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 Misra, M. Articles by Klibanski, A. Search for Related Content PubMed PubMed Citation Articles by Misra, M. Articles by Klibanski, A.

Growth Hormone and Ghrelin Responses to an Oral Glucose Load in Adolescent Girls with Anorexia Nervosa and Controls

Neuroendocrine Unit (M.M., K.K.M., K.R., A.A., C.A., A.K.), and Eating Disorders Unit (D.B.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Endocrine Unit (M.M.), Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts 02114; Core Laboratory (G.N.), General Clinical Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114; and Core Laboratory (J.B.), General Clinical Research Center, Massachusetts Institute of Technology, Boston, Massachusetts 02142

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 associated with high levels of GH and low levels of IGF-I suggestive of a nutritionally acquired lack of GH action or GH resistance. The suppression of GH levels after administration of inhibitors of GH secretion such as oral glucose is the definitive test to distinguish normal from pathological states of GH excess, such as acromegaly. However, suppression of GH by glucose has not been well characterized in states of adaptive GH excess, such as AN, especially in a younger adolescent population with relatively higher GH levels, compared with adults. In this study, we investigated GH suppression after a 100-g oral glucose load over a 1-h period in 19 adolescent girls with AN and 20 healthy controls of similar chronologic and bone age. We also compared nocturnal GH secretion characteristics by deconvolutional analysis in both groups to determine differences in secretory patterns between adolescents whose GH values suppressed vs. those whose values did not after oral glucose. Fasting levels of ghrelin, a GH secretagogue, and suppression of ghrelin with oral glucose were also determined to assess whether GH suppression or nonsuppression could be related to ghrelin values at respective time points.

At 0 min (0') of the oral glucose tolerance test, girls with AN had significantly lower levels of glucose (P = 0.009) and higher levels of GH (P = 0.04) than controls. Nadir GH values were higher in AN than in controls (2.0 ± 1.8 vs. 0.5 ± 0.5 ng/ml, P = 0.001). Only 31.6% of girls with AN suppressed their GH values to 1 ng/ml or less vs. 85.0% of healthy adolescents (P = 0.0005). All healthy controls had nadir postglucose GH values of 2 ng/ml or less. Nadir GH concentrations during the oral glucose tolerance test correlated directly with all measures of GH secretion [basal (r = 0.37, P = 0.02), pulsatile (r = 0.56, P = 0.0002), and total (r = 0.57, P = 0.0002)]. Adolescent girls who did not suppress their GH values to 1 ng/ml or less had significantly higher levels of ghrelin at 0', 30', and 60' (P = 0.02, 0.004, and 0.008), significantly higher GH at 0' (P = 0.001), and higher nocturnal basal (P = 0.002), pulsatile (P = 0.05), and total GH secretion (P = 0.03) than those who did suppress below this level. Ghrelin values were higher in AN than in controls at each time point (P = 0.02, 0.0002, and 0.01 at 0', 30', and 60') but did not predict GH values at these time points.

Adolescent girls with AN fail to adequately suppress their GH values after a 100-g oral glucose load. This lack of suppression may be related to the higher GH secretion seen in adolescents with this disorder. In contrast, all healthy adolescents suppress their GH values to 2 ng/ml or less but not 1 ng/ml or less after a glucose load. Although ghrelin values are higher in AN than in controls, we could not demonstrate a relationship between ghrelin and GH values. The inability of healthy girls to uniformly suppress GH levels to 1 ng/ml or less, a normal level defined for adults, may be related to higher GH secretion in the pubertal years, compared with adult life. Further studies are needed to define GH suppression in an adolescent population.

This work was supported in part by National Institutes of Health Grants M01-RR-01066 and 1RO1 DK062249, NIH Nutrition Training Grant DK07703, and an Eli Lilly fellowship grant.

Results from this work were presented in part at the 85th Annual Meeting of The Endocrine Society, Philadelphia, Pennsylvania, June 2003.

Abbreviations: AN, Anorexia nervosa; ApEn, approximate entropy; BMI, body mass index; IRMA, immunoradiometric assay; OGTT, oral glucose tolerance test.

This article has been cited by other articles:

				M. Misra, J. Cord, R. Prabhakaran, K. K. Miller, and A. Klibanski Growth Hormone Suppression after an Oral Glucose Load in Children J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4623 - 4629. [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]

				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 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]

				U. Jaakkola, T. Kuusela, T. Jartti, U. Pesonen, M. Koulu, T. Vahlberg, and J. Kallio The Leu7Pro Polymorphism of PreproNPY Is Associated with Decreased Insulin Secretion, Delayed Ghrelin Suppression, and Increased Cardiovascular Responsiveness to Norepinephrine during Oral Glucose Tolerance Test J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3646 - 3652. [Abstract] [Full Text] [PDF]

				S. Stock, P. Leichner, A. C. K. Wong, M. A. Ghatei, T. J. Kieffer, S. R. Bloom, and J.-P. Chanoine Ghrelin, Peptide YY, Glucose-Dependent Insulinotropic Polypeptide, and Hunger Responses to a Mixed Meal in Anorexic, Obese, and Control Female Adolescents J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2161 - 2168. [Abstract] [Full Text] [PDF]

				U. Meier and A. M. Gressner Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin Clin. Chem., September 1, 2004; 50(9): 1511 - 1525. [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]