z z 22 125 daltons 191 amino acid

生長激素小檔案 z正常生長所必需的內分泌，由腦下垂體直 接分泌進入血液中 z分子量為: 22, 125 daltons, 共有191 amino acid z功用: 1. Tissue growth: skeletal, cell, organ growth, 2. Protein Metabolism, 3. Lipid Metabolism, 4. Glucose Metabolism, 5. Mineral Metabolism, 6. Connective Tissue Metabolism

同義字 z. Human growth hormone z. Recombinant growth hormone z. Somatotrophine z. Somatropin

生長激素的歷史 z. Pituitary-derived human growth hormone(1958) z. National Pituitary Agency was founded by the National Institutes of Health in 1963 to coordinate the collection of human pituitary z 1985, three death linked to Creutzfeldt-Jakob disease z. Recombinant human Growth Hormone (1985)

腦下垂體的功能 Pituitary Gland Anterior lobe TSH FSH LH Corticotropin Prolactin Growth hormone Posterior lobe Oxytocin Vasopressin

腦下垂體功能低下Hypopituitarism(1) 診斷: A. Screen- monitor GH level (1)Clonidine : oral 0. 15 mg/m 2 then 1 hr, (2)Exercise test: Rigrous exercise 20 min (3)Sleep: After sleep 40~90 min (4)L-dopa: After oral L-dopa 60 min BW<10 kg, give 125 mg, 30 kg give 250 mg, >30 kg, give 500 mg (5)Propranolol: After oral Propranolol 60 min, 0. 75 mg, max 40 mg

腦下垂體功能低下Hypopituitarism(2) 診斷: B. Definitive Tests- monitor GH level 至少須任意兩項顯示所有GH<7 ng/ml才能判定 (1)Insulin tolerance test, insulin hypoglycemia test (2)Arginine infusion test (3)Glucagone test (4)L-dopa test (5)Clonidine test

腦下垂體功能低下Hypopituitarism(3) 診斷: C. Physiologic tests (1) Overnight GH profile (2) 24 hrs GH profile D. Supplement (1)24 hr urine GH concentration (2)IGF-1

Disturbance of Growth-Short stature 生長曲線 Height < 97% average or Height < Mean +- 2 SD Target height (corrected midparental height) Boy target height= (Father h. + Mother h +12)/2 Girl target height= (Father h. + Mother h -12)/2

身材矮小的原因 Primary Disturbance of growth 1. Skeletal dysplasias 軟骨營養障礙(Chondrodystrophy), 成骨不全( osteogenesis imperfecta) 2. Chromosome disorder 三倍體 (trisomy) 15, 18, 21 or 45, X 3. Congentila errors of metabolism(先天性代謝異常) 4. 子宮內發育遲緩( IUGR): infection, alcohol 5. 家族身材矮小(Family short stature )

身材矮小的原因 Secondary disturbance of growth 營養缺乏, 神經性厭食症(anorexia nervosa) CNS Disorder-間腦症候群 diencephalic syndrome CV Disorder- 先天性心臟病 Resp Disorder- cystic fibrosis, obstructive sleep apnea GI Disorder- 慢性肝炎或胃腸道疾病 GU disorder- 慢性腎衰竭 Hemat disorder- 慢性貧血 Metabolic disorder- 肝糖貯積症 Infection

導致身材矮小的原因 Secondary disturbance of growth Endocrine Disorders 腦下垂體功能低下 Hypopituitarism 生長激素分泌不足 Growth hormone deficiency 甲狀腺功能低下Hypothyroidism 庫興氏症Cushing Syndrome 假性副甲狀腺功能低下Pseudohypoparathyroidism 骨垢過早閉合Premature epiphyseal fusion androgen excess estrogen excess 青春期遲發 Constitutional delay of Growth and puberty

Disturbance of Growth. Short stature Therapy Somatotropin SC 0. 18~0. 3 mg/kg/wk Genotropin Somatotropin Saizen Craniopharygioma Surgery remove tumor + Radiation Monitor Hypothyroidism DI Glucose intolerance anterior hormone deficiency pseudotumor cerebri scoliosis

Turner syndrome的臨床表徵 成長不良症（Failure to thrive), 身材矮小 (Short stature) 淋巴性水腫（Lymphedema esp. during neonatal period） 翼狀頸（Webbed neck） 頸項皮膚鬆弛（Loose neck skin） 髮線過低（Low hair line） 小頜（Micrognathia） 盾狀胸（Broad chest, shield chest） 乳頭發育不良（Underdeveloped nipple） 手肘外翻（Cubitus valgus） 第 4掌骨短小（Short 4 th metacarpal, metatarsal） 耳朵凸出（Prominent ear）上顎高拱（High arched palate） 指甲彎曲（Curved finger nails, hyperconvex fingernails） 手指伸直過度（Hyperextension of fingers） 色素痣（Pigmented nevi）心臟病（Heart disease） 腎臟病（Kidney disease）

Turner syndrome的併發症 非狹窄性兩瓣性主動脈瓣 (isolated nonstenotic bicuspid aortic valves) 主動脈瓣狹窄 (aortic stenosis) 主動脈縮窄 (aortic coarctation) 肺靜脈回流異常 (anomalous pulmonary venous drainage) 腎臟異常 (renal malformations)

Prader-Willi syndrome 臨床上的特徵(2): 4. 內分泌的表現 生殖器發育不全、性腺功能低下 hypogenitalism/hypogonadism* (95%) 肥胖(obesity)(94%) 隱睪症(cryptorchidism) (88%) 身材矮小(short stature)(76%) 骨骼年齡延遲(delayed bone age) (50%) 經期問題( menstrual problems) (39%) 5. 顱顏部的特徵* 杏仁眼(almond-shaped eyes) (75%) 前額窄(narrow-bifrontal diameter )(75%) 斜視(strabismus) (52%) 早期齲齒/琺瑯質發育不全 (40%) 6. 肌肉骨骼的特徵 小手及小腳(small hands and feet)(83%) 脊柱側凸 (scoliosis)(44%)

重要的 Somatropin 藥物不良反應 輝瑞藥廠(Pfizer) 改變了仿單的內容: 生長激素對下列患者屬於禁忌: 具有嚴重肥胖或是有嚴重呼吸功能不全者的小胖威 利患者(Prader-Willi syndrome) Risk factors: severe obesity history of respiratory impairment or sleep apnea, unidentified respiratory infection. Male patients with one or more of these risk factors.

Prader Willi syndrome的基因

Genetic Code 15 q 11 -13 ccattttaca gagtgctgat tgggtccact gtacagagtg ctgattggtc cattttatag 61 attgctgatt ggtgcattta caatcctcta gctagacaca gagtgctgat tggtgcattt 121 acaatccttt agctagacag aaatgttctg caagttccca ctccacccag gaagtccagc 181 tggcttcact tctcactagg gtgaaatgct cttgcatggt taggatgctg gaactctggg 241 accgcctccg aagaagcaac cttcctattg tacggactcc caaggtgcaa acgttagtct 301 cagtgtgcct ttcatgaaga gtggtttctt tctggctgcc ctagagagaa gactggcagt 361 ggagcatgca tctggagggc agagacggca ggcggtaccc cggcgcgccg gcggtggagc 421 tcctgcagac gtccgtgccc agcggactcg ctgaacttgt ggccggcaag cgcaggcttc 481 ctcggggagc cggtggagct gacccctcgc actcctgccc caggggggct gccgggcaga 541 gctcttgggc tcctgcaggc caggagtttg cttcattcct cacaaaaggg aggtgagttt 601 aaaatagtgc catcttgtaa atgtggactt cacacagatt gggtttccat gagcatcgtt 661 cccccacgtt tgtagtggga aaaatttcca gaaattttgc aagaattttt ccagcattag 721 atcactttcc tggcttagtt tttgatgact gatatttgta aaatatgatg aacttaattt 781 agctccaaaa gataataaaa atagaaaaaa

SOMATROPIN, E-COLI DERIVED z. GENOTROPIN MINIQUICK z. HUMATROPE z. NORDITROPIN z. NUTROPIN AQ PEN CARTRIDGE z. NUTROPIN DEPOT

生長激素可能的副作用(5) z. Idiopathic intracranial hypertension (IIH) z症狀為: headache, blurred vision, diplopia, nausea, vomiting, 其症狀停藥後就消失

Appropriate Monitoring of GH Therapy z blood glucose in diabetics (somatropin may induce insulin resistance) z funduscopic examination (for intracranial hypertension) z malignant transformation of skin lesions z patients with chronic renal insufficiency should have periodic exams to identify evidence of renal osteodystrophy z patients with Turner syndrome should be evaluated for otitis media and other ear disorders z recurrence of preexisting tumors z thyroid function

Growth Hormone Deficiency z. Growth hormone affects many parts of the body, including the bones, muscles, and fat. z. Children need growth hormone to grow taller. Adults also need growth hormone to maintain health. When the body does not produce enough of this hormone, growth hormone deficiency (GHD) occurs.

導致成人生長激素缺乏的原因 z腦部受損 z腦腫瘤(Pituitary adenoma) zsurgery or radiation therapy for a pituitary adenoma

生長激素替代療法在成人治療目 標 z. Restore normal body composition z. Improve muscle and cardiac function z. Normalize serum lipid concentration z. Improve the quality of life

Reference: z Vance ML. Mauras N. Growth hormone therapy in adults and children. , New England Journal of Medicine. 341(16): 1206 -16, 1999 Oct 14. z Joseph T. Dipiro. Pharmcotheapy: A Pathophysiologic Approach. 4 th Edition, p 1287~1291 z Fradkin JE, Mills JL, Schonberger LB, et al. Risk of leukemia after treatment with pituitary growth hormone. JAMA 1993; 270: 2829 -32. z Blethen SL, Allen DB, Graves D, August G, Moshang T, Rosenfeld RG. Safety of recombinant deoxyribonucleic acid-derived growth hormone: the National Cooperative Growth Study experience. J Clin Endocrinol Metab 1996; 81: 1704 -10. z Guidelines for the use of growth hormone in children with short stature: a report by the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. J Pediatr 1995; 127: 857 -67.

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