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Biomedical subjects

C Invitti

Publications and source records attributed to C Invitti.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa.

High plasma growth hormone (GH) levels, associated with abnormal hormone responses to provocative stimuli, point to an altered GH secretion in anorexia nervosa. The GH-releasing effect of acutely administered glucocorticoids, firmly established in normal subjects, has not been reported in these patients. In this study, acute iv administration of 4 mg of dexamethasone, compared with saline, increased plasma GH in nine normal-weight women (AUC 848.2 +/- 127.95 vs 242.8 +/- 55.35 micrograms.l-1.min-1, p < 0.05, respectively) but was ineffective in 11 anorectic patients (AUC 3271.8 +/- 1407.11 vs 2780.0 +/- 1162.04 micrograms.l-1.min-1, NS). After dexamethasone, a significant lowering of plasma cortisol was observed in normal women (AUC 25367.0 +/- 3128.43 vs 47347.1 +/- 4456.61 nmol.l-1.min-1, after dexamethasone and saline, respectively, p < 0.05), but not in anorectic patients (AUC 77809.3 +/- 8499.92 vs 78454.9 +/- 7603.62 nmol.l-1.min-1, NS). In both groups, plasma adrenocorticotrophin (ACTH) displayed a significant decrease after dexamethasone (AUC 523.6 +/- 92.08 vs 874.2 +/- 115.03 pmol.l-1.min-1, p < 0.05, after dexamethasone and saline, respectively, in anorectic patients and 377.5 +/- 38.41 vs 1004.9 +/- 200.51 pmol.l-1.min-1, p < 0.05, in controls). However, when considering the hormonal decremental areas, a significant dexamethasone-induced ACTH inhibition, compared to saline, was evidenced in normal (delta AUC -414.4 +/- 65.75 vs 222.9 +/- 42.40 pmol.l-1.min-1, p < 0.05) but not in anorectic women (delta AUC -254.2 +/- 96.92 vs 2.9 +/- 132.32 pmol.l-1.min-1, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Plasma galanin concentrations in obese, normal weight and anorectic women.

OBJECTIVE: Galanin is believed to play a role in the control of eating behavior. No information is available on its concentrations in the biological fluids in human obesity, and this study aimed to clarify this. MEASUREMENTS: We measured plasma galanin and serum insulin levels in 30 obese, 35 normal weight and 11 anorectic women. RESULTS: Mean galanin values were quite similar in obese and control subjects (76.8 +/- 3.20 vs 76.1 +/- 2.33 pg/ml) and only slightly reduced in anorectic patients (67.9 +/- 2.30 pg/ml). Insulin levels were significantly increased and decreased in obese and anorectic patients, respectively, compared to controls. Insulin correlated positively with BMI in the whole group of subjects studied (r = 0.72, P < 0.0001) and in the obese subgroup (r = 0.56, P < 0.02). No correlations could be detected between WH ratio, insulin and galanin concentrations and between galanin and BMI. CONCLUSIONS: In conclusion, plasma galanin concentrations appear to be comparable in obese, normal weight and anorectic subjects. This does not exclude a role of galanin in the regulation of eating behavior since variations of the peptide in discrete brain areas may not be detectable in general circulation and peripheral sources of the peptide may contribute to its plasma levels. Also, our data suggest that galanin does not play a major role in the regulation of insulin secretion in humans.

Adolescent↗
PubMed1995

Cerebrospinal fluid and plasma concentrations of SRIH, beta-endorphin, CRH, NPY and GHRH in obese and normal weight subjects.

Numerous hypothalamic peptides are involved in the control of eating behaviour. We assessed plasma and cerebrospinal fluid (CSF) levels of SRIH, beta-endorphin (beta-EP), CRH, NPY and GHRH in a group of massively obese patients and in normal weight subjects. In the obese patients, CSF SRIH and beta-EP levels were significantly reduced and increased, respectively, compared with controls (20.6 +/- 2.62, mean +/- s.e.m., vs 34.5 +/- 2.14 pg/ml, P < 0.05, for SRIH and 111.2 +/- 5.00 vs 80.4 +/- 5.32 pg/ml, P < 0.001, for beta-EP). Considering the data of obese and control subjects altogether, SRIH and beta-EP concentrations correlated negatively and positively, respectively, with BMI values (r = -0.641, P < 0.005 and r = 0.518, P < 0.05). No significant differences were observed in CSF levels of CRH, NPY and GHRH between obese and normal weight subjects, though GHRH levels were close to the assay sensitivity. CSF concentrations of CRH were positively correlated with those of SRIH in obese patients (r = 0.60, P < 0.05) and with those of NPY both in obese (r = 0.69, P < 0.02) and in control subjects (r = 0.83, P < 0.005). Plasma levels of SRIH, beta-EP, NPY and GHRH did not differ significantly in the two groups of subjects; plasma CRH was undetectable. Our results argue against the hypothesis of an enhanced SRIH tone as the cause of impaired GH secretion in obese patients, a primary defect in GHRH or GH release seems more likely. Moreover, they emphasise the importance of an increased tone of endogenous opioids in the pathophysiology of human obesity.

Adult↗
PubMed1995

Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome.

OBJECTIVES: The aim of this work was to clarify the mechanisms underlying growth hormone (GH) hyposecretion in Cushing's syndrome (CS) and in obesity. We studied the GH response to GH-releasing hormone (GHRH) alone and combined with arginine or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin release. DESIGN: Three tests with GHRH alone (1 microgram/kg i.v. at 0 min) and combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD, 120 mg orally at -60 min) were performed 3 days apart and in random order in eight women with CS (five with ACTH-dependent and three with ACTH-independent hypercortisolism, age 18-56, BMI 26.1 +/- 1.5 Kg/m2) and 11 with OB (age 17-54, BMI 42.9 +/- 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 +/- 0.3 Kg/m2) were studied as controls (C). MEASUREMENTS: Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (micrograms/L) or as areas under the curve (AUC, micrograms/L/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (micrograms/L) with reference to a pure recombinant IGF-I preparation. RESULTS: Basal GH levels in CS were similar to those registered in OB (mean +/- s.e.m. 0.7 +/- 0.1 vs 0.9 +/- 0.2 microgram/L) and lower than in C (3.4 +/- 0.5 microgram/L, P < 0.00001). On the other hand, IGF-I levels were similar in all groups. The GHRH-induced GH rise in CS was lower, though not significantly, to that observed in OB (AUC: 65.6 +/- 13.2 vs 192.5 +/- 61.7 microgram/L/h) and both GH responses were significantly lower than that of C (1029.9 +/- 98.0 micrograms/L/h, P < 0.00001). ARG enhanced the GHRH-induced GH release in CS (331.9 +/- 51.9 micrograms/L/h vs GHRH alone, P < 0.0001), OB (852.4 +/- 162.1 micrograms/L/h, P < 0.0001) and C (3362.6 +/- 386.0 micrograms/L/h, P < 0.0002). However, the GH response to GHRH plus ARG in CS was lower (P < 0.002) than that in OB which, in turn, was lower than that in C (P < 0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C (2808.5 +/- 221.2 micrograms/L/h, P < 0.00001) and, to a lesser extent, in OB (627.3 +/- 84.7 micrograms/L/h, P < 0.0002) but not in CS (102.9 +/- 25.0 micrograms/L/h). CONCLUSIONS: Our results indicate that the GH releasable pool is reduced in obesity and, to an even greater extent, in Cushing's syndrome. The inability of pyridostigmine and arginine to restore a normal GH response to GHRH in these conditions makes the existence of a hypothalamic somatostatinergic hyperactivity unlikely.

Adolescent↗
PubMed1994

[Cushing's syndrome. Recent findings].

Cushing's syndrome is presently divided into ACTH-dependent and ACTH-independent forms. Eighty percent of the former is caused by an ACTH-secreting pituitary adenoma (Cushing's disease), presently considered of monoclonal origin. Fifteen percent of the ACTH-dependent forms are due to ectopic secretion of ACTH and/or CRH by tumors. The ACTH-independent forms are due to adrenal tumors or are iatrogenic. A peculiar form of Cushing's syndrome is the nodular adrenal hyperplasia which may be ACTH-dependent or independent according to the stage of the disease. Definitely rare is the micronodular adrenal dysplasia, a form of ACTH-independent hypercortisolism which is part of a multi-tumoral syndrome (Carney's complex) and is attributed to circulating antibodies which bind to the ACTH receptors promoting adrenal growth and steroidogenesis. The diagnosis of Cushing's syndrome is firstly directed to ascertain the existence of hypercortisolism, then to establish its cause. However, the functional exploration of the hypothalamic-pituitary-adrenal axis on which the laboratory diagnosis is founded may provide misleading results in major depression, chronic ethylism, liver or renal failure, polycystic ovary syndrome as well as during therapy with antiepileptic drugs, rifampicin and estrogens. Furthermore, Cushing's syndrome may have an intermittent or cyclic pattern. Defining the cause of Cushing's syndrome may also be difficult due to the overlapping of clinical and laboratory findings in pituitary and ectopic ACTH hypersecretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗
PubMed1993

Enhanced prolactin responsiveness to galanin in patients with Cushing's disease.

OBJECTIVE: Galanin is believed to play a role in the control of prolactin (PRL) secretion in the rat. Such a role is uncertain in humans where the neuropeptide is expressed by the corticotrophs. However, in clinical conditions of enhanced ACTH secretion, increased PRL levels are often observed. Therefore, we evaluated the effect of galanin infusion on serum PRL levels in patients with Cushing's disease and in control subjects. For comparison, the PRL responses to TRH and metoclopramide were also investigated in the same patients. DESIGN: Four tests were performed: (a) 40-minute infusion of 0.3 micrograms/kg/min of galanin; (b) infusion of normal saline only; (c) metoclopramide test (10 mg as i.v. bolus); (d) TRH test (200 mg as i.v. bolus). PATIENTS: Twenty-four normal subjects and nine patients suffering from active Cushing's disease were investigated. MEASUREMENTS: Serum concentrations of PRL were measured by radioimmunoassay on blood samples collected before and for 90 minutes after drug or saline administration. RESULTS: Serum baseline PRL levels were superimposable in normal subjects and in patients with Cushing's disease. In normal subjects, infusion of galanin induced a distinct PRL increase compared to saline (mean +/- SEM incremental areas 6514 +/- 2572 vs 540 +/- 571 mU/l/90 min, P = 0.05, respectively). In patients with Cushing's disease, galanin evoked a remarkable PRL rise with hormone levels which were significantly greater (P < 0.001) than those observed in the same patients after infusion of saline (21908 +/- 4180 vs 534 +/- 1556 mU/l/90 min) or after galanin administration in controls (P < 0.01). The PRL response to TRH and, much more so, to metoclopramide was significantly lower in patients with Cushing's disease than in normal subjects (42125 +/- 8000 vs 73181 +/- 7246 mU/l/90 min, P < 0.01 after TRH and 79095 +/- 27265 vs 229049 +/- 10602 mU/l/90 min, P < 0.01 after metoclopramide). CONCLUSIONS: Galanin appears to be a specific, though weak, PRL secretagogue in normal subjects. The galanin-induced PRL release was significantly increased in patients with Cushing's disease. A number of hypothetical mechanisms may underlie the enhanced PRL reactivity to galanin in Cushing's disease. This finding together with the impaired PRL responsiveness to TRH and metoclopramide, also observed in this study, is a further example of a dysregulation of PRL secretion in patients with Cushing's disease.

Adult↗
PubMed1993

Effect of octreotide on catecholamine plasma levels in patients with chromaffin cell tumors.

Many chromaffin cell tumors contain somatostatin (SS), and most of them are receptor-positive by in vitro autoradiography and by in vivo administration of radiolabeled SS analogs. We evaluated the effect of a 2-hour infusion of 50 micrograms octreotide on plasma norepinephrine (NE) and epinephrine (E) levels in 6 patients with chromaffin cell tumors. To ascertain the biological activity of octreotide, plasma insulin levels were also measured. Infusion of octreotide was followed in all the patients but 1 by a progressive decrease of plasma NE levels. On the average, plasma NE decreased significantly during octreotide administration, halving its baseline levels at the end of the infusion (51.3 +/- 11.46%, p < 0.05) and rising again slowly thereafter. A slight reduction of plasma E levels was also recorded at the end of octreotide infusion (76.1 +/- 13.77% of baseline, NS) with a prompt return of hormone concentrations to preinfusion values. During octreotide administration, plasma insulin displayed an early and steep fall (49.7 +/- 4.61% of baseline, p < 0.03, at 60 min) with a tendency to escape from inhibition before termination of the infusion. In 5/6 patients, 2 of whom were normotensive before the study and 1 the day of the test, blood pressure did not change during octreotide infusion. In the other patient, blood pressure fell from baseline values of 160/100 to 120/70 mm Hg at 120 min and rebounded to 205/100 mm Hg at 240 min. In conclusion, the short-term administration of low-dose octreotide is capable of lowering NE levels, though with no consistent effect on blood pressure, in patients with chromaffin cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1991

Effect of sandostatin on CRF-stimulated secretion of ACTH, beta-lipotropin and beta-endorphin.

The influence exerted by somatostatin on the secretion of ACTH and opioid peptides has still to be clarified. To gain further information on this issue, we performed in 10 normal volunteers two CRF tests (100 micrograms i.v.) one of which was preceded by s.c. injection of 100 micrograms of the long-acting somatostatin analogue SMS 201-995 (Sandostatin, Sandoz) (SMS), given 30 minutes before CRF. Premedication with SMS markedly inhibited the response of beta-EP to CRF, leaving unchanged the response of beta-LPH, ACTH and cortisol; mean incremental areas of beta-EP were 199.8 +/- 49.31 (SEM) vs 532.9 +/- 95.91 pmol 120 min (P less than 0.01) in the CRF test with and without SMS, respectively. To interpret the selective inhibitory effect of SMS on CRF-stimulated beta-EP secretion, it can be hypothesized that: a) the action of SMS was confined to a population of pituicytes preferentially secreting beta-EP; b) SMS interfered with the processing of POMC inhibiting the formation of beta-EP; c) SMS acted on extrapituitary, possibly peripheral, sources of beta-EP. In conclusion, this study indicates that, in man, somatostatin selectively inhibits the CRF-induced secretion of beta-EP, but not that of ACTH and beta-LPH, by an action that may be exerted at pituitary or extrapituitary level. This is a further example of dissociated secretion of POMC-derived peptides.

Adrenocorticotropic Hormone↗
PubMed1991

Increased urinary free cortisol and decreased serum corticosteroid-binding globulin in polycystic ovary syndrome.

The adrenal participation in the pathogenesis of polycystic ovary syndrome is still under debate. In order to reappraise androgen and glucocorticoid secretion in this disease, we measured serum androstenedione, dehydroepiandrosterone-sulphate, total and free testosterone, sex hormone-binding globulin, LH, FSH, PRL, cortisol, corticosteroid-binding globulin, and urinary free cortisol in 45 women with polycystic ovary syndrome and 27 controls, subdivided in obese and normal-weight subjects. Androstenedione, total and free testosterone were significantly increased, whereas sex hormone-binding globulin tended to be reduced in patients with polycystic ovary syndrome compared with controls, reaching a significant difference between obese patients and matched controls. Free testosterone and sex hormone-binding globulin were significantly increased and reduced, respectively, in obese compared with normal-weight patients. Urinary free cortisol and serum corticosteroid-binding globulin were significantly increased (p less than 0.001) and decreased (p less than 0.005), respectively. Urinary free cortisol exceeded the upper limit of the normal range in 50% of our patients. No appreciable differences were found in PRL and cortisol levels. Besides confirming a hyperandrogenic state, our findings point to an overactivity of the hypothalamic-pituitary-adrenal axis with subsequent diminution of corticosteroid-binding globulin in polycystic ovary syndrome. They also indicate that urinary free cortisol is not a reliable index in differentiating polycystic ovary syndrome from Cushing's disease.

Adult↗
PubMed1990

Treatment of Cushing's syndrome with the long-acting somatostatin analogue SMS 201-995 (sandostatin).

Three patients with Cushing's disease and one patient with paraneoplastic hypercortisolism were treated for 24-49 days with the long-acting analogue of somatostatin, SMS 201-995, Sandoz (SMS), administered in increasing doses up to 400-1200 micrograms daily. In the three Cushing's patients during SMS treatment plasma ACTH displayed an initial rise and a subsequent decrease. The pattern of urinary free cortisol (UFC) tended to be opposite to that of ACTH. In one of these patients, UFC continued to decrease throughout the treatment, without becoming normal. In the patient with paraneoplastic hypercortisolism, SMS was associated with a progressive decrease, though not the normalization, of UFC and of ACTH and cortisol levels. The reciprocal changes of the ACTH and UFC levels observed in the three Cushing's patients receiving SMS suggest that the peptide may act temporarily by inhibiting glucocorticoid secretion. In view of the marked reduction of UFC recorded in 1 of the 3 Cushing's patients and in the patient with paraneoplastic Cushing's syndrome, administration of SMS seems worth trying in cases of ACTH-dependent hypercortisolism requiring medical treatment.

Adrenocortical Hyperfunction↗
PubMed1989

Alpha 2-adrenoceptor sensitivity in anorexia nervosa: GH response to clonidine or GHRH stimulation.

Growth hormone (GH) response to clonidine and growth hormone-releasing hormone (GHRH) stimulation, together with baseline somatomedin C (SmC) levels, were examined in parallel in a group of 21 patients with anorexia nervosa (AN) and in 10 controls. In addition, the Hamilton Rating Scale for Depression (HRS) was administered to the patients. Clonidine (2.5 micrograms/kg body weight, iv) induced GH elevations that were not significantly different between patients and controls. In contrast, GHRH (1 microgram/kg body weight, iv) produced a significantly higher GH response in anorectics than in controls. The ratio between GH responses (area under the curve, or AUC) to GHRH and to clonidine was significantly higher in patients than in controls. Baseline SmC levels (6 patients) were significantly lower in anorectics than in controls. Minor depressive symptomatology was present in all patients. When viewed in relation to the GH hyperresponsiveness to GHRH, the apparent normality of the response to clonidine in anorectics reflects the existence of an actual alpha 2-adrenoceptor subsensitivity. As clonidine reportedly acts via release of endogenous GHRH, an excessive, rather than a normal, GH response to clonidine was to be anticipated.

Adolescent↗
PubMed1988

Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients.

In 10 untreated epileptic patients, we evaluated the functional integrity of the hypothalamic-pituitary axis before and during chronic treatment with sodium valproate, a gamma-aminobutyric acid-mimetic compound. The GH response to L-dopa (250-500 mg po) was absent in 3 and severely impaired in 2 of the 10 patients though being, on the average, only slightly lower in the epileptic subjects than in normal controls. Conversely, the GH rise following GHRH (0.5 micrograms/kg body weight, iv) was normal in 9 of the patients. A significant blunting of the GH response to L-dopa occurred in the 7 patients initially responsive after 6 month of sodium valproate (P less than 0.05). The GH response to GHRH also underwent an evident though not significant attenuation. The ACTH and the ACTH/cortisol elevations elicited by metyrapone (35 mg/kg body weight infused over 4 h), and by CRH (1 microgram/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P less than 0.05, less than 0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH (200 micrograms iv) remained normal over the whole study period. Growth arrest ensued in 1 patient after 6 months of sodium valproate and disappeared after drug withdrawal. These observations point to a defective hypothalamic control of GH secretion in some epileptic patients. They also indicate that chronic administration of sodium valproate, hence activation of central gamma-aminobutyric acid system, results in a blunting of the stimulated GH and ACTH secretion. Occasionally, a reversible arrest of skeletal growth may also ensue.

Adolescent↗
PubMed1987

Clonidine stimulation in anorexia nervosa: growth hormone, cortisol, and beta-endorphin responses.

Clinical and biochemical findings link anorexia nervosa (AN) and primary effective disorders (PAD). Clonidine, an alpha 2-adrenoceptor agonist, has been shown to blunt growth hormone (GH) response and greatly lower plasma cortisol in PAD patients. We examined the GH, cortisol, and beta-endorphin (beta-EP) responses to an acute clonidine challenge (150 micrograms i.v. as a bolus) before and after 30 days of treatment with desmethylimipramine in 14 women with AN. Both before and after treatment, the AN patients showed normal plasma GH and cortisol responses, but an increased plasma beta-EP response. The increased beta-EP response in AN was independent of weight and depressive symptomatology. Our data indicate that alpha 2-adrenoceptors involved in the control of GH and adrenocorticotropic hormone are not altered in AN. The increased beta-EP response may indicate elevated opioid activity in the hypothalamo-pituitary system of AN patients.

Adolescent↗
PubMed1985

Neuroendocrine and psychopathological measures in anorexia nervosa: resemblances to primary affective disorders.

Clinical and biochemical data suggest a link between anorexia nervosa (AN) and primary affective disorders (PAD). In 14 female patients, aged 15-40 years, with 7-month to 11-year histories of AN, we studied circadian cortisol periodicity, response to the dexamethasone suppression test (DST), and plasma levels of beta-endorphin and beta-lipotropin before and after desimipramine therapy. Possible correlations were sought among neuroendocrine impairments, weight loss, and depressive symptomatology. Impaired circadian cortisol periodicity, blunted DST response, and increased beta-endorphin plasma levels, observed in a subgroup of patients, could not be related to weight loss, either before or after therapy. Instead, a trend toward a relationship between neuroendocrine impairments and depressive symptoms was observed before and after treatment.

Adolescent↗
PubMed1985

Evidence against a self-inhibition of ACTH secretion in man.

To ascertain the physiological relevance of an autoregulation of adrenocorticotropin hormone(ACTH) secretion in man, we studied the effect of alsactide (beta-Ala1, Lys17-ACTH1-17-4-amino-N-butylamide), a synthetic ACTH analogue with potent steroidogenic activity but not recognized in the endogenous ACTH immunoassay, on plasma ACTH pattern in patients with Addison's disease. Three experimental models were employed as follows: (a) in 6 patients, whose steroid replacement therapy had been discontinued 36 h previously, we compared the effect of alsactide, administered at two dose levels (10 or 100 micrograms i.v. als bolus followed by the same dose infused over 2 h, and of placebo, on the plasma ACTH pattern; (b) the previous experiment was repeated in 4 patients in whom cortone replacement therapy was substituted for 3 days with dexamethasone, 0.5-1.5 mg daily p.o., so as to lower plasma ACTH levels to within the high normal range; (c) in 4 patients off therapy for 36 h, we evaluated the ACTH response to synthetic ovine corticotropin-releasing factor, 1 microgram/kg body weight injected intravenously, occurring during concomitant administration of alsactide, 100 micrograms i.v. as bolus plus 100 micrograms infused over 2 h, or placebo. Compared to placebo, alsactide did not significantly affect the pattern of ACTH under any of the experimental conditions investigated. Collectively, our findings, although they have to be interpreted with caution, do not support the idea that a self-regulation mechanism plays an important role in the control of ACTH secretion in man.

Addison Disease↗