손발 커짐을 주소로 내원한 48세 여자환자 내분비대사 내과 R3 정명화/ Prof. 김성운

Chief Complaint Present illness Case : F/48 11917118 김O옥 Chief Complaint Increasing size of both hands and feet Onset : 10 years ago Present illness F/48, 1년 전 제2형 당뇨병 진단받은자로 점차적인 손발 커짐 및 얼굴 변형 등에 대한 자세한 검사 및 치료 위해 타병원 경유 본원 내분비대사내과 방문함.

PMHx DM (+) : Glimepiride 2mg qd HTN (+) : Losartan 50mg qd Dyslipidemia (+) : Rosuvastatin 10mg qd Pulmonary Tbc(+) : 15년 전, 항결핵약 복용 후 완치 판정 FHx PHx Smoking (-) Alcohol (-)

Review of Systems General general weakness (-) fever(-) fatigue (-) dizziness (-) weight gain (+) : 13 kg/10 yrs Skin Rash(-) pigmentation (-) alopecia (-) flushing(-) Head and Neck headache (-) voice change (+) : deep Eye and ENT sore throat (-) blunted visual field (-) decreased visual acuity (-/-) enlarged nose and lips Resp. & cardiac Dyspnea(-) cough(-) sputum(-) Chest pain(-)palpitation(-) Gastrointestinal A/N/V/D/C (-/-/-/-/-) Abdominal pain (-) Musculoskeletal generalized myalgia (+) enlarged both hands and feet Gynecological Amenorrhea (+): for 10 years galactorrhea (-)

Physical Examination Height: 163 cm Body weight: 62 Kg BMI: 23.3 Kg/m2 Vital sign: 120/70 mmHg – 80/min – 22/min – 36.3°C General alert consciousness generally well-looking appearance Skin Pigmentation (-) oily skin (+) Head and Neck Isocoric pupil with PLR(++/++) LNE(-) Frontal bossing (+) prognathism (-) Eye and ENT proptosis (+) large fleshy nose (+) full lips (+) Chest Symmetric chest expansion Clear breath sound without rale Abdomen Soft abdomen Td/rTd (-/-)

Physical Examination Abdomen soft abdomen Td/rTd (-/-) Back & Ext. CVA Td (-/-) pretibial pitting edema(-/-) Increased both hand, foot Neurology Sensory: intact , motor : intact

patient patient

타병원 검사 자료 2007-06-18 24.4 GH (<5.0) 503.0 IGF-I (75~430) 141.0 (ng/mL) 24.4 IGF-I (75~430) 503.0 PRL (<18) 141.0 ACTH (<80 at 9am) (pg/mL) 122.0

Sellar MRI (타병원 시행, 2007-07-02)

Impression #1. Acromegaly due to GH-secreting pituitary macroadenoma R/O plurihormonal pituitary macroadenoma (possibly with Pit-1 expression) #2. Known T2DM #3. Known HTN #4. Known dyslipidemia

Diagnostic Plan #1. Acromegaly due to GH-secreting pituitary macroadenoma R/O plurihormonal pituitary macroadenoma - 75g glucose loading GH suppression test - IGF-I level - TRH stimulation for GH - Evaluation for other pituitary hormones - Somatostatin suppression test - Transsphenoidal approach for surgical biopsy - Colonoscopy

Therapeutic Plan #1. Acromegaly due to GH-secreting pituitary macroadenoma R/O plurihormonal pituitary macroadenoma - Medical therapy Somatostatin analogue Bromocriptine - Radiation therapy

#2. Known T2DM #3. Known HTN #4. Known dyslipidemia - Glimepiride , losartan , rosuvastatin 유지

Laboratory Findings CBC/DC 5,630/mm3 -12.0 g/dl- 35.1% - 254,000/mm3 (seg.59.3%) (MCV 91.2 fL MCH 31.3 pg MCHC 34.3 g/dL) Chemistry TB/DB 0.85/0.05 mg/dL T-pro/alb 6.7/3.7 g/dL AST/ALT 21/25 U/L ALP/GGT 63/12 U/L Glucose 202 mg/dL BUN/Cr 13/0.5 mg/dL Na/K/Cl 141/3.8/105 mmol/L Ca/P 9.4/4.6 mg/dL LD/CK 293/75 U/L Uric acid 3.7 mg/dL T-Chol/TG 239/210 mg/dL HDL/LDL 52/140 mg/dL TFT T3 135 ng/dL fT4 1.09 ng/dL TSH 1.5 mU/mL HbA1C 7.1% U/A RBC 0~1/HPF WBC 0~1/HPF Protein (-)

Chest PA

ECG

75g Glucose Loading GH Suppression Test IGF-I 624 ng/mL (252-430) IGFBP-3 4,157 ng/mL -30 min 0 min 30 min 60 min 90 min 120 min Glucose (mg/dL) 126 219 192 223 250 GH (ng/mL) 16.0 14.0 13.0 10.0 7.6 Insulin (µU/mL) 28.6 278.5 C-peptide 3.0 8.8 Insulinogenic index 2.69 HOMA-IR 4.10

TRH Stimulation Test T3 135 ng/mL FT4 1.09 ng/dL TRH 200 µg 16.0 13.0 -30 min 0 min 30 min 60 min 90 min 120 min GH (ng/mL) 16.0 13.0 86.0 44.0 26.0 10.0 PRL 114.5 >300 230.4 218.0 202.6 TSH (µU/mL) 1.5 9.4 7.8 5.3 4.1 T3 135 ng/mL FT4 1.09 ng/dL

Double Stimulation Test 62 Kg, RI 0.2U/Kg, LHRH 100 µg E2 47.4 pg/mL progesterone 1.39 ng/mL testosterone 0.13 ng/mL -30 min 0 min 30 min 60 min 90 min 120 min Glucose (mg/dL) 119 53 71 85 101 GH (ng/mL) 18.0 16.0 13.0 11.0 9.4 9.2 ACTH (pg/mL) 41.5 71.3 345.4 162.9 54.9 34.2 Cortisol (µg/dL) 12.4 22.9 33.4 22.0 19.7 FSH (mIU/mL) 1.8 5.5 8.7 9.5 9.0 LH 0.2 1.2 1.6 1.4

Somatostatin Suppression Test octreotide 100 µg -30 min 0 min 1 hour 2 hours 3 hours 4 hours GH (ng/mL) 23.0 14.0 11.0 9.9 8.7

Colonoscopy 0.4cm

Visual Field left right

Clinical Course I Transsphenoidal approach (TSA) (2007-08-07) biopsy no acute complication

Microscopic Findings - HE stain 2cc volume HE X100 HE X400

Microscopic Findings - IHC stain GH PRL TSH ACTH FSH LH

Microscopic Findings - IHC stain Pit-1

Microscopic Findings - IHC stain Ki-67 < 1% p53 (+)

Microscopic Findings at CFS 3.3 mm tumor CD56 carcinoid tumor synaptophysin chromogranin

Final Diagnosis #1. Acromegaly due to plurihormonal pituitary adenoma with Pit-1 expression #2. Rectal carcinoid tumor s/p endoscopic resection

Clinical Course III – GH/IGF-1/PRL PRL, IGF-1 (ng/mL) 600.0 IGF-I 450.0 300.0 150.0 TSA date Oct-LAR 20mg Oct-LAR 30mg BRCT 2.5mg BRCT 5.0mg BRCT 7.5mg

2007 2008 2009 2010