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Acute effects of a single administration of dexamethasone on basal and growth hormone-releasing hormone stimulated GH secretion in acromegaly
Authors:Marco Losa  Maura Arosio  Alberto Cusin  Orietta Biella  Eva Palmieri  Giovanni Faglia  Massimo Giovanelli
Affiliation:Chair of Neurosurgery, Ospedale San Raffaele IRCCS, University of Milano;Institute of Endocrine Sciences, Ospedale Maggiore, University of Milano, Milano, Italy
Abstract:
A single administration of dexamethasone causes both an early stimulatory and a late inhibitory effect on GH secretion in normal subjects. OBJECTIVE We investigated the effects of a single administration of dexamethasone on basal and GH-releasing hormone-stimulated GH secretion in eight patients with active acromegaly. DESIGN On three different days the patients received 4 mg i.v. dexamethasone, 1 μg/kg body weight GH-releasing hormone 1-29, or matched placebos in different order. PATIENTS Eight subjects with active acromegaly, five of whom had not been treated previously, while the other three had received octreotide therapy which was stopped at least 7 days before testing. MEASUREMENTS Serum GH levels were measured in duplicate by a commercially available RIA kit. RESULTS Dexamethasone administration caused a significant decline of mean ± SE GH levels from 51.8 ± 13.8 to 30.0 ± 9.2 mU/l at 180 minutes, that was not influenced by placebo administration at 180 minutes. On the contrary, when GH-releasing hormone substituted placebo administration, GH levels increased from 34.0 ± 9.8 mU/l at 180 minutes to 56.0 ± 15.6 mU/l at 195 minutes. The GH increase was higher when GH-releasing hormone was given without dexamethasone pretreatment (from 52.4 ± 13.0 mU/l at 180 minutes to 86.4 ± 25.4 mU/l at 195 minutes). Analysis of the GH area under the curve confirmed the significant inhibition of GH secretion after dexamethasone administration and the significant reduction of the GH response to GH-releasing hormone in the study with dexamethasone pretreatment. CONCLUSIONS At variance with data in normal subjects, acute i.v. administration of dexamethasone inhibits basal GH secretion and partially suppresses the GH response to GH-releasing hormone in acromegaly. Both alterations in the regulatory mechanism of adenomatous cells and perturbations of hypothalamic regulatory influences, induced by the state of chronic GH hypersecretion, are likely explanations of the different response to dexamethasone.
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