GH-releasing peptide (GHRP-6)-induced ACTH release in patients with Addison’s disease: Effect of glucocorticoid withdrawal

• Published in: Journal of endocrinological investigation Vol. 26; no. 2; pp. 143 - 147
• Main Authors: Martins, Manoel Ricardo Alves, Pinto, A-C. A. R., Brunner, E., Silva, M. R. D., Lengyel, A-M. J.
• Format: Journal Article
• Language: English
• Published: Milano Kurtis 01.02.2003
• Subjects: Addison Disease - drug therapy; Addison Disease - metabolism; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adrenocorticotropic Hormone - blood; Adrenocorticotropic Hormone - secretion; Adult; Biological and medical sciences; Endocrinopathies; Female; Glucocorticoids - therapeutic use; Humans; Hydrocortisone - blood; Hypothalamo-Hypophyseal System - drug effects; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oligopeptides - pharmacology; Oligopeptides - therapeutic use; Pituitary-Adrenal System - drug effects; Prednisone - therapeutic use; Endocrinopathy; Human; Replacement therapy; Addison disease; Adrenal cortex diseases; Steroid hormone; Peptide hormone; Glucocorticoid; Adrenal insufficiency; Adrenocorticotropic hormone; Adenohypophyseal hormone; Hypocorticism; Adrenal hormone; Adrenal gland diseases; Hormone replacement therapy; Comparative study; Hypothalamohypophysocorticoadrenal axis; Provocation test
• ISSN: 0391-4097; 1720-8386
• DOI: 10.1007/BF03345143

GH releasing peptide (GHRP-6) is a synthetic hexapeptide with potent GH releasing activity both in man and in animals. This peptide is also able to stimulate ACTH and cortisol (F) release. It has been suggested that the ACTH responsiveness to GHRP-6 is modulated by circulating glucocorticoid levels. To further clarify this hypothesis, we studied the effect of GHRP-6 (1 ug/kg, iv) on ACTH and F release in patients with Addison's disease (no.=6) during replacement therapy and after 72 h of glucocorticoid withdrawal. Seven controls were also submitted to a single GHRP-6 test. In control subjects, ACTH values (pmol/l; mean +/- SE) increased from 2.9 +/- 0.8 to 4.7 +/- 1.4 (peak). AUC (pmol.min/l) values were 170.3 +/- 48.8. F (nmol/l) values increased from 257.0 +/- 42.9 to 367.0 +/- 50.8. In patients with Addison's disease there was an increase in ACTH levels from 38.1 +/- 17.1 to 174.9 +/- 79.4 after GHRP-6 administration. AUC values were 5490.4 +/- 2269.1. After 72 h withdrawal of glucocorticoid, there was an increase in basal ACTH values (191.2 +/- 97.3), and a trend toward an increase in ACTH levels after GHRP-6 (p=0.053). Patients with Addison's disease on therapy showed a significantly higher ACTH response to GHRP-6 when compared to controls. Our results show that in patients with Addison's disease on replacement there is an increased ACTH release after GHRP-6 administration, compared to controls. After 72 h glucocorticoid withdrawal, this enhanced responsiveness is not maintained. Our data suggest that circulating glucocorticoids modulate GHRP-6-induced ACTH release and that multiple mechanisms may be involved in this process.