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Biomedical subjects

M Boscaro

Publications and source records attributed to M Boscaro.

At least 109 records · Page 6Linked to original sources
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 report of an Italian family with heterozygous protein C deficiency.

A heterozygote protein C deficit was found in 4 members of the same family. The propositus is a 40 year old male with a clear thrombotic tendency. This included repeated thrombophlebitis of the right leg, and one episode of pulmonary embolism. Arterial thrombosis was not noted. The anticoagulant therapy undertaken by the patient appears to be of some benefit in the sense that no recurrence of thrombotic manifestations occurred. One brother and two nephews of the propositus, even though asymptomatic showed reduced levels of Protein C both as activity and antigen. The parallel reduction of Protein C activity and antigen points towards a "true" deficit of Protein C. The normal, although reduced, pattern in the crossed immunoelectrophoresis supplies further confirmation to this interpretation.

Adult↗
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

Increased factor VIII/vWf levels in patients with reduced platelet number.

Factor VIII/von Willebrand factor (VIII/vWf) related properties were studied in twenty six patients with thrombocytopenia. Fifteen patients were affected by idiopathic thrombocytopenic purpura (ITP) and 11 patients by thrombocytopenia of a different nature or non-ITP (n-ITP). All patients showed an enhancement of platelet associated IgG (PAIgG). A significant increase of factor VIII ristocetin cofactor (VIII R: RCoF) and factor VIII related antigen (VIII R:Ag) was found in ITP patients while normal values were observed for factor VIII coagulant (VIII:C). All factor VIII/vWf components, on the contrary, were increased in n-ITP group with a prevalence of VIII R:RCoF as observed in ITP group even though with lower mean values. Multimeric analysis of VIII/vWf demonstrated a higher concentration of all multimeric components, with major representation of higher molecular weight multimers (HMWM) in patients of both groups. Two patients were studied before and after improvement in platelet count. A decrease of vWf related properties (VIII R:RCoF and VIII R:Ag) concomitant with the increase in platelet count was found. In n-ITP patients a statistical correlation between VIII R:RCoF and PAIgG was also observed while no correlation was found between other factor VIII/vWf components and PAIgG both in ITP and n-ITP patients.

Adolescent↗
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

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↗
PubMed1987

ACTH response to corticotropin releasing hormone in Cushing's disease before and after ketoconazole: in vivo and in vitro studies.

Ketoconazole has been used as a palliative treatment of Cushing's syndrome, due to its ability to lower cortisol production. We evaluated the effects of ovine Corticotropin Releasing Hormone (oCRH) 100 micrograms i.v. on ACTH and cortisol levels in 6 patients with Cushing's disease before and after treatment with ketoconazole 600 mg/day. Both hormones increased after oCRH. During ketoconazole, cortisol was lowered to normal levels and its response to oCRH was impaired. After treatment, basal ACTH showed variable changes while the response to oCRH was markedly enhanced compared to that before ketoconazole. In vitro: In a continuous perfusion system of isolated anterior pituitary cells from rats or human anterior pituitary adenoma, producing ACTH, ketoconazole 10(-5)-10(-6) M showed no inhibitory effects on both basal or lisine-vasopressin and oCRH stimulated ACTH secretion. Our findings confirm the inhibitory action of ketoconazole on basal and stimulated cortisol secretion. No inhibition of ACTH levels was observed both in vivo and in vitro.

Adenoma↗
PubMed1986

Serum levels of calcitonin in Cushing's syndrome.

Serum levels of calcitonin (CT) were studied in 21 patients with Cushing's syndrome (CS), 18 females and 3 males aging from 16 to 59 years, and in 70 age and sex matched normal subjects. Patients with CS showed CT values significantly lower than those found in controls (9.9 +/- 5.0 pg/ml vs. 15.9 +/- 6.3 pg/ml, mean +/- SD; p less than 0.01), while no difference was observed in total serum calcium and phosphate and calcium corrected for albumin. No correlation between CT and serum calcium and phosphate, serum cortisol and urinary free cortisol was found. It is possible that low CT levels are involved in the pathogenesis of bone loss observed in CS.

Adolescent↗
PubMed1986

Effect of verapamil on the aldosterone-stimulating properties of metoclopramide: in vitro and in vivo studies.

The role of calcium in the regulation of aldosterone secretion has been recently clarified. Angiotensin II and potassium stimulate aldosterone secretion through a calcium-entry dependent mechanism, while ACTH action is both calcium and cyclic AMP dependent. To establish whether also the so-called aldosterone dopaminergic regulatory system is calcium-dependent we have studied, in vitro and in vivo, the effect of verapamil, a calcium entry blocker agent, on the aldosterone-stimulating properties of the antidopaminergic drug, metoclopramide. In the rat adrenal cells perfusion system, verapamil blocked both angiotensin II and metoclopramide-stimulated aldosterone. This effect on metoclopramide action seems to be present also in vivo in normal subjects: in fact aldosterone response was slightly but significantly reduced after pretreatment with verapamil. In conclusion the results suggest that also the dopaminergic system could regulate aldosterone secretion through calcium-mediated mechanisms.

Adrenal Glands↗
PubMed1986

Opioid modulation of normal and pathological human chromaffin tissue.

To evaluate whether opioid receptor blockade might modulate sympathetic-adrenal activity, we studied the effects of placebo or naloxone administration on plasma catecholamine (CA) levels in a group of 13 normal subjects and 15 hypertensive patients suspected to have a pheochromocytoma. Diagnostic evaluation confirmed the presence of pheochromocytoma in 9 patients. Among these, 4 had a unilateral epinephrine (E)-secreting tumor, 3 had bilateral E-secreting tumors due to multiple endocrine adenomatosis type IIa, and 2 had a unilateral norepinephrine (NE)-secreting tumor. In each subject studied, CA secretion was evaluated by calculating the area (0-30 min) under the plasma hormone curves after placebo or naloxone administration. In normal subjects naloxone caused a significant increase (P less than 0.005) of E secretion, whereas NE did not change. Similarly, in the group of hypertensive patients, E secretion increased after naloxone (P less than 0.01). In pheochromocytoma patients naloxone caused a significant increase in E (P less than 0.05) and NE (P less than 0.01) secretion from E-producing tumors but no increase in the patients with NE-secreting pheochromocytomas. The study suggests that CA secretion from normal and pathological chromaffin tissue is modulated by endogenous opioids; this modulation seems particularly evident in patients with E-secreting pheochromocytoma.

Adolescent↗
PubMed1986

Effect of ketanserin on the in vitro regulation of aldosterone.

Serotonin (5-HT) is known to be a potent stimulator of aldosterone release in vitro and, to a lesser degree, in vivo. Since ketanserin, a specific 5-HT2-receptor antagonist, decreases aldosterone levels in some hypertensive patients, we have performed in vitro experiments to elucidate the mechanism by which ketanserin interferes with aldosterone regulation. After collagenase dispersion, rat zona glomerulosa cells were either perfused and resuspended in Biogel or incubated in Earle's medium and bovine serum albumin. The cells were stimulated with serotonin, angiotensin II, potassium (K+) and adrenocorticotrophic hormone (ACTH) in the presence or absence of ketanserin. Ketanserin did not decrease baseline aldosterone secretion although it reduced the stimulatory capacity of serotonin and K+, and had a minimal effect on ACTH. Furthermore, we demonstrated that ketanserin is able to have a significant effect on the adrenal response to angiotensin II. These data indicate that antiserotoninergic agents may act directly at the level of the adrenal glomerulosa by interfering with specific serotoninergic receptors and modifying the adrenal sensitivity to angiotensin II and K+. The importance of these findings in the clinical use of these antihypertensive drugs remains to be established.

Adrenocorticotropic Hormone↗
PubMed1985

Further studies on the hypercoagulable state of patients with Cushing's syndrome.

Factors XII, XI, IX and VIII, plasminogen and alpha 2-antiplasmin levels were found to be increased in a group of patients affected by Cushing's syndrome. High activity of these coagulation factors could be due to their increased release and synthesis mediated by cortisol. A significant correlation between the main arterial pressure and either factor VIII antigen, ristocetin cofactor or factor XII activity was found. Moreover a similar correlation between factor XII activity and either factor VIII antigen or ristocetin cofactor was seen. In conclusion, the presence of a hypercoagulable state in Cushing's syndrome seems confirmed. Synergic release of factor XII and factor VIII from endothelium could be due to high blood vessel tone secondary to hypercorticism. Finally, decreased fibrinolytic activity was suspected according to plasminogen and alpha 2-antiplasmin increase.

Blood Coagulation Disorders↗