarism, SCFE 서론 1) 두개인두종 (craniopharyngioma) 은전체두개강내종양중약 2~5% 의빈도를차지하며 [1], 종양의위치및크기에따라뇌압상승이나시신경증상을초래할수있고시상하부및뇌하수체의이상을초래하여내분비적증상을일으키기도한다 [1,2]. 시상하부-뇌하수체기능에이상이발생하는경우성장호르몬과성선자극호르몬이가장흔히영향을받으며중추성요붕증이발생할수도있다 [3]. 또한치료로이용되는종양절제술이나방사선치료도뇌하수체기능저하증이나요붕증을초래할수있다 [4]. 대퇴골두골단분리증 (slipped capital femoral epiphysis) 은대퇴골두가대퇴경부에대하여후하방으로전위되어발생하 는드문질환으로급성장기인사춘기에주로발생하는것으로알려져있다 [5]. 발생원인은명확하지않으나일부내분비이상과의관련성으로성장호르몬을비롯한몇가지호르몬의불균형에의해골단판의연골세포대사가촉진되고비후세포대가넓어져전단력에대해약해지게되어골단분리증이야기된다고제시되고있다 [6,7] 국내에서내분비질환과연관된대퇴골두골단분리증의몇예가보고된바있으나 [8] 성인기에범뇌하수체기능저하증과동반되어발생한대퇴골두골단분리증의보고는드물다. 저자등은두개인두종의치료후에발생된범뇌하수체기능저하증이있는성인남자에서골성장지연과골성장판유합지연으로인한대퇴골두골단분리증이발생된 1예를경험하였기에보고하는바이다. 접수일자 : 2008년 1월 9일통과일자 : 2008년 4월 23일책임저자 : 정동진, 전남대학교의과대학내과학교실

대한내분비학회지 : 제 23 권제 3 호 2008 증 환자 : 송OO, 남자, 29세가족력 : 특이한병력없음. 과거력및현병력 : 내원 1주일전부터발생한좌측고관절동통을주소로방문하였다. 환자는 9세경부터다음과다뇨증이있었으며 17세경점차악화되는두통및시야결손으로타병원에내원하여두개인두종으로진단받고종양제거술을시행받았다.

2 대한내분비학회지 : 제 23 권제 3 호 2008 증 환자 : 송OO, 남자, 29세가족력 : 특이한병력없음. 과거력및현병력 : 내원 1주일전부터발생한좌측고관절동통을주소로방문하였다. 환자는 9세경부터다음과다뇨증이있었으며 17세경점차악화되는두통및시야결손으로타병원에내원하여두개인두종으로진단받고종양제거술을시행받았다. 수술후에잔여종양이남아있었으나요붕증증상과시야결손은호전을보여추적관찰하였으며 Fig. 1. Frontal view of external genitalia of the patient showed hypoplastic genitalia with no pubic hair. Penis was 3 cm in length. The volume of right testis was 2 cc, and that of left was 1 cc. 례 21세에잔여종양에대하여한차례감마나이프시술 (gamma-knife surgery) 을받았고그후로추적관찰이되지않았다. 이학적소견 : 내원시신장 157 cm (< 3 percentile), 체중 40 kg (< 10 percentile) 이었으며혈압 120/70 mmhg, 맥박수 76회 / 분, 호흡수 18회 / 분, 체온 36.6 이었다. 액모및음모는전혀관찰할수없었고고환및음경의크기가나이에비하여작았다 (Fig. 1). 좌측고관절에압통과외전 30 도및내회전 10도의운동제한이있었다. 검사소견 : 내원시말초혈액검사상백혈구 8,200/mm 3, 헤모글로빈 9.2 g/dl, 혈소판 202,000/mm 3, 혈청생화학검사상 BUN 9.5 mg/dl, 크레아티닌 0.9 mg/dl, 나트륨 136 meq/l, 칼륨 4.2 meq/l, 총칼슘 8.0 mg/dl, 이온화칼슘 4.4 mg/dl, 마그네슘 1.8 meq/l, 인산염 3.1 meq/l이었으며, 공복혈당 76 mg/dl, 당화혈색소 5.7%, 총콜레스테롤 257 mg/dl, 고밀도지단백콜레스테롤 63.8 mg/dl, 저밀도지단백콜레스테롤 175 mg/dl, 중성지방 191 mg/dl, alkaline phosphatase 116 U/L ( 참고치 : 35~129), serum C-terminal peptide of type I collagen (CTX) 0.42 ng/ml ( 참고치 : 0.01~1), 25-hydroxyvitamin D 31.8 ng/ml, PTH 21 pg/ml ( 참고치 : 5~55) 이었다. 소변삼투압 44 mosm/kg, 혈청삼투압 282 mosm/kg, 24시간소변량은 4,300 cc/day였다. 수분이뇨 (water diuresis) 에대한감별진단을위해수분제한검사를시행하였고 (Table 1) 중추성요붕증에합당한 Table 1. Water deprivation test & pitressin stimulation test Time U-Osm (mosm/kg) S-Osm (mosm/kg) Urine output (ml) ADH (pg/ml) 6 AM MD Pitressin 5 unit subcutaneous injection 2 PM ADH, antidiuretic hormone; S-Osm, serum osmolarity U-Osm, urine osmolarity. Table 2. Anterior pituitary hormone stimulation test before tumor resection at the age of 17 Basal Stimulated Cortisol (μg/dl) GH (ng/ml) 0.4 < 0.1 LH (miu/ml) < 0.1 < 0.1 FSH (miu/ml) < 0.1 < 0.1 TSH (μiu/ml) 0.92 T 3 (ng/dl) 125 T 4 (μg/dl) 6.3 Free T 4 (ng/dl) 1.1 FSH, follicle-stimulating hormone; GH, growth hormone; LH, luteinizing hormone; TSH, thyroid stimulating hormone

- 정진욱외 4 인 : 두개인두종치료후범뇌하수체기능저하증이발생한성인환자에서동반된대퇴골두골단분리증 1 예 - Table 3. Combined anterior pituitary hormone stimulation test * at the age of 29 Basal Stimulated Cortisol (μg/dl) < 0.1 < 0.

14 Total Testosterone (ng/ml) < 0.01 E 2 < 20 IGF-1 (ng/ml) 115 * After regular insulin 5 u, TRH 400 μg, LHRH 100 μg. IGF-1 (age-adjusted normal range: 114~492). A B Fig. 2. A. Preoperative both hip A-P view showed downward and posterior slipping of the left femoral epiphysis.

All carpal bones were shown. The epiphyseal growth plates of metacarpal, phalangeal, distal ulnar and radial bone were not closed. 소견을보였다. 갑상선호르몬검사상 TSH 5.58 IU/mL ( 참고치 : 0.4~4.

3 - 정진욱외 4 인 : 두개인두종치료후범뇌하수체기능저하증이발생한성인환자에서동반된대퇴골두골단분리증 1 예 - Table 3. Combined anterior pituitary hormone stimulation test * at the age of 29 Basal Stimulated Cortisol (μg/dl) < 0.1 < 0.1 ACTH (pg/ml) GH (ng/ml) < 0.1 < 0.1 Prolactin (ng/ml) LH (miu/ml) FSH (miu/ml) TSH (μiu/ml) T 3 (ng/dl) 63 Free T 4 (ng/dl) 0.14 Total Testosterone (ng/ml) < 0.01 E 2 < 20 IGF-1 (ng/ml) 115 * After regular insulin 5 u, TRH 400 μg, LHRH 100 μg. IGF-1 (age-adjusted normal range: 114~492). A B Fig. 2. A. Preoperative both hip A-P view showed downward and posterior slipping of the left femoral epiphysis. B. Postoperative both hip A-P view showed internal fixation with cannulated screw of both femoral epiphysis. Fig. 3. Hand X-ray showed bone age corresponding with 12 years. All carpal bones were shown. The epiphyseal growth plates of metacarpal, phalangeal, distal ulnar and radial bone were not closed. 소견을보였다. 갑상선호르몬검사상 TSH 5.58 IU/mL ( 참고치 : 0.4~4.5), T 3 63 ng/dl ( 참고치 : 80~220), 유리 T μg/dl ( 참고치 : 0.7~2) 였다. 17세에타병원에서두개인두종제거술전시행한뇌하수체자극검사에서성장호르몬과성선자극호르몬의반응이저하된소견을보였으며 (Table 2) 본원내원후시행한호르몬검사에서는범뇌하수체기능저하증을보였다 (Table 3). 방사선소견 : 고관절의전후면방사선학적검사에서대퇴골두성장판이아직유합되지않았으며좌측대퇴골두가후하방전위를보이는대퇴골두골단분리증을보였다 (Fig. 2A). 수근관절촬영에서골연령은 12세로환자의연령에비해지연되어있었으며성장판은아직폐쇄되지않았다 (Fig. 3). 뇌하수체자기공명영상촬영에서터어키안내부의종괴는관찰되지않았다 (Fig. 4). DXA (dual energy x-ray absorptiometry) 를이용한골밀도검사에서 L 1-L 4 에서골밀도 g/cm 2, T-score -3.6, Z-score -2.7을보였다. 치료및경과 : 좌측대퇴골두골단분리증은비관혈적정복술및나사내고정술을시행하였으며예방목적으로우측대퇴골단에대해서도같은시술을시행하였다 (Fig. 2B). 환자는범뇌하수체기능저하증에대하여경구프레드니솔론 7.5 mg/day, levothyroxine 0.1 mg/day, testosterone undecanoate 1 g 근육주사 (1회 6주간격, 그후 3개월간격 ) 및성장호르몬 20 U/week 피하주사를하였으며중추성요붕증에대해 desmopressin 0.25 mg/day를경구투여하였다. Desmopressin 투여후 24시간요량은약 1,200 cc 정도로유지중이며, 호

대한내분비학회지 : 제 23 권제 3 호 2008 A B Fig. 4. A. Preoperative sagittal T1 - weighted sellar MRI showed 1.8 cm sized well circumscribed mass with suprasellar extension. B. 12 years later, sagittal T1 - weighted sellar MRI showed empty sella with no remnant mass.

5, Z-score -2.6 및 alkaline phosphatase 136 U/L, serum CTX 0.51 ng/ml을보였다. 좌측대퇴골두골단에고정했던나사는경과관찰중통증으로제거하였으며고관절전치환술예정으로현재외래추적관찰중이다.

4 대한내분비학회지 : 제 23 권제 3 호 2008 A B Fig. 4. A. Preoperative sagittal T1 - weighted sellar MRI showed 1.8 cm sized well circumscribed mass with suprasellar extension. B. 12 years later, sagittal T1 - weighted sellar MRI showed empty sella with no remnant mass. 르몬투여후 1년경과후에신장 159 cm, 체중 55 kg이되었고성장호르몬치료전 IGF-I은 115 ng/dl에서 1년치료후 290 ng/dl로정상범위로회복되었다. 남성호르몬치료전 Tanner stage I에서치료후 Tanner stage IV로이차성징을보였으며골밀도검사에서 L 1~L 4 에서골밀도 g/cm 2, T-score -3.5, Z-score -2.6 및 alkaline phosphatase 136 U/L, serum CTX 0.51 ng/ml을보였다. 좌측대퇴골두골단에고정했던나사는경과관찰중통증으로제거하였으며고관절전치환술예정으로현재외래추적관찰중이다. 고찰대퇴골두골단분리증은대퇴골두가여러가지원인에의하여골단판을통해분리가일어나대퇴경부의후하방으로전위되어발생하는드문질환으로남자에서 10~16세, 여자에서는 10~14세경에주로발생하는것으로알려져있다 [5]. 그원인으로내분비이상, 비만, 물리적이상, 골연령, 성성숙도등과관련이있을것으로보고되고있으나아직명확하게밝혀져있지않다 [5~8]. 1950년 Harris는성호르몬에대한성장호르몬의상대적증가가대퇴골두골단분리증과관련이있다고주장하였으며 [6] Loder 등 [5] 은대퇴골두골단분리증과관련된내분비질환으로갑상선기능저하증 (40%) 이가장흔히동반되었고성장호르몬결핍 (25%), 성선기능저하증을포함한기타내분비질환 (35%) 이관련되었으며갑상선기능저하증과대퇴골두골단분리증사이의진단간격은평균 1.5년, 성장호르몬결핍과대퇴골두골단분리증사이의진단간격은평균 1.8년이었다고보고하였다. Wilcox 등 [9] 은대퇴골두골단분리증을가진환자의 87 % 에서성장호르몬, 76% 에서성호르몬, 25% 에서갑상선호르몬이감소되어있었으며이는절대적인호르몬수치의감소라기보다는미세한호르몬불균형이영향을미쳐서전단력이가해질때전위가일어나는것으로보고하였다. 범뇌하수체기능저하증환자에서대퇴골두골단분리증의발생빈도는아직알려져 있지않으나성장호르몬치료를받지않은성장호르몬결핍증환자 7,719명중 6명 (0.08%) 에서대퇴골두골단분리증이발생하였다고보고된바있으며 [10] 성장호르몬치료중이나거인증및갑상선기능저하증의치료중에발생된예가보고되고있다 [5,7]. 골단성장판 (epiphyseal growth plate) 은연골세포들이층을이루어 resting zone, proliferative zone, hypertrophied zone 및 calcified zone을형성하는데 [11] 급성장기인사춘기에대퇴골두골단분리증의발생빈도가높은이유로는대퇴골두와경부의성장판이성장기골격중약한부분이며또한성장기에 hypertrophied zone의연골세포가비정상적으로비후되고두꺼워져골단성장판이전단력에약해질수있기때문이라고설명된다 [7]. 여러호르몬들이직접적으로영향을미치거나다른호르몬의작용을변화시켜골단성장판의구조와기능에영향을미치는것으로알려져있다. 갑상선호르몬은성장판연골세포의증식과분화를촉진하고성장판의구조를유지하는역할을하며이러한갑상선호르몬의작용은성장판연골세포에있는갑상선호르몬수용체에직접적으로작용하거나성장호르몬과 IGF-1을통하여이루어진다 [12]. 또한갑상선호르몬은성장판의정상적인무기질침착 (mineralization) 과유합에도중요한역할을한다 [13]. 따라서갑상선기능저하증이있는경우성장호르몬과 IGF-1의작용이저하되고연골세포대사의변화및연골세포변성이증가하고세포외간질에서황산화점액다당류 (sulfated mucopolysaccharide) 에변화가생겨전단력에대하여취약해질수있다 [14]. 에스트로겐은성장판연골세포에있는에스트로겐수용체에작용하여연골세포증식과무지질침착을유도하여성장판폭을유지시켜주고골흡수와골모세포활성도를억제하여안정화에기여한다 [12]. 또한성장판연골세포의증식능력이소실되면성장판의유합이발생하는데에스트로겐은연골세포가가지고있는증식능력의소진을유도하고성장판의노쇠화를초래하여성장판이유합하는데기여한다 [15]. 따라서에스트

5 - 정진욱외 4 인 : 두개인두종치료후범뇌하수체기능저하증이발생한성인환자에서동반된대퇴골두골단분리증 1 예 - 로겐결핍은 proliferative zone과 hypertrophied zone의폭을증가시켜성장판의불안정성을초래할수있다 [12]. 안드로겐또한테스토스테론의방향화로생긴에스트라디올이연골세포에영향을미치거나골세포와연골세포에존재하는안드로겐수용체에작용하여성장판을안정화시킨다 [12]. 성장호르몬은성장판내연골세포에있는성장호르몬수용체에직접적으로작용하거나간과연골세포에서 IGF-1의합성을촉진하여연골세포의증식, 비대연골세포로의분화, 간질분비등에관여한다 [12,16]. 따라서골단성장판에영향을미치는이러한호르몬들에불균형이발생하게되면전단력에취약해져대퇴골두골단분리증이발생할것으로설명되고있다 [5~9,17]. 대퇴골두골단분리증의치료시이차성대퇴골두골단분리증을예방하기위해양측의고정술이권고되고있는데 Wells 등 [17] 은내분비이상을가진환자에서양측성대퇴골두골단분리증의위험성이높다고하였으며 Hägglund 등 [18] 은일측성대퇴골두골단분리증을가진환자의 40% 에서시간이지난후에반대측에도발병을보였다고보고하였다. 이증례에서도좌측대퇴골두골단분리증에대한치료시이차성골두골단분리증을예방하기위해양측에나사내고정술을시행하였다. 두개인두종 (craniopharyngioma) 은뇌하수체주머니 (Rathke's pouch) 의배아편평상피잔유물에서기원하며어느연령이나발생할수있으나 5~14세소아와 65~74세무렵에가장높은발생률을보인다 [19]. 임상증상은종양의크기, 위치및주위조직의침범여부에따라다양하여국내보고에따르면시력및시야장애 (81.1%), 두통 (59.7%) 이비교적흔하게나타났으며그외내분비적증상으로다뇨 (37.8%), 치모감소 (scanty pubic hair) (37.8%), 성장부진 (35.1%), 성기능장애 (21.6%) 등이관찰되었다 [2]. 두개인두종이있는경우종양에의한시상하부- 뇌하수체기능손상으로진단시약 85% 의환자에서호르몬결핍이보일수있으며 [20] 성장호르몬은 35~95%, FSH/LH는 38~82%, ACTH는 21~62%, TSH는 21~42% 에서각각결핍이관찰되었고요붕증은 6~38% 에서동반되었다고보고되었다 [1]. 치료는수술적제거나방사선치료를할수있으며이러한치료방법은또한뇌하수체호르몬의결핍을초래할수있다. 두개인두종치료후 54~100% 에서 3가지이상의호르몬결핍이발생되었으며성장호르몬의결핍이 88%, FSH 90%, LH 86%, ACTH 80%, TSH 65% 에서관찰되었다고보고되었다 [1,4]. 뇌하수체종양과는대조적으로두개인두종의수술적제거후에종양에의해발생한호르몬결핍이회복되는것은매우드물다 [4]. 본증례에서 17세에타병원에서두개인두종의수술전에시행한호르몬검사와임상증상을고려해볼때두개인두종으로인한성장호르몬, 성선자극호르몬, 항이뇨호르몬이 영향을받았을것으로보이며또한수술과방사선치료를받고난후 29세에좌측고관절동통이발생하여내원후시행한검사에서범뇌하수체기능부전소견을보였다. 따라서골단판에미치는여러호르몬들의감소로인해골단판유합이일어나지않고불안정하여드문연령대인 29세에서도대퇴골두골단분리증이발병한것으로설명될수있다. 본증례에서처럼뇌하수체기능부전이있는환자에서고관절동통이있는경우드물기는하나대퇴골두골단분리증이동반될수있기때문에이에대한주의가필요할것으로사료된다. 요약두개인두종은종양의위치및크기에따라뇌압상승이나시신경증상을초래할수있으며종양자체나치료에의해서도시상하부 -뇌하수체기능이상이발생할수있다. 대퇴골두골단분리증은대퇴골두가대퇴경부에대하여후하방으로전위되어발생하는드문질환으로원인은명확하지않으나골단성장판에영향을미치는호르몬의불균형에의해전단력에대해약해지게되어발생되며주로급성장기에발생하는것으로알려져있다. 저자등은두개인두종의치료후에발생된범뇌하수체기능저하증이있는성인남자에서골성장지연과골성장판유합지연으로인한대퇴골두골단분리증이발생된 1예를경험하였기에보고하는바이다. 참고문헌 1. Karavitaki N, Cudlip S, Adams CB, Wass JA: Craniopharyngiomas. Endocr Rev 27: , Chung JH, Lee HC, Yoo NC, Chung YS, Lim SK, Kim KR, Huh KB: Clinical aspects on craniopharyngioma. J Kor Soc Endocrinol 6: , Paja M, Lucas T, García-Uría J, Salamé F, Barceló B, Estrada J: Hypothalamic-pituitary dysfunction in patients with craniopharyngioma. Clin Endocrinol (Oxf) 42: , Karavitaki N, Brufani C, Warner JT, Adams CB, Richards P, Ansorge O, Shine B, Turner HE, Wass JA: Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow -up. Clin Endocrinol (Oxf) 62: , Loder RT, Wittenberg B, DeSilva G: Slipped capital femoral epiphysis associated with endocrine disorders. J Pediatr Orthop 15: , Harris WR: The endocrine basis of slipping of the upper femoral epiphysis. An experimental study. J

6 대한내분비학회지 : 제 23 권제 3 호 2008 Bone and Joint Surg 32:5, Blethen SL, Rundle AC: Slipped capital femoral epiphysis in children treated with growth hormone. A summary of the National Cooperative Growth Study experience. Horm Res 46: , Jeon HJ, Ko BS, Kim DH, Bae JH, Oh TG, Kang SB: Kallmann s syndrome associated with slipped capital femoral epiphysis. J Kor Soc Endocrinol 11: , Wilcox PG, Weiner DS, Leighley B: Maturation factors in slipped capital femoral epiphysis. J Pediatr Orthop 8: , Rappaport EB, Fife D: Slipped capital femoral epiphysis in growth hormone-deficient patients. Am J Dis Child 139: , Ippolito E, Mickelson MR, Ponseti IV: A histochemical study of slipped capital femoral epiphysis. J Bone Joint Surg Am 63: , Hochberg Z: Clinical physiology and pathology of the growth plate. Best Pract Res Clin Endocrinol Metab 16: , Alini M, Kofsky Y, Wu W, Pidoux I, Poole AR: In serum-free culture thyroid hormones can induce full expression of chondrocyte hypertrophy leading to matrix calcification. J Bone Miner Res 11: , Dearden LC: Enhanced mineralization of the tibial epiphyseal plate in the rat following propylthiouracil treatment: a histochemical, light, and electron microscopic study. Anat Rec 178: , Weise M, De-Levi S, Barnes KM, Gafni RI, Abad V, Baron J: Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci U S A 98: , Isaksson OG, Lindahl A, Nilsson A, Isgaard J: Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev 8: , Wells D, King JD, Roe TF, Kaufman FR: Review of slipped capital femoral epiphysis associated with endocrine disease. J Pediatr Orthop 13: , Hägglund G, Hansson LI, Ordeberg G, Sandström S: Bilaterality in slipped upper femoral epiphysis. J Bone Joint Surg Br 70: , Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM: The descriptive epidemiology of craniopharyngioma. J Neurosurg 89: , Van Effenterre R, Boch AL: Craniopharyngioma in adults and children: a study of 122 surgical cases. J Neurosurg 97:3-11,

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<313320C1F5B7CA C0CCBDC2C1D62DB1E8BAB4C1D D E687770> 대한내과학회지 : 제 85 권제 4 호 2013 http://dx.doi.org/10.3904/kjm.2013.85.4.420 뇌하수체줄기형성부전으로발생한시상하부성뇌하수체기능저하증 1예 1 건양대학교의과대학내과학교실, 내분비대사내과, 2 가천대학교의학전문대학원내과학교실 이승주 1 윤혜진 1 조아름 1 엄유진 1 박근용 1 임동미 1 김병준 2 Hypothalamic