Search PubMed⌕ Search

Biomedical subjects

M Boscaro

Publications and source records attributed to M Boscaro.

At least 127 records · Page 7Linked to original sources
PubMed1985

Evidence for ectopic ACTH production years after bilateral adrenalectomy for Cushing's syndrome: in vivo and in vitro studies.

Three patients presented with hyperpigmentation and high plasma levels of ACTH 4-5 years after bilateral adrenalectomy for Cushing's "disease". X-rays and ct-scan of the lungs showed a small pulmonary mass in all. ACTH levels (1100-2000 pg/ml) were not suppressible by high doses hydrocortisone. A carcinoid tumor was removed in two cases and a chemodectoma in the third. Evidence for ACTH secretion by these tumors was provided by both decrease of ACTH levels after surgery and/or in vitro studies. Both carcinoid cultures showed a basal ACTH production, which was clearly increased by LVP (10(-7) M) and CRF (10(-7) M). Our findings in vitro studies suggest the presence of specific receptor sites for physiological stimuli (LVP and CRF) in tumor cell membranes.

Adrenalectomy↗
PubMed1985

Alpha-1 adrenergic blockade: a possible mechanism of action of dopaminergic drugs on ACTH secretion.

In some cases of Cushing's syndrome both bromocriptine and lisuride inhibit the secretion of ACTH but it is still unknown if they act at pituitary or at higher levels. In order to evaluate this aspect, we set up an in vitro perfusion system with anterior pituitary cells from rats and from human ACTH-secreting tumors. In both preparations lysine-vasopressin (LVP) and epinephrine (EPI) stimulated ACTH secretion; prazosin (alpha-1 blocker) inhibited the EPI but not the LVP-mediated stimulation. Similarly, the infusion of lisuride blocked ACTH response to EPI but not to LVP. These data may suggest that "dopaminergic" drugs could act by an adrenergic blockade and not necessarily by a dopaminergic inhibition.

Adenoma↗
PubMed1985

Effect of short and long-term administration of lisuride in Cushing's disease.

To define the role of dopaminergic drugs on pituitary ACTH secretion, we studied the effect of a dopamine-agonist, lisuride, on a group of 9 patients with pituitary dependent Cushing's syndrome. Lisuride (0.4-0.6 mg/day) was administered for two days: in only two out of eight cases the ACTH levels, sampled every 30 min for 6 h (08:00-14:00 h), showed some reduction when compared with the control day. Two of the nonresponders (R.P.; B.F.) and one untested patient (L.E.) were then treated chronically with a similar amount of lisuride per day for 20 days (L.E.) and for 4 months (B.F.; R.P.). One patient (L.E.) showed a clear decrease in urinary free cortisol without clinical improvement; while in the other two cases, followed for a longer period of time, a clinical improvement was observed together with a decrease of the hormonal parameters. In conclusion, lisuride may occasionally reduce ACTH secretion in patients with pituitary dependent Cushing's syndrome, but the acute test fails to identify the patients who would benefit from this treatment.

Adrenocorticotropic Hormone↗
PubMed1985

Effect of ketanserin in primary aldosteronism.

Serotonin is known to have aldosterone-stimulating properties in humans, which are counteracted by the serotonin-antagonist metergoline. Suppression of aldosterone levels by cyproheptadine in patients with idiopathic aldosteronism has also been shown. Since ketanserin, a more specific 5-HT2-serotoninergic (5-HT2) antagonist, has been shown to affect aldosterone secretion in essential hypertension, we have further investigated this mechanism by injecting ketanserin (10 mg i.v.) in 10 patients with primary aldosteronism (four adenoma, six idiopathic aldosteronism). A transient decrease (20% when compared with the basal levels) of plasma aldosterone was seen at 30 min. A concomitant decrease of plasma cortisol was also noticed, whereas plasma renin activity and potassium did not change. Blood pressure decreased in all cases. These observations suggest that ketanserin acts directly at the adrenal level by interfering with a possible modulatory activity of serotonin. However, an adrenocorticotropic hormone-mediated effect cannot be completely ruled out at the present time.

Aldosterone↗
PubMed1985

Adrenal scintigraphy in the morphological and functional evaluation of Cushing's syndrome.

In recent years, cholesterol adrenal scintigraphy has been employed in the morphofunctional study of adrenal hypercorticism. Particularly in Cushing's syndrome, this noninvasive procedure can give a determinant contribution to distinguish ACTH-dependent from ACTH-independent forms. In our Institute, adrenal scintigraphy was performed in 77 patients with Cushing's syndrome diagnosed on clinical grounds confirmed by laboratory investigations and functional tests (17 with cortisol-secreting adenoma, 54 with pituitary ACTH-dependent bilateral adrenal hyperplasia, 2 with ectopic ACTH-dependent bilateral hyperplasia and 4 with bilateral nodular hyperplasia). Three distinct scintigraphic patterns have been identified. The 56 patients with ACTH-dependent Cushing's syndrome showed bilateral symmetric or slightly asymmetric visualization of the adrenal glands; in the 17 patients with ACTH-independent Cushing's syndrome the adrenal scintigraphy only visualized the gland harboring the adenoma; finally, a marked asymmetric visualization of the glands was observed in the 4 patients with adrenal nodular hyperplasia. These data confirm that adrenal scintigraphy is able to distinguish between ACTH-dependent and ACTH-independent Cushing's syndrome and reliably lateralizes adenomas when they are present. Moreover, the morphofunctional information obtained by this procedure, together with the high resolution morphological data by computerized tomography, allows to recognize the presence of bilateral nodular hyperplasia, an uncommon cause of Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed1985

Prolonged treatment of Cushing's disease by ketoconazole.

Ketoconazole, used in clinical practice as an antifungal medication, recently was found to be a potent inhibitor of gonadal and adrenal steroidogenesis in vitro and in vivo. The effects of prolonged treatment with this agent in Cushing's disease were investigated in five patients who had recurrent severe hypercortisolism after selective transsphenoidal surgery. The patients received the drug for at least 2 months. Urinary cortisol markedly decreased in all patients immediately after the beginning of treatment with ketoconazole (800 mg/day) and remained within low normal levels when the daily dose was lowered to 600 mg/day. Plasma cortisol also decreased. After 4-6 weeks of treatment, the clinical features of the disease regressed in all patients without signs of toxicity. These findings indicate that ketoconazole may be a valuable drug for the management of patients with Cushing's disease because of its ability to correct hypercortisolism quickly.

Administration, Oral↗
PubMed1983

Pituitary microadenomas: surgical results and morphological findings.

The results of transsphenoidal microsurgery in treating 22 patients with pituitary microadenomas are reported. Histological and ultrastructural comparative studies were performed in attempting to obtain a more accurate morphological classification of pituitary microadenomas.

Adenoma↗
PubMed1983

Effect of metergoline on the aldosterone-stimulating properties of metoclopramide.

The mechanism by which metoclopramide stimulates aldosterone secretion is still unclear, since it cannot be explained by known regulatory systems. On the other hand we have recently shown that serotonin is also a potent aldosterone-stimulatory substance in man and its action can be blunted by the antiserotoninergic drug, metergoline. To test if metoclopramide could act through a serotoninergic pathway we have studied the effect of metergoline on the aldosterone response to metoclopramide in 8 normal subjects. The effect of metoclopramide (10 mg i.v.) on plasma aldosterone, PRA, cortisol, prolactin and K was studied before and after acute metergoline administration. Metergoline pretreatment significantly reduced the aldosterone response to metoclopramide, together with a slight reduction of prolactin, whereas no changes were seen on PRA, cortisol and K. In vitro, metoclopramide induced a significant aldosterone output from human adrenal adenoma cells, which was partially reduced by metergoline and not by bromocriptine. Despite a lack of specificity of metergoline these data may suggest the hypothesis of a serotoninergic component in the aldosterone-stimulating properties of metoclopramide.

Adenoma↗
PubMed1983

Effect of bromocriptine in pituitary-dependent Cushing's syndrome.

To assess the therapeutic value of a dopaminergic drug on abnormal ACTH secretion, we studied the effect of bromocriptine during short and long-term treatment in nine patients with active pituitary-dependent Cushing's syndrome. The single oral dose effect of bromocriptine (2.5 mg at 0800 h) on ACTH samples obtained every half hour for 3 h, was studied in six patients with Cushing's disease; in no case was suppression of ACTH observed. In five patients, the effect of bromocriptine was also investigated after its administration for two consecutive days (5 mg/d) with plasma samples taken every half hour for 12 h; in three cases no suppression of plasma ACTH was observed, while the other two showed a significant decrease. Three of our patients (a nonresponder to the single dose, a responder to the two-day treatment, and an untested patient) were subjected to prolonged bromocriptine administration (2-45 months). In the first two patients only, biochemical data and clinical symptoms showed improvement, while the other patient showed only initial benefit. These data show that bromocriptine may occasionally reduce ACTH secretion in pituitary-dependent Cushing's syndrome, and that a single oral dose bromocriptine test fails to identify the patients who will benefit from this treatment.

Adrenocorticotropic Hormone↗
PubMed1983

Clotting changes in Cushing's syndrome: elevated factor VIII activity.

Thirteen women and 2 men affected by Cushing's syndrome were investigated. The following parameters were used: plasma and urinary cortisol levels, factor VIII assay (antigen, activity and von Willebrand factor) together with other coagulative assays. Samples were taken before surgery or before medical and/or radiation therapy and every 30-50 days after treatment and continued for 11 months. Cortisol and factor VIII were increased before treatment and decreased slowly after treatment to become normal in 3-4 months. Other clotting tests did not show any significant changes. High plasma cortisol levels seem to stimulate the production of factor VIII. Patients with Cushing's syndrome often exhibit thromboembolic complications after surgery. The clotting abnormalities responsible for such complications may be due to increased factor VIII activities.

Adrenalectomy↗
PubMed1982

Increased factor VIII associated activities in Cushing's syndrome: a probable hypercoagulable state.

Thirteen women and 2 men affected by Cushing's syndrome were investigated. The following parameters were used: plasma and urinary cortisol levels, factor VIII assay (antigen, activity and von Willebrand factor) together with other coagulative assays. Samples were taken before surgery or before medical and/or radiation therapy and every 30-50 days after treatment and continued for 11 months. Cortisol and factor VIII were increased before treatment and decreased slowly after treatment to become normal in 3-4 months. Other clotting tests did not show significant changes. It seems that high plasma cortisol levels may stimulate the production of factor VIII. Patients with Cushing's syndrome often exhibit thromboembolic complications after surgery. It is likely that the clotting abnormalities responsible for such complications is the increased factor VIII activities level.

Blood Coagulation Disorders↗
PubMed1982

An in vitro stimulatory effect of indoleamines on aldosterone biosynthesis in the rat.

The effect of the indoleamines, serotonin, 5-methoxy-tryptamine, 5-methoxytryptophol and melatonin on aldosterone biosynthesis by rat adrenals in vitro has been studied. In all experiments incremental doses of each of the indoleamines tested produced a progressive increase in aldosterone secretion. Serotonin (10(-6) mol/l) produced a 5-fold increase in aldosterone secretion by isolated perfused rat zona glomerulosa cells obtained from animals on a normal sodium diet compared to the basal levels. Higher (9-fold) responses were elicited when the cells were from sodium deficient rats and lower (3-fold) when the rats were sodium loaded. 5-methoxytryptamine (10(-6) mol/l) was a more potent aldosterone agonist (8-fold increase) and the aldosterone response was similarly affected by change in sodium intake. Smaller responses were found when cells were stimulated by 5-methoxytryptophol (10(-4) mol/l, 3.5-fold) or melatonin (10(-4) mol/l, 3-fold). The dopamine agonist serotonin antagonist Lisuride completely inhibited the aldosterone response to 5-methoxytryptamine (10(-8) mol/l) and serotonin (10(-7) mol/l). These results suggest that pineal indoles could play a role in aldosterone biosynthesis and indicate that changes in sodium balance affect the aldosterone response to indoles in the same way as has been described for other aldosterone secretagogues.

5-Methoxytryptamine↗
PubMed1982

Peripheral and renal vein plasma renin activity in hypertensive urological patients.

Upright plasma renin activity (PRA) was measured in 112 patients suffering from urological diseases associated with hypertension, and was found to be predominantly low. In 40 cases with normal or elevated peripheral PRA, renal venous PRA was measured and their ratios calculated. There was a significant decrease of blood pressure in 14 patients who had undergone surgery and both ratios were significant. The patients whose blood pressure remained unchanged had no significant renal vein PRA ratios. However, one case with nonlateralising renal venous PRA ratios responded well to surgery. It is concluded that although peripheral vein PRA is of limited value in hypertension associated with urological diseases, the measurement of PRA in renal vein plasma offers, in a number of cases, useful prognostic information.

Adult↗
PubMed1982

Circadian secretion of ACTH, cortisol, and mineralocorticoids in Cushing's syndrome.

The behaviour of plasma levels of ACTH was studied in five untreated patients with pituitary-dependent Cushing's syndrome, with blood samples taken every half an hour for a total period of 24 hours; plasma cortisol, corticosterone, deoxycorticosterone (DOC) and aldosterone were also measured simultaneously. In all cases, above normal secretory impulses of ACTH and cortisol, at approximately the same height, were present throughout the day, while between these peaks the levels were in the normal range. Few peaks of ACTH and cortisol were simultaneous and rare secretory impulses of corticosterone, and deoxycorticosterone were in synchrony with those of ACTH or cortisol. DOC levels were found to have some peaks above normal levels while corticosterone levels presented rare elevated peaks during the day. Plasma aldosterone values on the other hand, were extremely low in all except in one case, where the variations may be interpreted as pure fluctuations. These findings confirm that: 1) In a number of cases, multiple samples of ACTH and cortisol (during the 24 hrs.) appear to be essential in order to distinguish pituitary-dependent Cushing's syndrome from normal; 2) In conditions of ACTH excess, DOC and corticosterone secretion seems to become progressively less ACTH-dependent as we proceed down the biosynthetic chain towards aldosterone, which is suppressed in most cases.

Adolescent↗
PubMed1981

Effect of angiotensin II and converting enzyme inhibitor (captopril) on blood pressure, plasma renin activity and aldosterone in primary aldosteronism.

1. Patients with idiopathic hyperaldosteronism (IHA) show a response of aldosterone to posture which is not present in patients with aldosterone-producing adenoma (APA). We have determined whether this could be explained by a different sensitivity to angiotensin II. 2. Angiotensin II was infused in gradually increasing doses in six patients with APA and in seven patients with IHA. No changes in aldosterone concentration were found at the end of each period in APA, whereas there was a significant increase in IHA; blood pressure rose by a similar extent in both groups. 3. In order to evaluate the role of endogenous angiotensin II, captopril, a converting enzyme inhibitor, was administered to six patients with APA and five patients with IHA at a dose of 75 mg/day for 1 week. There was a significant fall of mean blood pressure in IHA and only minimal changes in APA. Plasma renin activity and plasma in urinary aldosterone were unchanged in APA. In IHA there was a small increase in upright plasma renin activity and a slight decrease in both plasma and urinary aldosterone, but these changes were not significant. 4. These findings further support the idea that idiopathic hyperaldosteronism is a clinical state different from that occurring in primary aldosteronism due to adenoma, and may be more closely related to essential hypertension.

Aldosterone↗
PubMed1981

Effect of metoclopramide on plasma aldosterone in normal subjects, primary aldosteronism and hypopituitarism.

The behaviour of plasma renin, aldosterone, cortisol and prolactin after administration of a drug with antidopaminergic action, metoclopramide, was evaluated in 6 normal subjects, 8 patients affected by primary aldosteronism and in 5 patients affected by anterior hypopituitarism. In the first two groups, besides the predictable increase of prolactin under metoclopramide, a significant aldosterone increase was noted. Cortisol remained unchanged, and PRA was not significantly increased. A similar pattern of aldosterone, cortisol and PRA was also found in patients with hypopituitarism. However, the plasma prolactin did not increase in this group. The comparative examination of three groups of patients leads us to conclude that aldosterone increase is not imputable to ACTH, renin or to prolactin. This may be explained by a possible direct effect of the antidopaminergic drug at the adrenal level, which is more likely than an effect through some yet undetermined factor.

Aldosterone↗
PubMed1981

Effects of two different angiotensin II antagonists on aldosterone secretion by isolated perfused rat zona glomerulosa cells.

Isolated perfused rat zona glomerulosa cells have been used to determine the specificity of the angiotensin II antagonists, [Sar1,Ala8]angiotensin II and [Sar1,Ile8]angiotensin II. Both antagonists inhibited the aldosterone response to angiotensin II but did not affect serotonin- or potassium-induced aldosterone secretion. However, in contrast to [Sar1,Ala8]angiotensin II, [Sar1,Ile8]angiotensin II inhibited the aldosterone response to ACTH. These results suggest that there are differences in the specificity of these two analogs and that studies with [Sar1,Ile8]angiotensin II and its effect on aldosterone secretion should be interpreted with caution.

1-Sarcosine-8-Isoleucine Angiotensin II↗