| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School (M.M., K.K.M., J.B., A.H., A.A., J.C., A.K.); Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School (M.M.), and Eating Disorders Unit, Massachusetts General Hospital and Harvard Medical School (D.B.H.), Boston, Massachusetts 02114; Eating Disorders Center (M.O.), Dover, New Hampshire 03820; and University of Virginia Medical School (M.L.J.), Charlottesville, Virginia 22908
Address all correspondence and requests for reprints to: Anne Klibanski, M.D., BUL 457B, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: aklibanski{at}partners.org.
Anorexia nervosa (AN) is a disorder that is increasing in frequency in adolescents, and the age of onset is often in the prepubertal years, potentially affecting the development of peak bone mass and linear growth. The GH-IGF-I axis plays an important role in bone formation, and alterations in GH secretory patterns have been described in adult women with AN. However, GH secretory dynamics in adolescents with AN have not been described, and the effects of alterations in GH secretory patterns and GH concentration on bone metabolism in AN are not known. We examined patterns of GH secretion by deconvolutional analysis, and GH concentration by Cluster analysis, in adolescent girls with AN (n = 22) and controls (n = 20) of comparable bone age and pubertal stage. We also examined the roles of cortisol, leptin, and estradiol in the regulation of GH secretion and concentration, and the relationship of GH secretory patterns and concentration to bone metabolism. Basal GH secretion and secretory pulse number in adolescent girls with AN were increased compared with control values (P = 0.03 and 0.007, respectively), and increased disorderliness of GH secretion (approximate entropy) was found in AN (P = 0.004). Mean and nadir GH concentrations and total area under the concentration curve were increased (P = 0.03, 0.002, and 0.03, respectively), and IGF-I levels were decreased (P = 0.0002) in girls with AN compared with healthy adolescent girls. IGF-I levels correlated negatively with nadir GH concentrations (r = -0.35; P = 0.02). Serum cortisol levels were higher in girls with AN than in controls (P < 0.0001) and correlated inversely with IGF-I (r = -0.58; P = 0.0001) and weakly with GH concentration (area under the concentration curve; r = -0.43; P = 0.05). A strong inverse relationship between markers of nutritional status (body mass index, fat mass, and leptin) and basal and pulsatile GH secretion, and mean and nadir GH concentrations was observed. GH concentration predicted levels of all markers of bone formation and a marker of bone resorption (N-telopeptide) in healthy controls, but not in AN. We demonstrate increases in basal GH secretion, number of secretory bursts, and GH concentration in adolescents with AN compared with controls, accompanied by low IGF-I levels. These data are consistent with the hypothesis that an acquired GH resistance occurs in this undernourished group. We also demonstrate that GH secretion and concentration are nutritionally regulated, and that the effects of nutrition exceed the effects of cortisol on GH concentration. Acquired GH resistance may play a role in the osteopenia and decreased peak bone mass frequently associated with AN.
This work was supported in part by NIH Grant M01-RR-01066, NIH Nutrition Training Grant DK-07703, and a fellowship grant from Eli Lilly & Co.
This work was presented in part at the 84th Annual Meeting of The Endocrine Society, San Francisco, CA, 2002; the American Pediatric Society/Society for Pediatric Research Meeting, Seattle, WA, 2003; and the 85th Annual Meeting of The Endocrine Society, Philadelphia, PA, 2003.
Abbreviations: AN, Anorexia nervosa; ApEn, approximate entropy; AUC, area under the concentration curve; BA, bone age; BMAD, bone mineral apparent density; BMD, bone mineral density; BMI, body mass index; BSAP, bone-specific alkaline phosphatase; DPD, deoxypyridinoline; DXA, dual energy x-ray absorptiometry; GCRC, General Clinical Research Center; NTX, N-telopeptide; OC, osteocalcin; PICP, C-terminal propeptide of type I procollagen; UFC, urinary free cortisol.
This article has been cited by other articles:
 |
|
 |
|
  M. A. Goldstein, D. B. Herzog, M. Misra, and P. Sagar Case 29-2008 -- A 19-Year-Old Man with Weight Loss and Abdominal Pain N. Engl. J. Med., September 18, 2008; 359(12): 1272 - 1283. [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 M. Misra, M. A. Bredella, P. Tsai, N. Mendes, K. K. Miller, and A. Klibanski Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E385 - E392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Chan, C. J. Williams, P. Raciti, J. Blakeman, T. Kelesidis, I. Kelesidis, M. L. Johnson, M. O. Thorner, and C. S. Mantzoros Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2819 - 2827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Prabhakaran, M. Misra, K. K. Miller, K. Kruczek, S. Sundaralingam, D. B. Herzog, D. K. Katzman, and A. Klibanski Determinants of Height in Adolescent Girls With Anorexia Nervosa Pediatrics, June 1, 2008; 121(6): e1517 - e1523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, R. Prabhakaran, K. K. Miller, M. A. Goldstein, D. Mickley, L. Clauss, P. Lockhart, J. Cord, D. B. Herzog, D. K. Katzman, et al. Prognostic Indicators of Changes in Bone Density Measures in Adolescent Girls with Anorexia Nervosa-II J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1292 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, K. K. Miller, J. Cord, R. Prabhakaran, D. B. Herzog, M. Goldstein, D. K. Katzman, and A. Klibanski Relationships between Serum Adipokines, Insulin Levels, and Bone Density in Girls with Anorexia Nervosa J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2046 - 2052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Misra, P. Tsai, E. J Anderson, J. L Hubbard, K. Gallagher, L. A Soyka, K. K Miller, D. B Herzog, and A. Klibanski Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 698 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, K. K. Miller, P. Tsai, K. Gallagher, A. Lin, N. Lee, D. B. Herzog, and A. Klibanski Elevated Peptide YY Levels in Adolescent Girls with Anorexia Nervosa J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1027 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Engstrom, P. Burman, C. Holdstock, M. Ohrvall, M. Sundbom, and F A. Karlsson Effects of gastric bypass on the GH/IGF-I axis in severe obesity - and a comparison with GH deficiency Eur. J. Endocrinol., January 1, 2006; 154(1): 53 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, K. K. Miller, V. Stewart, E. Hunter, K. Kuo, D. B. Herzog, and A. Klibanski Ghrelin and Bone Metabolism in Adolescent Girls with Anorexia Nervosa and Healthy Adolescents J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5082 - 5087. [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 leptin in adolescent girls with anorexia nervosa and healthy adolescents Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E373 - E381. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Misra, A. Aggarwal, K. K. Miller, C. Almazan, M. Worley, L. A. Soyka, D. B. Herzog, and A. Klibanski Effects of Anorexia Nervosa on Clinical, Hematologic, Biochemical, and Bone Density Parameters in Community-Dwelling Adolescent Girls Pediatrics, December 1, 2004; 114(6): 1574 - 1583. [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]
|
|
|
|
|
|
C. K. Welt, J. L. Chan, J. Bullen, R. Murphy, P. Smith, A. M. DePaoli, A. Karalis, and C. S. Mantzoros Recombinant Human Leptin in Women with Hypothalamic Amenorrhea N. Engl. J. Med., September 2, 2004; 351(10): 987 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Grinspoon, K. K. Miller, D. B. Herzog, K. A. Grieco, and A. Klibanski Effects of Estrogen and Recombinant Human Insulin-Like Growth Factor-I on Ghrelin Secretion in Severe Undernutrition J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3988 - 3993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Misra, K. K. Miller, C. Almazan, K. Ramaswamy, A. Aggarwal, D. B. Herzog, G. Neubauer, J. Breu, and A. Klibanski Hormonal and Body Composition Predictors of Soluble Leptin Receptor, Leptin, and Free Leptin Index in Adolescent Girls with Anorexia Nervosa and Controls and Relation to Insulin Sensitivity J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3486 - 3495. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
