title: Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery.
abstract: The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.
authors.affiliation: Department of Endocrinology, Leiden University Medical Center, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: van den Berg
authors.forename: S M
authors.initials: SM
authors.lastname: Pincus
authors.forename: M
authors.initials: M
authors.lastname: Frölich
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: F
authors.initials: F
authors.lastname: Roelfsema
mesh_terms: D000172:Acromegaly / Q000601:surgery*; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D010902:Pituitary Gland / Q000601:surgery*; D013997:Time Factors
chemical_list: D019382:Human Growth Hormone