Moderate doses of hGH (0.64 mg/d) improve lipids but not cardiovascular function in GH-deficient adults with normal baseline cardiac function

Journal of Clinical Endocrinology and Metabolism

Volumn 96, Issue 1, 2011, Pages 122-132

  Newman, Connie B ^a   Frisch, Katalin A ^a   Rosenzweig, Barry ^a   Roubenoff, Ronenn ^c   Rey, Mariano ^a   Kidder, Teresa ^a   Kong, Yuan ^a   Pursnani, Amit ^a   Sedlis, Steven P ^a,b   Schwartzbard, Arthur ^a,b   Kleinberg, David L ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b New York Veterans Affairs Harbor Healthcare System   (United States)

^c TUFTS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HUMAN GROWTH HORMONE; LIPID; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; SOMATOMEDIN C;

ACNE; ADULT; AGED; ANKLE SWELLING; ARTHRALGIA; ARTICLE; BODY COMPOSITION; BODY FAT; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; DIASTOLE; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG WITHDRAWAL; ECHOCARDIOGRAPHY; EVENING DOSAGE; EXERCISE; FATIGUE; FEMALE; GENERALIZED BODY ACHE; GROWTH HORMONE DEFICIENCY; HAND PAIN; HEART FUNCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HEART LEFT VENTRICLE MASS; HUMAN; JOINT STIFFNESS; JOINT SWELLING; KNEE PAIN; KNEE SWELLING; MALE; MUSCLE CRAMP; MYALGIA; OXYGEN CONSUMPTION; PAIN; PARESTHESIA; PITUITARY DWARFISM; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SYSTOLE; TREATMENT DURATION; WRIST PAIN; WRIST SWELLING;

EID: 78650864827     PISSN: 0021972X     EISSN: 0021972X     Source Type: Journal    
DOI: 10.1210/jc.2010-1204     Document Type: Article

References (80)

1. de Boer H, Blok GJ, Van der Veen EA 1995 Clinical aspects of growth hormone deficiency in adults. Endocr Rev 16:63-86
2. Barkan AL, Clemmons DR, Molitch ME, Stewart PM, Young Jr WF 2000 Growth hormone therapy for hypopituitary adults: time or re-appraisal. Trends Endocrinol Metab 11:238-245
3. Giustina A, Barkan A, Chanson P, Grossman A, Hoffman A, Ghigo E, Casanueva F, Colao A, Lamberts S, Sheppard M, Melmed S 2008 Guidelines for the treatment of growth hormone excess and growth hormone deficiency in adults. J Endocrinol Invest 31:820-838
4. Melmed S, Kleinberg D 2008 Anterior pituitary. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Williams textbook of endocrinology. Philadelphia: Saunders Elsevier; 155-261
5. Rosén T, Bengtsson BA 1990 Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336:285-288 (Pubitemid 20229130)
6. Bülow B, Hagmar L, Eskilsson J, Erfurth EM 2000 Hypopituitary females have a high incidence of cardiovascular morbidity and increased prevalence of cardiovascular risk factors. J Clin Endocrinol Metab 85:574-584 (Pubitemid 32279601)
7. Bates AS, Van't Hoff W, Jones PJ, Clayton RN 1996 The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 81: 1169-1172
8. Svensson J, Bengtsson BA, Rosén T, Odén A, Johannsson G 2004 Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab 89:3306-3312 (Pubitemid 38960692)
9. Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, Sheppard MC, Stewart PM 2001 Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 357:425-431
10. Hew FL, O'Neal D, Kamarudin N, Alford FP, Best JD 1998 Growth hormone deficiency and cardiovascular risk. Baillieres Clin Endocrinol Metab 12:199-216 (Pubitemid 29051941)
11. Abs R, Feldt-Rasmussen U, Mattsson AF, Monson JP, Bengtsson BA, Góth MI, Wilton P, Koltowska-Häggström M 2006 Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults: a KIMS database analysis. Eur J Endocrinol 155:79-90
12. Widdowson WM, Gibney J 2008 The effect of growth hormone replacement on exercise capacity in patients with GH deficiency: a metaanalysis. J Clin Endocrinol Metab 93:4413-4417
13. Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Ingemann-Hansen T, Skakkebaek NE, Christiansen JS 1989 Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1:1221-1225 (Pubitemid 19140325)
14. Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH 1991 Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance. J Appl Physiol 70:695-700
15. Whitehead HM, Boreham C, Mcllrath EM, Sheridan B, Kennedy L, Brew Atkinson A, Hadden DR 1992 Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study. Clin Endocrinol (Oxf) 36:45-52
16. Caidahl K, Eden S, Bengtsson BA 1994 Cardiovascular and renal effects of growth hormone. Clin Endocrinol (Oxf) 40:393-400
17. Nass R, Huber RM, Klauss V, Müller OA, Schopohl J, Strasburger CJ 1995 Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood. J Clin Endocrinol Metab 80:552-557
18. Jørgensen JO, Vahl N, Hansen TB, Theusen L, Hagen C, Christiansen JS 1996 Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition. Clin Endocrinol (Oxf) 45:681-688
19. Gullestad L, Birkeland K, Bjønerheim R, Djøseland O, Trygstad O, Simonsen S 1998 Exercise capacity and hormonal response in adults with childhood onset growth hormone deficiency during long-term somatropin treatment. Growth Horm IGF Res 8:377-384
20. Rodriguez-Arnao J, Jabbar A, Fulcher K, Besser GM, Ross RJ 1999 Effects of growth hormone replacement on physical performance and body composition in GH deficient adults. Clin Endocrinol (Oxf) 51:53-60 (Pubitemid 29339535)
21. Woodhouse LJ, Asa SL, Thomas SG, Ezzat S 1999 Measures of submaximal aerobic performance evaluate and predict functional response to growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 84:4570-4577
22. Thomas SG, Esposito JG, Ezzat S 2003 Exercise training benefits growth hormone (GH)-deficient adults in the absence or presence of GH treatment. J Clin Endocrinol Metab 88:5734-5738 (Pubitemid 38033043)
23. Bollerslev J, Hallén J, Fougner KJ, Jørgensen AP, Kristo C, Fagertun H, Gudmundsen O, Burman P, Schreiner T 2005 Low-dose GH improves exercise capacity in adults with GH deficiency: effects of a 22-month placebo-controlled, crossover trial. Eur J Endocrinol 153:379-387
24. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML, Stephens PA 2006 Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 91:1621-1634
25. Bruce RA 1971 Exercise testing of patients with coronary heart disease. Principles and normal standards for evaluation. Ann Clin Res 3:323-332
26. Naughton J, Balke B, Nagle F 1964 Refinements in method of evaluation and physical conditioning before and after myocardial infarction. Am J Cardiol 14:837-843
27. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I 1989 Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 2:358-361
28. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ 2005 Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18:1440-1463
29. Blum WF, Schweizer R 2003 Insulin-like growth factors and their binding proteins. In: Ranke MB, ed. Diagnostics of endocrine function in children and adolescents. Basel: Karger; 166-199
30. Chapin B 2008 Exercise stress testing. In: Libby P, Bonow RO, Zipes DP, Mann DL, eds. Braunwalds' heart disease. Philadelphia: Saunders Elsevier; 195-226
31. Connolly H 2008 Echocardiography. In: Libby P, Bonow RO, Zipes DP, Mann DL, eds. Braunwald's heart disease. Philadelphia: Saunders Elsevier; 227-326
32. Degerblad M, Almkvist O, Grunditz R, Hall K, Kaijser L, Knutsson E, Ringertz H, Thoren M 1990 Physical and psychological capabilities during substitution therapy with recombinant growth hormone in adults with growth hormone deficiency. Acta Endocrinol (Copenh) 123:185-193
33. Vahl N, Jørgensen JO, Hansen TB, Klausen IB, Jurik AG, Hagen C, Christiansen JS 1998 The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study. Int J Obes Relat Metab Disord 22:529-536
34. Elgzyri T, Castenfors J, Hagg E, Backman C, Thoren M, Bramnert M 2004 The effects of GH replacement therapy on cardiac morphology and function, exercise capacity and serum lipids in elderly patients with GH deficiency. Clin Endocrinol (Oxf) 61:113-122 (Pubitemid 38951654)
35. Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Møller J,Müller J, Skakkebaek NE, Christiansen JS 1991 Long-term growth hormone treatment in growth hormone deficient adults. Acta Endocrinol (Copenh) 125:449-453
36. Jørgensen JO, Thuesen L, Müller J, Ovesen P, Skakkebaek NE, Christiansen JS 1994 Three years of growth hormone treatment in growth hormone-deficient adults: near normalization of body composition and physical performance. Eur J Endocrinol 130:224-228
37. Johannsson G, Bengtsson BA, Andersson B, Isgaard J, Caidahl K 1996 Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults. Preliminary data in a small group of patients. Clin Endocrinol (Oxf) 45:305-314
38. Chrisoulidou A, Beshyah SA, Rutherford O, Spinks TJ, Mayet J, Kyd P, Anyaoku V, Haida A, Ariff B, Murphy M, Thomas E, Robinson S, Foale R, Johnston DG 2000 Effects of 7 years of growth hormone replacement therapy in hypopituitary adults. J Clin Endocrinol Metab 85:3762-3769
39. Casajús JA, Ferrández Longás A, Mayayo E, Labarta JI, Ulied MA 2003 Physical repercussions of childhood-onset growth hormone (GH) deficiency and hGH treatment in adulthood. J Pediatr Endocrinol Metab 16:27-34
40. Jallad RS, Liberman B, Vianna CB, Vieira ML, Ramires JA, Knoepfelmacher M 2003 Effects of growth hormone replacement therapy on metabolic and cardiac parameters, in adult patients with childhood-onset growth hormone deficiency. Growth Horm IGF Res 13:81-88 (Pubitemid 36701653)
41. Brandou F, Aloulou I, Razimbaud A, Fedou C, Mercier J, Brun JF 2006 Lower ability to oxidize lipids in adult patients with growth hormone (GH) deficiency: reversal under GH treatment. Clin Endocrinol (Oxf) 65:423-428
42. Hartman ML, Weltman A, Zagar A, Qualy RL, Hoffman AR, Merriam GR 2008 Growth hormone replacement therapy in adults with growth hormone deficiency improves maximal oxygen consumption independently of dosing regimen or physical activity. J Clin Endocrinol Metab 93:125-130
43. Ezzat S, Fear S, Gaillard RC, Gayle C, Landy H, Marcovitz S, Mattioni T, Nussey S, Rees A, Svanberg E 2002 Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults. J Clin Endocrinol Metab 87:2725-2733
44. Sneppen SB, Steensgaard-Hansen F, Feldt-Rasmussen U 2002 Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised, placebo-controlled, double-blind study. Horm Res 58:21-29
45. Blum WF, Shavrikova EP, Edwards DJ, Rosilio M, Hartman ML, Marín F, Valle D, van der Lely AJ, Attanasio AF, Strasburger CJ, Henrich G, Herschbach P 2003 Decreased quality of life in adult pateints with growth hormone deficiency compared with general populations using the new, validated, self-weighted questionnaire, questions on life satisfaction hypopituitarism module. J Clin Endocrinol Metab 88:4158-4167
46. Böger RH, Skamira C, Bode-Böger SM, Brabant G, von zur Muhlen A, Frolich JC 1996 Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest 98:2706-2713
47. Beshyah SA, Shahi M, Skinner E, Sharp P, Foale R, Johnston DG 1994 Cardiovascular effects of growth hormone replacement therapy in hypopituitary adults. Eur J Endocrinol 130:451-458 (Pubitemid 24165770)
48. Valcavi R, Gaddi O, Zini M, Iavicoli M, Mellino U, Portioli I 1995 Cardiac performance and mass in adults with hypopituitarism: effects of one year of growth hormone treatment. J Clin Endocrinol Metab 80:659-666
49. Chung YS, Lee HC, Hwang SK, Paik IK, Lee JH, Huh KB 1994 Growth hormone replacement therapy in adults with growth hormone deficiency; thrice weekly low dose administration. J Korean Med Sci 9:169-178
50. Sartorio A, Ferrero S, Conti A, Bragato R, Malfatto G, Leonetti G, Faglia G 1997 Adults with childhood-onset growth hormone deficiency: effects of growth hormone treatment on cardiac structure. J Intern Med 241:515-520 (Pubitemid 27315833)
51. Amato G, Carella C, Fazio S, La Montagna G, Cittadini A, Sabatini D, Marciano-Mone C, Saccá L, Bellastella A 1993 Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 77:1671-1676
52. Colao A, di Somma C, Cuocolo A, Spinelli L, Tedesco N, Pivonello R, Bonaduce D, Salvatore M, Lombardi G 2001 Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients withGH deficiency. J Clin Endocrinol Metab 86:1874-1881
53. Thuesen L, Jørgensen JO, Müller JR, Kristensen BO, Skakkebaek NE, Vahl N, Christiansen JS 1994 Short and long-term cardiovascular effects of growth hormone therapy in growth hormone deficient adults. Clin Endocrinol (Oxf) 41:615-620
54. Cuneo RC, Salomon F, Wilmshurst P, Byrne C, Wiles CM, Hesp R, Sönksen PH 1991 Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the reninaldosterone system. Clin Sci (Lond) 81:587-592
55. Yuen KC, Frystyk J, White DK, Twickler TB, Koppeschaar HP, Harris PE, Fryklund L, Murgatroyd PR, Dunger DB 2005 Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low dose growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf) 63:428-436 (Pubitemid 41442337)
56. Link K, Bulow B, Westman K, Salmonsson EC, Eskilsson J, Erfurth EM2001 Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency. Clin Endocrinol (Oxf) 55:741-748
57. Baum HB, Biller BM, Finkelstein JS, Cannistraro KB, Oppenhein DS, Schoenfeld DA, Michel TH, Wittink H, Klibanski A 1996 Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann Intern Med 125:883-890
58. ter Maaten JC, de Boer H, Kamp O, Stuurman L, van der Veen EA 1999 Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency. J Clin Endocrinol Metab 84:2373-2380
59. Gillberg P, Bramnert M, Thorén M, Werner S, Johannsson G 2001 Commencing growth hormone replacement in adults with a fixed low dose. Effects on serum lipoproteins, glucose metabolism, body composition, and cardiovascular function. Growth Horm IGF Res 11:273-281
60. Maison P, Chanson P 2003 Cardiac effects of growth hormone in adults with growth hormone deficiency: a meta-analysis. Circulation 108:2648-2652
61. Fernholm R, Bramnert M, Hägg E, Hilding A, Baylink DJ, Mohan S, Thorén M 2000 Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. J Clin Endocrinol Metab 85:4104-4112
62. Verhelst J, Abs R, Vandeweghe M, Mockel J, Legros JJ, Copinschi G, Mahler C, Velkeniers B, Vanhaelst L, Van Aelst A, De Rijdt D, Stevenaert A, Beckers A 1997 Two years of replacement therapy in adults with growth hormone deficiency. Clin Endocrinol (Oxf) 47: 485-494
63. Chihara K, Koledova E, Shimatsu A, Kato Y, Kohno H, Tanaka T, Teramoto A, Bates PC, Attanasio AF 2004 Adult GH deficiency in Japanese patients: effects of GH treatment in a randomised, placebo-controlled trial. Eur J Endocrinol 151:343-350
64. Chihara K, Kato Y, Kohno H, Takano K, Tanaka T, Teramoto A, Shimatsu A 2006 Efficacy and safety of growth hormone (GH) in the treatment of adult Japanese patients with GH deficiency: a randomised, placebo-controlled study. Growth Horm IGF Res 16:132-142
65. Chihara K, Kato Y, Shimatsu A, Tanaka T, Kohno H 2008 Efficacy and safety of individualized growth hormone treatment in adult Japanese patients with growth hormone deficiency. Growth Horm IGF Res 18:394-403 (Pubitemid 351944034)
66. Beauregard C, Utz AL, Schaub AE, Nachtigall L, Biller BM, Miller KK, Klibanski A 2008 Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 93:2063-2071
67. Sneppen SB, Hoeck HC, Kollerup G, Sørensen OH, Laurberg P, Feldt-Rasmussen U 2002 Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults: an 18-month randomised, placebo-controlled, double blinded trial. Eur J Endocrinol 146:187-195
68. Webster JM, Stewart M, al-Maskari M, Osman I, Kendall-Taylor P, Mitcheson J, Laker MF 1997 The effect of growth hormone replacement therapy for up to 12 months on lipoprotein composition and lipoprotein(a) in growth hormone-deficient adults. Atherosclerosis 133:115-121
69. Binnerts A, Swart GR, Wilson JHP, Hoogerbrugge N, Pols HA, Birkenhager JC, Lamberts SW 1992 The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol (Oxf) 37:79-87
70. Cuneo RC, Salomon F, Watts GF, Hesp R, Sönksen PH 1993 Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism 42:1519-1523
71. Weaver JU, Monson JP, Noonan K, John WG, Edwards A, Evans KA, Cunningham J 1995 The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults. J Clin Endocrinol Metab 80:153-159
72. Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA 1997 Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 82:550-555 (Pubitemid 27068627)
73. Christopher M, Hew FL, Oakley M, Rantzau C, Alford F 1998 Defects of insulin action and skeletal muscle glucose metabolism in growth hormone-deficient adults persist after 24 months of recombinant human growth hormone therapy. J Clin Endocrinol Metab 83:1668-1681
74. Russell-Jones DL, Watts GF, Weissberger A, Naoumova R, Myers J, Thompson GR, Sönksen PH 1994 The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients. Clin Endocrinol (Oxf) 41:345-350
75. Beshyah SA, Henderson A, Niththyananthan R, Skinner E, Anyaoku V, Richmond W, Sharp P, Johnston DG 1995 The effects of short and long term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance. J Clin Endocrinol Metab 80:356-363
76. Cuneo RC, Judd S, Wallace JD, Perry-Keene D, Burger H, Lim-Tio S, Strauss B, Stockigt J, Topliss D, Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages S, Cheung NW, Hurley 1998 The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults. J Clin Endocrinol Metab 83:107-116
77. Attanasio AF, Lamberts SW, Matranga AM, Birkett MA, Bates PC, Valk NK, Hilsted J, Bengtsson BA, Strasburger CJ 1997 Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. J Clin Endocrinol Metab 82:82-88
78. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 2001 Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA 285:2486-2497
79. Tobert JA 2003 Lovastatin and beyond: the history of the HMG-COA reductase inhibitors. Nat Rev 2:517-526
80. Monson JP, Jonsson P, Koltowska-Haggstrom M, Kourides I 2007 Growth hormone (GH) replacement decreases serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor (statin) therapy. Clin Endocrinol (Oxf) 67:623-628