This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Woodhouse, L. J. Articles by Ezzat, S. Search for Related Content PubMed PubMed Citation Articles by Woodhouse, L. J. Articles by Ezzat, S.

Measures of Submaximal Aerobic Performance Evaluate and Predict Functional Response to Growth Hormone (GH) Treatment in GH-Deficient Adults¹

Departments of Physical Therapy, Laboratory Medicine and Pathobiology, and Medicine, The University of Toronto, Toronto, Ontario M5G 1X5, Canada

Address correspondence and requests for reprints to: Dr. Shereen Ezzat, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. E-mail: sezzat{at}mtsinai.on.ca

The impact of GH on functional performance in GH-deficient adults is not well understood. To investigate the effects of GH on skeletal muscle, physical, and functional capacity, we randomized 28 GH-deficient adults to receive 3 months of recombinant human GH [rhGH: somatotropin, 6.25 µg/kg lean body mass (LBM) for 1 month, 12.5 µg/kg LBM thereafter] in a double-blind placebo-controlled cross-over trial. We measured muscle fiber type, size, and insulin-like growth factor I messenger RNA, aerobic capacity [maximal oxygen uptake (VO₂max), ventilation threshold (VeT)], isokinetic strength, oxygen-cost-of-walking at normal and fast speeds, and fatigue determined by the profile of mood states questionnaire. As expected, GH treatment decreased body fat, increased LBM, increased muscle fiber size, and increased muscle insulin-like growth factor-I messenger RNA 5-fold; however, muscle strength remained unchanged. At baseline, VeT occurred at a high percentage of maximal VO₂max (73.3% ± 2.6) because of low VO₂max (1.74 ± 0.1 L/min or 20.7 ± 1.3 mL/kg·min). Walking required high oxygen consumptions representing from 83 ± 4% of VeT at normal speeds to 120 ± 5% of VeT at fast speeds. After rhGH, there was a significant (P = 0.03) increase in VeT (18%), compared with placebo. This was paralleled by a nonsignificant rise in VO₂max. Functionally, rhGH treatment decreased the oxygen cost of walking, relative to VeT, at normal (14% decrease, P = 0.019) and fast (21% decrease, P = 0.004) SPW speeds. A 3-variable model (baseline fast SPW speed, VeT/VO₂max, and VeT) accounted for 39% of the variance of change in self-reported fatigue. These data indicate that GH-deficient adults require a high fraction of VeT for daily activities, explaining the perception of increased fatigue and impaired physical performance. The actions of rhGH on muscle fiber size translate into physiological improvement in submaximal aerobic capacity and result in functional improvement in walking ability but do not necessarily alter strength. Thus, measures of effort-independent submaximal aerobic performance provide novel objective determinants of functional impairment and fatigue and can be used to evaluate and predict response to GH treatment.

This article has been cited by other articles:

				K. A. Mossberg, B. E. Masel, C. R. Gilkison, and R. J. Urban Aerobic Capacity and Growth Hormone Deficiency after Traumatic Brain Injury J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2581 - 2587. [Abstract] [Full Text] [PDF]

				M. L. Hartman, A. Weltman, A. Zagar, R. L. Qualy, A. R. Hoffman, and G. R. Merriam 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., January 1, 2008; 93(1): 125 - 130. [Abstract] [Full Text] [PDF]

				J. Gibney, M.-L. Healy, and P. H. Sonksen The Growth Hormone/Insulin-Like Growth Factor-I Axis in Exercise and Sport Endocr. Rev., October 1, 2007; 28(6): 603 - 624. [Abstract] [Full Text] [PDF]

				L. J. Woodhouse, A. Mukherjee, S. M. Shalet, and S. Ezzat The Influence of Growth Hormone Status on Physical Impairments, Functional Limitations, and Health-Related Quality of Life in Adults Endocr. Rev., May 1, 2006; 27(3): 287 - 317. [Abstract] [Full Text] [PDF]

				M. E. Molitch, D. R. Clemmons, S. Malozowski, G. R. Merriam, S. M. Shalet, M. L. Vance, and for The Endocrine Society's Clinical Guidelines Su Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1621 - 1634. [Abstract] [Full Text] [PDF]

				M. G. Giannoulis, P. H. Sonksen, M. Umpleby, L. Breen, C. Pentecost, M. Whyte, C. V. McMillan, C. Bradley, and F. C. Martin The Effects of Growth Hormone and/or Testosterone in Healthy Elderly Men: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 477 - 484. [Abstract] [Full Text] [PDF]

				M. L. Healy, J. Gibney, C. Pentecost, P. Croos, D. L. Russell-Jones, P. H. Sonksen, and A. M. Umpleby Effects of High-Dose Growth Hormone on Glucose and Glycerol Metabolism at Rest and during Exercise in Endurance-Trained Athletes J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 320 - 327. [Abstract] [Full Text] [PDF]

				A. R. Hoffman, B. M. K. Biller, D. Cook, J. Baptista, B. L. Silverman, L. Dao, K. M. Attie, P. Fielder, T. Maneatis, B. Lippe, et al. Efficacy of a Long-Acting Growth Hormone (GH) Preparation in Patients with Adult GH Deficiency J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6431 - 6440. [Abstract] [Full Text] [PDF]

				A. Mukherjee, J. E Adams, L. Smethurst, and S. M Shalet Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults Eur. J. Endocrinol., November 1, 2005; 153(5): 661 - 668. [Abstract] [Full Text] [PDF]

				J. G. Esposito, S. G. Thomas, L. Kingdon, and S. Ezzat Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E494 - E503. [Abstract] [Full Text] [PDF]

				K Briot, P Garnero, A Le Henanff, M Dougados, and C Roux Body weight, body composition, and bone turnover changes in patients with spondyloarthropathy receiving anti-tumour necrosis factor {alpha} treatment Ann Rheum Dis, August 1, 2005; 64(8): 1137 - 1140. [Abstract] [Full Text] [PDF]

				A. Berggren, C. Ehrnborg, T. Rosen, L. Ellegard, B.-A. Bengtsson, and K. Caidahl Short-Term Administration of Supraphysiological Recombinant Human Growth Hormone (GH) Does Not Increase Maximum Endurance Exercise Capacity in Healthy, Active Young Men and Women with Normal GH-Insulin-Like Growth Factor I Axes J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3268 - 3273. [Abstract] [Full Text] [PDF]

				J. G. Esposito, S. G. Thomas, L. Kingdon, and S. Ezzat Growth Hormone Treatment Improves Peripheral Muscle Oxygen Extraction-Utilization during Exercise in Patients with Human Immunodeficiency Virus-Associated Wasting: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5124 - 5131. [Abstract] [Full Text] [PDF]

				B. A. Irving, J. T. Patrie, S. M. Anderson, D. D. Watson-Winfield, K. I. Frick, W. S. Evans, J. D. Veldhuis, and A. Weltman The Effects of Time following Acute Growth Hormone Administration on Metabolic and Power Output Measures during Acute Exercise J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4298 - 4305. [Abstract] [Full Text] [PDF]

				S. G. Thomas, J. G. Esposito, and S. Ezzat Exercise Training Benefits Growth Hormone (GH)-Deficient Adults in the Absence or Presence of GH Treatment J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5734 - 5738. [Abstract] [Full Text] [PDF]

				W. Liu, S. G. Thomas, S. L. Asa, N. Gonzalez-Cadavid, S. Bhasin, and S. Ezzat Myostatin Is a Skeletal Muscle Target of Growth Hormone Anabolic Action J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5490 - 5496. [Abstract] [Full Text] [PDF]

				J. Gibney, M. L. Healy, M. Stolinski, S. B. Bowes, C. Pentecost, L. Breen, C. McMillan, D. L. Russell-Jones, P. H. Sonksen, and A. M. Umpleby Effect of Growth Hormone (GH) on Glycerol and Free Fatty Acid Metabolism during Exhaustive Exercise in GH-Deficient Adults J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1792 - 1797. [Abstract] [Full Text] [PDF]

				K. T. Brill, A. L. Weltman, A. Gentili, J. T. Patrie, D. A. Fryburg, J. B. Hanks, R. J. Urban, and J. D. Veldhuis Single and Combined Effects of Growth Hormone and Testosterone Administration on Measures of Body Composition, Physical Performance, Mood, Sexual Function, Bone Turnover, and Muscle Gene Expression in Healthy Older Men J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5649 - 5657. [Abstract] [Full Text] [PDF]

				Why start an adult on growth hormone? DTB, October 1, 2002; 40(10): 75 - 78. [Abstract] [Full Text] [PDF]

				K. H. W. Lange, J. L. Andersen, N. Beyer, F. Isaksson, B. Larsson, M. H. Rasmussen, A. Juul, J. Bulow, and M. Kjar GH Administration Changes Myosin Heavy Chain Isoforms in Skeletal Muscle But Does Not Augment Muscle Strength or Hypertrophy, Either Alone or Combined with Resistance Exercise Training in Healthy Elderly Men J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 513 - 523. [Abstract] [Full Text] [PDF]

				W. M. Drake, S. J. Howell, J. P. Monson, and S. M. Shalet Optimizing GH Therapy in Adults and Children Endocr. Rev., August 1, 2001; 22(4): 425 - 450. [Abstract] [Full Text] [PDF]

				A. Sartorio, C. Lafortuna, and M. V. Narici Physical Performance in Growth Hormone- Deficient Adults J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1839 - 1839. [Full Text]

				L. J. Woodhouse, S. L. Asa, S. G. Thomas, and S. Ezzat Growth Hormone Deficiency and Physical Function J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1839a - 1840. [Full Text]