Biomedical subjects

F Camanni

Publications and source records attributed to F Camanni.

At least 91 records · Page 5Linked to original sources

PubMed1996

Reevaluation of growth hormone (GH) secretion in 69 adults diagnosed as GH-deficient patients during childhood.

At present, the most appropriate method for diagnosing GH deficiency (GHD) in adults remains unclear. Recently, it has been demonstrated that GHD in adults can be identified by insulin tolerance test (ITT). Moreover, it has been described that the GHRH plus pyridostigmine (GHRH+PD) test is more accurate than an arginine, glucagon, levodopa, or GHRH test to diagnose GHD in adults. In the current study, firstly we reevaluated GH secretion by the GHRH+PD test in adults previously diagnosed as GH deficient in childhood. The study included 69 patients and 38 healthy subjects. After the GHRH+PD test, the patients and the healthy subjects had peak GH levels of 10.6 +/- 11.2 and 56.7 +/- 28.1 micrograms/L, respectively (P < 0.001). The patients were divided into two groups, responder patients and nonresponder patients, considering an arbitrary cut-off of 10 micrograms/L as the GH peak after the GHRH+PD test. Thirty-nine patients had GH peak below 10 micrograms/L (1.9 +/- 1.7 micrograms/L), whereas the remaining 30 patients above 10 micrograms/L (21.6 +/- 8.] micrograms/L; P < 0.001). Secondly, we compared the GHRH+PD test and the ITT in diagnosing GHD. Twenty-one of the 39 patients with a GH peak below 10 micrograms/L and 29 of the 30 patients with a GH peak above 10 micrograms/L after the GHRH+PD test underwent an ITT. The GH peak after insulin administration was 2.1 +/- 1.7 micrograms/L in nonresponder patients and 21.1 +/- 9.3 micrograms/L in responder patients after the GHRH+PD test (P < 0.001). Three of the responder patients to the GHRH+PD test were identified as GH deficient by the ITT. The relative diagnostic accuracies of the two tests to discriminate GH-deficient patients from healthy subjects were similar (ITT vs. GHRH test: sensitivity, 100%, specificity, 90%; GHRH+PD vs. ITT; sensitivity, 88%; specificity, 100%). In conclusion, in adults previously diagnosed as GH deficient, it is mandatory to reevaluate GH secretion. GHRH+PD and/or ITT are able to diagnose GHD in adults with similar accuracies. Taking into account the potential side-effects of the ITT, however, the GHRH+PD test is the most reliable and safe test to accurately diagnose GHD status in adults.

Adult↗

PubMed1996

Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children.

The reliability of provocative stimuli of GH secretion in the diagnosis of GH deficiency is still controversial. Until now, normative values of GH response to various stimuli have not been established properly. In 472 children and adolescents with normal stature (n = 295, height SDS range -1.5 to 1.2) or normal short stature (n = 177, height SDS range -3.7 to -1.8), we studied the GH response to physical exercise, insulin-induced hypoglycemia, arginine (ARG), clonidine, levodopa, glucagon, pyridostigmine (PD), GHRH, PD + GHRH, and ARG + GHRH. The peak GH responses (range) to various stimuli were: 1) physical exercise: 3.0-28.3 micrograms/L; 2) insulin-induced hypoglycemia: 2.7-46.4 micrograms/L; 3) ARG: 0.5-48.4 micrograms/L; 4) clonidine: 3.8-86.0 micrograms/L; 5) levodopa: 1.9-40.0 micrograms/L; 6) glucagon: 1.9-49.5 micrograms/L; 7) PD: 2.5-35.0 micrograms/L; 8) GHRH: 2.7-102.7 micrograms/L; 9)PD + GHRH: 19.6-106.0 micrograms/L; and 10) ARG + GHRH: 19.4-120.0 micrograms/L. Our results show that all conventional stimuli of GH secretion frequently failed to increase GH levels, showing values lower than that arbitrarily assumed, so far, as minimum normal GH peak, i.e. 7 or 10 micrograms/L. When combined with PD or ARG (substances inhibiting hypothalamic somatostatin release), GHRH becomes the most powerful test to explore the secretory capacity of somatotrope cells (the GH response being always higher than 19 micrograms/L). Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction.

Adolescent↗

PubMed1996

New approach to the diagnosis of growth hormone deficiency in adults.

Pyridostigmine (PD), a muscarinic cholinergic agonist, and arginine (ARG) clearly increase the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) in man. The current study was undertaken to investigate the value and safety of PD + GHRH and ARG + GHRH tests as well as the measurement of serum insulin-like growth factor I (IGF-I) in diagnosing GH deficiency in adults. Fifty-four patients considered GH deficient from extensive organic or idiopathic pituitary disease and 326 healthy adults were studied. The IGF-I concentrations were lower than the 3rd percentile of normal values in only 31 of the 54 (57.4%) patients with hypopituitarism. However, the IGF-I levels in hypopituitary patients and in normal subjects overlapped more frequently between 41 and 60 years (50%) and between 61 and 80 years (92.3%) as opposed to between 20 and 40 years (8.6%). In contrast to the IGF-I measurement, the ranges of peak GH responses to PD + GHRH and ARG + GHRH tests were clearly differentiated between the hypopituitary (0.2-6.8 and 0.1-9.5 microg/l, respectively) and normal (17.7-114 and 16.1-119 microg/l, respectively). However, the PD + GHRH test was reliable only in subjects of 20-40 years of age. In conclusion, IGF-I measurement had no value in the diagnosis of GH deficiency in adults aged over 40 years, but is reliable enough when young adults of 20-40 years of age are considered. Both PD + GHRH and ARG + GHRH testing should be considered more reliable biochemical measurements of GH deficiency. In contrast to the PD + GHRH test, the ARG + GHRH test is reliable throughout the adult lifespan and appears to be the most appropriate for patient compliance and safety.

Adult↗

PubMed1996

Effects of glucose load and/or arginine on insulin and growth hormone secretion in hyperprolactinemia and obesity.

In hyperprolactinemic patients an exaggerated glucose-induced insulin secretion has been reported, but these results have not been confirmed by other researchers. On the other hand, there are few data concerning somatotrope secretion in this condition. In order to clarify these points, in seven normal weight hyperprolactinemic female patients (HP: age 18-46 years, body mass index = 21.8 +/- 0.6 kg/m(2), basal prolactin = 91.7 +/- 16.5 micrograms/l) we studied the effects of glucose load (100 g orally) and/or arginine (0.5 g/kg infused over 30 min) on insulin glucose and growth hormone (GH) levels. These results were compared with those obtained in seven patients with simple obesity (OB: age 23-48 years, body mass index = 38.3 +/- 2.6 kg/m(2)) in whom exaggerated insulin and low GH secretion are well known. Seven normal women (NS: age 26-32 years, body mass index = 20.6 +/- 1/9 kg/m(2)) were studied as controls. The insulin response to glucose in HP (area under curve = 11,460.8 +/- 1407.5 mU x min x l(-1)) was not significantly different from NS (7743.7 +/- 882.9 mU x min x l(-1)) and OB (14,504.8 +/- 1659.9 mU x min x l(-1)). The arginine-induced insulin release in HP and OB was similar (4219.4 +/- 631.7 and 4107.3 +/- 643.2 mU x min x l(-1), respectively), both being higher (p < 0.02) than in NS (2178.1 +/- 290.9 mU x min x l(-1). Glucose and arginine had an additive effect on insulin release in HP and NS (19,769.1 +/- 3249.6 and 10,996.6 +/- 1201.0 mU x min 1(-1), respectively) and a synergistic effect in OB (28 117.3 +/- 5224.7 mU x min x l(-1)). In HP the insulin response to the combined administration of glucose and arginine was not significantly different from the one in OB, and both were higher (p < 0.05) than in NS. The increase in glucose levels after glucose administered on its own or combined with arginine was higher (p < 0.02) and longer lasting in OB than in NS and HP. After arginine in OB, the glucose levels did not show the late decrease under baseline values observed in HP and NS. Glucose inhibited GH secretion both in HP and NS (p < 0.05), while arginine stimulated it in all groups, although the GH response in HP and NS was higher (p < 0.03) than in OB. The arginine-induced GH secretion was inhibited by glucose in HP and NS but not in OB. These results demonstrate that both in hyperprolactinemic patients and in obesity there is a clear increase in insulin secretion. The insulin hyperresponsiveness in hyperprolactinemia is more clearly demonstrated by combined stimulation with glucose and arginine. In spite of similar insulin hypersecretion in hyperprolactinemic and obese patients, GH secretion is reduced only in the latter; with these data the hypothesis that somatotrope insufficiency in obesity is due to hyperinsulinism is unlikely.

Adolescent↗

PubMed1996

Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging.

The function of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis is reduced in aging, although the secretory capacity of somatotrope cells is preserved. Previous studies have suggested that continuous administration of GH-releasing peptides (GHRPs) results in homologous desensitization to the GH-releasing effect of the peptides. In the present study we have studied whether healthy elderly subjects would remain responsive to short-term, intermittent treatment with Hexarelin (HEX), a GHRP, and whether this treatment would result in an increase in serum IGF-I. In study I, the effect of an 8-day treatment with intranasal administration of 1.25 mg (about 18 micrograms/kg) t.i.d. HEX on the acute GH response to the hexapeptide and on serum IGF-I, IGF binding protein 3 (IGFBP-3), prolactin and cortisol levels was studied in seven elderly subjects (four males and three females, aged 67-80 years). In study II, the same parameters were studied before and after a 15-day treatment with oral administration of 20 mg (about 300 micrograms/kg) t.i.d. HEX in seven elderly women (aged 63-80 years). The GH response to the intranasal HEX administration was not significantly higher than that induced by 1 microgram/kg iv GHRH (229.4 +/- 35.9 vs 145.8 +/- 26.9 micrograms.l-1.h-1) and was maintained with a trend towards increase after an 8-day treatment with the peptide (342.5 +/- 199.3 micrograms.l-1.h-1). On the other hand, HEX treatment did not significantly modify IGF-I (138.7 +/- 11.1 vs 122.4 +/- 14.1 micrograms/l) but increased IGFBP-3 levels (2.4 +/- 0.2 vs 1.6 +/- 0.2 mg/l, p < 0.02). The GH response to the oral HEX administration was also not significantly higher than that to iv GHRH (257.6 +/- 72.0 vs 179.0 +/- 42.8 micrograms.l-1.h-1) and did not change after a 15-day treatment with the peptide (237.8 +/- 42.8 micrograms.l-1.h-1). Both IGF-I and IGFBP-3 levels were slightly but significantly increased by oral HEX treatment (156.0 +/- 10.7 vs 141.6 +/- 13.6 micrograms/l, p < 0.03, 3.4 +/- 0.2 vs 3.1 +/- 0.2 mg/l, p < 0.03, respectively). Neither intranasal nor oral HEX treatment modified PRL or cortisol levels and did not induce any side effect. In conclusion, these results indicate that chronic but intermittent treatment with HEX, administered either by intranasal or oral route, does not desensitize the GH response to the peptide. Moreover, after HEX treatment a trend towards increase was shown for IGF-I and IGFBP-3 levels. Thus, our findings strengthen the hypothesis that prolonged treatment with HEX may restore the reduced GH release in aging.

Administration, Intranasal↗

PubMed1996

Acute administration of recombinant human growth hormone inhibits the somatotrope responsiveness to growth hormone-releasing hormone in childhood.

In adulthood the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) is inhibited by previous acute administration of either GH or GHRH and it is restored by substances that inhibit hypothalamic somatostatin release. Because in children the GH response to GHRH is not affected by previous neurohormone administration, it has been suggested that in childhood a GH increase is not able to trigger the somatostatin-mediated negative GH autofeedback mechanism. To verify this hypothesis, in 25 children (8 girls and 17 boys; 15 prepubertal and 10 in pubertal stages II-IV) with familial short stature (normal height velocity and insulin-like growth factor I levels) we studied the effect of acute i.v. administration of different recombinant human GH doses (group 1, N = 5, 0.06 U/kg; group 2, N = 6, 0.01 U/kg; group 3, N = 7, 0.005 U/kg at - 150 min) or saline on the GH response to GHRH (1 microgram/kg i.v. at 0 min). In another group (N = 7), we studied the effect of 0.005 U/kg iv recombinant human GH or saline on the GH response to GHRH combined with arginine (0.5 g/kg i.v. over 30 min), which likely inhibits hypothalamic somatostatin release. Serum GH increases after recombinant human GH were dose-dependent (GH peak, mean +/- SEM, 171.7 +/- 24.4, 33.3 +/- 3.9 and 21.8 +/- 5.1 micrograms/l, respectively). The administration of recombinant human GH strongly inhibited the GHRH-induced GH rise in all groups (group 1, 7.1 +/- 1.7 vs 23.1 +/- 7.6 micrograms/l, p < 0.05; group 2, 9.5 +/- 2.8 vs 26.9 +/- 8.5 micrograms/l, p < 0.05; group 3, 9.1 +/- 2.7 vs 34.8 +/- 7.2 micrograms/l, p < 0.02). The GH response to arginine + GHRH (56.9 +/- 13.3 micrograms/l) was higher than that to GHRH alone recorded in group 1 (p < 0.005), group 2 (p < 0.01) and group 3 (p < 0.01), while exogenous recombinant human GH failed to inhibit it (45.0 +/- 9.4 micrograms/l). Our results demonstrate that in childhood, as well as in adulthood, recombinant human GH administration inhibits the somatotrope responsiveness to GHRH. This inhibitory effect is likely to be mediated by hypothalamic somatostatin release.

Arginine↗

PubMed1996

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

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 microg/kg i.v.) + ARG (0.5 g/kg i.v.) 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 microg/l), Y (70.4 +/- 10.1 vs 76.2 10.7 microg/l) and E (57.9 14.8 vs 52.1 +/- 8.0 microg/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 microg/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.

Adult↗

PubMed1996

Somatotrope responsiveness to Hexarelin, a synthetic hexapeptide, is refractory to the inhibitory effect of glucose in obesity.

Both spontaneous and stimulated growth hormone (GH) secretion is reduced in obesity, in which state insensitivity to the inhibitory effect of hyperglycemia also has been reported. To further investigate this point, in eight male obese (OB) patients (27-49 years old; body mass index = 39.5 +/- 1.7 kg/m2) we studied the effect of oral glucose load (100 g) on the GH response to Hexarelin (HEX, 2 micrograms/kg iv), a synthetic hexapeptide belonging to the GH-releasing peptide family, which has been reported to be able to induce a marked GH rise even in obese patients. As a control group, six male age-matched normal subjects (NS) were studied (26-35 years old; body mass index = 22.3 +/- 1.5 kg/m2). In all subjects the GH response to growth hormone-releasing hormone (GHRH, 1 microgram/kg iv) was also studied. Basal GH and insulin-like growth factor I (IGF-I) levels in OB and NS were similar (0.3 +/- 0.1 vs 0.5 +/- 1.0 microgram/l and 166.7 +/- 12.3 vs 145.4 +/- 6.9 micrograms/l, respectively). Hexarelin induced a clear GH rise in OB (peak: 20.0 +/- 2.9 micrograms/l; AUC: 1193.0 +/- 213.7 micrograms.l-1.120 min-1) but this response was clearly lower (p < 0.0002) than that observed in NS (62.6 +/- 7.3 micrograms/l, 4587.5 +/- 614.9 micrograms.l-1.120 min-1). The GHRH-induced GH rise was lower (p < 0.002) in OB (4.4 +/- 1.2 micrograms/l, 331.0 +/- 95.9 micrograms.l-1.120 min-1) than that in NS (20.2 +/- 1.9 micrograms/l, 1281.0 +/- 157.5 micrograms.l-1 .120 min-1) and both were lower (p < 0.05) than those induced by HEX. In NS, glucose significantly blunted the GH response to HEX (38.4 +/- 7.2 micrograms/l, 2236.5 +/- 514.8 micrograms.l-1.120 min-1, p < 0.05) but failed to modify it in OB (19.4 +/- 2.7 micrograms/l, 934.5 +/- 151.3 micrograms.l-1. 120 min-1). Plasma glucose peaks after oral glucose load in OB and NS were similar (164.5 +/- 9.7 vs 145.8 +/- 4.6 mg/dl). In conclusion, the present data demonstrate that, in contrast to normal subjects, in obese patients HEX has a reduced GH-releasing effect that is not inhibited by glucose. In OB patients as well as in normal subjects HEX releases more GH than GHRH. These findings strengthen the evidence that GH secretion in obesity is refractory either to stimulatory inputs or to the inhibitory effect of hyperglycemia.

Administration, Oral↗

PubMed1996

Diagnosis and drug therapy of prolactinoma.

A prolactin-secreting pituitary tumour is the most frequent cause of hyperprolactinaemia that commonly occurs in clinical practice. Prolactinomas occur more frequently in women than in men and may differ in size, invasive growth and secretory activity. At presentation, macroadenomas are more frequently diagnosed in men. Specific immunohistochemical stains are necessary to prove the presence of prolactin in the tumour cells. The main investigations in the diagnosis of a prolactin-secreting adenoma are hormonal and radiological. As prolactin is a pulsatile hormone, it is a general rule to obtain several blood samples by taking a single sample on 3 separate days or 3 sequential samples (every 30 minutes) in restful conditions. Prolactin levels of 100 to 200 micrograms/L are commonly considered diagnostic for the presence of a prolactinoma; however, prolactinoma cannot be excluded in the presence of lower levels, and prolactin levels > 100 micrograms/L are present in some patients with idiopathic hyperprolactinaemia. Several dynamic function tests have been proposed to differentiate idiopathic from tumorous hyperprolactinaemia. Although they could be used for group discrimination, these tests cannot be used for individual patients. To differentiate between a prolactinoma and a pseudoprolactinoma, thyrotrophin response to a dopamine receptor antagonist may be used, as only prolactinomas may have an increased response. A short course of dopaminergic drugs may also be of some help, as in macroprolactinomas only a shrinkage may be observed. After hyperprolactinaemia is confirmed, imaging with computerised tomography (CT) and magnetic resonance imaging (MRI) are necessary to define the presence of a lesion compatible with a pituitary tumour. There is now a general agreement that medical therapy is of first choice in patients with prolactinomas. Bromocriptine, the most common drug used in this condition, is a semisynthetic ergot alkaloid that directly stimulates specific pituitary cell membrane dopamine D2 receptors and inhibits prolactin synthesis and secretion. In most patients, a reduction or normalisation of prolactin levels is usually observed, together with the disappearance or improvement of clinical symptoms. The sensitivity to bromocriptine is variable and patients may need different dose of the drug. Bromocriptine is also able to shrink the tumour in most patients; however, a few reports of disease progression during therapy have been described. The need for close follow-up, including prolactin levels and CT or MRI studies, is therefore emphasised. Bromocriptine is conventionally given in 2 or 3 daily doses; however, a single evening dose has been shown to be equally effective. Bromocriptine is usually well tolerated by the majority of patients; some adverse effects (nausea, vomiting, postural hypotension) may be initially present, but they usually wear off in time. To prevent such adverse effects it is advisable to start treatment with a low dose during the evening meal and gradually increase the dose over days or weeks. A few patients are unable to tolerate oral bromocriptine, so different formulations of bromocriptine or alternative dopamine agonist drugs (lisuride, terguride, metergoline, dihydroergocryptine, quinagolide, cabergoline, pergolide) have been proposed. Of particular clinical relevance because of their good tolerability and sustained activity are cabergoline and quinagolide. Particular attention should be paid to pregnancy in prolactinoma patients, as tumour enlargement has been reported. As the risk for this occurrence is low in patients with microprolactinoma, there is a general agreement that the drug can be stopped once pregnancy is diagnosed. In patients with macroprolactinoma the risk of tumour enlargement is higher. Therefore, primary therapy with bromocriptine until the tumour has shrank is suggested before pregnancy is attempted. Bromocriptine should be stopped as soon as pregnancy is confirmed, but re

Bromocriptine↗

PubMed1996

Human aging and the GH-IGF-I axis.

The activity of the GH-IGF-I axis undergoes an age-related reduction and in the elderly both spontaneous GH secretion and IGF-I levels are frequently low overlapping with those usually recorded in GH deficient patients. Hypoactivity of the GH-IGF-I axis could explain age-related changes in body composition, function and metabolism, as also indicated by evidence that treatment with rhGH reverses these alterations. The mechanisms underlying the hypoactivity of the GH-IGF-I axis in the aged likely include changes in nutrition and lifestyle, e.g. reduction of physical exercise. However, alterations of neurohormonal hypothalamic control of GH secretion, including reduced activity of GHRH-secreting neurons and somatostatinergic hyper-activity, seem to play a major role. The exaggerated somatostatinergic hyperactivity could be due, in turn, to the impairment of cholinergic activity found in the aging brain. Age-related variations in the activity of other neurotransmitters, such as catecholamines, amino acids, e.g. arginine, neuropeptides, e.g. galanin and/or a putative natural GHRP-like ligand, could play a key role in causing the reduced activity of the GH-IGF-I axis. It is still unclear whether it is of benefit to restore GH secretion in aging. As the pituitary GH releasable pool is preserved in the elderly, it would be more appropriate to increase GH by GH secretagogues such as the new synthetic GH-releasing peptides (GHRPs) or non-peptidyl GHRP mimetics which are active even with oral administration.

Aging↗

PubMed1995

Interaction of salbutamol and galanin on both basal and growth hormone releasing hormone-stimulated growth hormone secretion in humans.

Beta adrenergic receptors mediate the inhibitory influence of catecholamines on GH secretion in man, likely via stimulation of hypothalamic somatostatin release. To further clarify the role of beta adrenergic receptors in the neural control of GH secretion, in 7 normal females (age 21-27 yr) we studied the interaction of salbutamol (SAL 0.08 mg/kg orally), a beta 2-adrenergic agonist, with GHRH (1 microgram/kg i.v.) and/or galanin (GAL 15 micrograms/kg i.v.), a neuropeptide endowed with a GH-releasing effect which is likely mediated by concomitant stimulation of GHRH- and inhibition of somatostatin-secreting neurons. SAL inhibited the GH response to GHRH (AUC: 282.6 +/- 102.7 vs 1083.6 +/- 176.5 micrograms/l/h, p < 0.05) and, although not significantly, that to GAL (263.9 +/- 103.7 vs 418.4 +/- 70.4 micrograms/l/h). GAL enhanced the GHRH-induced GH rise (2129.5 +/- 362.2 micrograms/l/h, p < 0.05) but SAL pretreatment inhibited this effect (1249.8 +/- 257.1 micrograms/l/h, p < 0.02) so that the GH response to the combined administration of GHRH, GAL and SAL overlapped with that to the neurohormone alone. In conclusion, our results show that the inhibitory influence of beta adrenergic activation on GH secretion overrides the stimulatory one of galanin. They strengthen the view that in man beta-adrenergic receptors and galanin modulate GH secretion having opposite influences aimed to balance the function of the GH-IGF-I axis.

Adrenergic alpha-Agonists↗

PubMed1995

Ectopic aldosteronoma associated to another adrenocortical adenoma in the adrenal gland of the same side.

The occurrence of tumors originating from aberrant adrenocortical tissue in ectopic site is very rare. Up to now only two cases of ectopic aldosterone-producing adenoma have been described. We have observed another case of ectopic aldosteronoma, located in the retrocaval region, laterally to the body of the 12th thoracic vertebra. This ectopic tumor was associated to another adrenocortical adenoma, in the adrenal gland of the same side. The diagnostic implications of this observation are discussed.

Adenoma↗

PubMed1995

Metabolic modulation of the growth hormone-releasing activity of hexarelin in man.

Hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a new potent synthetic growth hormone (GH)-releasing hexapeptide. The mechanism of action of hexarelin in man has never been evaluated. Hexarelin may act directly on specific pituitary receptors and indirectly on the hypothalamus. To elucidate its mechanism of action in man, we studied the interaction of hexarelin with glucose and free fatty acids (FFA), two metabolic factors known to inhibit both basal and GH-releasing hormone (GHRH) stimulated GH secretion. Glucose is thought to inhibit GH secretion via stimulation of endogenous somatostatin release, whereas FFA could also act directly on somatotrope cells. Therefore, we investigated the effect of oral glucose (100 g) and lipid-heparin infusion (250 mL of a 10% lipid solution + 2,500 U heparin) on the GH response to a maximal dose (2 micrograms/kg intravenously [IV]) of hexarelin or GHRH in six normal men. Hexarelin elicited a clear-cut GH response (mean +/- SEM; peak, 62.6 +/- 8.0 micrograms/L) that was higher (P < .01) than that observed after GHRH (peak, 19.8 +/- 2.4 micrograms/L). Although similar increases in plasma glucose were observed with the two peptides, oral glucose almost abolished the GH response to GHRH (peak, 5.6 +/- 0.9 micrograms/L, P < .01) while only blunting the somatotrope response to hexarelin (peak, 38.4 +/- 7.9 micrograms/L, P < .05). Similarly, lipid-heparin infusion nearly abolished the GH response to GHRH (peak, 4.9 +/- 1.0 micrograms/L, P < .01) while only blunting the somatotrope response to hexarelin (peak, 34.2 +/- 4.5 micrograms/L, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1995

Blunted GH response to growth hormone-releasing hormone (GHRH) alone or combined with arginine in non-insulin-dependent diabetes mellitus.

An increased spontaneous and stimulated growth hormone (GH) secretion is well documented in insulin-dependent diabetes mellitus. On the contrary, in non-insulin-dependent diabetes mellitus (NIDDM) conflicting results arise from literature. In 14 patients with NIDDM, 7 normal weight (NWD) and 7 obese (OD), we investigated the somatotrope responsiveness to GHRH (1 microgram/kg) alone or combined with arginine (ARG, 0.5 g/kg), which is able to enhance the GH response to GHRH, probably by inhibiting somatostatin release from hypothalamus. Baseline IGF-I, IRI FFA and glucose levels were also determined. Twelve healthy normal subjects (NS) and 12 obese patients (OP) were evaluated as control groups. GH but not IGF-I levels were higher (p < 0.05) in NS than in OP (1.5 +/- 0.5 vs 0.5 +/- 0.2 microgram/l). Insulin levels were higher (p < 0.05) in OP than in NS, NWD and OD (18.7 +/- 1.8 vs 8.7 +/- 0.5, 6.4 +/- 1.9 and 11.8 +/- 1.2 microU/l). FFA were higher (p < 0.05) in NWD. OD and OP than in NS (0.69 +/- 0.04, 0.70 +/- 0.04 and 0.65 +/- 0.06 vs 0.39 +/- 0.03 mmol/l). Plasma glucose was higher (p < 0.05) in diabetic patients than in normal and obese subjects. GH responses to GHRH in NWD, OD and OP were similar (AUC: 221.6 +/- 33.3, 206.0 +/- 35.9 and 177.2 +/- 57.3 micrograms/l/min, respectively) and all lower (p < 0.05) than that in NS (776.7 +/- 206.5 micrograms/l/min). ARG determined a significant increase of GHRH-induced GH release in all groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Short-term fasting in obesity fails to restore the blunted GH responsiveness to GH-releasing hormone alone or combined with arginine.

OBJECTIVE: Fasting is known to clearly increase both spontaneous and GHRH-stimulated GH secretion in normal subjects and this effect is likely to be due to hypothalamic mechanism(s). Our aim was to clarify the effect of a 3 or 4-day fast, on the GH response to GHRH alone or combined with arginine, an amino acid probably acting via inhibition of hypothalamic somatostatin release. DESIGN: Two tests with GHRH (1 microgram/kg i.v.), administered either alone or in combination with arginine (ARG, 0.5 g/kg i.v.) were performed, in a randomized order at least 3 days apart. In obese women the two tests were repeated after a 3 or 4-day fast. PATIENTS: Seven obese women (OB, aged 17-54 years, BMI 42.4 +/- 3.6 kg/m2, waist-hip ratio (WHR) 0.85 +/- 0.01) and ten healthy women, as control subjects (CS, aged 20-44 years, BMI 23.1 +/- 1.1 kg/m2, WHR 0.79 +/- 0.01) were studied. MEASUREMENTS: Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (mU/l) or as areas under the curve (AUC, mU/l/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (microgram/l) with reference to a pure recombinant IGF-I preparation. Results are expressed as mean +/- SEM. RESULTS: Basal GH and IGF-I levels in OB were lower than in CS (0.8 +/- 0.2 vs 4.8 +/- 1.0 mU/l, P < 0.0001 and 120.1 +/- 21.4 vs 188.7 +/- 13.1 micrograms/l, P < 0.02, respectively). The GHRH-induced GH rise in OB was lower (P < 0.00001) than in CS (AUC 340.2 +/- 81.0 vs 2125.0 +/- 199.6 mU/l/h). ARG increased the GHRH-induced GH rise in both groups, but in OB the GH response to ARG+GHRH (1458.4 +/- 439.0 mU/l/h, P < 0.03 vs GHRH alone) remained lower (P < 0.0001) than in CS (6396.2 +/- 772.2 mU/l/h, P < 0.01 vs GHRH alone). In spite of a reduction in body weight and IGF-I, insulin and glucose levels, in OB fasting failed to modify both the basal GH levels and the somatotroph responsiveness to GHRH when administered either alone or combined with ARG. An increase in free fatty acids (FFA) was also found after fasting. CONCLUSIONS: The results of this study demonstrate that in obesity the somatotroph hyporesponsiveness to GHRH, either alone or combined with arginine, is not improved by short-term fasting. As fasting is considered a CNS mediated stimulus to GH secretion, its ineffectiveness in obesity does not support a hypothalamic pathogenesis and suggests that long standing metabolic alterations, such as hyperinsulinaemia and/or elevated free fatty acids, could play a major role in causing GH insufficiency in obese patients.

Adult↗

PubMed1995

Reduced serum levels of dehydroepiandrosterone sulphate in adrenal incidentalomas: a marker of adrenocortical tumour.

BACKGROUND AND OBJECTIVE: Reduced serum levels of dehydroepiandrosterone sulphate (DHEAS) have been shown in patients with Cushing's syndrome resulting from adrenocortical adenoma, in contrast with normal DHEAS levels in patients with Cushing's disease. The aim of this study was to verify whether patients with incidentally discovered adrenocortical adenomas also have reduced levels of DHEAS. DESIGN: Evaluation of serum DHEAS, serum and urinary cortisol, plasma ACTH and low dose dexamethasone suppression test in patients with adrenal incidentaloma and Cushing's syndrome. PATIENTS: Thirty-two patients with adrenal incidentaloma and, as controls, 17 patients with overt Cushing's syndrome, were studied. RESULTS: Serum DHEAS levels lower than normal were found in 21/24 (87.5%) patients with adrenocortical incidentaloma, but in only 1/8 patients with a mass of non-adrenocortical origin. This patient had massive bilateral metastatic infiltration of both adrenal glands and primary adrenal failure. The prevalence of low DHEAS levels in the two groups was significantly different (P = 0.0001). In patients with adrenocortical incidentaloma, the prevalence of low DHEAS levels was significantly higher (P = 0.0001) than that found for some hormonal alterations indicating pre-clinical hypercortisolism (high urinary cortisol, unsuppressed serum cortisol after low dose dexamethasone administration and low plasma ACTH). Low DHEAS levels were found in all patients with Cushing's syndrome due to adrenocortical adenoma but in none of those with Cushing's disease. CONCLUSIONS: Our results indicate that the finding of low DHEAS levels can be considered a marker of the adrenocortical origin of an adrenal incidentaloma, provided adrenal failure has been excluded.

17-alpha-Hydroxyprogesterone↗

PubMed1995

Modulation of growth hormone-releasing activity of hexarelin in man.

Hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a new synthetic growth hormone (GH)-releasing hexapeptide. The mechanism of action of hexarelin in man is not fully elucidated. As for other GH-releasing peptides, an action on both the pituitary gland and the hypothalamus has been hypothesized. In the present study, we evaluated the modulation of GH-releasing activity of hexarelin in man. In a first experiment conducted on 6 healthy male volunteers, we studied the interaction of the maximally effective intravenous dose of hexarelin (2 micrograms/kg i.v.) with GH-releasing hormone (GHRH, 2 micrograms/kg i.v.) and somatostatin (2 micrograms/kg/h i.v.). In a second experiment involving another 6 male subjects, we evaluated the interaction of hexarelin with neuroactive substances, such as pirenzepine (0.6 mg/kg i.v.), pyridostigmine (120 mg p.o.) and arginine (0.5 g/kg i.v.), thought to modulate endogenous somatostatin secretion. Hexarelin induced a higher increase in GH levels as compared to GHRH (integrated output calculated as area under the curve AUC0-120 4,693 +/- 691 vs. 1,494 +/- 102 micrograms.min/l, p < 0.01). Coadministration of hexarelin and GHRH produced a higher GH response than hexarelin alone (AUC0-120 7,395 +/- 450 micrograms.min/l, p < 0.05). Somatostatin abolished the GH response to GHRH (AUC0-120 363 +/- 89 micrograms.min/l, p < 0.01), while it only blunted that to hexarelin (AUC0-120 1,314 +/- 297 micrograms.min/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

In obesity the somatotrope response to either growth hormone-releasing hormone or arginine is inhibited by somatostatin or pirenzepine but not by glucose.

It is known that spontaneous and stimulated GH secretion is reduced in obesity. On the other hand, it has been recently reported that, in obese subjects, plasma GH levels did not change during a hyperglycemic clamp. To further study the sensitivity of somatotrope cells to inhibitory influences in obesity, we studied the effect of somatostatin, pirenzepine, or glucose on the GH response to GHRH or arginine in 32 obese patients and 30 controls. Basal GH levels were lower in obese than in normal subjects (1.0 +/- 0.6 vs. 4.8 +/- 0.7 micrograms/L, P < 0.05), while insulin-like growth factor-I levels were similar in both groups (137.3 +/- 13.2 vs. 138.8 +/- 12.2 micrograms/L). In obese as well as in control subjects pirenzepine abolished the GH response to either GHRH (AUC0-120: 43.7 +/- 9.6 vs. 258.3 +/- 59.9 micrograms/L/h, P < 0.04 and 113.0 +/- 75.0 vs. 870.5 +/- 255 micrograms/L.h, P < 0.01, respectively) or arginine (6.5 +/- 2.5 vs. 118.7 +/- 55.9 micrograms/L.h, P < 0.05 and 47.7 +/- 7.3 vs. 334.0 +/- 157.5 micrograms/L.h, P < 0.01, respectively). Differently from pirenzepine, glucose blunted the GH response to either GHRH or arginine in control subjects (260.8 +/- 38.3 vs. 479.5 +/- 83.9 micrograms/L.h, P < 0.03 and 294.8 +/- 46.3 vs. 625.1 +/- 139.1 micrograms/L.h, P < 0.05, respectively), but failed to modify it in obese patients (193.7 +/- 39.4 vs. 172.4 +/- 33.6 micrograms/L.h and 121.1 +/- 43.4 vs. 155.1 +/- 39.7 micrograms/L.h, respectively). On the other hand, somatostatin deeply blunted the GHRH-induced GH release in obese patients (58.5 +/- 25.4 vs. 548.7 +/- 196.6 micrograms/L.h, P < 0.05) as well as in controls (181.4 +/- 44.4 vs. 759.7 +/- 46.6 micrograms/L.h, P < 0.04). In conclusion, our results show that, in obesity, the stimulated GH release is refractory to the inhibitory effect of glucose but not of pirenzepine, in spite of their likely common mechanism of action, i.e. increase of hypothalamic somatostatin release. Exogenous somatostatin is able to abolish GH secretion both in normal and obese subjects. These data suggest the existence of a peculiar inhability of hyperglycemia to trigger somatostatinergic release in obesity.

Adult↗