증례로본당뇨병의진단과치료 서울대학교의과대학내과학교실분당서울대학교병원내분비내과 장학철 내 용 Drug induced hypoglycemia Insulinoma Autoimmune hypoglycemia Cushing syndrome in type 2 diabetes Bariatric surgery in obese type 2 diabetes 분당서울대학교병원 145
증례로본당뇨병의진단과치료 Case 1. 박 OO(F/74) C.C.: 의식변화, 내원당일 (12 N) P. I. 20여년전당뇨병으로진단, 경구혈당강하제복용중. (Glimepride 4 mg qd + MTF 500 mg bid +glucobay 100 mg tid) 이전에저혈당없었음. 3일전 OPD 방문 (118-218-6.7%) acute symptomatic cystitis로 Ciprobay 500 mg bid를추가처방 내원당일점심에소화가잘안되어소화제를복용하였고, 이후말을잘못하고사람을잘못알아보는증세가있어응급실내원. BST 34 mg/dl로 D50W 주사후증상호전됨. 최근운동을열심히하였으나당일은하지않았음. PMHx. DM/HTN/Tbc /CLD (+/+/-/-) s/p PCI, Known 2VD Drug (+): GMP 4 mg qd, metformin 500 mg bid, glucobay 100 mg tid, sensival 10 mg qd, lipitor 5 mg qd (Plavix 75 mg, astrix 100 mg, norvasc 5 mg, atacand 16 mg) Ciprofloxacin (3일전부터복용 ) Social Hx. Alcohol/Smoking: denied P/E No physical abnormal finding except consciousness 146 분당서울대학교병원
Last OPD Lab. CBC 6370 10.8 287K E 134 5.0 95 29 mmol/l BUN/Cr 17/0.83 mg/dl FBS/PP2 113/218mg/dL HbA1C 6.7% Insulin 5.6 (5-15) uiu/ml C-peptide 0.9 (0.5-1.5) ng/ml ER Lab. FBS: 46 E: 126-3.6-90-25 Initial Assessment : Hypoglycemia R/O Ciprofloxacin induced hypoglycemia Initial Plan Ciprofloxacin 중단 SMBG check. OPD 방문 분당서울대학교병원 147
증례로본당뇨병의진단과치료 OPD Follow-up 1 wk Later SMBG: fasting 90-100 저혈당 1번 GMP 2 mg qd 1 mon Later SMBG: fasting 130-140 저혈당2번 (BSL 70, 60) Glimepiride 1 mg bid 2 mon Later 저혈당 (-) HbA1C 7.1% FBS 135 mg/dl Glimepiride 1 mg bid 유지 Quinolones and glucose metabolism Population-based, nested case-control studies identified adults 66 years of age who were treated in the hospital for hypoglycemia (788 patients) or hyperglycemia (470 patients) after outpatient treatment with a macrolide, second-generation cephalosporin, or respiratory fluoroquinolone. As compared with macrolide treatment, gatifloxacin and levofloxacin were associated with an increased risk of hypoglycemia (adjusted odds ratio 4.3, 95% CI, 2.9-6.3; and 1.5, 95% CI, 1.2-2.0; respectively). No increased risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. Gatifloxacin as compared to macrolides was also significantly associated with hyperglycemia (adjusted odds ratio, 16.7, 95% CI, 10.4-26.8). No increased risk for hyperglycemia was seen with the other antibiotics. Risks were similar regardless of the presence or absence of diabetes. These effects have been associated with drug-induced changes in insulin secretion. 148 분당서울대학교병원
분당서울대학교병원 149
증례로본당뇨병의진단과치료 Case 2. 이 OO (M/48) C.C: Hypoglycemia( 내원 15일전경 ) P. I: 이전에건강하였음. 3-4년전부터식사후 3시간정도지나면손발이저린느낌이있었으나심하지않았음. 1년전처음으로순간적인의식소실이있어운전도중사고가날뻔하였음. 내원 15일전경, 저녁식사시술과고기를먹었고다음날새벽의식저하발생하여가족에의해외부병원방문. 당시 BSL 30으로입원하여 w/u. 경구당부하검사상당뇨병이의심된다고듣고당뇨병인데저혈당이오는게이상하여본원내원함. PMHx. DM/HTN/Tbc/CLD (-/-/-/-) Drug: AAP, Etodolac, Antiacid ( 어깨근육통 ), alfuzocin (BPH) Op Hx: Rt. COM으로 op. (20대) Social Hx. Alcohol: social Smoking: 15PY Review of System G/W(-) E/F(-) HA/Dz (-/-) Wt loss(-) F/C(-/-) C/S/R(-/-/-) C/D/P(-/-/-) Abd pain(-) A/N/V/D/C(-/-/-/-/-) H/M/H(-/-/-) Urinary Sx(-) 150 분당서울대학교병원
P/E 164 cm, 65 kg V/S: 126/84 mmhg 71/min 20/min 36.6 G/A: not so ill-looking, alert, oriented HEENT: L/R(++/++) isocoric prompt not anemic, anicteric not so dehydrated tongue PI(-) PTH(-/-) Neck: LNE(-/-) JVE(-/-) Chest: symm exp without retraction CBS without crackle, wheezing RHB without murmur Abdomen: soft, flat NABS T/RT(-/-) L/S/K(-/-/-) shifting dullness(-/-) B&Ext: CVAT(-/-) P/C/C(-/-/-) Possible diagnosis Hypoglycemia Reactive hypoglycemia Alcohol Diagnostic test 75g OGTT 72hr fasting test 분당서울대학교병원 151
증례로본당뇨병의진단과치료 Lab. finding 75 g OGTT Basal: 63 mg/dl 30 : 162 mg/dl 60 : 196 mg/dl 90 : 201 mg/dl 120 216 mg/dl 72 hr fasting test Glucose 51 mg/dl Insulin 16.5 (5-15)uIU/ml C-peptide 2.9 (0.5-1.5) ng/ml Insulin Ab 5.4 (0-7)% HbA1c-NGSP 5.1 (4.0-6.0)% R/O insulinoma 로 Pancreas CT/octreotide scan Pancreatobiliary CT : No abnormal finding Octreotide scan : No abnormal uptake of In-111- Pentetreotide 152 분당서울대학교병원
Intraarterial Calcium Stimulation Test Insulinoma, probably in Basal 30 60 head 90 120 Gastroduodenal a. 19.2 120.5 119.5 34.6 Splenic a. 34.5 35.8 35.4 37.6 31.1 SMA 24.3 24.7 25.1 27.0 27.5 Hepatic a. 23.0 28.0 30.8 29.9 25.0 EUS - Pancrease head portion 11.5 mm 의 Irregular margin well demarkated rim 을가지는 homogenous hypoechoic mass 관찰됨. -P-duct 2.2 mm 로 normal size 보임 Imp >C/W insulinoma 분당서울대학교병원 153
증례로본당뇨병의진단과치료 Enucleation of Pancreas Tumor WELL- IFFERENTIATED ENDOCRINE NEOPLASM, benign with 1) size: 0.9 x 0.7 cm 2) confined to the pancreas 3) no angiolymphatic or perineural inv asion 4) mitotic activity: <1/10HPF 5) clear surgical resection margin Synaptophysin (+) CD34 (-) CD56(+) Chromogranin (-) Ki-67 (+, <1%) B-catenin (+) Case 3 김 OO (F/29) C.C.: Hypoglycemia (3 weeks ago) P. I. 내원 3주전부터 night sweating, 식전에 G/W 발생함. 1주전눈앞이어른거리는증상이있었고, 화장실가다가어지러워쓰러졌으나의식은있었음. 이에외부병원에방문하여시행한 BST 상 42로체크됨. 전날저녁은소량먹고아침은안먹은상태였음. 혈액검사상 insulinoma 의심되어 pancreas MRI 시행하였으나 localization 되지않음. 보호자원하여본원전원. 154 분당서울대학교병원
PMHx. DM/HTN/Tbc/CLD (-/-/-/-) Drug (-) Op Hx. (-) Social Hx. Alcohol/Smoking: denied P/E No abnormal finding Possible diagnosis Hypoglycemia Reactive hypoglycemia << Insulinoma Nesidioblastosis Autoimmune hypoglycemia 분당서울대학교병원 155
증례로본당뇨병의진단과치료 O/S Chart Review @ o/s lab BSL 42 C-peptide 28.68 (1.1-4.4) ng/ml insulin 1000 (2.6-24.9) uiu/ml @ 72hr fasting test ( 금식 6시간만에저혈당발생 ) Glucose 28 mg/dl C-peptide 26.95 (1.1-4.4) ng/ml Insulin 1000 (2.6-24.9) uiu/ml HbA1C 5.1% proinsulin, insulin Ab, GH, glucagon: pending @ o/s Abd. CT & MRI: No focal lesion in the pancreas. Insulin Ab 96.6 (0-7)% Insulin Receptor Ab (+) EUS: No abnormal finding @ Autoimmune hypogycemia 에대해 Pd 60 mg (1 mg/kg) 1 주간 사용해도저혈당반복되어 90 mg 로증량후호전되어퇴원. 외래에서 Pd tapering 중. 2 달후 Lab >insulin 697.0 (5-15) uiu/ml c-peptide 2.1 (0.5-1.5) ng/ml insulin Ab 77.2 (0-7)% 156 분당서울대학교병원
Case 4 정 OO (F/68) C.C. > general weakness (1년전 ) P. I> 10년전HTN, 5년전DM 진단받고medication 중. 내원 1년전부터 general weakness 발생하였고, 5개월전부터점차더심해짐. 당시 myalgia (-), febrile sensation (-), upper extremity < lower extremity weakness, easy fatigability (+). 이에인근의원방문하였고이전에잘조절되던혈당이 BST 430 mg/dl으로상승되어큰병원방문권유받음. 체중이한달동안 3 kg 가량감소함. Local clinic Lab. Na/K 140/2.47, BUN/Cr 18.7/0.5 ABGA 7.602-37.5-74.2-36.2 SaO2 96.8% PRA 1.15 aldosterone 10.42 cortisol 16.99 K replacement 시행하였으나 hypokalemia 및 metabolic alkalosis 지속되고 G/W도호전보이지않아외부종합병원방문. Local Hospital Lab. Hb A1c 7.7% VBGA 7.57-50 - 39.6-46.2 SvO2 80.6% Na/K 148/2.0 BUN/Cr 16.1/0.4 ACTH/cortisol 697.6 (6~60 pg/ml) / 94.43 (5.6~23.1 ug/dl) renin/aldosterone 0.53 (0.2~2.8 ng/ml/h)/132.6 (10~160 pg/ml) (PAC/PRA = 24.9 <30) 분당서울대학교병원 157
증례로본당뇨병의진단과치료 PMHx > DM(+): 5YA, glimepiride 2 mg qd HTN (+): 10YA, ACEI, CCB 복용중 Social Hx. > alcohol/smoking (-/-) P/E >153 cm/ 46.5 kg V/S 145/80-90 - 20-36.6 moon face (+), anemic, alopecia soft, truncal obesity (+) muscle wasting (+), striae (-) O/S Chart Review Assessment > #1. R/O Cushing s syndrome #2. hypertension #3. type 2 DM #4. hypokalemia/metabolic alkalosis Plan > Low dose dexamethasone suppression test High dose dexamethasone suppression test Brain MRI IPSS 158 분당서울대학교병원
O/S Chart Review Low dose dexamethasone suppression test Not suppressed Time Serum 24hr urine Cortisol ACTH 17-KS 17-OHCS Cr (mg/day) Free cortisol baseline 80.47 594.6 20.06 10.63 482 1312.97 24hr 81.26 423.1 19.28 12.26 544 1925.47 48hr 71.8 216.1 24.71 22.42 502 2573.82 High dose dexamethasone suppression test Not suppressed Time Serum 24hr urine Cortisol ACTH 17-KS 17-OHCS Cr (mg/day) Free cortisol baseline 65.88 431.4 24hr 63.42 581.5 12.96 15.75 286 1120.75 48hr 66.95 323.7 10.94 16.54 336 1563.84 O/S Brain MRI c/w Empty sella 분당서울대학교병원 159
증례로본당뇨병의진단과치료 O/S Adrenal CT Bilateral adrenal hyperplasia O/S Chart Review PET-CT Rt. middle lobe 에 0.9 cm sized nodular lesion EGD hemorrhagic gastritis/ulcer lesion IPSS: 양측에서 ACTH 차이없음. Colonoscopy: No abnormal finding 160 분당서울대학교병원
O/S Chart Review Medical adrenalectomy 로 ketoconazole 투여시작하였으나, 이후 AST/ ALT 급격히상승하여중단하고 hepatotonics 추가하며경과관찰함. hypokalemia 지속되어 potassium replacement 하면서 aldactone/ amiloride 투여하면서 K 2.5-3.4 사이가유지함. etopic ACTH syndrome 의 primary lesion 발견하지못한상태로 adrenalectomy 고려하였으나환자 / 보호자 second opinion 구하기희망 하였음. DXA: bone densitometry Femur BMD (g/cm 2 ) T-score Z-score neck 0.735-1.4 1.0 wards 0.520-2.8 0.1 troch 0.403-3.2-1.7 shaft 0.829 total 0.714-1.8 0.0 Lumbar BMD (g/cm 2 ) T-score Z-score L1 0.718-2.9-0.5 L2 0.703-3.5-1.2 L3 0.737-3.2-0.9 L4 1.110-0.1 2.2 L1-3 0.720-3.2-0.9 L1-4 0.853-2.1 0.2 L2-4 0.882-2.0 0.3 분당서울대학교병원 161
증례로본당뇨병의진단과치료 Hospital course S >G/W (+) back pain (+) melena (+) O >V/S 121/101-104 - 20-36.0 CBC 8.3/25.9-10510 - 171000 (seg. 89.1%) electrolyte 138-4.5-98 - 26 Ca/P 8.6/3.7 glucose 207 BUN/Cr 30/0.7 uric acid 3.4 LFT 104-5.5/3.3-0.7-188/19/39 A> #1. Ectopic ACTH syndrome - R/O bilateral adrenal hyperplasia - R/O RML nodule #2. melena -R/O PUD #3. hypertension #4. type 2 DM #5. hypokalemia/metabolic alkalosis P >EGD Hospital course EGD > Blood가가득차있어서정확한관찰이어려움. High body에 huge ulcer와함께 vessel exposure 있어 Hemoclippint & band ligation시행했으나 control 되지않아 histoacryl & green plast apply하여임시적지혈시행함. Imp)BGU A1 bleeding emergent angiography 시행. active bleeding은없음. 162 분당서울대학교병원
Hospital course Laparoscopic bilateral adrenalectomy : pathology >adrenal cortical hyperplasia, bilateral Pd 10mg qd/fludrocortisone 0.05 mg qd 항목 2011-02-22 2010-10-18 2010-06-15 2009-12-16 2009-08-21 ACTH 108 173 397 160 122 Basal Cortisol 0.2 0.2 0.4 0.2 <0.3 2009-05-19 2009-02-03 2008-10-17 2008-09-02 2008-07-05 2008-07-03 40 113 147 616 1308 1260 13.6 0.2 0.3 0.6 Case 5 최 OO (F/55) C.C >Poor glycemic control P. I > 25 년전당뇨병진단, 경구혈당강하제복용을시작함. 당뇨병진단당시체중 104 kg 2005 년 8 월시력감소있어안과에서 R) PRP 2 회시행. 당시 L) vitrectomy 예정으로내분비내과의뢰됨. FBS 192, PP2 352, HbA1C 8.9% 로안과입원시혈당조절및영양상담, 교육받고 Humulin 7:3 30 10 U 으로퇴원함. OPD F-U 중시력안좋아인슐린을보호자가저녁에만놓아주고, 경구약을강력히원하여 amaryl 4-2 mg bid + metformin 500 mg bid 로변경함. 2008 년 3 월몸이왼쪽으로기우는증상및 dysarthria 발생하여 ER 내원. Rt. thalamic acute infarction 진단받고입원함 FBS 155 mg/dl HbA1C 9.7%, fasting insulin 10.5, c-peptide 1.7 OHA 를처방받고퇴원 분당서울대학교병원 163
증례로본당뇨병의진단과치료 Present illness 2008 년 7 월신경과퇴원이후내분비내과 f/u 함. 2008-08-23 2009-02-17 2009-05-14 2009-08-06 2009-11-05 2010-01-28 2010-04-22 Height 165 Bwt.(BMI) 109.5(40.2) 103(36.7) 110(40.4) HbA1c 6.5 6.8 8.5 8.6 7.5 8.2 8.7 FBS 143 203 157 PP2 205 215 265 313 146 233 281 Insulin 13.8 24.1 C-Peptide 1.3 2 AST 27 21 44 ALT 17 25 48 T.chol 152 152 TG 225 181 HDL 49 44 LDL 55 62 M/C ratio 0.0155 38.92 50.52 17.78 16.5 2009.11. ABI: Normal (Rt. 1.18/ Lt. 1.07), mild low TBI (Rt. 0.70/Lt. 0.69) QST: U/E very mild hypoesthesia, L/E Profound hypoesthesia 2009년 11월 Bariatric surgery 위해외과에의뢰함. -BMI >35 kg/m 2 + significant co-morbidity (stroke) Preop w/u. -PFT: WNL - SPECT: Reversible mild perfusion defect in apex, apico-mid anterior wall (LAD territory)--> 임상소견과일치하지는않음. - Coronary CT: 1. No significant stenosis at coronary vessels (ca scoring; 0) with normal systolic function (EF=64.7%) 164 분당서울대학교병원
2010. 5. 28. Laparoscopic sleeve gastrectomy 시행함. Amaryl 4 mg qd + Glupa 850 g tid 로퇴원함. OPD F/U 2010-07-06 2010-11-02 2011-03-08 Height 165 Bwt. 98.2 92 88 HbA1c 6 5.4 6.1 FBS 80 91 PP2 177 153 143 Insulin 12.4 C-Peptide 1.9 AST 24 ALT 17 T.chol 138 TG 49 HDL 62 LDL 57 Glimel 2mg qd 로감량 Glimel 중단 Glupa 850mg tid만유지 분당서울대학교병원 165