Acute dexamethasone administration enhances GH responsiveness to GH releasing peptide-6 (GHRP-6) in man

OBJECTIVE Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release. GHRP-6 is a synthetic hexapeptide that increases GH secretion by a mechanism of action not yet fully known, but apparently not by inhibition of hypothalamic somatostatin release, the aim of this study was to evaluate the effect of acute dexamethasone administration on GH responsiveness to GHRP-6 in man,DESIGN One group of subjects received iv GHRP-6 (1 mu g/kg), ON-releasing hormone (GHRH; 100 mu g), GHRH plus GHRP-6 or saline 3.5 h after oral acute dexamethasone administration (4 mg; at 0600 h), A second study group was treated with GHRP-6, GHRH or GHRP-6 plus GHRH after placebo ingestion, following the same protocol,PATIENTS Sixteen normal subjects (mean age: 29 +/- 3.3 years), with normal BMI (22.4 +/- 2.0 kg/m(2)), were studied, Eight subjects received dexamethasone and the other eight were treated with placebo.MEASUREMENTS Serum GH was measured by a two site monoclonal antibody immunofluorometric assay,RESULTS in the placebo-treated subjects, mean peak GH (mU/I; mean +/- SE) and AUC (mU.min/I) values after GHRP-6 administration (peak: 43.8 +/- 9.0; AUC: 2262.0 +/- 459.2) did not differ from those observed after GHRH injection (peak: 49.8 +/- 12.0; AUC: 2903.4 +/- 872.6). the association of the two peptides markedly increased GH levels (peak: 172.4 +/- 34.2; AUC: 10393.0 +/- 1894.8) compared with the isolated administration of GHRP-6 or GHRH. in the subjects who received dexamethasone 3.5 h before saline injection, GH baseline values were significantly higher than those observed after 90 min of sampling (12.4 +/- 9.4 vs. 4.6 +/- 2.0). Mean GH peak and AUC values after GHRP-6 (peak: 78.8 +/- 11.0; AUG: 4114.6 +/- 588.2) and after GHRH administration (peak: 46.8 +/- 16.0; AUG: 3006.8 +/- 1010.0) did not differ significantly in the dexamethasone-treated subjects. in this study group, the administration of the two peptides together caused a significant increase in both peak (119.2 +/- 16.0) and AUC values (7377.0 +/- 937.2) compared with the response obtained after each peptide alone, When the two groups were compared, a significant increase in GH responsiveness to GHRP-6 was observed after dexamethasone administration compared with placebo. No differences in GH response to GHRH, or to the administration of the two peptides together, were seen between the two groups,CONCLUSIONS Oral dexamethasone, at a dose of 4 mg, enhances GH releasing peptide-6-induced GH release when administered 3.5 h earlier. These results suggest that dexamethasone and GHRP-6 could act at different sites of GH releasing mechanisms, Further studies are necessary to elucidate these findings.Universidade Federal de São Paulo, Div Endocrinol, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Endocrinol, Dept Med, São Paulo, BrazilWeb of Scienc

Different effects of growth hormone releasing peptide (GHRP-6) and GH-releasing hormone on GH release in endogenous and exogenous hypercortisolism

OBJECTIVE Chronic hypercortisolism is associated with decreased OH responsiveness to GHRH, GHRP-6 is a synthetic hexapeptide that releases GH in several species, including man, As GHRH and GHRP-6 apparently stimulate GH release by different mechanisms, we evaluated the ON responses to these peptides in patients with endogenous and exogenous glucocorticoid excess and also in control subjects.DESIGN Six patients with endogenous hypercortisolism, nine with exogenous glucocorticoid excess; and 10 normal controls were submitted to three tests, in random order, with GHRH (100 mu g), GHRP-6 (1 mu g/kg) or GHRP+GHRP-6, in the same doses, i.v., on separate days.MEASUREMENTS GH was measured by immunofluorometric assay, IGF-I was determined by radio immunoassay, Plasma glucose was measured by the glucose-oxidase technique.RESULTS Peak GH values (mean+/-SE; mu g/l) after GHRH were significantly blunted in endogenous (2.0 +/- 0.7) and exogenous (3.6 +/- 1.2) hypercortisolae mic patients compared to controls (24.9 +/- 5.1), the endogenous group had lower peak GH values after GHRP-6 alone (7.7 +/- 1.9) or together with GHRH (18.8 +/- 5.8) than those observed in controls (GHRP-6: 22.1 +/- 3.6; GHRH+GHRP-6: 77.4 +/- 15.0) and in exogenous hypercortisolism (27.4 +/- 6.2 and 78.1 +/- 19.9). There were no differences in the GH responses to GHRP-6 alone or in combination with GHRH when controls were compared to the exogenous group, No changes in plasma IGF-I and glucose levels were observed.CONCLUSIONS Our results suggest that hypercortisolism had a different effect on the ON-releasing mechanisms stimulated by GHRH and GHRP-6. Moreover, in endogenous hypercortisolism both GHRN and GHRP-6 pathways are affected, while in the exogenous group GHRP-6 releasing mechanisms are apparently preserved.Universidade Federal de São Paulo, EPM, UNIFESP, DIV ENDOCRINOL, C POSTAL 20266, BR-04034970 São Paulo, BRAZILUniversidade Federal de São Paulo, EPM, UNIFESP, DIV ENDOCRINOL, C POSTAL 20266, BR-04034970 São Paulo, BRAZILWeb of Scienc

Effect of low-dose oral and intravenous dexamethasone administration on growth hormone secretion in children

Acute dexamethasone administration (2 mg/m(2) i.v. and 4 mg orally) increases growth hormone (CH) release in children. Wie evaluated the effect of a low intravenous dose (1 mg/m(2)) of dexamethasone on GH secretion in 8 short normal children and in 6 GH-deficient children. There was a significant GH increase at 120, 150 and 180 min in short normal children (maximal value: 18.9 +/- 2.1 mu g/l; (X) over bar + EP), compared to placebo administration. in contrast, no significant GH elevation was seen in GH-deficient children (1.3 +/- 0.4 mu g/l). There was no difference in the GH response after intravenous dexamethasone and oral clonidine in these same 8 short normal children and 6 GH-deficient children. Although no significant GH release was observed after dexamethasone or clonidine in GH deficiency, an increase in GH after GH-releasing hormone was seen (6.1 +/- 1.9 mu g/l). There was a significant GH increase (18.5 +/- 3.3 mu g/l) after low-dose (2-mg) oral dexamethasone administration in another 8 short normal children, which was similar to values after intravenous injection. No side effects were noted after intravenous or oral dexamethasone. in conclusion, low-dose intravenous or oral dexamethasone administration causes a marked GH release in short normal children, probably mediated by hypothalamic structures.UNIFESP, ESCOLA PAULISTA MED, DIV ENDOCRINOL, DEPT MED, CP 20266, BR-04034970 São Paulo, SP, BRAZILUNIFESP, ESCOLA PAULISTA MED, DIV ENDOCRINOL, DEPT MED, CP 20266, BR-04034970 São Paulo, SP, BRAZILWeb of Scienc

Giant aneurysms of the sellar region simulating pituitary adenomas: A diagnosis to be considered

Aneurysms of the sellar region are commonly mistaken for pituitary adenomas, since they have similar clinical, endocrinological and neurological symptoms. The authors describe three patients with giant aneurysms of the internal carotid artery which were initially diagnosed as pituitary tumors. In all patients the clinical presentation was nonspecific, and consisted mainly of neurological symptoms such as headaches and visual field defects. Endocrine abnormalities were also found in the three cases. Patient no. 1 had short stature, lack of GH response to clonidine stimulation, low IGF - 1 levels and blunted TSH response to TRH. Patient no. 2 had gonadotropin deficiency and patient no. 3 had hyperprolactinemia. CT scans showed a densely enhanced lesion in all patients, which was heterogeneous in one case and homogeneous in the remaining. Carotid angiography confirmed the diagnosis of aneurysm. Preoperative angiographic studies are necessary for the differential diagnosis of an aneurysm from a pituitary tumor. Furthermore, these studies could prevent the serious consequences of a transsphenoidal surgical approach in misdiagnosed cases.ESCOLA PAULISTA MED SCH,DIV ENDOCRINOL,CAIXA POSTAL 20266,BR-04034 SAO PAULO,SP,BRAZILESCOLA PAULISTA MED SCH,DIV ENDOCRINOL,CAIXA POSTAL 20266,BR-04034 SAO PAULO,SP,BRAZILWeb of Scienc

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

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+/-7.1 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 (1191.2+/-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. (C) 2003, Editrice Kurtis.Univ Fed Sao Paulo, Div Endocrinol, UNIFESP EPM, BR-04034970 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Endocrinol, UNIFESP EPM, BR-04034970 Sao Paulo, SP, BrazilWeb of Scienc

A prolactin-secreting tumor in a patient with Klinefelter's syndrome: A case report

We report the case of a patient with Klinefelter's syndrome who developed a prolactin (PRL)-secreting tumor. The patient developed headaches, visual alterations and also symptoms of hypogonadism despite appropriate testosterone (T) replacement therapy, The diagnosis of hyperprolactinemia was then suspected. The laboratory findings confirmed the hypothesis, showing high levels of serum PRL. The patient was initially treated with oral bromocriptine, and afterwards with the injectable form. There was a marked decrease in PRL levels and in tumor size. Although some neoplasms, like breast carcinoma and germ cell tumors, are known to occur more frequently in patients with Klinefelter's syndrome, an association with PRL-secreting tumor has not been reported yet. In conclusion, symptoms of hypogonadism in patients with Klinefelter's syndrome receiving appropriate T replacement therapy can suggest the presence of hyperprolactinemia.UNIV FED RIO GRANDE SUL,DEPT MED,PORTO ALEGRE,RS,BRAZILWeb of Scienc