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Biomedical subjects

F Cavagnini

Publications and source records attributed to F Cavagnini.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effects of recombinant human insulin-like growth factor I administration on growth hormone (GH) secretion, both spontaneous and stimulated by GH-releasing hormone or hexarelin, a peptidyl GH secretagogue, in humans.

The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH secretion occurs at the pituitary, as well as the hypothalamic level, via stimulation of SS and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted humans, though its effect on the GH response to GHRH is still controversial. GH secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the GH-releasing activity of GHS is strong, reproducible, and even partially refractory to inhibitory influences such as exogenous somatostatin. We studied the effects of rhIGF-I administration (20 microg/kg s.c. at 0 min) on GH secretion, either spontaneous or stimulated by GHRH (2 microg/kg i.v. at +180 min) or Hexarelin (HEX, 2.0 microg/kg i.v at +180 min), a GHS, in eight normal young women (age, mean +/- SEM, 28.3 +/- 1.2 yr; body mass index, 20.1 +/- 0.5 kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3 +/- 30.5 vs. 274.4 +/- 25.3 microg/L, P < 0.05) within the physiological range from +120 to +300 min. No variation in glucose or insulin levels was recorded. rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)(0-300 min) 140.6 +/- 66.3 vs. 114.6 +/- 32.1 microg/L x h], whereas it inhibited the GH response to both GHRH (AUC(180-300 min) 447.7 +/- 159.4 vs. 715.9 +/- 104.3 microg/L x h, P < 0.05) and HEX (620.3 +/- 110.4 vs. 1705.9 +/- 328.9 microg/L x h, P < 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH (41.7 +/- 12.8%) was lower than that on the response to HEX (57.7 +/- 11.0%). In fact, the GH response to GHRH alone was clearly lower than that to HEX alone (P < 0.05), whereas the GH responses to GHRH and HEXwere similar after rhIGF-I. Our findings show that the sc administration of low rhIGF-I doses inhibits the GH response to GHRH and, even more, that to HEX; whereas, at least in this experimental design in fed conditions, it does not modify the spontaneous GH secretion. Because GHS generally show partial refractoriness to inhibitory inputs, including exogenous somatostatin, the present results point toward a peculiar sensitivity of GHS to the negative feedback action of IGF-I.

Adult↗
PubMed1999

Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis.

The past 45 yr' experience with Cushing's syndrome (CS) has led to the awareness of its complex nature and, by the same token, brought about an increase in the diagnostic and therapeutic dilemmas. We carried out a retrospective multicentre study on the diagnostic work-up and treatment in 426 patients with CS, subdivided as follows: 288 with Cushing's disease (CD), 80 with an adrenal adenoma, 24 with an adrenal carcinoma, 25 with ectopic ACTH and/or CRH secretion, and 9 with ACTH-independent nodular adrenal hyperplasia. Normal urinary free cortisol (UFC) values among multiple collections were recorded in about 10% of patients with CS. In 28% of patients with ACTH-independent CS, basal ACTH concentrations were within the normal range but did not respond to CRH stimulation. Measurement of ACTH levels by immunoradiometric assay, rather than by RIA, offered a greater chance of recognizing patients with ACTH-independent CS or ectopic secretion. A 50% increase in ACTH or cortisol levels after CRH yielded a diagnostic accuracy of 86% and 61%, respectively, in the differential diagnosis of ACTH-dependent CS. An 80% decrease in cortisol levels after 8 mg dexamethasone overnight, or in UFC values after the classical 2-day administration, excluded an ectopic secretion but carried a low negative predictive value given the high number of nonsuppressors among patients with CD. Pituitary imaging identified an adenoma in 61% of patients with CD. At inferior petrosal sinus sampling, an ACTH centre: periphery gradient after CRH less than 3, correctly classified all patients with ectopic secretion but misdiagnosed 15% of 76 patients with CD. Transsphenoidal pituitary surgery, the standard therapy for CD, resulted in complete remission (appearance of clinical signs of adrenal insufficiency associated with low/normal UFC excretion and, when available, low/normal morning plasma ACTH and cortisol levels) in 69% of patients. The overall relapse rate after pituitary surgery was 17%. The probability of relapse-free survival, as assessed by Kaplan-Meier analysis, was 95% at 12 months, 84% at 2 yr, and 80% at 3 yr. Risk of relapse was significantly correlated with postoperative baseline plasma ACTH and cortisol peak after CRH. No relapses were observed among patients who did not respond to CRH. Other therapeutic approaches for CD, such as pituitary irradiation and medical therapy, resulted in normalization of cortisol secretion in about half of treated cases. In summary, an accurate selection of the available diagnostic tools leads to the correct diagnosis in the majority of patients with CS. The therapeutic options for CD, adrenal carcinoma, and ectopic secretion are, as yet, not fully satisfactory. The high incidence of relapse after pituitary surgery calls for a prolonged follow-up.

Adenoma↗
PubMed1999

Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo and in vitro.

Galanin, a brain-gut peptide, is also synthesized and released by the pituitary. In man, galanin-like immunoreactivity and galanin messenger RNA have been detected specifically in normal and tumoral corticotropes, but little is known about the production and release of galanin by the human pituitary. We evaluated galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients with Cushing's disease before and after CRH administration. For comparison, the galanin response to CRH was evaluated in 8 normal controls. Galanin secretion by pituitary tumor cultures ranged from 30-230 pmol/4 h. Incubation with CRH induced an increase in galanin concentrations (100 pM CRH: 151 +/- 32%; 1 nM CRH: 232 +/- 43%; 10 nM CRH: 246 +/- 35%; and 100 nM CRH: 270 +/- 44% unstimulated levels at 24 h, P < 0.05). The stimulatory effect of CRH seemed to be dose-dependent. Basal and CRH-stimulated ACTH and galanin concentrations also exhibited a strong positive correlation in single tumor cultures. At IPS sampling, mean basal plasma galanin concentrations in the dominant IPS were somewhat higher than those registered at the periphery (18.6 +/- 1.94 vs. 15.8 +/- 1.60 pmol/L, P = 0.05). Administration of CRH induced a modest but significant increase in galanin concentrations at all three sampling sites. No correlations were found between ACTH and galanin levels in the IPSs and at the periphery. Different from what was observed in patients with Cushing's disease, CRH did not modify plasma galanin concentrations in normal subjects. In conclusion, this study demonstrates that galanin is released by human tumoral corticotropes and responds to CRH. The role of locally produced galanin is, as yet, unknown but may possibly be that of a autocrine/paracrine modulator.

Adenoma↗
PubMed1998

Corticotropin-releasing hormone is produced by rat corticotropes and modulates ACTH secretion in a paracrine/autocrine fashion.

Anterior pituitary hormone secretion is mainly regulated by hypothalamic releasing factors, which reach the pituitary via portal vessels. It has been demonstrated recently that these peptides can also be produced by the pituitary itself, thus possibly modulating hormone secretion in a paracrine/autocrine fashion. The object of this study was to seek evidence for the synthesis and secretion of corticotropin-releasing hormone (CRH) within the anterior pituitary and to ascertain its biological relevance. Messenger RNA from adult rat anterior pituitary fragments and cell cultures was reverse transcribed and subjected to PCR amplification using primers specific to the rat CRH gene. As in the hypothalamus, a single 232-bp band was obtained. The correspondence of the amplified fragment to the sequence of the CRH gene was confirmed by Southern blotting and restriction enzyme digestion. Combined in situ reverse transcription-PCR amplification/immunocytochemistry demonstrated the presence of CRH mRNA in corticotropes. Medium from anterior pituitary primary cultures contained approximately 7 pg/microg protein of CRH immunoreactivity which presented the same chromatographic profile on HPLC as the mature CRH peptide. Incubation of anterior pituitary cells with an antibody directed against CRH markedly reduced basal ACTH secretion compared with serum-treated control wells (0.89+/-0.11 vs. 1.74+/-0.14 ng/200,000 cells in control wells after 1 h, P < 0.05; 1.17+/-0.10 vs. 2.16+/-0. 39 ng/200,000 cells after 2 h, P < 0.05; 1.45+/-0.12 vs. 3.12+/-0.61 ng/200,000 cells after 3 h, P < 0.05). Further, the ACTH response to potassium and to forskolin was markedly blunted by the CRH antiserum as well as by the CRH antagonist, alpha-helical CRH(9-41). In conclusion, this study demonstrates the presence of CRH mRNA in normal rat corticotropes and the secretion of the mature peptide by the anterior pituitary, pointing to the production of CRH at the site of its target cells. In addition, intrapituitary CRH contributes in a paracrine/autocrine fashion to ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1998

Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans.

BACKGROUND: Previous studies have shown that sympathetic cardiovascular outflow is increased in obese normotensive subjects and that this increase is associated with a baroreflex impairment. The purpose of this study was to determine whether these abnormalities are irreversible or can be favorably affected by body weight reduction. METHODS AND RESULTS: In 20 obese normotensive subjects (age, 31.3+/-1.7 years; body mass index, 37.6+/-0.9 kg/m2, mean+/-SEM), we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (ECG), postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography) at rest and during baroreceptor stimulation and deactivation induced by increases and reductions of blood pressure via stepwise intravenous infusions of phenylephrine and nitroprusside. Measurements were repeated in 10 subjects after a 16-week hypocaloric diet with normal sodium content (4600 to 5000 J and 210 mmol NaCl/d) and in the remaining 10 subjects after a 16-week observation period without any reduction in the caloric intake. The hypocaloric diet significantly reduced body mass index, slightly reduced blood pressure, and caused a significant and marked decrease in both muscle sympathetic nerve activity (from 50.0+/-5.1 to 32.9+/-4.6 bursts per 100 heart beats, P<.01) and plasma norepinephrine (from 356.2+/-43 to 258.4+/-29 pg/mL, P<.05). This was associated with a significant improvement in the sensitivity of the baroreceptor heart rate (+71.5 +/- 11%, P<.01) and muscle sympathetic nerve activity (+124.5 +/- 22%, P<.001) reflex. Total body glucose uptake also increased significantly (+60.8 +/- 12.0%, P<.05), indicating an increase in insulin sensitivity. All variables remained unchanged in subjects not undergoing caloric restriction. CONCLUSIONS: In obese normotensive subjects, a reduction in body weight induced by a hypocaloric diet with normal sodium content exerts a marked reduction in sympathetic activity owing to central sympathoinhibition. This can be due to the consequences of an increased insulin sensitivity but also to a restoration of the baroreflex control of the cardiovascular system with weight loss.

Adult↗
PubMed1998

Plasma somatostatin-like immunoreactivity and somatostatin-28 levels in obese men.

Somatostatin (SS) impairs nutrient absorption. It has been suggested that hyposomatostatinaemia may be involved in the pathogenesis of obesity. However, data on postprandial SS-like immunoreactivity (SLI) levels in obese subjects are controversial and the levels of SS-28, the main molecular form of circulating SLI in healthy subjects, have not been determined. To characterise the fasting and postprandial plasma pattern of SLI and SS-28 in obese men, we studied eight obese men (age 24-32 yr, BMI 33-42 kg/m2), with normal glucose tolerance test and normal gastric emptying of solids, and eight healthy men (age 24-39 yr, BMI 21-24 kg/m2). Blood samples were taken at regular intervals in fasting conditions and for 2 h after a standard solid-liquid meal (2.3 MJ). Plasma SLI and SS-28 were measured by RIA. Our results showed that fasting and postprandial plasma SLI and SS-28 levels were not significantly different in healthy and obese subjects. In conclusion SS-28 is the predominant form of circulating SLI in obese subjects. The normal pattern of fasting and postprandial plasma SLI and SS-28 levels in such subjects suggests that somatostatin does not have a pathogenetic role in obesity.

Adult↗
PubMed1998

Altered morning and nighttime pulsatile corticotropin and cortisol release in polycystic ovary syndrome.

An overdrive of the hypothalamic-pituitary-adrenal (HPA) axis has been postulated in patients with polycystic ovary syndrome (PCOS). However, little is known concerning the pulsatile modes of corticotropin (ACTH) and cortisol secretion in these patients. To further investigate this issue, spontaneous ACTH and cortisol release were evaluated in 16 normal-weight patients with PCOS and 16 control women. Nine PCOS patients and eight controls were studied between 8 AM and 12 AM (noon), and seven PCOS patients and eight controls between 11 PM and 3 AM. Venous blood samples were taken at 10-minute intervals. Cluster analysis was used to assess ACTH and cortisol pulse frequency and amplitude, deconvolution to calculate mean hormone secretion rates, and approximative entropy (ApEn) to measure the orderliness of ACTH and cortisol time-series data. PCOS patients compared with controls displayed increased ACTH and cortisol release (area under the curve [AUC] and mean plasma concentration) both in the morning and at night. This was not due to increased hormonal secretory burst frequency, but to higher hormonal interpeak valley concentrations and, in the case of ACTH, nighttime pulse amplitudes. Mean ACTH and cortisol secretion rates also were increased in PCOS patients. Further, both controls and PCOS patients exhibited significant (0 to 20 minutes lagged) concordance between individual daytime pulsatile ACTH and cortisol release episodes. As shown by increased ApEn values, PCOS patients had more disorderly daytime cortisol release. In addition, the normal daytime correlation between the amount of pulsatile ACTH and cortisol release as observed in the controls was lost in PCOS patients. Finally, cross-correlation analysis showed a more prominent negative correlation in PCOS patients versus controls between plasma cortisol and 40- to 120-minute delayed ACTH concentrations in the morning, indicating a more sustained negative feedback of cortisol on ACTH release in PCOS at this time. Taken together, these findings demonstrate the existence of multifaceted dysregulation of the HPA axis in PCOS.

Adolescent↗
PubMed1998

Discriminating between body fat and fluid changes in the obese adult using bioimpedance vector analysis.

OBJECTIVE: Conventional body composition methods may produce biased quantification of fat and fat-free mass in obese subjects, due to possible violation of the assumption of constant (73%) tissue hydration. We used an assumption-free, graphical method for interpreting body weight variation in obesity using bioelectrical measurements. DESIGN: 540 obese subjects with body mass index (BMI) > 31 kg/m2 without apparent edema were compared to 726 healthy subjects with BMI < 31 kg/m2 and to 50 renal patients with apparent edema. A subgroup of 48 obese subjects were evaluated again after weight loss (8.6 kg, 3 BMI units) following one-month energy restriction (5 MJ/d, 1200 kcal/d). 32 obese uremic patients were evaluated before and after a dialysis session (3.2 kg fluid removed). Direct measurements obtained from standard 50 kHz frequency bioelectrical impedance analyzer were used as impedance vectors in the Resistance-Reactance Graph. RESULTS: 1) Impedance vectors of obese subjects could be discriminated from those of edematous patients with 91% correct allocation; 2) A significant lengthening of vectors was observed after fluid loss of 3 kg in obese subjects; but 3) A body weight loss of about 9 kg after energy restriction was associated with no vector displacement. CONCLUSION: A different impedance vector pattern was associated with body weight loss in obesity due to fluid removal (vector lengthening) versus an energy-restricted diet (no vector displacement).

Adolescent↗
PubMed1998

Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women.

OBJECTIVE: Severe energy restriction in the treatment of obesity is limited by catabolism of body protein stores and, consequently, loss of lean as well as fat tissue. Growth hormone (GH), whose secretion is markedly impaired in obesity, is endowed with both lipolytic and protein anabolic properties. The aim of this study was to verify the effects of GH administration on body composition, plasma leptin levels and energy metabolism in obese patients undergoing severe dietary restriction. DESIGN: Single-blind placebo-controlled study. Twenty obese women were fed a diet of 41.86 kJ/kg ideal body weight (IBW) daily for 4 weeks: 10 of them were randomly assigned to a 4 week treatment with biosynthetic GH (rhGH, Saizen, Serono, Rome, Italy), 1 U/kg IBW/week in daily subcutaneous injections; the other 10 patients, matched for age and BMI, received vehicle only. SUBJECTS: Twenty women with simple obesity (age: 25.4+/-1.07 y, BMI: 35.9+/-0.35 kg/m2). MEASUREMENTS: Plasma IGF-I and leptin, serum markers of bone turnover (serum bone isoenzyme of alkaline phosphatase, osteocalcin and urinary hydroxyproline), nitrogen balance, body composition (by DEXA), and resting energy expenditure (REE, by indirect calorimetry) were evaluated at baseline and after 4 weeks. RESULTS: Mean IGF-I plasma levels, not influenced by energy restriction in patients receiving placebo, displayed a significant increase in the group treated with rhGH. The mean weight reduction and fat mass loss were not significantly different in the two groups (6.0+/-0.51 vs 7.2+/-0.30 kg, NS, and 5.36+/-0.460 vs 4.28+/-0.572 kg, NS, with rhGH and placebo, respectively). Likewise, plasma leptin levels decreased significantly in weight-reduced subjects receiving either rhGH (from 16.2+/-2.37 to 6.4+/-0.39 ng/ml, P < 0.05) or placebo (from 14.3+/-2.55 to 7.7+/-3.77 ng/ml, P < 0.05). On the contrary, the mean decrease of lean body mass (LBM) was significantly lower in the GH-treated patients than in those receiving vehicle (1.52+/-0.60 vs 3.79+/-0.45 kg, P < 0.05). In keeping with these findings, the mean daily nitrogen balance was significantly less negative in the GH-treated subjects than in the vehicle-injected patients (mean of the 4 week daily urine collections -185.7+/-40.33 vs -363.9+/-55.47 mmol/d, P < 0.05, respectively). Further, a significant reduction of mean REE was recorded in the energy-restricted placebo-treated patients (from 8807+/-498 to 7580+/-321 kJ/24 h, P < 0.05), but not in the patients receiving rhGH (from 8367+/-580 to 8903+/-478 kJ/24 h, NS). Actually, when corrected for LBM, REE was even increased by GH administration (from 197.9+/-11.76 to 219.3+/-9.87 kJ/kg LBM/24 h, P < 0.05), whereas it was unchanged in the placebo group (from 201.7+/-13.85 to 190.0+/-9.87 kJ/kg LBM/24 h, NS). A tendency of serum markers of bone turnover to increase was observed in the patients treated with rhGH, however with no changes in bone mineral content and density. CONCLUSION: rhGH treatment, though unable to enhance diet-induced weight and fat mass reduction, was effective in stimulating IGF-I production and conserving LBM and increasing its energy metabolism even in the presence of severe energy restriction.

Adult↗
PubMed1997

Effect of chronic treatment with biosynthetic growth hormone (GH) on the GH response to double GH-releasing hormone administration in children with short stature.

Growth hormone (GH) exerts a negative feedback on its own secretion through direct and indirect mechanisms. Normal children, unlike adults, display consecutive GH responses after repeated GH-releasing hormone (GHRH) administration. In this study, we investigated the effects of long-term GH administration on this peculiar secretory pattern. Eight children with severe short stature and impaired GH responses to suprapituitary provocative stimuli associated with normal GH responsiveness to GHRH, underwent, while on chronic treatment with biosynthetic GH and on the 10th day following drug withdrawal, a double bolus GHRH test (two GHRH injections of 1 microg/kg b.w. given as i.v. boluses two hours apart). During GH therapy the GH response to the first GHRH bolus appeared to be reduced, though not significantly so, compared to that observed at diagnosis; after treatment withdrawal, this response returned quite similar to pretreatment. Both during and after treatment, the GH response to the second GHRH bolus was comparable for magnitude to that evoked by the first application. In conclusion, even prolonged treatments with rhGH do not induce persisting alterations of the physiological mechanisms subserving GH regulation.

Adolescent↗
PubMed1997

Spontaneous nocturnal growth hormone secretion in anorexia nervosa.

In anorexia nervosa, serum GH levels are increased under basal conditions and respond abnormally to provocative stimuli. We report here, for the first time, an analysis of pulsatile GH secretion in these patients performed by Cluster algorithm. Seven anorectic and six normal weight, healthy women underwent serial blood sampling at 20-min intervals form 2030-0830 h for GH estimation. The total area under the curve (AUC; micrograms per L/min) was elevated 4-fold in anorectic patients compared to controls (4743.0 +/- 1520.09 vs. 1148.6 +/- 519.27; P < 0.01), largely due to an increase in the non-pulsatile fraction (3212.5 +/- 990.45 vs. 378.7 +/- 123.27; P < 0.01). Accordingly, the valley mean value was higher in anorectic than in control subjects (5.9 +/- 2.25 vs. 1.0 +/- 1.30 micrograms/L; P < 0.01). Furthermore, pulsatile AUC was also greater in anorectic patients (1530.4 +/- 654.72 vs. 769.8 +/- 404.02; P < 0.01) due to a significant increase in GH peak frequency (5.0 +/- 0.81 vs. 3.0 +/- 0.89; P < 0.01). No correlations were observed in these patients between body mass index and any of the parameters of spontaneous GH release, whereas a positive correlation was found between insulin-like growth factor I levels and pulsatile AUC (r2 = 0.583; P < 0.05), peak height (r2 = 0.743; P = 0.01), peak increment (r2 = 0.801; P < 0.01), and GH valley mean (r2 = 0.576; P < 0.05). In conclusion, it appears that the enhanced GH secretion in anorexia nervosa is the result of an increased frequency of secretory pulses superimposed on enhanced tonic GH secretion. Although this latter is consistent with a reduction of hypothalamic SRIH tone, the former may be accounted for by an increased number of GHRH discharges. Considering that in normal weight and obese subjects parameters of GH release are negatively correlated with adiposity indexes, the lack of such a negative correlation in our patients suggests that the enhancement of spontaneous GH release in anorectic patients is not merely the consequence of malnutrition-dependent impairment of insulin-like growth factor I production, but reflects a more complex hypothalamic dysregulation of GH release.

Adolescent↗
PubMed1997

Expression of corticotropin-releasing hormone and its R1 receptor in human endometrial stromal cells.

Corticotropin-releasing hormone (CRH) is a hypothalamic neuropeptide that has been identified also in several peripheral tissues, including organs of the reproductive system. In man, CRH is synthesized and released by the gonads, the placenta, maternal decidua, and the epithelial endometrium. So far, CRH has been demonstrated in endometrial stromal cells only after decidualization. The aim of this study was to seek evidence of the production and secretion of CRH by endometrial stromal cells in different phases of the menstrual cycle and to look for gene expression of the recently identified CRH receptor R1. Total RNA was extracted from stromal cells monolayers established from endometrial samples collected during both proliferative and secretive phases. After reverse transcription, polymerase chain reaction (PCR) amplification was carried out using primers specific to CRH and to CRH receptor R1, resulting in the expected bands, respectively 233 bp for CRH and 274 bp for CRH-R1. The identity of the obtained CRH PCR product was confirmed by restriction enzyme analysis and by Southern blotting. Purification by high performance liquid chromatography (HPLC) of stromal cell culture medium revealed a major peak of CRH immunoreactivity coeluting with the standard CRH(1-41), thus indicating the secretion of the mature peptide. Our study demonstrates the synthesis and secretion of CRH by endometrial stromal cells at all phases of the menstrual cycle. We also demonstrate the expression of the CRH receptor R1 gene. It can be hypothesized that CRH contributes via autocrine/paracrine mechanisms to endometrial physiology.

Blotting, Southern↗
PubMed1997

Dopamine infusion enhances the adrenocorticotropic hormone and cortisol response to metoclopramide in hyperprolactinemic patients but not in normal subjects.

Based on the facts that prolactin and adrenocorticotropic hormone (ACTH) each seem to influence the secretion of the other, that dopamine is the established inhibitory factor for prolactin secretion and negatively modulates ACTH release, and finally that alterations of the central dopaminergic tone have been postulated in tumorous hyperprolactinemia, we studied the effects of pharmacological manipulations of the dopaminergic system on ACTH and cortisol secretion in patients bearing a prolactinoma and in normal subjects. Twenty-seven patients with a prolactin-secreting pituitary tumor and 12 healthy controls were submitted to three tests: (a) 4-h saline infusion; (b) 10 mg metoclopramide (MTC) as an intravenous bolus after a 2-h saline infusion; and (c) 4-h dopamine infusion at the dose of 0.01 microgram/kg/min with a 10-mg intravenous bolus of MTC given at the second hour of dopamine infusion. Administration of MTC, compared to saline, caused a moderate (not significant) plasma ACTH increase, and a significant cortisol increase (p < 0.05), both in hyperprolactinemic and normal subjects, without statistically significant differences between the two group. When MTC was administered during dopamine infusion, the ACTH and cortisol elevation was significantly potentiated in prolactinoma patients while it was similar in magnitude to that recorded after MTC alone in control subjects. These findings support the concept of an inhibitory role exerted by dopamine and are compatible with a stimulatory influence exerted by prolactin on corticotropin-releasing hormone and ACTH secretion, and also favor the view of a reduced central dopaminergic tone in patients with tumorous hyperprolactinemia.

Adrenocorticotropic Hormone↗
PubMed1996

Effect of chronic treatment with octreotide nasal powder on serum levels of growth hormone, insulin-like growth factor I, insulin-like growth factor binding proteins 1 and 3 in acromegalic patients.

Octreotide nasal powder is a delivery system of the somatostatin analogue developed to overcome the inconvenience of repeated subcutaneous administrations. Eight patients with clinically active acromegaly were treated for three months with octreotide nasal powder which was administered at the initial dosage of 0.125 mg tid, doubling the dosage up to 2 mg tid in order to obtain a mean GH value below 5 micrograms/l during 8 daytime hours. In 4 of these patients, treatment was prolonged till the sixth month. Blood samples were taken on days 15, 29, 43, 55, 90, 120, 150, 180 for GH, IGF-I, IGFBP-3, IGFBP-1 and insulin measurements. Before treatment, mean daytime GH and morning IGF-I serum levels were both increased but not correlated with each other. Serum IGFBP-3 levels were higher than normal and positively correlated with those of GH, IGF-I and insulin. Insulin levels were elevated and positively correlated with those of GH but not with those of IGF-I and IGFBP-1. Serum IGFBP-1 levels were in the low normal range and not correlated with any of the other parameters. Treatment with octreotide nasal powder induced in all patients a marked decrease of GH which lowered below 5 micrograms/l in 7/8 patients and IGF-I levels, which fell within the normal range in 1 patient. Serum IGFBP-3 and insulin concentrations decreased by 26% and 71%, respectively, and those of IGFBP-1 underwent an only transient increase in 5/8 patients. Opposite changes of insulin and IGFBP-1 levels, with a decrease of the former followed by an increase of the latter were noted during the 8 hours following an octreotide nasal insufflation. During chronic octreotide treatment, positive correlations were found between GH and IGF-I, GH and IGFBP-3, IGF-I and IGFBP-3, insulin and IGFBP-3 and insulin and IGF-I. An improvement of the clinical picture was registered in all patients after a few days of octreotide nasal powder administration. Treatment was well tolerated, with only mild side effects and no significant changes in the nasal mucosa, and the patients' compliance was excellent.

Acromegaly↗
PubMed1996

No difference between micro- and macroprolactinomas in the prolactin responsiveness to metoclopramide and dopamine administration.

Differences between micro- and macroprolactinomas, as regards the prolactin secretory pattern in response to pharmacological challenges, have been reported in in vivo and in vitro models, and interpreted as being due to different dopaminergic regulation of prolactin release. In 32 patients with prolactin-secreting tumors, 19 with microprolactinomas and 13 with macroprolactinomas, and ten healthy volunteers, we evaluated the prolactin secretion in response to pharmacological manipulations of central dopaminergic tone. To this end, three tests were performed, in random order: (1) 4-h saline infusion; (2) 10 mg metoclopramide as i.v. bolus; (3) 4-h dopamine infusion (0.01 microgram/kg/min) with a 10-mg metoclopramide bolus given after the second hour of infusion. Dopamine infusion, compared to saline, caused a significant prolactin decrease in all the three groups of subjects, without significant difference between micro- and macroprolactinoma patients. In prolactinoma patients, administration of metoclopramide induced a significant rise in plasma prolactin which, however, was significantly lower than the one displayed by controls. Again, no difference was observed between the two groups of hyperprolactinemic patients. Dopamine infusion induced a significant and comparable increase in the prolactin response to metoclopramide in micro- and macroprolactinoma patients, while it was ineffective in control subjects. In conclusion, no differences appear to exist between micro- and macroprolactinoma patients as regards the prolactin secretory pattern during pharmacological modifications of the dopaminergic tone. A central dopaminergic defect and an increased prolactin turnover with attendant reduction of the intracellular hormone pool may both be involved in the reduced prolactin release following provocative stimuli in patients with prolactinoma.

Adolescent↗
PubMed1996

Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

OBJECTIVE: To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. DESIGN: Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. SUBJECTS: Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). MEASUREMENTS: Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. RESULTS: In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. CONCLUSION: A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

Adolescent↗
PubMed1996

Obesity and the sympathetic nervous system.

Several epidemiological studies have shown that obesity represents an independent risk factor for development of cardiovascular diseases, including hypertension, myocardial ischaemia, and cardiac arrhythmias. Although the metabolic and the haemodynamic alterations occurring in the obese state have been well defined for several years, our knowledge on the sympathetic alterations occurring in this condition is more scarce and controversial. This paper reviews the evidence that human obesity is characterized by abnormalities in sympathetic cardiovascular control, in the light of the results of recent studies performed by employing a sensitive technique to assess sympathetic activity in humans, i.e. microneurography. Evidence is provided that sympathetic overactivity is a common hallmark of the obese state, even when blood pressure levels are within the normal range. It will also discuss the potential mechanisms responsible for this sympathetic activation, suggesting that overweight-related metabolic alterations, such as the insulin resistance state, and abnormalities in sympathetic cardiovascular control exerted by arterial baroreceptors may play a pathogenetic role. Finally, the effects of body weight reduction on the sympathetic overactivity which characterizes the obese state will also be examined.

Energy Intake↗