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Biomedical subjects

F Mantero

Publications and source records attributed to F Mantero.

At least 127 records · Page 7Linked to original sources
PubMed1989

Leucine kinetics and the effects of hyperinsulinemia in patients with Cushing's syndrome.

As muscle wasting and resistance to insulin-mediated glucose utilization are features of Cushing's syndrome (CS), we examined glucose and amino acid metabolism in six patients with CS and six normal subjects before and during euglycemic hyperinsulinemic clamp studies (plasma insulin concentrations, approximately 0.36, approximately 0.65, and approximately 10.05 mmol/L). The two groups had similar body mass index values. In the postabsorptive state, leucine and alpha-ketoisocaproate (KIC) rates of appearance (Ra), KIC oxidation, and nonoxidized leucine-carbon flux, an index of leucine entering protein (Leu----P), were comparable in CS patients [2.38 +/- 0.14 (+/- SE), 0.22 +/- 0.04, and 2.16 +/- 0.12 mumol/kg.min) and in normal subjects (2.73 +/- 0.25, 0.17 +/- 0.02, and 2.59 +/- 0.22 mumol/kg.min). During the euglycemic clamp studies the leucine and KIC Ra values, KIC oxidation, and Leu----P decreased to a similar extent in both groups. In contrast, insulin-mediated glucose utilization was impaired in the CS patients at each clamp step (P less than 0.05). In summary, postabsorptive whole body leucine metabolism is normal in patients with CS and is normally suppressed by hyperinsulinemia, indicating a dissociation in insulin sensitivity with respect to glucose and amino acid metabolism.

Adolescent↗
PubMed1989

Acute and chronic effect of nifedipine in primary aldosteronism.

Since calcium entry blocker drugs can interfere with aldosterone secretion in vitro, a similar effect in vivo, in man, has been suggested and partially confirmed. The data available in primary aldosteronism are more controversial. Therefore, we have studied the acute and chronic effect of nifedipine in 7 patients with idiopathic hyperaldosteronism (IHA) and 8 with aldosterone producing adenoma (APA). On 2 different days, 10 mg of nifedipine or placebo were given sublingually to the patients and blood pressure and heart rate were recorded every 5 min. for 60 min. Plasma aldosterone, cortisol, PRA and serum K+ were measured at 0, 30 and 60 min. 5 patients with IHA and 6 with APA received nifedipine 20 mg per os bid for 3 months; the same parameters were evaluated on days 0, 30, 60 and 90; urinary aldosterone was measured on days 0, 30, 60 and 90. BP decreased in both groups both after acute and chronic administration of nifedipine. Plasma aldosterone showed a similar trend either after acute nifedipine or placebo; however, during chronic treatment it was slightly decreased in IHA patients. Cortisol, PRA, urinary aldosterone and K+ remained unchanged. In conclusion, nifedipine is an effective antihypertensive agent also in primary aldosteronism; its aldosterone inhibiting properties are minimal and seem to be present only during long-term therapy in IHA.

Adenoma↗
PubMed1989

Plasma ouabain-like activity in essential hypertensive patients and in subjects with primary aldosteronism.

Plasma from 37 essential hypertensive patients, from 11 subjects with primary aldosteronism and from 23 normotensive subjects was tested for ouabain-like activity. Despite a very substantial overlap, hypertensive patients (both essential and secondary) showed significantly higher levels of a ouabain-like plasma factor compared to normotensive controls. No substantial differences could be detected, however, between the two forms of hypertension; in particular, no significant changes were observed in the low-PRA subgroup. Our results are hardly compatible with the hypothesis that this substance may be of crucial importance in the development either of essential hypertension or of primary aldosteronism.

Adolescent↗
PubMed1988

Effects of naloxone on adrenal cortex regulation in patients with primary aldosteronism.

Excess production of proopiomelanocortin (POMC)-derived peptides with aldosterone-stimulating activity has been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To further investigate this issue, the opiate receptor antagonist naloxone was administered to 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. Clinical and hormonal effects of iv administration of naloxone (10 mg as a bolus) were compared with those obtained in 8 normal subjects. In normals as well as in APA and IHA patients, naloxone caused a significant increase in plasma cortisol, and no change in ACTH, plasma renin activity (PRA) and aldosterone levels. All subjects were retested after 2 mg dexamethasone. ACTH and cortisol were reduced and PRA was unchanged in all groups, without modifications after naloxone. Baseline aldosterone showed no significant changes in all groups. While normal subjects and APA failed to show any aldosterone response to naloxone after dexamethasone, IHA patients demonstrated a significant decrease. beta-endorphin concentrations were in the normal range before and after dexamethasone. In conclusion, naloxone may have a direct action upon adrenal zona fasciculata increasing the cortisol responsiveness to physiological levels of ACTH in either normals or APA and IHA patients. The decrease of aldosterone induced by naloxone in IHA may be due to an intraadrenal opioid control of zona glomerulosa in this disorder.

Adenoma↗
PubMed1988

Effect of naloxone on the adrenal cortex in primary aldosteronism.

Endogenous opioids have been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To investigate this issue, the opiate antagonist naloxone was administered to 8 normals and 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. In normals, APA, and IHA, naloxone caused a significant increase in plasma cortisol and no change in ACTH, renin activity (PRA), and aldosterone levels. All subjects were retested after dexamethasone 2 mg. ACTH and cortisol were reduced and PRA was unchanged without modifications after naloxone. Baseline aldosterone was unaltered in all. While normals and APA failed to show any aldosterone response to naloxone under dexamethasone, IHA patients demonstrated a significant decrease. beta-Endorphin concentrations were in the normal range before and after dexamethasone. In normals as well as in APA and IHA, naloxone may act directly on the adrenal cortex increasing zona fasciculata responsiveness to physiological levels of ACTH. The decrease of aldosterone induced by naloxone in IHA under dexamethasone may be due to an intra-adrenal opioid control of zona glomerulosa in this disorder.

Adenoma↗
PubMed1988

Cardiovascular and hormonal responses to DDAVP before and after beta-blockade in patients with mild essential hypertension.

The aim of this study was to assess the cardiovascular and hormonal responses to 1-desamino-8,D-arginine vasopressin (DDAVP) in hypertensive patients before and after non-selective beta-blockade. We infused DDAVP at 400 ng/kg body weight for 10 min in nine subjects with mild essential hypertension before and 14 days after administration of nadolol at 80 mg/day. Blood pressure and heart rate were recorded, and blood was drawn at 0, 30 and 60 min for measurement of plasma renin activity, aldosterone, cortisol, noradrenaline, adrenaline and dopamine. Before the administration of nadolol, DDAVP induced a significant decrease in blood pressure, and significant increases in the heart rate, plasma renin activity, cortisol and noradrenaline; there were no changes in adrenaline or dopamine. After the administration of nadolol, baseline noradrenaline was significantly increased, while cortisol, adrenaline and dopamine remained unchanged. A second infusion of DDAVP did not significantly alter blood pressure, [corrected] heart rate, noradrenaline, adrenaline or dopamine, but plasma renin activity, aldosterone and cortisol still showed a significant increase. The blunted hypotensive effect of DDAVP after the administration of nadolol may be aspecific, due to lower basal blood pressure levels, or may indicate a mechanism of action common to both drugs. A similar post-DDAVP increase before and after beta-blockade suggests that the drug has a direct effect on the renin-secretory apparatus. An indirect effect, mediated by changes in intrarenal haemodynamics or by other factors with renin-stimulating activity, e.g. tissue plasminogen activator, can also be hypothesized.

Adult↗
PubMed1988

Stressful life events in the pathogenesis of Cushing's syndrome.

Some clinical observations suggested that stressful life events may play an aetiological role in Cushing's syndrome. However, there are no controlled investigations using standardized methods of life events assessment to substantiate this hypothesis. Events in the year before the first signs of disease onset were investigated in 30 consecutive patients with Cushing's syndrome (26 with a pituitary-dependent form, three with an adrenal adenoma, and one with an adrenal carcinoma) and 30 control subjects matched for sociodemographic variables by means of Paykel's Interview for Recent Life Events. Patients with Cushing's syndrome reported significantly more stressful life events than a normal control group (P less than 0.001) and had significantly more of the following: exits (P less than 0.05), undesirable (P less than 0.01) and uncontrolled (P less than 0.01) events. More events that had an objective negative impact (P less than 0.001) and more independent events (unlikely to be a consequence of the illness; P less than 0.001) were also reported. Such ratings were carried out by an independent rater unaware whether the event had occurred in patients or controls. The results are suggestive of a causal relationship between stressful life events and Cushing's syndrome. Such relationship largely pertains to the hypothalamic-pituitary forms of the illness. This is in agreement with a multifactorial model of pathogenesis in Cushing's disease and with current understanding of the complex interdependence of neurophysiological, biochemical and behavioural factors.

Adrenal Gland Neoplasms↗
PubMed1988

Evidence for ultra-short loop autoregulation of adrenocorticotropin secretion in man.

The existence of feedback inhibition of ACTH on its own secretion has been postulated. To investigate its existence in man, the effects of synthetic ACTH 1-24 on endogenous ACTH secretion were tested in 13 patients with Addison's disease. Plasma ACTH was measured using an immunoradiometric assay, specific for endogenous ACTH 1-39. Ten patients were given 50 micrograms ACTH 1-24 as a bolus iv dose followed by a 50-microgram infusion in 90 min. Blood samples for ACTH and cortisol assay were obtained at 0, 15, 30, 60, 90, and 120 min. As a control, a saline infusion was given 2 days earlier. Three other patients were given 100 micrograms ovine corticotropin-releasing hormone (oCRH) iv and ACTH 1-24 as described above. Blood samples for ACTH and cortisol assay were drawn every 15 min for 2 hours. A CRH test was performed during saline infusion as a control 2 days earlier. In all patients steroid replacement therapy was maintained during the studies. ACTH 1-24 caused a significant decrease (P less than 0.01) in endogenous plasma ACTH at 15 min compared to saline. oCHR administration markedly stimulated ACTH release in the three patients tested, and the ACTH response to oCRH was completely inhibited by the simultaneous administration of ACTH 1-24. These findings strongly support the presence of ACTH autoregulation in man. The complete inhibition of the ACTH response to oCRH by exogenous ACTH 1-24 provides evidence for ultra-short feed-back inhibition at the pituitary level.

Addison Disease↗
PubMed1988

The natural history of adrenal function in autoimmune patients with adrenal autoantibodies.

Adrenal autoantibodies (AA) were found in 23 of 2571 (0.9%) patients with organ-specific autoimmune diseases, in one of 632 first-degree relatives of insulin-dependent diabetic patients, and in none of 375 normal controls. In AA-positive subjects the prevalence of human leucocyte antigens (HLA)-A1, -B8 and -DR3 was significantly higher with respect to the general population. Two groups were followed (15 subjects persistently positive for AA and 51 negative subjects) for a mean period of 3.2 years. Yearly tests were made for AA and adrenal function. Of the 15 subjects persistently positive for AA, six developed Addison's disease after a period varying from 6 months to 10 years. Of the 51 subjects initially negative, two became positive during follow-up, and one of these developed Addison's disease 15 months later. In contrast, all the remaining 49 persistently negative subjects maintained normal adrenal function tests. Overall, of the 17 positive subjects, seven (41%) developed Addison's disease, three (18%) showed various degrees of subclinical adrenocortical failure and the remaining seven maintained normal glandular function. In the positive patients the yearly incidence of detriment in adrenal function was 19%. Patients who developed Addison's disease showed significant association with HLA-B8 phenotype. The development from normal adrenocortical function to overt Addison's disease seemed to progress through four distinct stages of functional impairment: increased plasma renin activity with normal/low aldosterone (stage 1), low cortisol response after i.v. administration of ACTH (stage 2), increased ACTH (stage 3), and low basal cortisol (stage 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

An ultrastructural stereologic study of aldosterone secreting adrenal adenomas and of adjacent zona glomerulosa.

The ultrastructure of four aldosterone secreting adenomas and of the adjacent zona glomerulosa has been described by the use of stereological techniques. Adenomatous cells (about 2800 microns 3 in volume) invariably displayed a striking abundance of lipid droplets, which occupied about 30% of the cytoplasm. Mitochondria prevalently contained tubulo-lamellar or lamellar cristae, but some cells exhibited organelles with vesicular cristae. Smooth endoplasmic reticulum (SER) was not very abundant. Small lipofuscin-pigment granules were frequently seen and in a few cells they were exceedingly numerous. Zona glomerulosa cells were smaller (about 950 microns 3 in volume) and possessed mitochondria with typical tubulo-lamellar cristae, a plentiful SER and few lipid droplets. They showed the ultrastructural features of elements actively engaged in steroid synthesis. The possible origin of aldosteronoma cells from the zona glomerulosa is discussed.

Adenoma↗
PubMed1987

Dexamethasone-suppressible hyperaldosteronism: pathophysiology, clinical aspects, and new insights into the pathogenesis.

A profile of dexamethasone-suppressible hyperaldosteronism (DSH), a variant of primary aldosteronism, is drawn by reviewing its pathophysiological and clinical aspects. Genetic studies show no HLA linkage and point to an autosomal dominant mode of inheritance, suggesting that the prevalence of this disease has been underestimated in the past. Hypertension, hypokalemia, suppressed renin, and high aldosterone values characterize DSH in the basal state, similar to the other forms of primary aldosteronism, i.e., aldosterone-producing adenoma (APA) or bilateral idiopathic adrenal hyperplasia (IAH). Biochemically DSH and APA can be differentiated from IAH since in both aldosterone does not respond to upright posture, to angiotensin II infusion, and to angiotensin-converting enzyme (ACE) captopril. In contrast, morphologically DSH is similar to IAH, since neither macroscopic nor histologic examinations of the adrenals give evidence of any unilateral abnormality. However, DSH is differentiated from APA and IAH by the hyperresponsiveness of aldosterone to acute ACTH administration as well as by the failure of aldosterone to escape from prolonged ACTH stimulation. The final diagnosis of DSH rests upon the prompt reversal of the features of mineralocorticoid excess by glucocorticoid therapy. In some cases hypertension is unresponsive to dexamethasone and needs alternative treatment. The main pathogenetic hypotheses point to a pituitary and/or an adrenal abnormality, but the intrinsic nature of the disease remains to be elucidated.

Adenoma↗
PubMed1987

Corticotropin releasing hormone stimulation test: diagnostic aspects in Cushing's syndrome.

The effect of exogenous ovine Corticotropin-Releasing Hormone (oCRH) on plasma ACTH and cortisol levels was investigated in 10 normal volunteers and in 37 patients with Cushing's syndrome (26 with pituitary-dependent disease, 5 with an adrenal adenoma, 2 with an adrenal carcinoma and 4 with bilateral nodular hyperplasia). In all normal subjects and in patients with Cushing's disease, oCRH 100 micrograms as a bolus produced an increase in both plasma ACTH and cortisol. The peak of ACTH occurred after 15-30 min, while plasma cortisol showed highest levels between 30 and 60 min after oCRH administration. The hormonal response in Cushing's disease showed great variability with a clear hyperresponsiveness at least in 6 out of 26 patients with Cushing's disease. A slight and delayed response occurred in 3 cases of bilateral nodular adrenal hyperplasia, while a fourth case showed hyperresponsiveness similar to that found in pituitary-dependent Cushing's disease. No response was observed in patients with an adrenal tumor. Eleven patients with Cushing's disease were tested before and 1 month after pituitary microadenomectomy. After surgery basal cortisol levels were reduced in 10 and became unresponsive or less responsive to oCRH. ACTH patterns were variable with a normal response only in few cases. Although this test seems of limited value in the diagnosis of hypercortisolism, it is a useful tool to differentiate some types of Cushing's syndrome (adrenal tumor from pituitary-dependent Cushing's disease). Variable patterns of response in cases with bilateral nodular adrenal hyperplasia limit the usefulness of this test in recognizing this rare form of hypercortisolism.

Adolescent↗
PubMed1987

Effect of verapamil on aldosterone secretion in primary aldosteronism.

Intracytoplasmic calcium seems to act as second messenger for aldosterone secretion. Both in vitro and in vivo studies demonstrate that drugs which block calcium entry cause a decreased responsiveness of glomerulosa cells to Angiotensin II and potassium. In order to evaluate the effect of a calcium channel blocking agent (Verapamil) in conditions of abnormal aldosterone secretion, we have studied 11 patients with primary aldosteronism, 5 with idiopathic hyperaldosteronism (IHA) and 6 with aldosterone producing adenoma (APA). In our study plasma aldosterone levels decreased after Verapamil infusion in IHA whereas no significant variations were observed in APA patients. These results suggest that calcium blockade can interfere with a possible regulatory system which plays a greater role in idiopathic aldosteronism.

Aldosterone↗
PubMed1987

Alpha-h-ANP injection in normals, low renin hypertension and primary aldosteronism.

Atrial natriuretic peptide, a hormone secreted by the heart, is involved in salt and fluid homeostasis and also exerts an inhibitory effect on aldosterone production in vitro. In order to elucidate if this effect is also present in man, 6 normal volunteers, 5 low renin hypertensive patients (LRH) and 7 patients with primary aldosteronism (PA) have received 100 micrograms of alpha-h-Anp as bolus i.v. (The decrease in blood pressure was mild and transient in all groups, whereas a marked diuretic effect was observed in all hypertensives even in PA where high levels of endogenous ANP have been found. In normals we observed a significant decrease of plasma aldosterone values while in PA and LRH this effect was not evident. This phenomenon associated with a greater natriuretic effect in LRH and PA, as compared with normals, demonstrates the lack of the correlation between ANP-induced diuresis and aldosterone inhibiting properties.

Adult↗
PubMed1987

Effects of naloxone on the pituitary-adrenal axis in patients with dexamethasone-suppressible hyperaldosteronism.

Endogenous opioids may normally modulate the function of the hypothalamo-pituitary-adrenal axis. We investigated whether opioid peptides play any role on aldosterone secretion in dexamethasone-suppressible hyperaldosteronism (DSH). Clinical and hormonal effects of i.v. administration of naloxone (10 mg as a bolus) in two siblings affected by this disease and in eight normal volunteers were studied. In normals, naloxone caused a significant increase in plasma cortisol compared with placebo, an insignificant increase in ACTH and no change in plasma renin activity (PRA) and aldosterone level. In DSH patients there was a slight increase in plasma cortisol, no change in PRA and a marked rise of aldosterone level. In five normals retested after dexamethasone 2 mg, baseline ACTH and cortisol were reduced and no response to naloxone was observed compared to naloxone alone. After dexamethasone, aldosterone levels were suppressed in DSH patients and unchanged in normals, and did not respond to naloxone in any case. In conclusion, naloxone may increase the responsiveness of adrenal zona fasciculata to physiological levels of ACTH in normals, since the slight increase in ACTH seems inadequate to explain per se the marked cortisol elevation. The marked aldosterone rise after naloxone indicates an underlying adrenal rather than pituitary abnormality in patients with DSH, and possibly implicates endogenous opioids.

Adrenocorticotropic Hormone↗
PubMed1987

Response of pituitary-adrenal axis to corticotrophin releasing hormone in patients with Cushing's disease before and after ketoconazole treatment.

Ketoconazole is an antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. It has been used successfully as a palliative treatment of Cushing's syndrome due to its ability to lower cortisol production. However, the effects of ketoconazole on ACTH and aldosterone secretion have not yet been clarified. We evaluated the effect of ovine corticotrophin releasing hormone (oCRH) (100 micrograms bolus) on plasma ACTH, cortisol and aldosterone levels in six patients with Cushing's disease before and after 4 to 6 weeks of treatment with ketoconazole 600 mg/d. Before treatment, plasma cortisol levels were high and significantly increased after oCRH stimulation in all cases, while various patterns of aldosterone secretion were observed. Patients with higher levels showed a greater response to oCRH, while two patients with very low aldosterone showed no response. ACTH showed a marked rise after oCRH administration in all patients with a maximum peak at 30-45 min. After ketoconazole treatment, both plasma cortisol and aldosterone were lowered and their response to oCRH was impaired. Basal ACTH levels were increased in four patients and ACTH response to oCRH was enhanced in all, compared to pretreatment. These findings confirm the inhibitory action of ketoconazole on basal and stimulated cortisol secretion. A similar inhibition affected aldosterone production, indicating that ketoconazole also interferes with the mineralocorticoid pathway. The enhanced response of ACTH to oCRH after the administration of ketoconazole argues against an inhibitory effect of this agent at the pituitary level and might best be explained by reduced negative cortisol feedback.

Adrenocorticotropic Hormone↗
PubMed1987

Effect of alpha-human atrial natriuretic peptide in low renin essential hypertension and primary aldosteronism.

Atrial natriuretic peptide (ANP), besides its diuretic and antihypertensive effects, exhibits an "in vitro" inhibitory action on aldosterone. In order to elucidate if these effects are present also "in vivo", we injected 100 micrograms of alpha-human ANP as a bolus in normal volunteers, low renin essential hypertensive subjects (LRH) and in patients with primary aldosteronism (PA). A transient hypotensive effect was seen in all patients, without significant variations of heart rate. The diuretic and saluretic effects of ANP were greater in hypertensive subjects, even in PA where endogenous ANP levels are known to be elevated. Plasma aldosterone values decreased significantly only in normal volunteers. In conclusion, in LRH and PA renal effects of ANP are not diminished, although its aldosterone-inhibiting properties are less evident than in normals.

Adolescent↗