This Article Full Text Full Text (PDF) Submit a related Letter to the Editor 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 Støving, R. K. Articles by Hagen, C. Search for Related Content PubMed PubMed Citation Articles by Støving, R. K. Articles by Hagen, C.

Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa: Indirect Evidence for Disruption of Feedback Regulation within the GH-Insulin-Like Growth Factor I Axis¹

Department of Endocrinology (M) and Center for Eating Disorders, Odense University Hospital (R.K.S., J.H., J.K., C.H.), DK-5000 Odense, Denmark; the Department of Internal Medicine, National Science Foundation Center for Biological Timing, University of Virginia Health Sciences Center (J.D.V.), Charlottesville, Virginia 22908; Medical Department M (Endocrinology and Diabetes), Medical Research Laboratory and Institute of Experimental Clinical Research, University Hospital of Aarhus (A.F.), DK-8000 Aarhus, Denmark; the Department of Medical Physiology, Panum Institute, University of Copenhagen (J.V.), DK-2200 Copenhagen, Denmark; and the Department of Clinical Chemistry, Sonderborg Hospital (O.G.K.), DK-6400 Sonderborg, Denmark

Address all correspondence and requests for reprints to: René Klinkby Støving, M.D., Department of Endocrinology (M), Odense University Hospital, DK- 5000 Odense C, Denmark.

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted at 20-min intervals in 8 nonfasting patients with AN [body mass index (BMI), 14.2 ± 0.8 kg/m²; mean ± SEM) and in 11 age-matched healthy women (BMI, 20.3 ± 0.5 kg/m²).

The deconvolution-estimated half-life of GH was not altered in the AN patients. The pituitary GH secretory burst frequency, burst mass, and burst duration were each significantly increased in women with AN compared to those in normal weight women. A 4-fold increase in daily pulsatile GH secretion was accompanied by a 20-fold increase in basal (nonpulsatile) GH secretion. There were significant negative correlations between BMI and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were positively correlated to GH secretion rates. Leptin levels were significantly inversely correlated to the pulsatile, but not the basal, GH secretion rate.

The present data demonstrate augmented basal as well as pulsatile GH secretion with disruption of the orderliness of the GH release process in AN. Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone.

This article has been cited by other articles:

				A. Giustina, G. Mazziotti, and E. Canalis Growth Hormone, Insulin-Like Growth Factors, and the Skeleton Endocr. Rev., August 1, 2008; 29(5): 535 - 559. [Abstract] [Full Text] [PDF]

				R. K. Stoving, J.-W. Chen, D. Glintborg, K. Brixen, A. Flyvbjerg, K. Horder, and J. Frystyk Bioactive Insulin-Like Growth Factor (IGF) I and IGF-Binding Protein-1 in Anorexia Nervosa J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2323 - 2329. [Abstract] [Full Text] [PDF]

				R. M. Luque, S. Park, and R. D. Kineman Severity of the Catabolic Condition Differentially Modulates Hypothalamic Expression of Growth Hormone-Releasing Hormone in the Fasted Mouse: Potential Role of Neuropeptide Y and Corticotropin-Releasing Hormone Endocrinology, January 1, 2007; 148(1): 300 - 309. [Abstract] [Full Text] [PDF]

				J. Svensson, G. Johannsson, A. Iranmanesh, K. Albertsson-Wikland, J. D Veldhuis, and B.-A. Bengtsson GH secretory pattern in young adults who discontinued GH treatment for GH deficiency and decreased longitudinal growth in childhood. Eur. J. Endocrinol., July 1, 2006; 155(1): 91 - 99. [Abstract] [Full Text] [PDF]

				D. Glintborg, R. K. Stoving, C. Hagen, A. P. Hermann, J. Frystyk, J. D. Veldhuis, A. Flyvbjerg, and M. Andersen Pioglitazone Treatment Increases Spontaneous Growth Hormone (GH) Secretion and Stimulated GH Levels in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5605 - 5612. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, K. Kuo, K. Griffin, V. Stewart, E. Hunter, D. B. Herzog, and A. Klibanski Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E347 - E356. [Abstract] [Full Text] [PDF]

				A. Fleischman, C. Brue, T. Y. Poussaint, M. Kieran, S. L. Pomeroy, L. Goumnerova, R. M. Scott, and L. E. Cohen Diencephalic Syndrome: A Cause of Failure to Thrive and a Model of Partial Growth Hormone Resistance Pediatrics, June 1, 2005; 115(6): e742 - e748. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, C. Almazan, M. Worley, D. B. Herzog, and A. Klibanski Hormonal Determinants of Regional Body Composition in Adolescent Girls with Anorexia Nervosa and Controls J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2580 - 2587. [Abstract] [Full Text] [PDF]

				K. H. Darzy, S. S. Pezzoli, M. O. Thorner, and S. M. Shalet The Dynamics of Growth Hormone (GH) Secretion in Adult Cancer Survivors with Severe GH Deficiency Acquired after Brain Irradiation in Childhood for Nonpituitary Brain Tumors: Evidence for Preserved Pulsatility and Diurnal Variation with Increased Secretory Disorderliness J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2794 - 2803. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, C. Almazan, K. Ramaswamy, W. Lapcharoensap, M. Worley, G. Neubauer, D. B. Herzog, and A. Klibanski Alterations in Cortisol Secretory Dynamics in Adolescent Girls with Anorexia Nervosa and Effects on Bone Metabolism J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4972 - 4980. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, D. B. Herzog, K. Ramaswamy, A. Aggarwal, C. Almazan, G. Neubauer, J. Breu, and A. Klibanski Growth Hormone and Ghrelin Responses to an Oral Glucose Load in Adolescent Girls with Anorexia Nervosa and Controls J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1605 - 1612. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, J. Bjornson, A. Hackman, A. Aggarwal, J. Chung, M. Ott, D. B. Herzog, M. L. Johnson, and A. Klibanski Alterations in Growth Hormone Secretory Dynamics in Adolescent Girls with Anorexia Nervosa and Effects on Bone Metabolism J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5615 - 5623. [Abstract] [Full Text] [PDF]

				M. Misra, L. A Soyka, K. K Miller, S. Grinspoon, L. L Levitsky, and A. Klibanski Regional body composition in adolescents with anorexia nervosa and changes with weight recovery Am. J. Clinical Nutrition, June 1, 2003; 77(6): 1361 - 1367. [Abstract] [Full Text] [PDF]

				V. Tolle, M. Kadem, M.-T. Bluet-Pajot, D. Frere, C. Foulon, C. Bossu, R. Dardennes, C. Mounier, P. Zizzari, F. Lang, et al. Balance in Ghrelin and Leptin Plasma Levels in Anorexia Nervosa Patients and Constitutionally Thin Women J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 109 - 116. [Abstract] [Full Text] [PDF]

				D. L. Waters, C. R. Qualls, R. Dorin, J. D. Veldhuis, and R. N. Baumgartner Increased Pulsatility, Process Irregularity, and Nocturnal Trough Concentrations of Growth Hormone in Amenorrheic Compared to Eumenorrheic Athletes J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1013 - 1019. [Abstract] [Full Text]

				R. G. Veldman, M. Frölich, S. M. Pincus, J. D. Veldhuis, and F. Roelfsema Apparently Complete Restoration of Normal Daily Adrenocorticotropin, Cortisol, Growth Hormone, and Prolactin Secretory Dynamics in Adults with Cushing's Disease after Clinically Successful Transsphenoidal Adenomectomy J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4039 - 4046. [Abstract] [Full Text]

				L. Gianotti, A. I. Pincelli, M. Scacchi, M. Rolla, D. Bellitti, E. Arvat, F. Lanfranco, A. Torsello, E. Ghigo, F. Cavagnini, et al. Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2805 - 2809. [Abstract] [Full Text]