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Journal of Clinical Endocrinology & Metabolism, Vol 77, 1671-1676, Copyright © 1993 by Endocrine Society

ARTICLES

Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses

G Amato, C Carella, S Fazio, G La Montagna, A Cittadini, D Sabatini, C Marciano- Mone, L Sacca and A Bellastella
Chair of Endocrinology, Faculty of Medicine and Surgery, Second University of Naples, Italy.

The effects of recombinant GH doses (10 micrograms/kg.day, 3 times a week for 6 months) lower than those previously used in the treatment of GH-deficient adults (GHDA) on body composition, bone mineral content, and heart structure and function were investigated in seven (six males and one female, aged 25-27 yr) GHDA. They were studied before treatment, after treatment, and 6 months after stopping therapy, and findings were compared with those for 20 sex-, age-, and body mass index-matched healthy controls. Before treatment, GHDA showed a significant reduction in insulin-like growth factor-I levels, an increase in bioimpedance and fat mass percentage, a reduction of bone density at both distal and proximal sites, a decrease in bone Gla- protein and procollagen III levels, and significant cardiac impairment supported by a reduction of left ventricular mass index and left ventricular systolic function with decreased fractional shortening and rate-adjusted mean velocity of circumferential fiber shortening. GH treatment normalized insulin-like growth factor-I levels, body composition and echocardiographic findings, but not bone density. Six months after stopping therapy, all parameters investigated returned to the pretreatment conditions. Our results suggest that prolonged GH deficiency induces alterations in body composition and bone metabolism and density, and impairment of cardiac structure and function in adult life. GH replacement therapy for 6 months, despite the low doses used by us, is able to improve all previously impaired biochemical and clinical features, except for bone density. This improvement disappears 6 months after the withdrawal of therapy.


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C Berry and A.L Clark
Catabolism in chronic heart failure
Eur. Heart J., April 1, 2000; 21(7): 521 - 532.
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T. MAHAJAN and S. L. LIGHTMAN
A Simple Test for Growth Hormone Deficiency in Adults
J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1473 - 1476.
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B.-A. Bengtsson and G. Johannsson
The Treatment of Growth Hormone Deficiency in Adults
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 933 - 937.
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B. M. K. Biller, G. Sesmilo, H. B. A. Baum, D. Hayden, D. Schoenfeld, and A. Klibanski
Withdrawal of Long-Term Physiological Growth Hormone (GH) Administration: Differential Effects on Bone Density and Body Composition in Men with Adult-Onset GH Deficiency
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 970 - 976.
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B. Bülow, L. Hagmar, J. Eskilsson, and E. M. Erfurth
Hypopituitary Females Have a High Incidence of Cardiovascular Morbidity and an Increased Prevalence of Cardiovascular Risk Factors
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 574 - 584.
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K. S. Leong, P. Mann, M. Wallymahmed, I. A. MacFarlane, and J. P. H. Wilding
Abnormal Heart Rate Variability in Adults with Growth Hormone Deficiency
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 628 - 633.
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Measures of Submaximal Aerobic Performance Evaluate and Predict Functional Response to Growth Hormone (GH) Treatment in GH-Deficient Adults
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4570 - 4577.
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A. Colao, A. Cuocolo, C. Di Somma, G. Cerbone, A. M. Della Morte, E. Nicolai, R. Lucci, M. Salvatore, and G. Lombardi
Impaired Cardiac Performance in Elderly Patients with Growth Hormone Deficiency
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3950 - 3955.
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T. Ryoke, Y. Gu, L. Mao, M. Hongo, R. G. Clark, K. L. Peterson, and J. Ross Jr
Progressive Cardiac Dysfunction and Fibrosis in the Cardiomyopathic Hamster and Effects of Growth Hormone and Angiotensin-Converting Enzyme Inhibition
Circulation, October 19, 1999; 100(16): 1734 - 1743.
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M. L. Vance and N. Mauras
Growth Hormone Therapy in Adults and Children
N. Engl. J. Med., October 14, 1999; 341(16): 1206 - 1216.
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V. Locatelli, G. Rossoni, F. Schweiger, A. Torsello, V. De Gennaro Colonna, M. Bernareggi, R. Deghenghi, E. E. Müller, and F. Berti
Growth Hormone-Independent Cardioprotective Effects of Hexarelin in the Rat
Endocrinology, September 1, 1999; 140(9): 4024 - 4031.
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A. Colao, C. Di Somma, R. Pivonello, S. Loche, G. Aimaretti, G. Cerbone, A. Faggiano, G. Corneli, E. Ghigo, and G. Lombardi
Bone Loss Is Correlated to the Severity of Growth Hormone Deficiency in Adult Patients with Hypopituitarism
J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1919 - 1924.
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J. Leger, C. Garel, A. Fjellestad-Paulsen, M. Hassan, and P. Czernichow
Human Growth Hormone Treatment of Short-Stature Children Born Small for Gestational Age: Effect on Muscle and Adipose Tissue Mass during a 3-Year Treatment Period and after 1 Year's Withdrawal
J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3512 - 3516.
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M. Y. Donath, G. Sütsch, X.-W. Yan, B. Piva, H.-P. Brunner, Y. Glatz, J. Zapf, F. Follath, E. R. Froesch, and W. Kiowski
Acute Cardiovascular Effects of Insulin-Like Growth Factor I in Patients with Chronic Heart Failure
J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3177 - 3183.
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N. Tanaka, T. Ryoke, M. Hongo, L. Mao, H. A. Rockman, R. G. Clark, and J. Ross Jr.
Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice
Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H393 - H399.
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A. Cittadini, Y. Ishiguro, H. Stromer, M. Spindler, A. C. Moses, R. Clark, P. S. Douglas, J. S. Ingwall, and J. P. Morgan
Insulin-like Growth Factor-1 but Not Growth Hormone Augments Mammalian Myocardial Contractility by Sensitizing the Myofilament to Ca2+ Through a Wortmannin-Sensitive Pathway : Studies in Rat and Ferret Isolated Muscles
Circ. Res., June 13, 1998; 83(1): 50 - 59.
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D. L. Russell-Jones, S. B. Bowes, S. E. Rees, N. C. Jackson, A. J. Weissberger, R. Hovorka, P. H. Sonksen, and A. M. Umpleby
Effect of growth hormone treatment on postprandial protein metabolism in growth hormone-deficient adults
Am J Physiol Endocrinol Metab, June 1, 1998; 274(6): E1050 - E1056.
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G. Aimaretti, G. Corneli, P. Razzore, S. Bellone, C. Baffoni, E. Arvat, F. Camanni, and E. Ghigo
Comparison between Insulin-Induced Hypoglycemia and Growth Hormone (GH)-Releasing Hormone + Arginine as Provocative Tests for the Diagnosis of GH Deficiency in Adults
J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1615 - 1618.
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S. M. Shalet, A. Toogood, A. Rahim, and B. M. D. Brennan
The Diagnosis of Growth Hormone Deficiency in Children and Adults
Endocr. Rev., April 1, 1998; 19(2): 203 - 223.
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C. Ohlsson, B.-A. Bengtsson, O. G. P. Isaksson, T. T. Andreassen, and M. C. Slootweg
Growth Hormone and Bone
Endocr. Rev., February 1, 1998; 19(1): 55 - 79.
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A. M. Boot, S. M. P. F. d. M. Keizer-Schrama, H. A. P. Pols, E. P. Krenning, and S. L. S. Drop
Bone Mineral Density and Body Composition before and during Treatment with Gonadotropin-Releasing Hormone Agonist in Children with Central Precocious and Early Puberty
J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 370 - 373.
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P. V. Carroll, E. R. Christ the members of Growth Hormone Research Soci, B. A. Bengtsson, L. Carlsson, J. S. Christiansen, D. Clemmons, R. Hintz, K. Ho, Z. Laron, P. Sizonenko, et al.
Growth Hormone Deficiency in Adulthood and the Effects of Growth Hormone Replacement: A Review
J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 382 - 395.
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R. Bottinelli, M. Narici, M. A. Pellegrino, B. Kayser, M. Canepari, G. Faglia, and A. Sartorio
Contractile Properties and Fiber Type Distribution of Quadriceps Muscles in Adults with Childhood-Onset Growth Hormone Deficiency
J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4133 - 4138.
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A. Cittadini, H. Stromer, D. E. Vatner, J. D. Grossman, S. E. Katz, R. Clark, J. P. Morgan, and P. S. Douglas
Consequences of Growth Hormone Deficiency on Cardiac Structure, Function, and {beta}-Adrenergic Pathway: Studies in Mutant Dwarf Rats
Endocrinology, December 1, 1997; 138(12): 5161 - 5169.
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E. R. Christ, M. H. Cummings, N. B. Westwood, B. M. Sawyer, T. C. Pearson, P. H. Sonksen, and D. L. Russell-Jones
The Importance of Growth Hormone in the Regulation of Erythropoiesis, Red Cell Mass, and Plasma Volume in Adults with Growth Hormone Deficiency
J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2985 - 2990.
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H. de Boer and E. A. van der Veen
Why Retest Young Adults with Childhood-Onset Growth Hormone Deficiency?
J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2032 - 2036.
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G. Johannsson, MD, B.-A. Bengtsson, and Ph. D.
Growth Hormone Therapy in GH-Deficient Adults: The Problem of the Dose--Authors' Response
J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1305 - 1306.
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R. Marcus M.D. and G. M. Reaven M.D.
Growth Hormone--Ready for Prime Time?
J. Clin. Endocrinol. Metab., March 1, 1997; 82(3): 725 - 726.
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A. F. Attanasio, S. W.J. Lamberts, A. M.C. Matranga, M. A. Birkett, P. C. Bates, N. K. Valk, J. Hilsted, B.-A. Bengtsson, and C. J. Strasburger
Adult Growth Hormone (GH)-Deficient Patients Demonstrate Heterogeneity Between Childhood Onset and Adult Onset Before and During Human GH Treatment
J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 82 - 88.
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S. Fisker, N. Vahl, J. O. L. Jorgensen, J. S. Christiansen, and H. Orskov
Abdominal Fat Determines Growth Hormone-Binding Protein Levels in Healthy Nonobese Adults
J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 123 - 128.
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H. Stromer, A. Cittadini, P. S. Douglas, and J. P. Morgan
Exogenously Administered Growth Hormone and Insulin-like Growth Factor-I Alter Intracellular Ca2+ Handling and Enhance Cardiac Performance: In Vitro Evaluation in the Isolated Isovolumic Buffer-Perfused Rat Heart
Circ. Res., August 1, 1996; 79(2): 227 - 236.
[Abstract] [Full Text]

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S. Fazio, D. Sabatini, B. Capaldo, C. Vigorito, A. Giordano, R. Guida, F. Pardo, B. Biondi, and L. Sacca
A Preliminary Study of Growth Hormone in the Treatment of Dilated Cardiomyopathy
N. Engl. J. Med., March 28, 1996; 334(13): 809 - 814.
[Abstract] [Full Text] [PDF]

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E. Loh and J. L. Swain
Growth Hormone for Heart Failure -- Cause for Cautious Optimism
N. Engl. J. Med., March 28, 1996; 334(13): 856 - 857.
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A. Cittadini, H. Stromer, S. E. Katz, R. Clark, A. C. Moses, J. P. Morgan, and P. S. Douglas
Differential Cardiac Effects of Growth Hormone and Insulin-like Growth Factor1 in the Rat : A Combined In Vivo and In Vitro Evaluation
Circulation, February 15, 1996; 93(4): 800 - 809.
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C. Lu, G. Schwartzbauer, M. A. Sperling, S. U. Devaskar, S. Thamotharan, P. D. Robbins, C. F. McTiernan, J.-L. Liu, J. Jiang, S. J. Frank, et al.
Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes
J. Biol. Chem., June 15, 2001; 276(25): 22892 - 22900.
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