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1 5.3mg ()

2

3 1

4 2SD 2 1.5SD

5 4 4 3 ( ) 瘙 3

6 嘔 気 嘔 吐 腹 痛 消 化 不 良 便 秘 4

7 24 p * p ** IGF-I (ng/ml) 77.12± ± ± [124.08, ] (p<0.0001) [119.27, ] (p<0.0001) 83.33± ± ±22.16 [-3.27, 11.73] (p=0.2672) * Wilcoxon SD [ 95%] **Wilcoxon : DXA 48 % / 43.85± ± ±4.23 [-0.20, 2.71] kg / 40.41± ± ±5.94 [2.65, 6.67] SD [ 95%] mg /kg/ ± ±10.30 kg 39.93± ±11.01 % p * 4.72±5.25 [2.97, 6.47] (p<0.0001) 1.03±4.38 [-0.45, 2.51] (p=0.1338) % p ** 3.69 [1.43, 5.95] (p=0.0003) * Wilcoxon SD [ 95%] **Wilcoxon 48 IGF-I / ± ± ± [ , -9.99] ng/ml / 87.56± ± ±96.94 [83.38, ] SD [ 95%] /35 /36 : DXA 5

8 ö 6

9 0.4mg 0.6mg 0.8mg 1.0mg 1.2mg 1.4mg 1.6mg 1.8mg 2.0mg ()

10

11 ( ) () D- D- () () D- D- 1

12 2SD 2 1.5SD

13 IGF-I

14 瘙 4 嘔 気 嘔 吐 腹 痛 消 化 不 良 便 秘

15 ± ±10.30 kg 39.93± ±11.01 % p * 4.72±5.25 [2.97, 6.47] (p<0.0001) 1.03±4.38 [-0.45, 2.51] (p=0.1338) % p ** 3.69 [1.43, 5.95] (p=0.0003) * Wilcoxon SD [ 95%] **Wilcoxon 24 p * p ** IGF-I (ng/ml) 77.12± ± ± [124.08, ] (p<0.0001) [119.27, ] (p<0.0001) 83.33± ± ±22.16 [-3.27, 11.73] (p=0.2672) * Wilcoxon SD [ 95%] **Wilcoxon : DXA 48 % / 43.85± ± ±4.23 [-0.20, 2.71] kg / 40.41± ± ±5.94 [2.65, 6.67] SD [ 95%] 48 IGF-I / ± ± ± [ , -9.99] ng/ml / 87.56± ± ±96.94 [83.38, ] SD [ 95%] /35 /36 : DXA 5

16 3 ö 6

17 12mg ()

18

19 1 2SD

20 2 1.5SD

21 4 43 瘙 3

22 嘔 気 嘔 吐 腹 痛 消 化 不 良 便 秘 mg 5.3 mg Cmax miu/lauc miuhr/ltmax hrt1/ hr 5.3 mg 5.3 mg 8 (2.8 mg ) mg

23 ± ±10.30 kg 39.93± ±11.01 % p * 4.72±5.25 [2.97, 6.47] (p<0.0001) 1.03±4.38 [-0.45, 2.51] (p=0.1338) % p ** 3.69 [1.43, 5.95] (p=0.0003) * Wilcoxon SD [ 95%] **Wilcoxon 24 p * p ** IGF-I (ng/ml) 77.12± ± ± [124.08, ] (p<0.0001) [119.27, ] (p<0.0001) 83.33± ± ±22.16 [-3.27, 11.73] (p=0.2672) * Wilcoxon SD [ 95%] **Wilcoxon : DXA 48 % / 43.85± ± ±4.23 [-0.20, 2.71] kg / 40.41± ± ±5.94 [2.65, 6.67] SD [ 95%] 48 IGF-I / ± ± ± [ , -9.99] ng/ml / 87.56± ± ±96.94 [83.38, ] SD [ 95%] /35 /36 : DXA ö 5

24 6

25 1.8.2 Page (1) (2) (1) 2 3 ng/ml GHRP-2 15 ng/ml 1 3 ng/ml GHRP-2 15 ng/ml (2) ng/ml GHRP-2 15 ng/ml 1.8 ng/ml GHRP-2 9 ng/ml

26 1.8.2 Page 2 Carroll Rosen GH GH GH GH AGHD GH AGHD GT37P36 24 p= p= p= (%) p * p ** GT p< p= P p= GT ± ± ±11.79 p< P= P ± ± ±7.11 p= *Wilcoxon SD **Wilcoxon

27 1.8.2 Page p * p ** LDL-mg/dL GT ± ± ±19.6 p= p= P ± ± ±23.1 p= HDL-mg/dL GT ± ± ±8.7 p= p= P ± ± ±8.4 p= mg/dl GT ± ± ±21.8 p= p= P ± ± ±23.9 p= *Wilcoxon SD **Wilcoxon , 6-3, 6-5, 6-7, 6-9, GH GH 3ng/mL EU AGHD GH QOL IGF-I 2SDS1

28 1.8.2 Page (1) (2) (1) 2 3 ng/ml GHRP-2 15 ng/ml 1 3 ng/ml GHRP-2 15 ng/ml (2) ng/ml GHRP-2 15 ng/ml 1.8 ng/ml GHRP-2 9 ng/ml Growth Hormone Research Society AGHD GH GH AGHD AGHD

29 1.8.2 Page 5 GH GH GH (1) : (2): GH pulsatile GH AGHD GH AGHD GH GH (1) 2 3 ng/ml GHRP-2 15 ng/ml 1 3 ng/ml GHRP-2 15 ng/ml AGHD GH GH (2) ng/ml GHRP-2 15 ng/ml 1.8 ng/ml GHRP-2 9 ng/ml GH

30 1.8.2 Page %: GT 24 p * kg ± ± ± ±11.73 kg 4.37±6.25 p= ±4.07 p= ± ± ±12.74 p= ± ± ±10.96 p= *Wilcoxon , 3-5 P 24 p * ± ± ± ± ± ± ± ± ±4.38 p= ±4.32 p= ±7.04 p= ±7.22 p= SD LDL-mg/dL : GT 24 p * ± ± ±17.3 p= ± ± ±22.4 p= *Wilcoxon P 24 p * ± ± ±26.7 p= ± ± ±18.8 p= SD

31 1.8.2 Page GH GH GH GH GH IGF-I GH AGHD kg 0.084mg IGF-I AGHD GH IGF-I IGF-I IGFBP-3 ALS (acid labile subunit)

32 1.8.2 Page 8 IGF-I IGF-I GH /3 GH IGF-I 17 ~ <20 20 ~ <30 30 ~ <40 40 ~ <50 50 ~ <60 60 ~ < IGF-I IGF-I ng/ml * ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 226 *1.96 SD IGF-I SDS mg/kg/ mg/kg/ mg/kg/ GHD 1/8 1/41/ mg/kg/ 8 IGF-I 1.0 mg/076

33 1.8.2 Page mg/kg/ mg/kg/ mg/kg/ mg/kg/08 IGF-I IGF-I SDS IGF-I SDS IGF-I IGF-I SDS IGF-I IGF-I SD IGF-I SDS GT mg/kg/ 8 0 SD mg/kg/ SD SD GT IGF-I IGF-I IGF-I SDS mg/kg/ GT ± ± ± ± ±2.390 (n=37) [-2.505, ] [-1.084, 0.152] [-0.244, 1.133] [0.664, 2.184] [0.021, 1.615] P ± ± ± ± ±1.345 (n=36) [-2.268, ] [-2.207, ] [-2.245, ] [-2.296, ] [-2.201, ] SD95%

34 1.8.2 Page 10 SDS 8 GT P GT IGF-Ing/mL 075 GT IGF-I IGF-I 24 * ± ~ ± ~ ~ < ± ~ ± ~ ± ~ ~ < ± ~ ~ ~ < ± ~ ~ <60 42 ~ ~ <70 46 ~ ~ < ± ~ ~ <60 37 ~ ~ <70 43 ~ ~ < ± ~ ~ <60 *1.96 SD 35 ~ ~ <70 SD 075 GT IGF-I SDS IGF-I SDS +2SD GT 38 19

35 1.8.2 Page 11 IGF-I SDS GT IGF-I SDS mg/kg/ 8 IGF-I 1.0 mg/ 48 GT/GT P/GT mg/kg/ mg/kg/ mg/kg/ mg/kg/ 076 P/GT IGF-I SDS IGF-I SD P/GT IGF-I IGF- I <60 60< IGF-I SDS ± ± ± ± ± ± ±1.491 GT/GT [0.164, [-0.876, [-1.141, [-0.624, [-0.141, [-0.177, [-0.055, N= ] 0.336] 0.188] 0.603] 0.976] 0.977] 0.970] P/GT N= ± ± ± ± ± ± ±1.269 [-2.201, ] [ ] [-0.848, 0.105] [-0.397, 0.381] [-0.257, 0.639] [-0.098, 0.966] [0.013, 0.872] SD95%

36 1.8.2 Page P/GT IGF-Ing/mL 076 P/GT IGF-I IGF-I * 48 ** ± ~ ± ~ ~ < ± ~ ± ~ ± ~ ~ < ± ~ ~ ~ < ± ~ ~ <60 42 ~ ~ <70 46 ~ ~ < ± ~ ~ <60 37 ~ ~ <70 43 ~ ~ < ± ~ ~ <60 35 ~ ~ <70 *075 **1.96 SD SD 076 IGF-I SDS GT/GT mg/kg/ mg/kg/ mg/kg/+2sd +2SD 075 P/GT IGF-I SDS 24 +2SD IGF-I GT/GT P/GT IGF-I SDS

37 1.8.2 Page IGF-I IGF-I GH IGF-I GH 4 IGF-I 076 P/GT ( )12 IGF-I %(14 /33 )20 IGF-I %(28 /33 ) -4 mg/ (mg/) (mg/) (mg/) (mg/) (mg/) (mg/) (mg/)

38 1.8.2 Page 14-4 mg/ (mg/) (mg/) (mg/) (mg/) (mg/) (mg/) (mg/) (: ) ( ) IGF-I4 IGF-I1212 IGF-I 24IGF-I IGF-IGH GH P/GT LDL GT LDL P/GT GT/GT

39 1.8.2 Page (kg) (kg) GT ± ± ±10.30 P ± ± ±11.01 GT ± ± ±7.54 P ± ± ±7.32 LDL- GT ± ± ± ± ±32.0 (mg/dl) P ± ± ± ± ± , 2-1, P/GT SD (kg) ± ± ±11.02 (kg) ± ± ±7.28 LDL ± ± ± ± ± ± ± ±32.1 (mg/dl) , 5.2.1, SD mg/kg/ 075 GT 10%8 21.6% %4 10.8% GT 2 5.4% GT GT 2 5.4%

40 1.8.2 Page GT mg/ # # # mg/ * * * * mg/ mg/ mg/ ** 36 # mg/kg/ mg/kg/ * ** %P/GT %GT/GT % % %5 14.3%4 11.4%4 11.4% % GOT ASTGOT4 11.4%4 11.4% GT/GT P/GT P/GT 1 GT/GT GT/GT P/GT 1 GT/GT %P/GT % 8 GT/GT %P/GT %

41 1.8.2 Page 17 GT/GT * mg GT/GT mg/ AST GOT ALTGPT mg/ mg/ mg/ mg/ CM ** mg/ mg/ * 1 mg/ 1kg mg/kg/ mg/kg/ mg/kg/ mg/kg/ ** # 076 1

42 1.8.2 Page 18 P/GT * mg P/GT mg/ a) mg/ mg/ ** a a GTP mg/ AST(GOT) b) 0.5 mg/ ALT(GPT) * 1 mg/ 1kg mg/kg/ mg/kg/ mg/kg/ mg/kg/ ** # a) b) mg/kg/ mg/ mg/kg/ P/GT GT/GT 1 P/GT mg/ GT/GT mg/ GT % % mg/kg/8 24 I IGF-I SDS SD

43 1.8.2 Page P/GT %2 8.3%3 075 GT 075 P/GT IGF-I 076 GT/GT % % mg/kg/ () mg/kg/ () mg/kg/ () IGF-I * IGF-I (ng/dl) SDS IGF-I (ng/dl) SDS * GT 43.2% P/GT 30.8%8 GT/GT 22.2% GT P/GT GT/GT

44 1.8.2 Page GH mg/ mg/ kg mg/ 80 kg kg mg/kg/ mg/kg/ mg/kg/ IGF-I SDS 0.003mg/kg/ IGF-I SDS 0.003mg/kg/ a) I GT P P/GT GT P GT P GT P ASTGOT ALTGPT GTP T T

45 1.8.2 Page I GT P P/GT GT P GT P GT P a) kg 0.003mg mg/ 1 mg/ 1 1 mg/ 6 3, AGHD

46 1.8.2 Page

47 1.8.2 Page P/GT ( )12 IGF-I %(14 /33 )20 IGF-I %(28 /33 ) IGF-I 4 IGF-I IGF-I 24 IGF-I IGF-I GH GH IGF-I GH

48 1.8.2 Page CDS 1 2SD 2 1.5SD [ ]

49 1.8.2 Page

50 1.8.2 Page 26 (1) 2SD mg// SD [ ]

51 1.8.2 Page 27 (1) 1) 2) 3) 4) IGF-I

52 1.8.2 Page

53 1.8.2 Page 29 瘙

54 1.8.2 Page 30 嘔 気, 嘔 吐, 腹 痛, 消 化 不 良, 便 秘

55 1.8.2 Page 31

56 1.8.2 Page mg

57 1.8.2 Page AGHD AGHD KIGS, KIMS GH AGHD KIMS AGHD ACTH 6.1%, 2.7%, 2.9%, 5.0% KIMS (6.1) ACTH (2.7) (2.9) 44 1 (2.2) (5.0) (14.4) 12 4 (33) (3.6) 50 2 (4) GHD GHD GH GH GH %GH KIMS GH GH

58 1.8.2 Page 34 AGHD

59 1.8.2 Page 35 KIGS Pfizer International Growth Database KIMS Pfizer Internatioal Metabolic Database IGFs 076 IGF-I SDS IGF-I SDS IGF-I SDS -1.96SDS1.96SDS IGF-I SDS IGF-I SDS IGF-I SDS 076 IGF-I SDS IGF-I IGF-I SDS GH IGF-I SDS IGF-I IGF-I IGF-I SDS

60 1.8.2 Page 36 HbA 1C HbA 1C 075 GT mg/kg/(8-24 ) (0-4 ) mg/kg/ () mg/kg/ () mg/kg/ () CTD P/GT( ) %075 GT IGF-I AGHD AGHD

61 1.8.2 Page GT GT A GH

62 1.8.2 Page a) / / GT P GT P % % % ASTGOT ALTGPT GTP T

63 1.8.2 Page / / GT P GT P % % % a) GH IGF-I

64 1.8.2 Page IGF-I IGF-I

65 1.8.2 Page 41 1) Carroll PV, Christ ER and the members of Growth Hormone Research Society Scientific Committee. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 1998; 83 (2): ) Rosén T, Bengtsson BÅ. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990; 336: ). GH. 6 ; ). GH. 16 ; ) Invited report of a workshop; Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on adult growth hormone deficiency. J Clin Endocrinol Metab 1998; 83 (2): ),,,,,,. IRMA IGF-I, IGF-II, IGFBP-3 : ; 44: ) Drake WM, Coyte D, Camacho-Hübner C, Jivanji NM, Kaltsas G, Wood D.F. et al. Optimizing Growth Hormone Replacement Therapy by Dose Titration in Hypopituitary Adults. Journal of Clinical Endocrinology and Metabolism 1998; 83(11): ),,. : 1., ;

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