title: 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 axis.
abstract: 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.
authors.affiliation: Department of Endocrinology (M) and Center for Eating Disorders, Odense University Hospital, Denmark.
authors.forename: R K
authors.initials: RK
authors.lastname: Støving
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: A
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: J
authors.initials: J
authors.lastname: Vinten
authors.forename: J
authors.initials: J
authors.lastname: Hangaard
authors.forename: O G
authors.initials: OG
authors.lastname: Koldkjaer
authors.forename: J
authors.initials: J
authors.lastname: Kristiansen
authors.forename: C
authors.initials: C
authors.lastname: Hagen
mesh_terms: D000204:Activity Cycles / Q000502:physiology; D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D015519:Bone Density; D005246:Feedback; D005260:Female; D006728:Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000502:physiology*
chemical_list: D006728:Hormones; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone