摘要
研究背景垂体肿瘤手术及放疗是引起成人生长激素缺乏的重要原因之一.成人生长激素缺乏会引起肌肉质量减少、肌力下降,内分泌和脂质代谢异常以及心血管事件增加,生活质量下降。国外有研究表明垂体瘤手术摘除肿瘤以后,自身生长激素多分泌不足,无法维持正常生理功能。而在国内,医师对垂体瘤术后患者的肾上腺激素、甲状腺激素、性腺激素水平关注较多,且能尽快补充,但对此类患者是否存在生长激素缺乏,以及缺乏水平、临床特点及激素补充治疗却鲜见报道。
研究目的研究垂体无功能腺瘤术后患者生长激素水平及是否缺乏,总结缺乏患者的临床特点,量化考察其生活质量及心理状态,为后期验证成人生长激素缺乏症患者应用生长激素的有效性及安全性提供理论基础。
研究方法对我院门诊就诊垂体无功能腺瘤术后并符合初选标准的31例患者进行临床研究。对所有患者均行ITT试验,隔夜晚10点开始禁食,试验前6h开始禁水,清晨空腹平卧行药物激发试验:晨9时胰岛素静脉推注,起始剂量按0.10～0.15U/Kg给药,分别于注射前30分钟,注射后0分钟、30分钟、45分钟、60分钟、90分钟、120分钟测指尖血糖,并同时于各时间点取血2ml测静脉葡萄糖,取3-5ml送往检验科测生长激素水平,共测7次静脉葡萄糖及GH,试验过程中注意观察低血糖等不良反应,积极对症;对经ITT试验确诊为GHD的患者,纳入后续的实验组(GHD组),另设健康者(NC组)作为对照组,同时行ITT试验对照;实验组(GHD组)及健康对照组(NC组)均行内分泌激素(甲状腺激素、性腺激素、肾上腺激素)及血常规、肝肾功、血脂、OGTT的检测及身高、体重、体重指数(BMI)、腰/臀比(WHR)、体脂率(FAT%)、腹部皮褶厚度、左右手握力等测量;并用成人生长激素缺乏症生活质量量表(QoL-AGHDA)及焦虑评分量表(SDS)、抑郁评分量表(SAS)评估对两组患者的生活质量及心理状态进行评估。
研究结果1)共31例患者符合初选条件,均顺利完成ITT试验。均于注射胰岛素30-45分钟间出现低血糖反应,且血浆葡萄糖最低水平≤2.2mmol/L或≤基础值的50%,为有效激发。其中29例患者(93.5%)表现为生长激素缺乏,23例患者GH峰值水平<=3μg/L,且曲线呈低平状态,表现为GH严重缺乏,2例GH峰值水平>5μg/L.表现为生长激素储备功能正常。2) GH严重缺乏组峰值点多集中出现于30分—60分之间,而相对缺乏组多集中于45-60分之间,且严重缺乏组患者生长激素激发后GH呈低平状。3)GHD组患者常表现为体力减低、食欲下降、睡眠质量差、性欲及记忆力低下。4)GHD组患者体脂率(FAT%)较NC组显著增高(27.082±6.20 VS 23.43±3.76,P=0.009);皮下脂肪厚度较正常对照组有增高趋势(31.04±8.44 VS 29.55±8.32),但无统计学差异;腰/臀比高于正常对照组(0.86±0.053 VS 0.83±0.76 P<0.05)5) GHD组甘油三酯较正常对照组显著增高(3.46±2.28 VS 1.07±0.37 P<0.01),血总胆固醇较正常组有升高趋势,但无统计学差异,高密度脂蛋白较正常组有下降趋势,亦无统计学差异。6)GHD组与相应的性别、左右手的对照组比较,握力均显著低于正常对照组(P<0.05)。7) GHD组QOL-AGHDA评分较NC组显著增高(7.96±3.35 VS4.57±2.22 P<0.05)。两两比较中,严重缺乏组评分显著高于NC组(P<0.05),相对缺乏组与NC组比较评分增高,但无统计学意义。8)GHD组患者焦虑20例,占68.9%。对照组焦虑12例,占31.5%。生长激素缺乏组焦虑评分明显高于对照组,二者有显著性差异( P< 0.05)。8)生长激素缺乏组患者抑郁13例,占44.82%;对照组抑郁9例,占25.7%;生长激素缺乏组抑郁评分较对照组有升高趋势,但二者无统计学差异( P>0.05)。
研究结论1、垂体无功能腺瘤患者术后多存在严重生长激缺乏,应加以重视并监测;2、垂体无功能腺瘤术后GHD患者,常表现为体力减低、食欲下降、睡眠质量差、性欲及记忆力低下,存在体脂率显著提高、血甘油三酯显著增高、握力显著下降等身体组分、脂质代谢、肌体活动能力下降的一系列病理生理改变;3、此类患者QOL-AGHDA评分显著增高,生活质量明显下降,并存在焦虑及抑郁情绪,应尽早发现,给以干预措施,提高生活质量。
Background Pituitary tumor surgery and radiotherapy is the one most important reason of adult growth hormone(GH) deficiency(AGHD) . AGHD often cause muscle quality reduce, strength decline, endocrine and lipid metabolic abnormal, cardiovascular events increase and the quality of life decline , while cause psychological problem. Research abroad show that the GH of the postoperative pituitary patients tumor insufficient , can not maintain the patient’s normal physiological function. In domestic, physicians pay more attention on the hormones (adrenal hormones, thyroid hormone,gonad hormone) level of the postoperative pituitary adenoma patients,however less attention on weather growth-hormone deficiency,and the level of growth hormone, clinical characteristics and hormone supplementary treatment .
Objective to test the GH-hormone of the nonfunctional pituitary postoperative patients and summarize clinical characteristics, investigate quality of life and psychological state, and providing theoretical basis for GH applicating in adult growth hormone deficiency patients.
Methods patients were in line with 0riginal Selection Standard in the outpatients of our hospital Twenty-nine patients were selected into trials group (GHD–group) by insulin tolerance test. The people who were healthy volunteers were selected into normal control group(NC-group). All the people were performed the drug probocation test,Insulin was intravenous injected with 0.10-0.15U/Kg,detected the fingertip capillary blood glucose levers at -30minuts before injection and 0、30、45、60、90minuts after injection,at the same time , their levers of growth hormone(GH) and blood glucose were also detected at -30、0、30、45、60、90、120 minuts,kept observing the reactions during the whole test.The people who were healthy volunteers were selected into normal control group(NC-group).The two group were tested by endocrine hormone examination(tetraiodothyronine、hebin、adrenal hormone)、blood routine examination、liver, renal function、blood lipid、OGTT (oral glucose tolerance test)、body height and weight、body mass index (BMI)、waist hip ratio (WHR)、FAT%、skin thickness、left and right hands grip strength.We evaluate the quality of life and the mental state by the analysis of Quality of Life Scale (QOL-AGHDA ,Holmes et al, 1995), Zung Self-Rating Anxiety Scale (SAS) and Zung self-rating depression scale (SDS) .
Results: 1、All the patients(thirty-one) in line with the primary selection standards finished the examination of ITT smoothly. They show hypoglycemic reaction and the lowest level of Glucose ,which was lower than 2.2mmol/L or lower than 50% of basic level. ,it indicated the test was effective. Twenty-nine patients show the GH deficiency, twenty-three patents show that the GH peak level was lower than 3μg/L, and the GH curves was in low and flat condition, which show the severe shortage of GH. Two patients whose GH peak levels were higher than 5μg/L show normal.2、The peak points in severe GH shortage group focus on the level between 30 to 60 minute, and the relative GH shortage group focus on the level between 45 to 60 minute .The GH level of patients in severe GH shortage group was in lower state .3、The patients in GHD group show decreased in weight、appetite、the Quality of sleep、libido and anamnesis which show no specificity.4、FAT% in GHD group increased significantly(27.082±6.20 VS 23.43±3.76,P=0.009)and the thickness of subcutaneous Fat was higher slightly than NC group(31.04±8.44 VS 29.55±8.32)which show no statistical difference. WHR in GHD group was higer than NC group (0.86±0.053 VS 0.83±0.76 P<0.05).5、Triglyceride in GHD group increased significantly than NC group. (3.46±2.28 VS 1.07±0.37 P<0.01).Blood total cholesterol was higher slightly than NC group which show no statistical difference. High density lipoprotein was lower slightly than NC group which show no statistical difference.6、The hand grip strengths in GHD group were lower than NC group Comparing with Corresponding gender and hands.(P<0.05).7、Scores of QOL-AGHDA in GHD group were higher significantly than NC group(7.96±3.35 VS4.57±2.22 )and show statistical difference. The scores in group which the Growth Hormone is in severe shortage increased significantly than NC group(P<0.05) and the scores in relative shortage group increased slightly which show no statistical difference.8、There were twenty patients in anxiety state who take 20% parts in GHD group ,and 12 who was 31.5% in NC group .the scores in GHD group were higher significantly than NC group and show statistical difference ( P< 0.05).9、there were thirteen patients in depression who take 44.82% parts in GHD group and nine who was 25.7% in NC group .the scores in GHD group were higher than NC group but show no statistical difference( P>0.05).
Conclusions: 1、Most of non-functioning pituitary adenoma postoperative patients are in severe shortage of Growth Hormone and should be paid more attention and monitored. 2、clinical symptoms of non-functioning pituitary adenoma patients after operation are no specificient. There are some characteristic Pathophysiological changes ,such as the FAT% and Triglyceride increase, the Lipid Metabolism and the body activity ability decrease . 3、The scores of QOL-AGHDA in non-functioning pituitary adenoma patients after operation are higher ,and the quality of life decreased severely .these patients are often afflicted by Anxiety and depression ,shoud be detected and treated earierly to promote the life quality..
引文
1. Hoffman AR, et al Growth hormone (GH) replacement therapy in adult-onset gh deficiency: effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial. .J Clin Endocrinol Metab. 2004 May;89(5):2048-56.
2. Molitch ME, et al.Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006 May;91(5):1621-34.
3. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. HoKK; 2007 GH Deficiency Consensus Workshop Participants. Eur J Endocrinol. 2007 Dec;157(6):695-700.
4. McKenna SP, Doward LC, et al. The QoL-AGHDA: an instrument for the assessment of quality of life in adults with growth hormone deficiency. Qual Life Res. 1999 Jun;8(4):373-83.
5. Aimaretti G,Corneli G,RazzoreP,BelloneS,Baffoni C,Arvat E,CamanniFMGhigo E1998 Comparison between insulin-ijduced hypoglycemia and growth (GH)-releasing hormone_arginine as provocative tests for the diagnosis lf GH deficiency in adults.GClin Endocrinol Metab 83:1615-1618.
6. Arafah BM,Prunty D,Ybarra J,Hlavin ML,Selman WR 2000 The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia,and hedaches in patients with pituitary adenomas.J Clin Endocrinol Metab 85:1789-1793
7. Galluzzi,F Diagnosis of growth hormone deficiency by using the arginine provocative test: is it possible to shorten testing time without altering validi. Hormone Research. 2009.vol.72.no.3
8.刘福平,郑纪红。成人生长激素缺乏症的诊断与治疗进展,中国现代医学杂志2003,21(13):41-43
9. Hoffman DM ,O’Sullivan A S, Freund J , et al. Adults with growth hormone deficiency have abnormal body composition but normal energy metabolism. J Clin Endocrinol Metab, 1995; 80: 72～77
10. Gibney J , Wallace JD , Spinks T , et al. The effects of 10 years of recombinant human growth hormone in adult GH - deficient patients[J ] . J Clin Endocrinol Metab , 1999 , 84 :2596 - 2062.
11. Attanasio AF , Lamberts SW J , Matranga AMC , et al. Adult growth hormone deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment [J ] . J Clin Endocrinol Metab , 1997 , 82 :85 - 88.
12. Attanasio A F,L amberts SWJ ,M at range MC, et al. Adult growth hormone (GH ) deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. J Clin Endocrin Metab, 1992: 82～88
13. Cummings MH , Christ E , Umpleby AM , et al. Anormalities of very low density lipoprotein apolipoprotein B - 100 metabolism contribute to the dyslipidemia of adult growth hormone deficiency[J ] . JClin Endocrinol Metab ,1997 , 82 :2010 - 2013.
14. Attanasio AF,Bates PC,Ho KK,et a1.Human growth hormone replacement in adult hypopituitary patients:long—term effects on body composition and lipid status—-3—-year results from the HypoCCS Database[J].Clin Endocrinol Metab,2002,87(4):1600-1606.
15. Svensson J,Fowelin J,Landin K,et a1.Effects of 7 years of GH—-replacement therapy on insulin sensitivity in GH-deficient adults[J].Clin Endocrinol Metab,2002,87(5):2121—2127.
16. Robin P F Dullaart1, Gerrit van den Berg1, Aafke M van der Knaap1, Janneke Dijck-Brouwer2, Geesje M Dallinga-Thie3, Peter M J Zelissen4, Wim J Sluiter1 and AndréP van Beek, HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (–629C>A) and modified by glucocorticoid treatment, European Journal of Endocrinology, 2010, 2(162), 227-234
17. Perrini S, Carreira MC, Conserva A, et al. Metabolic implications of growth hormone therapy[J]. J Endocrinol Invest, 2008, 31(9): 79-84
18. Carrol PV,Christ ER,Sonksen PH,et a1.Growth hormone replacement in adults withgrowth hormone deficiency:assessment of current knowledge[J].Trends Endocrinol Metab,2000,11(6):231—238.
19. Ro sen T ,Hansson T , Granhed H, et al. Reduced bone m ineral content in adult patients w ith growth hormone deficiency,A cta Endocrino, 1993, 129: 201～206
20. Svensson J,Stibrant—Sunnerhagen K,Johannsson G.Five years of growth hormone replacement therapy in adults age-and gender-related changes in isometric and isokinetic muscle strength[J].Clin Endocrinol Metab,2003,88(5):2061—2069.
21. S. Holmes, S. Shalet, Development of a questionnaire to assess the quality of life in adults with growth hormone deficiency, Endocrinol.Metab. 2 (1995) 63–69.
22. L. Doward, The development of the AGHDA: a measure to assess quality of life in adults with growth hormone deficiency, QoL. Life Res. 4 (1995) 420–421.
23. S. McKenna, L. Doward, J. Alonso, T. Kohlmann, M. Niero, L.Prieto, L. Wir_en, The QoL-AGHDA: an instrument for the assessment of quality of life in adults with growth hormone deficiency, QoL. Life Res. 8 (1999) 373–383.
24. S.P. McKenna, L.C. Doward, J. Alonso, et al , The QoLAGHDA:an instrument for the
25.刘红朝,雷霆等.垂体肿瘤患者经蝶手术后心理状态与生活质量的评估〔J〕.中国临床康复,2006,2(10):15-17
26. G. McGauley. The psychological consequences and quality of life in adults with growth hormone deficiency. Growth Hormone & IGF Research 2000, Supplement B, S63-$68
27. McKenna SP, Doward LC, Alonso Jet al. The QoL-AGHDA: an instrument for the assessment of quality of life in adults with growth hormone deficiency. Qual Life Res 1999; 8: 373-383.
28. D. Rudman, M. Kutner, C. Rogers, Impaired growth hormone secretion in the adult population. Relation to age and adiposity, J.Clin. Invest. 67 (1981) 1361–1369.
29. S. Salomon, R. Cuneo, R. Hesp, P. Soe`nksen, Growth hormone deficiency in adults, Acta. Paediatr. Scand. 356 (1989) 69.
30. L.J. Woodhouse, A. Mukherjee, S.M. Shalet, S. Ezzat, The influence of growth hormone status on physical impairments, functional limitations, and health-related quality of life in adults, Endocr. Rev. 27 (2006) 287–317.
31. R. Blizzard, S. Joyce, T. Mitchell, et al. Psychosocial impact of long-term growth hormone therapy, in: S. Raita, R. Tolman(Eds.), Human Growth Hormone, Plenum,New York, 1986, p.93.
32. Maria Koltowska-H?ggstr?m, Susan Hennessy, et al. Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA): Comparison of Normative Reference Data for the General Population of England and Wales with Results for Adult Hypopituitary Patients with Growth Hormone Deficiency. Horm Res 2005;64:46-54.
33. Moock, Albrecht,et al. Health-related quality of life and IGF-1 in GH-deficient adult patients on GH replacement therapy: analysis of the German KIMS data and the Study of Health in Pomerania. European journal of endocrinology , 2009, 160 (1) : P.17-24
34. Deijen JB, Arwert LI, Witlox J, Drent ML (2005) Differential effect sizes of growth hormone replacement on quality of life,well-being and health status in growth hormone deficient patients:ameta-analysis.Health Qual Life Outcomes 3:63. doi:10. 1186/1477-7525-3-63.
35. Yoshimi Suzukamo , Hiroyuki Noguchi , et al. Validation of the Japanese version of the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA).SCIENCE DIRECT Growth Hormone & IGF Research 16 (2006) 340–347.
36. Alexandra Chrisoulidou , et al.How much,and by what mechamisms,does growth hormone replacement improve the quality of life in GH-deficient adults Bailliere’s Clinical Endocrinology and Metabolism. 1998,12:261-276.
37. Mcgauley GA ,Cuneo RC,Salomon E Sonsken PH.Psychological well-being before and after growth hormone treatment in adults with growth hormone deficiency.Hormone Res.(1990)33(Suppl.4):52-54.
38. Wood GC, Bentall RP, Gopfert M, Edwards RHT. A comparative psychiatric assessment of patients with chronic fatigue syndrome and muscle disease. Psychol Med 1991; 21: 619-628.
39. Soares C de N, Musolino NR, Cunha Neto Met al. Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial. Arq Neuropsiquiatr 1999; 57: 182-189.
40. Burman P, HettaJ, Wide L etal. Growth hormone treatment affects brainneurotransmitters and thyroxine. Clin Endocrinol (Oxf) 1996; 44: 319-324.
41. Lesch KP, Rupp recht R, et al. Insulin - like growth factor -1 in depressed patients and controls. Acta Psychiatr Scan.1998 ; 78 (6) : 684 - 688.
42. Franz B, Buysse DJ , Cherry CR, et al. Insulin - like growth factor - 1 and growth hormone binding protein in depression:a preliminary communication. J Psychiatr Res. 1999; 33 (2) : 121 - 127.
43.权京菊,叶兰仙.胰岛素样生长因子- 1与抑郁症〔.J〕国际精神病学杂志. 2009,2 (36): 96-96.
1. Growth hormone (GH) replacement therapy in adult-onset gh deficiency: effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial. Hoffman AR, et al. J Clin Endocrinol Metab. 2004 May;89(5):2048-56.
2. CohenLE,Radovick S 2002 Molecular basis of combined pituitary hormone deficiencies.Endocr Rev 23:431d-442.
3. Dattani MT 2005 Growth hormone deficiency and combined pituitary hormone deficiency:does the genotype matter? Clin Endocrinol(Oxf)63:121-130.
4. Moseley CT,Phillips 3rd JA 2000 Pituitary gene mutations and the growth hormone pathway. Simin Reprod Med 18:21-29.
5. Hoffman DM ,O’Sullivan A S, Freund J , et al. Adults with growth hormone deficiency have abnormal body composition but normal energy metabolism. J Clin Endocrinol Metab, 1995; 80: 72～77
6. Gibney J , Wallace JD , Spinks T , et al. The effects of 10 years of recombinant human growth hormone in adult GH - deficient patients[J ] . J Clin Endocrinol Metab , 1999 , 84 :2596 - 2062.
7. Attanasio AF , Lamberts SW J , Matranga AMC , et al. Adult growth hormone deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment [J ] . J Clin Endocrinol Metab , 1997 , 82 :85 - 88.
8. Lissett CA,Shalet SM.Effects of growth hormone on bone and muscle[J].Growth Horm IGF Res,2000,10(Suppl B):95-101.
9. Murray RD,Columb B,Adams JE,at a1.Low bone mass is an infrequent feature ofthe adult growth hormone deficiency syndrome in middle-age adults and the elderly[J].Clin Endocrinol Metab,2004,89(3):1124-1130.
10. Attanasio A F,L amberts SWJ ,M at range MC, et al. Adult growth hormone (GH ) deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. J Clin Endocrin Metab, 1992: 82～88
11. Cummings MH , Christ E , Umpleby AM , et al. Anormalities of very low density lipoprotein apolipoprotein B - 100 metabolism contribute to the dyslipidemia of adult growth hormone deficiency[J ] . JClin Endocrinol Metab ,1997 , 82 :2010 - 2013.
12. Attanasio AF,Bates PC,Ho KK,et a1.Human growth hormone replacement in adult hypopituitary patients:long—term effects on body composition and lipid status—-3—-year results from the HypoCCS Database[J].Clin Endocrinol Metab,2002,87(4):1600-1606.
13. Svensson J,Fowelin J,Landin K,et a1.Effects of 7 years of GH—-replacement therapy on insulin sensitivity in GH-deficient adults[J].Clin Endocrinol Metab,2002,87(5):2121—2127.
14. Robin P F Dullaart1, Gerrit van den Berg1, Aafke M van der Knaap1, Janneke Dijck-Brouwer2, Geesje M Dallinga-Thie3, Peter M J Zelissen4, Wim J Sluiter1 and AndréP van Beek, HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (–629C>A) and modified by glucocorticoid treatment, European Journal of Endocrinology, 2010, 2(162), 227-234
15. Perrini S, Carreira MC, Conserva A, et al. Metabolic implications of growth hormone therapy[J]. J Endocrinol Invest, 2008, 31(9): 79-84
16. Ro sen T ,Hansson T , Granhed H, et al. Reduced bone m ineral content in adult patients w ith growth hormone deficiency,A cta Endocrino, 1993, 129: 201～206
17. Svensson J,Stibrant—Sunnerhagen K,Johannsson G.Five years of growth hormone replacement therapy in adults age-and gender-related changes in isometric and isokinetic muscle strength[J].Clin Endocrinol Metab,2003,88(5):2061—2069.
18. G. McGauley. The psychological consequences and quality of life in adults with growth hormone deficiency. Growth Hormone & IGF Research 2000, Supplement B, S63-$68
19. McKenna SP, Doward LC, Alonso Jet al. The QoL-AGHDA: an instrument for the assessment of quality of life in adults with growth hormone deficiency. Qual Life Res 1999; 8: 373-383.
20. D. Rudman, M. Kutner, C. Rogers, Impaired growth hormone secretion in the adult population. Relation to age and adiposity, J.Clin. Invest. 67 (1981) 1361–1369.
21. S. Salomon, R. Cuneo, R. Hesp, P. Soe`nksen, Growth hormone deficiency in adults, Acta. Paediatr. Scand. 356 (1989) 69.
22. L.J. Woodhouse, A. Mukherjee, S.M. Shalet, S. Ezzat, The influence of growth hormone status on physical impairments, functional limitations, and health-related quality of life in adults, Endocr. Rev. 27 (2006) 287–317.
23. R. Blizzard, S. Joyce, T. Mitchell, et al. Psychosocial impact of long-term growth hormone therapy, in: S. Raita, R. Tolman(Eds.), Human Growth Hormone, Plenum, New York, 1986, p.93.
24. Maria Koltowska-H?ggstr?m, Susan Hennessy, et al. Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA): Comparison of Normative Reference Data for the General Population of England and Wales with Results for Adult Hypopituitary Patients with Growth Hormone Deficiency. Horm Res 2005;64:46-54.
25. MOOCK, ALBRECHT,et al. Health-related quality of life and IGF-1 in GH-deficient adult patients on GH replacement therapy: analysis of the German KIMS data and the Study of Health in Pomerania. European journal of endocrinology , 2009, 160 (1) : P.17-24
26. Deijen JB, Arwert LI, Witlox J, Drent ML (2005) Differential effect sizes of growth hormone replacement on quality of life,well-being and health status in growth hormonedeficient patients:a meta-analysis. Health Qual Life Outcomes 3:63. doi:10.1186/1477-7525-3-63.
27. Yoshimi Suzukamo , Hiroyuki Noguchi , et al. Validation of the Japanese version of the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA).SCIENCE DIRECT Growth Hormone & IGF Research 16 (2006) 340–347.
28. ALEXANDRA CHRISOULIDOU , et al.How much,and by what mechamisms,does growth hormone replacement improve the quality of life in GH-deficient adults Bailliere’s Clinical Endocrinology and Metabolism. 1998,12:261-276.
29. MCGAULEY GA ,CUNEO RC,SALOMON E SONSKEN PH:Psychological well-being before and after growth hormone treatment in adults with growth hormone deficiency.Hormone Res.(1990)33(Suppl.4):52-54.
30. Wood GC, Bentall RP, Gopfert M, Edwards RHT. A comparative psychiatric assessment of patients with chronic fatigue syndrome and muscle disease. Psychol Med 1991; 21: 619-628.
31. Soares C de N, Musolino NR, Cunha Neto Met al. Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial. Arq Neuropsiquiatr 1999; 57: 182-189.
32. Burman P, HettaJ, Wide L etal. Growth hormone treatment affects brain neurotransmitters and thyroxine. Clin Endocrinol (Oxf) 1996; 44: 319-324.
33. Lesch KP, Rupp recht R, et al. Insulin - like growth factor -1 in depressed patients and controls. Acta Psychiatr Scan.1998 ; 78 (6) : 684 - 688.
34. Franz B, Buysse DJ , Cherry CR, et al. Insulin - like growth factor - 1 and growth hormone binding protein in depression:a preliminary communication. J Psychiatr Res. 1999; 33 (2) : 121 - 127.
35.权京菊,叶兰仙.胰岛素样生长因子- 1与抑郁症〔.J〕国际精神病学杂志. 2009,2 (36): 96-96.
36. Galluzzi,F Diagnosis of growth hormone deficiency by using the arginine provocative test: is it possible to shorten testing time without altering validi. Hormone Research. 2009.vol.72.no.3
37. Vance ML , Mauras N. Growth hormone therapy in adults and children[J ] . N Engl J Med ,1999 ,341 :1206.
38. 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 ] . J Clin Endocinol Metab , 1998 ,83 :379.
39. Cuneo RC , J udd S , Wallace JD , et al. The Australian multicenter trial of growth hormone treatment in GH - deficient adults[J ] . JClin Endocrinol Metab ,1998 , 83 :107 - 116.
40. FLORAKIS D,HUNG V,KALTSAS G et al:The safety profile of GH replacement therapy in adults Clin.Endocrinol.(1997)46:P473-81
41. Monson JP.Long-term experience with GH replacement therapy:efficacy and safety[J].Eur Endocrinol,2003,148(Suppl 2):S9—14.
