5.3mg ()

1

2SD 2 1.5SD 17 15 2

4 4 3 ( ) 瘙 3

嘔 気 嘔 吐 腹 痛 消 化 不 良 便 秘 4

24 p * p ** IGF-I (ng/ml) 77.12±60.19 238.97±143.60 161.85±113.30 [124.08, 199.63] (p<0.0001) 157.62 [119.27, 195.97] (p<0.0001) 83.33±50.51 87.56±54.66 4.23±22.16 [-3.27, 11.73] (p=0.2672) * Wilcoxon SD [ 95%] **Wilcoxon : DXA 48 % / 43.85±10.26 44.38±10.41 1.25±4.23 [-0.20, 2.71] kg / 40.41±11.01 42.14±11.02 4.66±5.94 [2.65, 6.67] SD [ 95%] 0.1 0.033 mg /kg/ 24 41.48±9.77 43.38±10.30 kg 39.93±10.34 40.41±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 / 249.30±140.71 190.18±73.16-59.13±143.05 [-108.27, -9.99] ng/ml / 87.56±54.66 203.74±91.01 116.18±96.94 [83.38, 148.98] SD [ 95%] /35 /36 : DXA 5

ö 6

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

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

2SD 2 1.5SD 17 15 2

IGF-I 4 43 3

瘙 4 嘔 気 嘔 吐 腹 痛 消 化 不 良 便 秘

25 3 24 41.48±9.77 43.38±10.30 kg 39.93±10.34 40.41±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±60.19 238.97±143.60 161.85±113.30 [124.08, 199.63] (p<0.0001) 157.62 [119.27, 195.97] (p<0.0001) 83.33±50.51 87.56±54.66 4.23±22.16 [-3.27, 11.73] (p=0.2672) * Wilcoxon SD [ 95%] **Wilcoxon : DXA 48 % / 43.85±10.26 44.38±10.41 1.25±4.23 [-0.20, 2.71] kg / 40.41±11.01 42.14±11.02 4.66±5.94 [2.65, 6.67] SD [ 95%] 48 IGF-I / 249.30±140.71 190.18±73.16-59.13±143.05 [-108.27, -9.99] ng/ml / 87.56±54.66 203.74±91.01 116.18±96.94 [83.38, 148.98] SD [ 95%] /35 /36 : DXA 5

3 ö 6

12mg ()

1 2SD

2 1.5SD 17 15 2

4 43 瘙 3

嘔 気 嘔 吐 腹 痛 消 化 不 良 便 秘 20 12 mg 5.3 mg Cmax 153 58 miu/lauc0-1420300 miuhr/ltmax 4.852.11 hrt1/2 3.642.41 hr 5.3 mg 5.3 mg 8 (2.8 mg )1 1.33 mg 2. 24 4

3.5 7.7 3.3 5.8 3.0 11.0 3.1 7.8 3.5 6.3 4.2 6.2 2.7 5.2 24 41.48±9.77 43.38±10.30 kg 39.93±10.34 40.41±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±60.19 238.97±143.60 161.85±113.30 [124.08, 199.63] (p<0.0001) 157.62 [119.27, 195.97] (p<0.0001) 83.33±50.51 87.56±54.66 4.23±22.16 [-3.27, 11.73] (p=0.2672) * Wilcoxon SD [ 95%] **Wilcoxon : DXA 48 % / 43.85±10.26 44.38±10.41 1.25±4.23 [-0.20, 2.71] kg / 40.41±11.01 42.14±11.02 4.66±5.94 [2.65, 6.67] SD [ 95%] 48 IGF-I / 249.30±140.71 190.18±73.16-59.13±143.05 [-108.27, -9.99] ng/ml / 87.56±54.66 203.74±91.01 116.18±96.94 [83.38, 148.98] SD [ 95%] /35 /36 : DXA ö 5

6

1.8.2 Page 1 1.8.2 1.8.2.1 (1) (2) (1) 2 3 ng/ml GHRP-2 15 ng/ml 1 3 ng/ml GHRP-2 15 ng/ml (2) 1 2 3 ng/ml GHRP-2 15 ng/ml 1.8 ng/ml GHRP-2 9 ng/ml

1.8.2 Page 2 Carroll Rosen GH GH GH GH AGHD GH AGHD 1.8.2.1.1 73GT37P36 24 p=0.00031.8.2-1 p=0.00041.8.2-2 p=0.0390 1.8.2-2 1.8.2-1 075 24 (%) p * p ** GT 37 41.489.77 43.3810.30 4.725.25 p<0.0001 p=0.0003 P 36 39.9310.34 40.4111.01 1.034.38 p=0.1338 GT 37 22.15 ± 7.15 20.22 ± 7.54-9.31±11.79 p<0.0001 P=0.0004 P 36 19.91±7.35 19.89±7.32 0.23±7.11 p=0.8349 *Wilcoxon SD **Wilcoxon 075 6 1-1 2-1

1.8.2 Page 3 1.8.2-2 075 24 24 p * p ** LDL-mg/dL GT 37 127.7±37.9 113.9±32.0-13.8±19.6 p=0.0001 p=0.0645 P 36 140.7±29.8 136.3±39.6-4.4±23.1 p=0.3328 HDL-mg/dL GT 37 52.1±15.1 55.0±16.8 2.9±8.7 p=0.0673 p=0.4009 P 36 49.4±13.2 50.3±13.8 0.9±8.4 p=0.5571 mg/dl GT 37 205.7±43.6 193.9±37.6-11.7±21.8 p=0.0026 p=0.0390 P 36 216.7±34.9 219.0±44.9 2.3±23.9 p=0.7913 *Wilcoxon SD **Wilcoxon 075 6 6-1, 6-3, 6-5, 6-7, 6-9, 6-11 075076 GH GH 3ng/mL 1.8.2.1.2 EU AGHD GH QOL 60-1 1-2 IGF-I 2SDS1

1.8.2 Page 4 1.8.2.2 (1) (2) (1) 2 3 ng/ml GHRP-2 15 ng/ml 1 3 ng/ml GHRP-2 15 ng/ml (2) 1 2 3 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

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) 2 1 2 3 ng/ml GHRP-2 15 ng/ml 1.8 ng/ml GHRP-2 9 ng/ml GH

1.8.2 Page 6 1.8.2-3 1.8.2-4 1.8.2-3 24 %: GT 24 p * kg 19 40.27±8.43 41.96±8.81 18 42.76±11.12 44.88±11.73 kg 4.37±6.25 p=0.0040 5.09±4.07 p=0.0001 19 22.28±7.71 20.70±8.28-8.24±12.74 p=0.0210 18 22.00±6.73 19.72±6.87-10.44±10.96 p=0.0005 *Wilcoxon 075 6 3-1, 3-5 P 24 p * 19 38.12±8.49 39.00±9.81 17 41.96±12.01 41.98±12.33 19 20.78±8.60 21.06±8.86 17 18.94±5.74 18.59±5.04 1.86±4.38 p=0.0469 0.10±4.32 p=0.7818 1.30±7.04 p=0.4423-0.97±7.22 p=0.4238 SD 1.8.2-4 24 LDL-mg/dL : GT 24 p * 19 122.8±40.5 109.6±33.2-13.2±17.3 p=0.0047 18 132.9±35.5 118.3±31.0-14.6±22.4 p=0.0149 *Wilcoxon 075 6 7-9 P 24 p * 19 141.1±26.0 134.4±34.5-6.7±26.7 p=0.3369 17 140.2±34.3 138.4±45.7-1.8±18.8 p=0.8701 SD

1.8.2 Page 7 1.8.2.3 GH GH GH GH GH IGF-I GH AGHD kg 0.084mg 1.8.2.3.1 1.8.2.3.1.1 IGF-I AGHD GH IGF-I IGF-I IGFBP-3 ALS (acid labile subunit)

1.8.2 Page 8 IGF-I 1.8.2-5 IGF-I GH 50 20 1/3 GH IGF-I 17 ~ <20 20 ~ <30 30 ~ <40 40 ~ <50 50 ~ <60 60 ~ <70 1.8.2-5 IGF-I IGF-I ng/ml * 12 347 219 ~ 509 8 391 264 ~ 542 20 364 233 ~ 525 141 202 85 ~ 369 101 234 119 ~ 389 242 215 96 ~ 382 104 169 67 ~ 318 40 171 73 ~ 311 144 170 69 ~ 316 75 131 41 ~ 272 31 139 46 ~ 282 106 134 43 ~ 275 95 125 59 ~ 215 36 126 37 ~ 266 131 125 52 ~ 230 29 124 42 ~ 250 15 84 37 ~ 150 44 110 35 ~ 226 *1.96 SD 1.8.2.3.1.2 IGF-I SDS 075 075 076 1.8.2-6075 4 0.003 mg/kg/ 4 8 0.006 mg/kg/ 8 24 0.012 mg/kg/ GHD 1/8 1/41/2 076 0.003 mg/kg/ 8 IGF-I 1.0 mg/076

1.8.2 Page 9 1.8.2-6 075 75 0.003mg/kg/04 0.006mg/kg/48 0.012mg/kg/824 24 076 71 0.003mg/kg/08 IGF-I 48 075 IGF-I SDS 1.8.2-7 1.8.2-1 IGF-I SDS IGF-I IGF-I SDS IGF-I IGF-I SD IGF-I SDS GT 0.006 mg/kg/ 8 0 SD 0.012 mg/kg/ 12 24 +1.424 SD+0.818 SD GT IGF-I 1.8.2-8 24 IGF-I 4065 1.8.2-7 075 IGF-I SDS 4 8 12 24 mg/kg/ 0.003 0.006 0.012 0.012 GT -1.964±1.621-0.466±1.854 0.444±2.064 1.424±2.279 0.818±2.390 (n=37) [-2.505, -1.424] [-1.084, 0.152] [-0.244, 1.133] [0.664, 2.184] [0.021, 1.615] P -1.835±1.279-1.772±1.286-1.798±1.323-1.810±1.436-1.746±1.345 (n=36) [-2.268, -1.402] [-2.207, -1.336] [-2.245, -1.350] [-2.296, -1.324] [-2.201, -1.291] 075 6 10-3 SD95%

1.8.2 Page 10 SDS 8 GT P 6 4 2 0-2 + -4-6 + + + -8 1.8.2-1 075 8 4-3 1.8.2-8 075 GT IGF-Ing/mL 075 GT IGF-I IGF-I 24 * 2029 3039 9 279.70±167.46 85 ~ 369 4 143.48±73.11 119 ~ 389 20 ~ <30 13 237.78±155.93 96 ~ 382 8 256.59±170.80 67 ~ 318 5 159.18±154.52 73 ~ 311 30 ~ <40 13 219.12±165.56 69 ~ 316 41 ~ 272 40 ~ <50 6 282.18±125.25 59 ~ 215 50 ~ <60 42 ~ 250 60 ~ <70 46 ~ 282 40 ~ <50 4065 5 241.80±81.90 37 ~ 266 50 ~ <60 37 ~ 150 60 ~ <70 43 ~ 275 40 ~ <50 11 263.83±104.75 52 ~ 230 50 ~ <60 *1.96 SD 35 ~ 226 60 ~ <70 SD 075 GT IGF-I SDS 1.8.2-2 IGF-I SDS +2SD GT 38 19

1.8.2 Page 11 IGF-I SDS 1.8.2-2 075 GT IGF-I SDS 075 8 9-21 076 0.003 mg/kg/ 8 IGF-I 1.0 mg/ 48 GT/GT P/GT 0.0010.014 mg/kg/ 0.0010.012 mg/kg/ 0.0056 mg/kg/ 0.0052 mg/kg/ 076 P/GT IGF-I SDS 1.8.2-9 IGF-I 075 0 SD P/GT IGF-I 1.8.2-10 48 IGF- I 4065 4065 50<60 60<70 1.8.2-9 076 IGF-I SDS 076 4 8 12 16 24 48 0.975±2.361-0.270±1.764-0.477±1.935-0.010±1.786 0.418±1.625 0.400±1.679 0.457±1.491 GT/GT [0.164, [-0.876, [-1.141, [-0.624, [-0.141, [-0.177, [-0.055, N=35 1.786] 0.336] 0.188] 0.603] 0.976] 0.977] 0.970] P/GT N=36-1.746±1.345-0.420±1.476-0.372±1.408-0.008±1.149 0.191±1.325 0.532±1.283 0.443±1.269 [-2.201, -1.291] [-0.920 0.079] 076 7.2.1 [-0.848, 0.105] [-0.397, 0.381] [-0.257, 0.639] [-0.098, 0.966] [0.013, 0.872] SD95%

1.8.2 Page 12 1.8.2-10 076 P/GT IGF-Ing/mL 076 P/GT IGF-I IGF-I * 48 ** 2029 3039 6 162.15±66.28 85 ~ 369 5 238.64±112.27 119 ~ 389 20 ~ <30 11 196.92±93.99 96 ~ 382 9 217.22±78.41 67 ~ 318 2 155.50±23.33 73 ~ 311 30 ~ <40 11 206.00±74.81 69 ~ 316 41 ~ 272 40 ~ <50 7 204.86±57.79 59 ~ 215 50 ~ <60 42 ~ 250 60 ~ <70 46 ~ 282 40 ~ <50 4065 6 165.60±92.37 37 ~ 266 50 ~ <60 37 ~ 150 60 ~ <70 43 ~ 275 40 ~ <50 13 186.74±75.10 52 ~ 230 50 ~ <60 35 ~ 226 60 ~ <70 *075 **1.96 SD SD 076 IGF-I SDS 1.8.2-3 075 GT/GT 0.0120 mg/kg/ 0.003 mg/kg/ 076 075 0.0120 mg/kg/+2sd +2SD 075 P/GT IGF-I SDS 24 +2SD 36 9 075 IGF-I GT/GT P/GT 1.8.2-3 076 IGF-I SDS 076 8-2

1.8.2 Page 13 1.8.2.3.1.3 IGF-I IGF-I GH 2 2-4 IGF-I GH 4 IGF-I 076 P/GT ( 1.8.2-11)12 IGF-I 16 42.4%(14 /33 )20 IGF-I 24 84.8%(28 /33 ) -4 mg/ 1.8.2-11 4-8 8-12 12-16 16-20 20-24 24-36 36-48 (mg/) (mg/) (mg/) (mg/) (mg/) (mg/) (mg/) 01-02 0.3 0.3 0.6 0.4 0.4 0.4 0.4 0.4 02-04 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 04-02 0.1 0.1 0.2 0.2 0.2 0.3 0.3 0.3 05-01 0.3 0.3 0.3 0.3 0.3 0.3 0.4 0.3 05-02 0.2 0.2 0.3 0.3 0.4 0.4 0.3 0.3 05-06 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 06-01 0.2 0.2 0.2 0.3 0.3 0.3 0.3 0.3 06-03 0.2 0.2 0.3 0.3 0.3 0.2 0.2 0.2 06-05 0.2 0.2 0.3 0.2 0.2 0.3 0.3 0.2 07-01 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 08-02 0.2 09-01 0.2 0.2 0.2 0.2 0.3 0.3 0.3 0.4 10-01 0.2 0.2 0.2 0.3 0.4 0.4 0.4 0.4 10-06 0.2 0.3 0.3 0.3 0.3 0.4 0.4 0.4 10-08 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 11-03 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 12-02 0.2 0.2 0.4 0.6 0.6 0.6 0.6 0.6 13-01 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 13-02 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.2 13-06 0.2 0.2 0.2 0.4 0.4 0.4 0.6 0.6 14-01 0.2 0.2 0.4 0.6 0.8 0.8 0.6 0.6 14-02 0.2 0.2 0.4 0.6 0.6 0.6 0.4 0.4 14-06 0.2 0.2 0.4 0.6 0.6 0.4 0.4 0.4 14-09 0.1 0.1 0.1 17-01 0.2 0.2 0.2 0.2 0.2 0.3 0.3 17-03 0.2 0.2 0.3 0.3 0.3 0.3 0.4 0.4

1.8.2 Page 14-4 mg/ 1.8.2-11 4-8 8-12 12-16 16-20 20-24 24-36 36-48 (mg/) (mg/) (mg/) (mg/) (mg/) (mg/) (mg/) 17-04 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 17-07 0.3 0.3 0.3 0.2 0.2 0.1 0.1 0.1 17-09 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 18-02 0.2 0.2 0.4 0.4 0.4 0.4 0.5 0.5 19-01 0.1 0.1 0.2 0.3 0.4 0.5 0.5 0.6 19-02 0.3 0.3 0.6 0.8 0.8 0.8 0.8 1.0 19-04 0.2 0.2 0.4 0.6 0.6 0.6 0.5 0.5 19-07 0.2 0.2 0.4 0.6 0.6 0.7 0.7 0.7 20-01 0.2 20-02 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 (: 076 3.5 1.2 ) ( ) 8 5 1 7 7 5 IGF-I4 IGF-I1212 IGF-I 24IGF-I IGF-IGH2441224 1GH 1.8.2.3.1.4 075 076 P/GT LDL- 1.8.2-12 1.8.2-13 GT LDL- 4 24 P/GT 075 076 48 GT/GT 24 48 2.7.3.5

1.8.2 Page 15 1.8.2-12 075 4 8 12 24 (kg) (kg) GT 37 41.48±9.77 43.21±9.71 43.38±10.30 P 36 39.93±10.34 40.28±11.11 40.41±11.01 GT 37 22.15±7.15 21.09±7.32 20.22±7.54 P 36 19.91±7.35 19.76±7.30 19.89±7.32 LDL- GT 37 127.7±37.9 117.9±31.8 115.9±35.6 115.9±32.3 113.9±32.0 (mg/dl) P 36 140.7±29.8 140.4±36.2 137.8±38.3 137.4±39.1 136.3±39.6 075 6 1-1, 2-1, 6-9 1.8.2-13 076 P/GT SD 076 4 8 12 16 20 24 48 (kg) 36 40.41±11.01 41.89±10.96 42.14±11.02 (kg) 36 19.89±7.32 19.01±7.45 18.59±7.28 LDL- 36 136.3±39.6 121.9±29.3 124.8±37.0 123.6±33.0 125.6±39.2 124.3±30.4 124.3±37.1 122.1±32.1 (mg/dl) 076 4.2.1, 5.2.1, 6.2.1 SD 1.8.2.3.1.5 1.8.2.3.1.5.1 075 0.012 mg/kg/ 075 GT 10%8 21.6% 4 10.8%4 10.8% 1 2 3 GT 2 5.4% 1.8.2-14 1 1 GT 3 8.1 GT 2 5.4%

1.8.2 Page 16 1.8.2-14 075 GT mg/ # # # 01-01 0.500 29 0.200 mg/57112 85 02-05 0.800 04-03 0.800 127 132 128 223* 140 140 223* 140 223* 140 223* 106 0.400 mg/106126 190 106 0.200 mg/127162 134 05-03 0.900 113 0.300 mg/144168 193 12-01 0.200 19 2021 22 15-01 0.200 1 21** 36 # 1 0.003 mg/kg/ 0.012 mg/kg/ * ** 1520 075 7 1-1 1.8.2.3.1.5.2 076 076 10%P/GT 5 13.9%GT/GT 7 20.0% 6 17.1% 5 14.3%5 14.3%4 11.4%4 11.4% 4 11.4% GOT ASTGOT4 11.4%4 11.4% GT/GT P/GT P/GT 1 GT/GT 3 2 1 3 GT/GT P/GT 1 GT/GT 4 11.4%P/GT 4 11.1% 8 GT/GT 7 20.0%P/GT 6 16.7% 13 1.8.2-15

1.8.2 Page 17 GT/GT 1.8.2-15 076 * mg GT/GT 0.200 24 2949 494 01-01 117 144 0.500 0.3 mg/117283 102 144 AST GOT 117 02-02 0.300 145172 173 ALTGPT 117 173 0.800-56 0.4 mg/-56-36 0.2 mg/-35112 29 0.200 57 0.1 mg/113307 141 0.200 57 0.1 mg/113307 364 04-03 285 392 0.100 308 285 336 CM 285 336 05-03 0.200 176 176 267** 06-02 0.400 142 144147 526 62 6363 113 0.900-11 11 29 141 337 09-02 0.2 mg/ 0.300 141 141336 337 141 428 12-01 0.200 1 23 36 14-11 0.200 20 2048 48 17-02 0.100 53 8184 183 98 100 116 17-06 0.400 116 151 0.3 mg/116150 116 176 * 1 mg/ 1kg mg/kg/ 0.0030.001 mg/kg/ 0.0060.001 mg/kg/ 0.0120.001 mg/kg/ ** # 076 1

1.8.2 Page 18 P/GT * mg P/GT 01-02 -18 0.4 mg/86336 117 02-04 0.100 18 2022 21 05-01 0.300 30 6 a) 113 06-03 0.300 69 253 0.2 mg/134336 96 295 0.2 mg/ 06-05 0.200 51 85140 337 211336 0.200 114 114118 134 07-01 180 180183 183 0.200 298 298298 337 333 333334 334 14-09 0.100 71 71 71** 17-01 0.200 110 111113 120 17-03 0.300 121 121121 540 18-02 0.500 332 7 a 341 335 7 a 341 0.200 -GTP 30 0.5 mg/177337 401 19-04 AST(GOT) 142 261 0.600 b) 0.5 mg/177337 ALT(GPT) 142 261 * 1 mg/ 1kg mg/kg/ 0.0030.001 mg/kg/ 0.0060.001 mg/kg/ 0.0120.001 mg/kg/ ** # 076 1 a) b) 0.0088 mg/kg/ 076 3.7.1 1.1.11.1.2 1.0 mg/0.0125 mg/kg/ P/GT GT/GT 1 P/GT 1 36 1.0 mg/ GT/GT 1 076 20 1.0 mg/ 2 1.8.2.3.1.5.3 075 GT 37 8 21.6% 5 13.5% 0.012 mg/kg/8 24 I 04 1.8.2-16 8 12 24 IGF-I SDS 8 7 +2 SD 1.8.2-17

1.8.2 Page 19 076 P/GT 36 5.6%2 8.3%3 075 GT 075 P/GT IGF-I 076 GT/GT 35 8 22.9% 6 17.1% 1 1 075 076 1.8.2-16 075 0.003 mg/kg/ () 0.006 mg/kg/ () 0.012 mg/kg/ () 1 3 0 5 3 1 0 6 075 21 1.8.2-17 075 824 IGF-I 12 24 * IGF-I (ng/dl) SDS IGF-I (ng/dl) SDS 01-01 113 236 0.98 422 3.21 01-03 72 300 2.35 339 2.77 04-01 119 113 331 2.62 342 2.73 04-03 106 162 539 4.15 304 1.80 09-02 141 499 3.99 32.7-3.18 12-01 73 120-0.92 147 0.13 17-02 85 474 3.56 336 2.16 17-10 60 93 353 4.26 298 3.40 *075 7 1-1 075 GT 43.2%16 076 P/GT 30.8%8 GT/GT 22.2%6 076 075 GT P/GT GT/GT 2.7.4.2.1.5.2

1.8.2 Page 20 1.8.2.3.2 GH 0.15 0.30 mg/ mg/ kg 0.150.3 mg/ 80 kg kg 0.00190.00375 mg/kg/ 0.00190.00375 mg/kg/ 0.003 mg/kg/ 1.8.2-1 075 IGF-I SDS 0.003mg/kg/ IGF-I SDS 0.003mg/kg/ 075076 1.8.2-18 1.8.2-18 24 a) 075 076 024 I GT P P/GT GT P GT P GT P 37 36 36 65 24 73 1 0 0 0 5 2 6 2 3 1 0 0 0 0 2 1 2 3 2 1 1 0 1 1 4 2 7 1 0 0 0 1 2 2 2 4 0 0 0 0 2 0 2 0 1 1 0 0 0 1 1 2 1 2 2 0 0 0 1 3 3 3 6 1 0 0 0 1 1 2 1 4 ASTGOT 1 0 0 0 0 0 1 0 2 ALTGPT 1 0 0 0 0 0 1 0 3 -GTP 0 0 0 0 0 0 0 0 2 3 0 0 0 1 0 4 0 3 T 3 0 0 0 0 0 0 0 0 3 T 1 0 1 0 0 0 2 0 1 2 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 2

1.8.2 Page 21 075 076 024 I GT P P/GT GT P GT P GT P 1 0 0 0 1 0 2 0 0 0 1 0 0 0 0 0 1 3 3 0 0 0 5 1 8 1 3 0 1 0 0 0 0 0 1 3 a) 2 2.7.4 6 1 1 kg 0.003mg 1 1 1.8.2.3.3 1 1 1.0 mg/ 1 mg/ 1 1 mg/ 6 3, 1.8.2.3.4 AGHD

1.8.2 Page 22 1.8.2.3.11.8.2.3.4

1.8.2 Page 23 1.8.2.4 076 P/GT ( 1.8.2-11)12 IGF-I 16 42.4%(14 /33 )20 IGF-I 24 84.8%(28 /33 ) IGF-I 4 IGF-I 12 12 IGF-I 24 IGF-I IGF-I GH 24 4 12 24 1 GH IGF-I 1.8.2-5 GH

1.8.2 Page 24 1.8.2.5 9 4 25 606 607 CDS 1 2SD 2 1.5SD [ ]

1.8.2 Page 25 17 15 1.8.2.2

1.8.2 Page 26 (1) 2SD 0.175 mg// 17 15 2SD [ ] 1.8.2.4

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

1.8.2 Page 28 4 4 3

1.8.2 Page 29 瘙

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

1.8.2 Page 31

1.8.2 Page 32 5.3 mg

1.8.2 Page 33 1.8.2.5.1 AGHD AGHD KIGS, KIMS GH AGHD KIMS AGHD 1.8.2-19ACTH 6.1%, 2.7%, 2.9%, 5.0% 1.8.2-19 KIMS 2003 8 2047 124 (6.1) ACTH 492 11 (2.7) 751 22 (2.9) 44 1 (2.2) 66 0 881 44 (5.0) 76 11 (14.4) 12 4 (33) 112 4 (3.6) 50 2 (4) 076 1 2 GHD GHD GH GH 1988 1993 GH 312 24.0%GH 254 42.5 KIMS GH GH

1.8.2 Page 34 AGHD 1.8.2.5.2

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

1.8.2 Page 36 HbA 1C HbA 1C 075 GT 075 1.8.2-20 075 0.012 mg/kg/(8-24 ) (0-4 )4-8 1 1.8.2-20 075 0.003 mg/kg/ () 0.006 mg/kg/ () 0.012 mg/kg/ () 1 3 0 5 3 1 0 6 CTD 2.5.5 24 076 24 P/GT(075 076 ) 2 7.7 %075 GT 076 076 IGF-I AGHD AGHD 1.8.2.5.3

1.8.2 Page 37 075 GT 2 2-05 12-01 GT 2-05 2-05 076 3 5-03 14-09 2-02 A 1.8.2.5.1 1 GH 075 076 1.8.2-21 2.7.4

1.8.2 Page 38 1.8.2-21 a) 075 076 075/076 075 075 076 075/076 075 GT P GT P 37 71 73 36 37 71 73 36 % 3286.5 6693.0 6893.2 3083.3 2259.5 4462.0 4663.0 925.0 155 565 673 110 65 251 284 24 % % 7 18.9 1419.7 1926.0 12.8 38.1 57.0 79.6 00.0 3 8.1 57.0 79.6 00.0 12.7 22.8 22.7 00.0 1437.8 2636.6 3142.5 719.4 821.6 1723.9 1723.3 25.6 5 13.5 912.7 1013.7 25.6 410.8 79.9 79.6 12.8 12.7 68.5 79.6 25.6 12.7 34.2 45.5 12.8 924.3 1216.9 1926.0 513.9 410.8 79.9 912.3 12.8 821.6 2028.2 2331.5 411.1 513.5 1014.1 1115.1 25.6 12.7 45.6 56.8 25.6 00.0 11.4 11.4 00.0 38.1 1115.5 1317.8 12.8 12.7 45.6 56.8 12.8 25.4 912.7 912.3 25.6 25.4 68.5 68.2 25.6 25.4 45.6 45.5 00.0 25.4 45.6 45.5 00.0 1335.1 3245.1 3649.3 1438.9 410.8 1318.3 1419.2 411.1 410.8 1419.7 1621.9 411.1 12.7 57.0 56.8 00.0 410.8 912.7 1216.4 513.9 12.7 34.2 45.5 00.0 410.8 1521.1 1926.0 616.7 25.4 45.6 68.2 12.8 616.2 1825.4 2027.4 822.2 25.4 811.3 912.3 38.3 00.0 68.5 68.2 00.0 00.0 22.8 22.7 00.0 718.9 1622.5 1926.0 925.0 25.4 79.9 811.0 12.8 718.9 2636.6 3041.1 719.4 12.7 811.3 811.0 12.8 00.0 79.9 79.6 38.3 00.0 00.0 00.0 00.0 25.4 34.2 56.8 00.0 12.7 00.0 11.4 00.0 25.4 45.6 56.8 12.8 12.7 22.8 34.1 12.8 25.4 79.9 912.3 25.6 00.0 00.0 00.0 00.0 25.4 45.6 68.2 00.0 00.0 22.8 22.7 00.0 12.7 1318.3 1419.2 12.8 12.7 912.7 1013.7 00.0 ASTGOT 12.7 811.3 912.3 12.8 12.7 57.0 68.2 00.0 ALTGPT 12.7 811.3 912.3 12.8 12.7 57.0 68.2 00.0 -GTP 00.0 57.0 56.8 00.0 00.0 45.6 45.5 00.0 616.2 1825.4 1824.7 12.8 616.2 1521.1 1520.5 00.0 38.1 1115.5 1115.1 00.0 38.1 912.7 912.3 00.0 410.8 811.3 811.0 12.8 25.4 68.5 68.2 12.8 T4 25.4 45.6 45.5 00.0 25.4 45.6 45.5 00.0 38.1 22.8 34.1 12.8 25.4 22.8 22.7 00.0 25.4 22.8 22.7 12.8 25.4 22.8 22.7 00.0 1540.5 4360.6 4561.6 1541.7 12.7 34.2 34.1 00.0 12.7 68.5 68.2 00.0 00.0 00.0 00.0 00.0 1335.1 3752.1 3953.4 1541.7 00.0 00.0 00.0 00.0

1.8.2 Page 39 075 076 075/076 075 075 076 075/076 075 GT P GT P 37 71 73 36 37 71 73 36 % 3286.5 6693.0 6893.2 3083.3 2259.5 4462.0 4663.0 925.0 155 565 673 110 65 251 284 24 % % 00.0 57.0 56.8 12.8 00.0 22.8 22.7 00.0 00.0 45.6 45.5 12.8 00.0 22.8 22.7 00.0 410.8 79.9 811.0 12.8 12.7 45.6 45.5 00.0 38.1 45.6 45.5 12.8 12.7 22.8 22.7 00.0 25.4 11.4 22.7 12.8 00.0 00.0 00.0 00.0 12.7 45.6 56.8 25.6 00.0 00.0 00.0 00.0 12.7 34.2 45.5 12.8 00.0 00.0 00.0 00.0 25.4 1014.1 1115.1 38.3 12.7 1014.1 1013.7 12.8 00.0 79.9 79.6 25.6 00.0 79.9 79.6 12.8 1335.1 3042.3 3345.2 25.6 924.3 1521.1 1824.7 25.6 821.6 1014.1 1317.8 12.8 821.6 912.7 1216.4 12.8 00.0 45.6 45.5 00.0 00.0 00.0 00.0 00.0 25.4 79.9 811.0 00.0 12.7 34.2 34.1 00.0 00.0 57.0 56.8 00.0 00.0 22.8 22.7 00.0 00.0 811.3 811.0 12.8 00.0 45.6 45.5 12.8 00.0 79.9 79.6 411.1 00.0 57.0 56.8 25.6 00.0 68.5 68.2 38.3 00.0 45.6 45.5 12.8 00.0 811.3 811.0 411.1 00.0 22.8 22.7 12.8 00.0 57.0 56.8 25.6 00.0 00.0 00.0 12.8 a) 5 2.7.4 2 1.8.2.5.4 65 GH IGF-I

1.8.2 Page 40 65 60 1.8.2.5.5 1.8.2.5.6 IGF-I IGF-I

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): 382-395. 2) Rosén T, Bengtsson BÅ. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990; 336: 285-288. 3). GH. 6 ; 37-40. 4). GH. 16 ; 122-123. 5) 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): 379-381. 6),,,,,,. IRMA IGF-I, IGF-II, IGFBP-3 : 1. 1996; 44: 1129-1138. 7) 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): 3913-9. 8),,. : 1., 2.. 1999; 35-41.