Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects

1990 ◽  
Vol 122 (3) ◽  
pp. 385-390 ◽  
Author(s):  
R. C. Castro ◽  
J. G. H. Vieira ◽  
A. R. Chacra ◽  
G. M. Besser ◽  
A. B. Grossman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Acetylcholinesterase Inhibitor ◽  
Random Order ◽  
Normal Subjects ◽  
Obese Patients ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Obese Subjects ◽  
Higher Doses ◽  
Hormone Responsiveness

Abstract Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1–29) NH2 100 μg iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 ± 4 vs 44 ± 16 μg/l; mean ± sem). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 ± 5 vs 77 ± 20 μg/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.

Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan

1996 ◽  
Vol 135 (5) ◽  
pp. 568-572 ◽  
Author(s):  
Maria Rosa Valetto ◽  
Jaele Bellone ◽  
Claudia Baffoni ◽  
Paola Savio ◽  
Gianluca Aimaretti ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Normal Subjects ◽  
Individual Variability ◽  
Hormone Response ◽  
Female Age ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Subject Variability ◽  
Within Subject Variability

Valetto MR, Bellone J, Baffoni C, Savio P, Aimaretti G, Gianotti L, Arvat E, Camanni F, Ghigo E. Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan. Eur J Endocrinol 1996;135:568–72. ISSN 0804–4643 The reliability and reproducibility of provocative stimuli of growth hormone (GH) secretion in the diagnosis of GH deficiency are still controversial both in childhood and in adulthood. The combined administration of GH-releasing hormone (GHRH) and arginine (ARG), which likely acts via inhibition of hypothalamic somatostatin release, is one of the most potent stimuli known so far and has been proposed recently as the best test to explore the maximal somatotrope capacity of somatotrope cells. However, it is well known that, usually, provocative stimuli of GH secretion suffer from poor reproducibility and that of the GHRH + ARG test has still to be verified. We aimed to verify the between- and within-subject variability of the GH response to the GHRH + ARG test in normal subjects during their lifespan as well as in hypopituitaric patients with GH deficiency (GHD). In 10 normal children (C: six male and four female, age 12.3 ± 0.9 years, body mass index (BMI) = 16.6 ± 0.7 kg/m2, pubertal stages I-III), 18 normal young adults (Y: ten male and eight female, age 31.1 ± 1.3 years, BMI = 21.4 ± 0.4 kg/m2), 12 normal elderly subjects (E: two male and ten female, age 74.4 ± 1.8 years, BMI= 22.6 ± 0.6 kg/m2) and 15 panhypopituitaric GH-deficient patients (GHD: nine male and six female, age 40.9 ± 4.1 years, BMI= 22.7 ± 1.0 kg/m2), we studied the inter- and intra-individual variability of the GH response to GHRH (1 μg/kg iv) + ARG (0.5 g/kg iv) in two different sessions at least 3 days apart. The GH responses to GHRH + ARG in C (1st vs 2nd session: 61.6 ± 8.1 vs 66.5 ± 9.4 μg/l), Y (70.4 ± 10.1 vs 76.2 ± 10.7 μg/l) and E (57.9 ± 14.8 vs 52.1 ± 8.0 μg/l) were similar and reproducible in all groups. The somatotrope responsiveness to GHRH + ARG also showed a limited within-subject variability (r = 0.71, 0.90 and 0.89 and p < 0.02, 0.0005 and 0.0005 for C, Y and E, respectively). Similarly in GHD, the GH response to the GHRH + ARG test showed a good inter- (1st vs 2nd session: 2.3 ± 0.5 vs 2.2 ± 0.6 μg/l) and intra-individual reproducibility (r = 0.70, p < 0.005). The GHRH + ARG-induced GH responses in GHD were markedly lower (p < 0.0005) than those in age-matched controls and no overlap was found between GH peak responses in GHD and normal subjects. In normal subjects, the GH response to GHRH + ARG is very marked, independent of age and shows limited inter- and intra-individual variability. The GH response to the GHRH + ARG test is strikingly reduced in panhypopituitaric patients with GHD, in whom the low somatotrope responsiveness is reproducible. Thus, these findings strengthen the hypothesis that GHRH + ARG should be considered the most reliable test to evaluate the maximal secretory capacity of somatotrope cells and to distinguish normal subjects from GHD patients in adulthood. E. Ghigo, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126, Torino, Italy

Growth hormone-releasing hormone in the diagnosis and treatment of growth hormone deficient children

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S123-S129
Author(s):  
R.J.M. ROSS ◽  
A. GROSSMAN ◽  
G.M. BESSER ◽  
M.O. SAVAGE
Keyword(s):  
Growth Hormone ◽  
Linear Growth ◽  
Gh Deficiency ◽  
Venous Blood ◽  
Alternative Therapy ◽  
Normal Subjects ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Depot Preparations

ABSTRACT A growth hormone-releasing hormone (GHRH) has recently been extracted and synthesised, and appears to be identical to human hypothalamic GHRH. Immunoreactive GHRH is found in the venous blood of normal subjects and GH-deficient children, but is probably not hypothalamic in origin and therefore not important in GH regulation. GHRH is a potent specific stimulator of GH secretion in man, and provides a valuable diagnostic test in differentiating hypothalamic from pituitary causes of GH deficiency. Preliminary data suggests that GHRH may promote linear growth in some GH deficient children. GHRH may well prove an important alternative therapy for GH deficient children especially if depot preparations or intranasal administration prove effective.

Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism

1992 ◽  
Vol 127 (6) ◽  
pp. 504-508 ◽  
Author(s):  
Andrea Giustina ◽  
Anna Rosa Bussi ◽  
Fabio Legati ◽  
Simonetta Bossoni ◽  
Massimo Licini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Random Order ◽  
Normal Subjects ◽  
Graves Disease ◽  
Growth Hormone Releasing Hormone ◽  
Gh Secretion ◽  
Hyperthyroid Patients ◽  
Secretory Capacity

Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25–50 years) and six healthy volunteers (3F, 3M, aged 27–76 years) underwent from - 10 to 30 min in random order: (i) porcine galanin, iv, 500 μg in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 μg, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2±2.5 μg/l) compared to normal subjects (20.7±4.8 μg/l, p< 0.05). GH peaks after GHRH+ galanin were also significantly lower in hyperthyroid subjects (12.5±3 μg/l) compared to normal subjects (43.8±6 μg/l, p<0.05). That galanin is not able to reverse the blunted GH response to GHRH in hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.

Pyridostigmine partially reverses dexamethasone-induced inhibition of the growth hormone response to growth hormone-releasing hormone

1992 ◽  
Vol 134 (3) ◽  
pp. 513-517 ◽  
Author(s):  
P. J. Trainer ◽  
J. M. W. Kirk ◽  
M. O. Savage ◽  
A. B. Grossman ◽  
G. M. Besser
Keyword(s):  
Growth Hormone ◽  
Area Under The Curve ◽  
Random Order ◽  
Suppressive Effect ◽  
Wilcoxon Test ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Site Of Action ◽  
Oral Glucocorticoids

ABSTRACT The GH response to insulin-induced hypoglycaemia and growth hormone-releasing hormone (GHRH) has been shown to be impaired in subjects with Cushing's syndrome and in healthy volunteers given oral glucocorticoids. Pyridostigmine is an anticholinesterase that stimulates GH secretion, probably by inhibition of hypothalamic somatostatin secretion. This work was designed to study the site of action of glucocorticoids in inhibiting the secretion of GH. Eight healthy male volunteers were studied on three occasions in random order. They took 2 mg oral dexamethasone or placebo at precisely 6-hourly intervals for 48 h before receiving 120 mg oral pyridostigmine or placebo, followed 60 min later by GHRH (100 μg) i.v. Samples for measuring GH were obtained at 15 min intervals for 2 h. The 'area under the curve' (AUC) for each of the treatments was significantly different: dexamethasone–pyridostigmine–GHRH (mean ± s.e.m., 1938 ± 631 mU/min per 1), dexamethasone–placebo–GHRH (634 ±211) and placebo–placebo–GHRH (4267 ± 1183) (P<0·02, Wilcoxon test). In conclusion, dexamethasone given for 48 h significantly inhibited the AUC for GH following treatment with GHRH. However, pretreatment with pyridostigmine significantly reversed the inhibition although this was still partial. Our data suggested that this short-term suppressive effect of dexamethasone was independent of GHRH, and most probably relates to stimulation of the release of somatostatin. Journal of Endocrinology (1992) 134, 513–517

scholarly journals Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

2000 ◽  
pp. 203-211
Author(s):  
JJ Diez ◽  
P Iglesias ◽  
J Sastre ◽  
A Gomez-Pan
Keyword(s):  
Growth Hormone ◽  
Normal Subjects ◽  
Thyrotropin Releasing Hormone ◽  
Constant Infusion ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Control Subjects ◽  
Human Erythropoietin ◽  
Trh Stimulation ◽  
Tsh Secretion

OBJECTIVE: Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. METHODS: We studied 16 patients (8 females, aged 29-68 years) with active acromegaly and 12 control subjects (7 females, 24-65 years). All participants were tested with TRH (400 microg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between -30 and 120 min for GH and PRL determinations, and between -30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. RESULTS: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any significant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a significant (P<0.05) increase in PRL concentrations at 15-120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were significantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were significantly lower in patients than in controls. Infusion with rhEPO modified neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. CONCLUSION: Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modified by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.

Nasal Absorption of Growth Hormone in Normal Subjects: Studies with Four Different Formulations

1994 ◽  
Vol 28 (7-8) ◽  
pp. 845-848 ◽  
Author(s):  
Torben Laursen ◽  
Per Ovesen ◽  
Birgitte Grandjean ◽  
Sigrid Jensen ◽  
Jens Otto L. Jørgensen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Maximum Concentration ◽  
Relative Concentration ◽  
Elevated Serum ◽  
Area Under The Curve ◽  
Random Order ◽  
Normal Subjects ◽  
Nasal Symptom ◽  
Subcutaneous Injections ◽  
Gh Secretion

OBJECTIVE: Current growth hormone (GH) therapy with daily subcutaneous injections results in elevated serum concentrations of GH lasting for several hours, whereas physiologic GH secretion is characterized by a short-duration peak and low basal concentrations. A closer imitation of this pattern might be achieved by administering GH nasally. We studied the effect on the absorption of nasally administered human GH of increasing concentrations of the enhancer didecanoyl-L-α-phosphatidylcholine (DDPC). DESIGN: Four formulations of nasal GH containing the enhancer DDPC in the relative concentrations 0, 4,8, and 16% w/w were administered in random order. SETTING: Participants were admitted to the hospital during the four study periods. INTERVENTIONS: On four occasions the subjects received GH 6 IU (2 mg) in each nostril. Blood was sampled frequently for four hours. Anterior rhinoscopy was performed at 0 and 4 h. During the study the subjects completed a questionnaire to record nasal symptoms. PATIENTS: Sixteen healthy subjects were examined at 0800 h after an overnight fast. MAIN OUTCOME MEASURES: Bioavailability of a nasal preparation of human GH: area under the curve (AUC), the maximum concentration(Cmax), and the time to reach maximum concentration (tmax). Scores for each nasal symptom were recorded as were the total scores. RESULTS: AUC, Cmax, and tmax,. were not significantly affected by increasing the DDPC concentration from 0 to 4 percent or from 8 to 16 percent. AUC and Cmax, however, increased significantly when the concentration of DDPC was changed from 4 to 8 percent. Mean (±SD) AUC (μg·h/L) increased from 20.51 ± 10.53(4 percent)to 46.14 ± 34.59 (8 percent), (p<0.005). Mean (±SD) of Cmax (μg.L) increased from 11.11 ± 5.02 (4 percent) to 28.22 ± 20.85 (8 percent), (p=0.OO2). Mean (±SD) of tmax (min) was not significantly different on the four occasions(range 40.6 ± 36.4 to 61.0 ± 45.2 min, p=0.13). The symptom scores (range 17.56–21.5, maximum 360) were not significantly different (p=0.59). CONCLUSIONS: Increasing the relative concentration of the enhancer DDPC increases the absorption of nasally administered GH.

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