Partial restoration of GH responsiveness to ghrelin in Cushing's disease after 6 months of ketoconazole treatment: comparison with GHRP-6 and GHRH

• Published in: European journal of endocrinology Vol. 161; no. 5; pp. 681 - 686
• Main Authors: Correa-Silva, Silvia R, Nascif, Sérgio O, Molica, Patrícia, Sá, Larissa B P C, Vieira, José G, Lengyel, Ana-Maria J
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.11.2009
• Subjects: Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Area Under Curve; Biological and medical sciences; Clinical Study; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Ghrelin - administration & dosage; Ghrelin - physiology; Growth Hormone-Releasing Hormone - administration & dosage; Growth Hormone-Releasing Hormone - physiology; Growth Hormone-Releasing Hormone - secretion; Human Growth Hormone - blood; Human Growth Hormone - secretion; Humans; Hydrocortisone - blood; Hydrocortisone - urine; Insulin-Like Growth Factor I - metabolism; Ketoconazole - administration & dosage; Male; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oligopeptides - administration & dosage; Oligopeptides - physiology; Pituitary ACTH Hypersecretion - drug therapy; Pituitary ACTH Hypersecretion - metabolism; Pituitary ACTH Hypersecretion - physiopathology; Statistics, Nonparametric; Vertebrates: endocrinology; Young Adult; Endocrinopathy; Imidazole derivatives; Adrenal cortex diseases; Ketoconazole; Somatotropin releasing factor; Cushing syndrome; Hyperadrenocorticism; Appetite stimulant; Hypothalamic hormone; Somatotropin; Antifungal agent; Treatment; Growth hormone-releasing hormone; Adenohypophyseal hormone; Partial; Restoration; Ghrelin; Adrenal gland diseases; GH-releasing peptide-6; Hormone releasing factor; Endocrinology; Comparative study
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-09-0459

ObjectiveIn Cushing's disease (CD), GH responsiveness to several stimuli, including ghrelin, GHRP-6, and GHRH, is blunted. Recovery of GH secretion after remission of hypercortisolism after transsphenoidal surgery, radiotherapy, or adrenalectomy is controversial. There are no studies evaluating the effect of primary clinical treatment with ketoconazole on GH secretion in CD. The aim of this study is to compare ghrelin-, GHRP-6-, and GHRH-induced GH release before and after ketoconazole in CD.DesignGH responses to ghrelin, GHRP-6, and GHRH of eight untreated patients with CD (mean age: 33.8±3.1 years; body mass index: 28.5±0.8 kg/m2) were evaluated before and after 3 and 6 months of ketoconazole treatment, and compared with 11 controls (32.1±2.5; 25.0±0.8).MethodsSerum GH was measured by an immunofluorometric assay and urinary free cortisol (UFC) by liquid chromatography and tandem mass spectrometry.ResultsAfter ketoconazole use, mean UFC decreased significantly (before: 222.4±35.0 μg/24 h; third month: 61.6±10.1; sixth month: 39.1±10.9). Ghrelin-induced GH secretion increased significantly after 6 months (peak before: 6.8±2.3 μg/l; sixth month: 16.0±3.6), but remained lower than that of controls (54.1±11.2). GH release after GHRP-6 increased, although not significantly, while GH responsiveness to GHRH was unchanged.ConclusionsGhrelin-induced GH release increases significantly after 6 months of ketoconazole treatment in CD. This could suggest that a decrease in cortisol levels during this time period can partially restore glucocorticoid-induced GH suppression in CD. GH-releasing mechanisms stimulated by ghrelin/GHS could be more sensitive, as no changes in GHRH-induced GH release were observed.