Biomedical subjects

S Rocco

Publications and source records attributed to S Rocco.

At least 19 recordsLinked to original sources

PubMed1998

Sodium regulating hormones at high altitude: basal and post-exercise levels.

High altitude (HA)-induced diuresis is associated with marked changes in sodium and water regulating hormones, particularly the renin-angiotensin-aldosterone system (RAAS) and atrial natriuretic hormone (ANH). These hormones are also strongly stimulated by physical exercise, which is a major component of daily activity at HA. In spite of the numerous studies in literature, a clear relationship between hormonal changes, HA diuresis, and physical exercise has not yet been established. We therefore evaluated the response of sodium regulating hormones to exhaustive exercise in a group of seven males exposed to prolonged HA hypoxia. The study was divided into four phases: sea level (SL1), after 7 (P1) and after 21 (P2) days at 5050 m (Italian National Research Council Pyramid Laboratory, Nepal), and back at sea level (SL2). At each phase plasma hematocrit (Ht), total body water (TBW), 24-hr sodium excretion (uNa), and urinary volume (uV) were evaluated together with PRA, plasma aldosterone, and ANH, in samples drawn basally from patients in upright position, and at the end of graded step-wise (30 W/2 min) maximal exercise. Levels of uNa and uV were raised at P1 and then declined at P2, with a parallel decrease in TBW and an increase in Ht. Basal PRA and aldosterone levels were suppressed both at P1 and P2 (from 1.9 +/- 0.4 to 0.08 +/- 0.03 and 0.5 +/- 0.1 ng/mL/3 h, and from 7.9 +/- 1.8 to 3.9 +/- 0.4 and 4.5 +/- 0.4 ng/dL, respectively; P < .05). Exhaustive exercise at HA did not induce any significant response in PRA and aldosterone, unlike SL1. Otherwise at P1 ANH levels remained unchanged both basally and during exercise, while at P2 they decreased significantly vs. SL1, both basally and after exercise (from 13.3 +/- 5.7 to 3.5 +/- 1.2 and from 40.2 +/- 10.2 to 17.5 +/- 8.3, respectively; P < .05). Our data show that PRA and aldosterone levels were constantly suppressed at HA and were unresponsive to exercise, whereas the ANH response was significantly stimulated during acute HA exposure, but not during chronic exposure. This suggests that hypoxia-induced chemoreceptor stimulation may cause the natriuretic phenomenon through direct suppression of the RAAS.

Adrenocorticotropic Hormone↗

PubMed1998

Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis.

OBJECTIVE: To investigate the safety and pharmacokinetics of a 28 day continuous subcutaneous infusion of recombinant human relaxin in patients with systemic sclerosis with diffuse scleroderma. METHODS: Thirty patients with stable diffuse scleroderma of moderate severity received recombinant human relaxin at 6, 12, 50, 100, and 200 microg/kg/day or placebo in a double blind, sequential panel, dose escalation study. RESULTS: All patients completed 28 days of study treatment. Steady state concentrations of serum relaxin were achieved by the 3rd day of infusion and were dose proportionate. Patients receiving 200 microg/kg/day achieved levels about 50-fold those of normal pregnancy. Pharmacokinetics of relaxin were nonlinear with hyperbolic increases of both t1/2 and volume of distribution and parallel decrease of elimination rate coefficient. An elimination transport system was suggested with saturation at serum relaxin concentration of 45 ng/ml. Adverse events included local infusion site rash and pain, minor bleeding episodes, and decreased hemoglobin concentration (mean reduction 1.1 g/dl). Standard measures of scleroderma were unchanged, although global assessment favored relaxin over placebo. CONCLUSION: Recombinant human relaxin in the doses used was safe and well tolerated. Longer term controlled trials are warranted to define the potential efficacy of relaxin in patients with diffuse scleroderma.

Adult↗

PubMed1997

Angiotensin II receptors in cortical and medullary adrenal tumors.

Several pieces of evidences suggest that angiotensin II (Ang II) has mitogenic effects, and a link between Ang II receptors and adrenal tumors can be suggested. In various adrenal tumors, aldosterone-producing adenoma (APA), Cushing's adrenal adenomas (Cush), pheochromocytomas (Pheo), and adrenal carcinomas, we studied the density, affinity, and subtype of Ang II receptors. Ang II binding was tested in cell membrane homogenates. [125I]Ang II was used as ligand, and Losartan and CGP 42112 were used as selective Ang II type 1 and type 2 antagonists, respectively. In APA, Ang II receptor density was 178.5 +/- 82.7 fmol/mg: however, due to the high degree of variability, the receptor density was not significantly higher than that in nontumorous adrenal cortex (59.3 +/- 8.4 fmol/mg). In Cush, the receptor density (27.6 +/- 8.2 fmol/mg; P < 0.05) was significantly lower than that in controls, whereas in Pheo and cortical carcinoma, Ang II binding was very low and in several cases almost undetectable. There was no remarkable difference in the Ang II receptor affinity among all tissues tested. The ratio between type 1 and type 2 Ang II receptors showed a large prevalence of type 1 in controls, APA, and three cases of Cush; in two cases of Cush, this ratio was reversed. In conclusion, our data indicate that Ang II receptors are normally expressed in APA and can also be detected in Cush, whereas they have a very low density in Pheo and adrenal carcinoma. Therefore, Ang II receptors are not involved in the lack of response to Ang II that is characteristic of APA; additionally, a reduction of Ang II receptors can be associated with dedifferentiation or malignancy of adrenal tumors. Further investigation of the expression and functional characterization of Ang II receptors is required to better clarify their possible role in adrenal tumorigenesis.

Adrenal Cortex↗

PubMed1997

Interleukin-6 receptor antagonists inhibit interleukin-11 biological activity.

The IL-6 receptor system comprises two functionally different chains: a binding chain (IL-6R) and a signal-transducing chain (gp130). The IL-6/IL-6R complexes associate with gp130, induce its dimerization and signal transduction. When IL-6 is complexed to IL-6R, two distinct sites of IL-6 are able to bind gp130. Other cytokines-oncostatin M (OM), leukemia inhibitory factor (LIF) or ciliary neurotrophic factor (CNTF) also use the gp130 transducer and induce its heterodimerization with LIF receptor (LIFR). A series of IL-6 mutants have been generated which function as IL-6 receptor antagonists (IL-6RA). These IL-6RA carried substitutions that increased their affinity with IL-6R and abolished 1 or the 2 sites of interaction with gp130. All the IL-6RA inhibited wild-type IL-6. The IL-6RA with one mutated binding site to gp130 inhibited IL-11 activity. They did not affect those of CNTF, LIF and OM, even when used at a very high concentration at which virtually all membrane IL-6R were bound to IL-6RA. IL-6RA with two mutated gp130 binding sites did not affect IL-11, CNTF, LIF or OM activities. The results indicate that the interaction of one gp130 chain with IL-6R/IL-6R complexes inhibited further the dimerization of gp130 induced by IL-11/IL-11R but not its heterodimerization with LIFR. Thus these IL-6RA can also function as IL-11 antagonists.

Antigens, CD↗

PubMed1996

Two different dosages of yeast derived recombinant hepatitis B vaccines: a comparison of immunogenicity.

The efficacy of a 10 or 20 micrograms antigen load of HB recombinant vaccines is still being debated. A comparison of anti-HBs titres in two groups of healthy subjects vaccinated by the same schedule (0, 1 and 6 months) employing recombinant HB vaccines with different antigen loads, 20 micrograms (group A, 251 subjects) and 10 micrograms (group B, 256 subjects) was carried out. A seroprotection rate of 99.6 and 99.2% was observed for group A and group B, respectively, at the end of primary immunization. No statistically significant difference in seroprotection rate was observed. Group A showed significantly higher GMTs than group B for all age groups and for both sexes except for males above 25 years. The difference was more marked for younger age groups and for the female sex. These data support the higher immunogenicity of vaccine with 20 micrograms antigen load as compared to vaccines with 10 micrograms antigen load.

Adolescent↗

PubMed1996

Blood cell flow cytometry in paroxysmal nocturnal hemoglobinuria: a tool for measuring the extent of the PNH clone.

The membrane expression of nine glycosyl phosphatidyl inositol (GPI)-linked molecules was analyzed by flow cytometry on circulating cells from 18 patients affected by paroxysmal nocturnal hemoglobinuria (PNH). The results allowed us to select CD66b, CD14, CD59, CD24 and CD59 monoclonal antibodies as the most suitable reagents for discriminating between normal and PNH cells in PMN, monocytes, RBC and B or T lymphocytes, respectively. In order to assess whether the analysis of distinct cell populations could provide differential information on the extent of the disease, we compared the proportion of residual normal cells in RBC, monocyte and PMN populations. The mean percentage of unaffected cells was higher in RBC as compared to PMN (50.5 +/- 18.7 vs 17.7 +/- 19.7, P < 0.0001). The proportion of normal PMN was, in turn, significantly greater than that of normal monocytes (17.7 +/- 19.7 vs 8.7 +/- 11.0; P < 0.05). The percentage of CD14+ monocytes was directly related to Hb concentration and platelet (Plt) count, and inversely to percent lysis at the Ham's test. The percentage of CD66b+ PMN was directly related to Plt count and Hb level, while the percentage of CD59+ RBC was associated, in an inverse fashion, only to the Ham's test. No significant correlation was found between cell marker expression and PMN count, reticulocytosis, bilirubin and serum LDH. By dividing the patients into two groups, according to high (> 10 percent) or low (< 10 percent) percentage of CD14+ monocytes, a statistical analysis showed that the main hematological parameters were significantly different.

Adult↗

PubMed1996

Echo Doppler color flow (EDCF) evaluation of vascular pathology in pediatric age groups.

Although rarely observed, vascular diseases in children constitute a complex clinical problem. Until recently the diagnostic approach to infant vascular diseases was based on invasive methods such as arteriography, but now the use of ultrasonographic methods such as Doppler c.w. and Echo Doppler Color Flow (EDCF) in angiology can offer new and interesting application even in the pediatric age range. In the present study 15 children affected by vascular diseases (eight with arteriovenous fistulas (AVF), two with pseudoaneurysms, and five with angiomas or cysts) either of iatrogenic or congenital etiology, were examined by Doppler c.w. and EDCF. In three additional cases a suspected vascular disease was not confirmed. The data obtained by Doppler c.w. and EDCF proved useful to perform a preoperative diagnosis; however some diagnostic criteria differed from those described in adulthood, as in the AVF cases, for instance, we observed the prevalence of indirect signs such as alterations of venous flow, and the presence of "multicolored speckled mass" and of "the spreading of the color in extravasal space" rather than a direct connection between an artery and a vein. Also pseudoaneurysms were easily detected by EDCF. In two cases of congenital AVF, the diagnosis was confirmed by arteriography. Surgery was performed in 9 children, 7 with AVF and 2 with pseudoaneurysm; in all cases, the vascular defect detected by ultrasonography was visualized and corrected. In 7 cases EDCF was also used in the follow-up. In conclusion this study suggests a possible more extensive use of ultrasonographic methods in the diagnostic approach to vascular diseases in pediatric age groups, and points out their validity in screening very young patients and in their surgical follow-up.

Arteriovenous Fistula↗

PubMed1995

Long-term treatment of mineralocorticoid excess syndromes.

Recognition of the pathogenesis of secondary forms of hypertension is often considered the key to appropriate choice of treatment. We here present the results of a prolonged clinical follow-up (from 1 to 20 years) of a large number of patients with mineralocorticoid excess syndromes (MES), including over 100 patients with primary aldosteronism (PA), 3 cases with dexamethasone-suppressible aldosteronism (DSA), 3 cases of apparent mineralocorticoid excess (AME) Type II, and 4 patients with 17-hydroxylase deficiency (17OHDS). The patients with PA have been divided in two subgroups, one of 69 cases followed between 1973 and 1982, and the second of 37 patients studied between 1983 and 1992; 33 further cases were not evaluated due to poor compliance. In group I, 26 patients underwent surgery (23 unilateral adenoma, 1 primary hyperplasia, 2 bilateral nodular hyperplasia); at 5 years 50% had normal blood pressure, 25% had mild hypertension and 25% had moderate to severe hypertension. Forty-three patients with either adenoma (APA) or idiopathic aldosteronism (IHA) received long-term spironolactone treatment. Among them, 13 required the addition of thiazide and/or beta-blockers, while 13 were switched to an amiloride/thiazide combination (+/- beta blockers) due to side-effects to spironolactone (gynecomastia 6/20 males, menstrual upset or breast pain in 7/23 females). In group II, 12 patients underwent surgery (11 adenoma, 1 primary hyperplasia) with a similar outcome at 3 years as in group I; 25 patients were put on either K canrenoate (11) or Ca++ channel blockers (14) with or without KCl supplementation; in 8 cases these two drugs were combined according to blood pressure levels achieved during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Hyperplasia, Congenital↗

PubMed1995

Morphology and function of the adrenal zona glomerulosa of transgenic rats TGR [mREN2] 27: effects of prolonged sodium restriction.

Heterozygous female transgenic rats for the murine Ren-2 gene (TGR) display a high blood pressure, together with a low kidney and high adrenal renin content. The effects of prolonged sodium restriction on the morphology and secretory activity of adrenal zona glomerulosa (ZG) of TGR and their age- and sex-matched Sprague-Dawley control rats (SDR) were investigated. Under basal conditions, TGR had a moderately hypertrophic ZG, that showed a significantly higher secretion of 18-hydroxylated (18OH) steroids: 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); ZG cells of TGR showed angiotensin II (AII)-binding site concentrations and ALDO secretory responses to AII similar to those of SDR ZG cells. Prolonged sodium restriction increased plasma ALDO level in both SDR and TGR, and significantly raised the volume of ZG. ZG hypertrophy was due to the increase in both the number and average volume of its parenchymal cells. The secretion of 18OH-steroids was markedly enhanced in both groups of rats; however, in TGR this rise was exclusively due to increases of 18OH-DOC and 18OH-B, while in SDR also ALDO production was enhanced. The yield of non-18OH-steroids was not affected. 11-Dehydrocorticosterone production was not changed in SDR, but doubled in TGR. ZG cells of sodium-restricted SDR and TGR displayed similar increases in their AII-binding site concentration and ALDO secretory response to AII. In conclusion, our present findings confirm that TGR possess a hypertrophic ZG and an elevated secretory capacity o 18OH-steroids, but show only slight differences in ZG and ZG-cell responses to prolonged sodium deprivation.

Animals↗

PubMed1995

Bacterial lipopolysaccharide stimulates glucocorticoid secretion in hypophysectomized rats.

The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats. Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after the injection. The stress evoked by the vehicle i.p. injection provoked significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but not in Hx animals. In intact rats, LPS enhanced (over the respective control value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at 120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was completely annulled, in both intact and Hx rats, by the simultaneous administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting peptide that are competitive inhibitors of CRH and ACTH, respectively. The hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis in rats, by stimulating not only the central (hypothalamo-pituitary), but also the peripheral (intra-adrenal) branch of the CRH/ACTH system.

Adrenocorticotropic Hormone↗

PubMed1995

[Primary hyperaldosteronism].

The diagnosis of primary aldosteronism (PA) is based on the finding of the combination of elevated urinary and/or plasma aldosterone and suppressed renin activity in patients with hypertension and hypokalemia. However, PA consists in a number of subsets, and diagnostic criteria for a correct identification of surgically remediable forms are of great interest. The methods and the results concerning our series of 113 patients with primary aldosteronism are presented in this review. Aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were the most frequent forms, 51% and 44% respectively. They had similar BP levels, but hypokalemia was most frequently found in APA. Urinary and upright plasma aldosterone were similar, but supine plasma aldosterone was lower in IHA. Plasma aldosterone response to upright posture and angiotensin II infusion was absent in most cases of APA and present in IHA, but occasionally renin-responsive adenoma were found. Captopril failed to decrease plasma aldosterone in most patients with APA, and in a subgroup of patients with IHA. Patients with adenoma had also higher values of the aldosterone precursor 18-OH-B, and of atrial natriuretic peptide (ANP), probably as a consequence of a greater degree of volume expansion. Among morphological studies, CT scan and adrenal radio-cholesterol scintiscan provided similar results (85% accuracy): adrenal vein catheterization clarified almost all the remaining cases. Among the subsets of PA, 3 familiar cases of dex-suppressible hyperaldosteronism were recognized, with characteristically high levels of aldo, 18-OH-B, 18-OH-cortisol and 18-oxo-cortisol, due to the genetic abnormalities of the 11-18 hydroxylase system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1994

Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study.

Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.

Adrenocorticotropic Hormone↗

PubMed1994

Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF.

The effect of SRIF and its antagonist cyclo(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr magnitude of Bzl)(SRIF-A) were studied in sham-operated and bilaterally adrenalectomized rats bearing ACTH- and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. SRIF-A (10(-5) M) completely annulled SRIF (10(-6) M)-induced inhibition of ANG-II (10(-8) M)-evoked rise in aldosterone (ALDO) secretion by both dispersed zona glomerulosa (ZG) cells and autotransplant slices. A 7-day intraperitoneal infusion with SRIF (0.3 nmol.kg-1.min-1) significantly lowered plasma ALDO concentration (PAC) in both groups of animals, without affecting plasma renin activity and the plasma levels of ACTH and corticosterone. This treatment caused a marked atrophy of adrenal ZG and its parenchymal cells (without inducing any significant change in the zona fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant slices from SRIF-infused rats evidenced a notable decrease in both their basal and maximally ACTH- or ANG-II-stimulated ALDO production. The simultaneous infusion of rats with SRIF-A (3 nmol.kg-1.min-1) completely reversed all these effects of SRIF. The prolonged infusion with SRIF-A alone caused, in sham-operated rats, a marked increase in PAC and a significant hypertrophy of ZG and ZG cells; basal and maximally-stimulated ALDO secretion of dispersed ZG cells was also notably raised. Conversely, SRIF-A infusion did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous SRIF is specifically involved in the negative control of the secretion and growth of the rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to SRIF but not to SRIF-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal zona medullaris may be the source of endogenous SRIF regulating ZG function.

Adrenal Cortex↗

PubMed1994

Glucose phosphate isomerase (GPI) "Morcone": a new variant from Italy.

Here we report the 4th Italian case of glucose phosphate isomerase (GPI) deficiency. The propositus is a young man suffering from chronic haemolytic anaemia since birth with occasional transfusion requirement. Biochemical characterization of the defective enzyme revealed increased affinity for F-6-P, decreased affinity for G-6-P and marked thermoinstability. Electrophoretic mobility appeared normal. GPI from both parents showed similar but less pronounced biochemical alterations. The variant described here seems to be different from those previously reported. Thus, we propose the provisional name of GPI "Morcone".

Adult↗

PubMed1993

Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats.

Within two weeks, hypophysectomy induced in rats a striking decrease in the level of circulating ACTH (the concentration of which was at the limit of sensitivity of our assay system), coupled with a net reduction in the plasma corticosterone concentration and an evident adrenal atrophy. Zona fasciculata, the main producer of glucocorticoids, was decreased in volume, due to a lowering in both the number and average volume of its parenchymal cells. Subcutaneous ACTH infusion (0.1 pmol.min-1), administered during the last week following hypophysectomy, restored the normal blood level of ACTH and completely reversed all effects of hypophysectomy on the adrenals. Subcutaneous infusion for one week with alpha-helical-CRH or corticotropin-inhibiting peptide (1 nmol.min-1), which are competitive inhibitors of CRH and ACTH, evoked a further significant lowering of plasma corticosterone concentration and markedly enhanced adrenal atrophy in hypophysectomized rats. These findings strongly suggest that an extrahypothalamic pituitary CRH/ACTH system may be involved in the maintenance of the growth and steroidogenic secretory activity of the rat adrenal cortex.

Adrenal Glands↗

PubMed1993

Arginine-vasopressin release mediates the aldosterone secretagogue effect of neurotensin in rats.

Acute and chronic systemic administrations of neurotensin (NT) and arginine-vasopressin (AVP) significantly increases plasma aldosterone concentration (PAC) in rats. Deamino-Pen1, Val4, D-Arg8-vasopressin (AVP-A), a potent AVP antagonist, completely reversed both acute and chronic aldosterone secretagogue actions of NT and AVP. AVP-A acute administration did not affect basal PAC, while chronic AVP-A treatment significantly lowered it. Taken together our findings suggest that both NT and AVP exert a marked aldosterone secretagogue effect in rats, and that the mechanism underlying NT action may involve the stimulation of AVP release. Moreover, they indicate that endogenous AVP plays an essential role in the maintenance of the mineralocorticoid secretory capacity of rat zona glomerulosa.

Aldosterone↗

PubMed1993

Differential diagnosis in primary aldosteronism.

The diagnosis of primary aldosteronism (PA) is based on the finding of the combination of elevated urinary and/or plasma aldosterone and suppressed renin activity in patients with hypertension and hypokalemia. However, PA consists of a number of subsets, and diagnostic criteria for a correct identification of surgically remediable forms are of great interest. The methods and the results concerning our series of 113 patients with PA are presented in this review. Aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were the most frequent forms, 51 and 44%, respectively. They had similar blood pressure levels, but hypokalemia was most frequently found in APA. Urinary and upright plasma aldosterone were similar, but supine plasma aldosterone was lower in IHA. Plasma aldosterone response to upright posture and angiotensin II infusion was absent in most cases of APA and present in IHA, but occasionally renin-responsive adenoma were found. Captopril failed to decrease plasma aldosterone in most patients with APA, and in a subgroup of patients with IHA. Patients with adenoma also had higher values of the aldosterone precursor 18-hydroxy-corticosterone, and of atrial natriuretic peptide, probably as a consequence of a greater degree of volume expansion. Among morphological studies, CT scan and adrenal radiocholesterol scintiscan provided similar results (85% accuracy): adrenal veins catheterization clarified almost all the remaining cases. Among the subsets of PA, 3 familiar cases of dexamethasone-suppressible hyperaldosteronism were recognized, with characteristically high levels of aldosterone, 18-hydroxy-corticosterone, 18-hydroxy-cortisol and 18-oxo-cortisol, due to the genetic abnormalities of the 11-18 hydroxylase system. Isolated cases of primary adrenal hyperplasia (with all functional tests resulting compatible with APA, but no tumour at surgery) and aldosterone producing carcinoma (1 case) have also been reported in the present study.

Diagnosis, Differential↗

PubMed1993

Effects of a calcium antagonist on the pituitary-adrenal axis.

It has been proposed that calcium is involved, as second messenger, in the regulation of various pituitary hormones including ACTH. Several evidences indicate that calcium-entry blockers agents (i.e. nifedipine) inhibit oCRH-dependent ACTH stimulation "in vitro". To further investigate these aspects we tested the effects of a calcium antagonist nitrendipine on basal and oCRH-stimulated ACTH secretion, in 6 hypertensive patients, with normal hypothalamus pituitary adrenal axis. Nitrendipine 20 mg per os once daily for 30 days, was efficacious in lowering blood pressure but did not modify ACTH and cortisol response to oCRH (200 micrograms i.v.), in spite of a minor inhibitory effect on the concomitant aldosterone response. These data indicate that ACTH secretion is not significantly modified by calcium antagonists, which can exert a detectable effect on adrenal zona glomerulosa.

Adrenocorticotropic Hormone↗