Biomedical subjects

F Fallo

Publications and source records attributed to F Fallo.

At least 55 records · Page 3Linked to original sources

PubMed1997

Coexistence of aldosteronoma and contralateral nonfunctioning adrenal adenoma in primary aldosteronism.

A case of primary aldosteronism is presented in which computed tomography showed bilateral adrenal tumors. Adrenal scintigraphy during dexamethasone suppression revealed bilateral radiotracer uptake, with markedly predominant visualization of the left side. The left adrenal gland was removed, and an aldosterone-producing adenoma was confirmed by histologic examination. Fifteen months after surgery, serum potassium and plasma aldosterone were normal, and a marked decrease of blood pressure was observed, indicating that the right adrenal tumor was a benign nonfunctioning mass. Unilateral adrenalectomy on the side of the scintigraphically predominant lesion reversed the clinical syndrome of primary aldosteronism.

Adenoma↗

PubMed1997

Autocrine-paracrine role of endothelin-1 in the regulation of aldosterone synthase expression and intracellular Ca2+ in human adrenocortical carcinoma NCI-H295 cells.

The role played by endothelin (ET-1) and its receptor subtypes A and B (ET(A) and ET(B)) in the functional regulation of human NCI-H295 adrenocortical carcinoma cells has been investigated. Reverse transcription-PCR with primers specific for prepro-ET-1, human ET-1 converting enzyme-1, ET(A), and ET(B) complementary DNAs consistently demonstrated the expression of all genes in NCI-H295 cells. The presence of mature ET-1 and both its receptor subtypes was confirmed by immunocytochemistry and autoradiography, respectively. Aldosterone synthase (AS) messenger RNA was also detected in NCI-H295 cells, and AS gene expression was enhanced by both ET-1 and the specific ET(B) agonist IRL-1620; this effect was not inhibited by either the ET(A) antagonist BQ-123 or the ET(B) antagonist BQ-788. A clear-cut increase in the intracellular Ca2+ concentration in NCI-H295 cells in response to ET(B), but not ET(A), activation was observed. In light of these findings, the following conclusions can be drawn: 1) NCI-H295 cells possess an active ET-1 biosynthetic pathway and are provided with ET(A) and ET(B) receptors; 2) ET-1 regulates in an autocrine/paracrine fashion the secretion of aldosterone by NCI-H295 cells by enhancing both AS transcription and raising the intracellular Ca2+ concentration; and 3) the former effect of ET-1 probably involves the activation of both receptor subtypes, whereas calcium response is exclusively mediated by the ET(B) receptor.

Adrenal Cortex Neoplasms↗

PubMed1997

Impaired potassium-stimulated aldosterone production: a possible explanation for normokalemic glucocorticoid-remediable aldosteronism.

Unlike other forms of primary aldosteronism, recent prospective studies have paradoxically revealed that glucocorticoid-remediable aldosteronism (GRA) is usually characterized by normal potassium (K+) levels. To evaluate this paradox we studied 10 GRA subjects and 14 healthy controls in two protocols: 1) the renal K+ excretory response to acute oral administration of 50 mmol K+ chloride and to fludrocortisone, 0.2 mg p.o. q12 h x 4 doses; and 2) the aldosterone response to administration of 50 mmol K+ chloride. The K+ excretion rate (KER) in GRA subjects (n = 6) at baseline (45.6 +/- 8.3 microEq/min), after K+ (134 +/- 34.2 microEq/min), and after fludrocortisone (100 +/- 35.0 microEq/min) was not significantly different than that seen in the control (n = 8) subjects (54.9 +/- 19.0, 154 +/- 35.5, 112 +/- 45.8 microEq/min, respectively). Thus the renal kaliuretic response to K+ ingestion and exogenous mineralocorticoid is normal in GRA. Serum aldosterone increased from 5.0 +/- 3.8 at baseline to a maximum of 13.1 +/- 6.6 ng/dL 60 min after K+ ingestion in control subjects (n = 7), but failed to increase in GRA subjects (n = 14), going from 8.7 +/- 3.8 (baseline) to 8.8 +/- 5.4 ng/dL at 60 min (P = 0.004 vs. control). The blunted aldosterone response to K+ in GRA in association with the sharp diurnal decline in aldosterone in this ACTH-regulated syndrome probably results in a milder degree of hyperaldosteronism compared with other forms of primary aldosteronism, thereby producing volume expansion with minimal renal K+ wasting.

Adult↗

PubMed1996

Effect of surgical treatment on hypertension in Cushing's syndrome.

The effect of a surgical cure of hypercortisolism on hypertension in 54 patients with Cushing's syndrome was assessed. The correlation between preoperative duration of hypertension and posttreatment blood pressure was significant (P < .01). Restoration of normal cortisol was associated with blood pressure normalization in 39 out of 54 cases. Duration of hypertension of patients with normalized blood pressure was significantly shorter than that of patients with persistent hypertension postoperatively (P < .0001). Duration of hypertension, ie, long-lasting exposure to increased cortisol, appears to be the determinant of persistent hypertension following successful surgery in Cushing's syndrome.

Adolescent↗

PubMed1996

Effects of taxol on the human NCI-H295 adrenocortical carcinoma cell line.

We investigated the effects of taxol, an antimicrotubule agent active in different cancers, on the human NCI-H295 steroid-secreting adrenocortical carcinoma cell line. Cells were incubated for 48, 72 or 96 h with taxol 10(-10)-10(-4) M. Cell viability was evaluated by MTT assay with IC50 calculation. Apoptosis was investigated by measuring DNA fragmentation with ELISA assay after cell exposure to taxol at IC50 for 24 h. For secretion studies, aldosterone, cortisol, testosterone and dehydroepiandrosterone-sulphate (DHEA-S) were measured by RIA in the conditioned medium after 96 h exposure to taxol 10(-10)-10(-6) M, and expressed as percentage of steroid production by control cells. By MTT, taxol induced a dose-dependent inhibition of cell proliferation, with ICs50 at 72-96 h corresponding to blood levels achieved in vivo in patients with other types of cancer. Nuclear fragmentation, morphologically confirmed at electron microscopy, showed a 4-fold increase after exposure to taxol. With 10(-6) M taxol, aldosterone decreased to 48%, cortisol to 61%, testosterone to 76% and DHEA-S to 89% of steroid production by control cells. Taxol is an effective cytotoxic and antiproliferative agent in a human adrenocortical steroid-secreting carcinoma cell line. Apoptosis induced by the drug is involved in neoplastic cell death.

Adrenal Cortex Neoplasms↗

PubMed1996

Aldosterone-producing adenomas do not contain glucocorticoid-remediable aldosteronism chimeric gene duplications.

In glucocorticoid-remediable aldosteronism (GRA) a chimeric gene has been described with the activity of aldosterone synthase, but the promoter of 11 beta-hydroxylase leading to ectopic expression of aldosterone synthase activity in the zona fasciculata. Similar to GRA, in aldosterone-producing adenomas (APA), the primary regulation of aldosterone production is ACTH, and there is increased production of the 18-oxygenated cortisol compounds, 18-oxocortisol and 18-hydroxycortisol. Because of these hormonal similarities, we tested whether a chimeric GRA-like gene was present in APA from 11 patients. A GRA-like chimeric gene was not found in the DNA from these tumors and, therefore, is not the mechanism responsible for hyperaldosteronism in APA.

Adenoma↗

PubMed1996

Risk factors and long-term outcome in pituitary-dependent Cushing's disease.

Although transphenoidal pituitary microsurgery has become the treatment of choice in Cushing's disease, other procedures, such as bilateral adrenalectomy and pituitary irradiation, are currently in use in its management. Indeed, no treatment has proven to be fully satisfactory for this condition. The rates of cure and recurrence after pituitary surgery or irradiation and the incidence of Nelson's syndrome after bilateral adrenalectomy are still open issues. A population of 162 patients with pituitary-dependent Cushing's disease was studied at 1 institution and had a follow-up of at least 2 yr after treatment (median, 7 yr). Patients were divided in subgroups according to the type of treatment: transsphenoidal pituitary microsurgery, bilateral adrenalectomy, or pituitary irradiation. Survival analysis was employed to characterize the outcome of treatment in each subgroup. Predictive factors for success of pituitary surgery were also evaluated. The estimated cumulative percentage of patients remaining in remission after successful pituitary surgery (n = 79) was 93.7% after 2 yr, 80.6% after 5 yr, 78.5% after 7 yr, and 74.1% after 10 yr. Of 8 risk factors examined, the following attained statistical significance: age, clinical severity, presence of major depression, pre- and posttreatment urinary cortisol levels, and posttreatment ACTH level. Pituitary surgery was successful in 79 of 103 patients (76.7%). Surgical failure was significantly associated with lack of pituitary adenoma and the clinical severity and presence of major depression. Of patients treated by bilateral adrenalectomy (n = 63), the estimated cumulative percentage remaining free of Nelson's syndrome was 87.1% after 2 yr, 79.3% after 7 yr, and 71.2% after 10 yr. The occurrence of Nelson's syndrome was significantly related to the pretreatment urinary cortisol level and the presence of pituitary adenoma at previous pituitary surgery. After cure by pituitary irradiation (n = 23), the estimated cumulative percentage of patients remaining in remission was 100% after 2 yr, 81.8% after 5 yr, 71.6% after 7 yr, and 65.1% after 10 yr. Previous pituitary surgery, although unsuccessful, appeared to be a protective factor for relapse. The results indicate that relapse after cure by either pituitary surgery or irradiation is a considerable clinical problem that increases over time. Our findings ascribe new importance to the clinical presentation of patients and indicate subgroups that are at high risk for relapse after pituitary surgery or irradiation and for developing Nelson's syndrome after bilateral adrenalectomy.

Adenoma↗

PubMed1996

Hormonal responses during various phases of autoimmune adrenal failure: no evidence for 21-hydroxylase enzyme activity inhibition in vivo.

Adrenal autoantibodies (ACA) are markers of adrenal cortex involvement in idiopathic Addison's disease. Recently the 21-hydroxylase (21-OH) enzyme has been discovered to be the major autoantigen of the ACA. A potential role of these antibodies in determining adrenal failure by inhibition of the 21-OH has been recently postulated. To test this hypothesis, cortisol and aldosterone (final products of adrenal steroid synthesis) and 17-hydroxyprogesterone (17-OH-progesterone) (as a marker of 21-OH impairment) have been investigated in baseline conditions and after ACTH (1-24) stimulation test in a group of 42 patients positive for both ACA and 21-OH autoantibodies. Patients were divided into five groups according to the stages (0-4) of adrenal failure. With progression toward overt Addison's disease, baseline 17-OH-progesterone, cortisol, and aldosterone remained almost unchanged but with impairment of their responses to ACTH (1-24) stimulation. The 17-OH-progesterone/cortisol ration remained normal both in basal conditions and after stimulation at stages 0-3. At stage 4 (overt Addison's disease), this ratio increased in baseline condition with no changes after ACTH (1-24), probably because of persistent 17-OH-progesterone gonadal production. In conclusion, there was a progressive and concomitant impairment of the synthesis of all steroids tested over various phases of adrenal failure. The pattern of response of the 17-OH-progesterone/cortisol ratio to ACTH stimulation in patients with 21-OH autoantibodies was not consistent with the autoantibodies inhibiting the 21-OH activity. This suggests that the inhibiting effect of 21-OH autoantibodies on 21-OH activity is not usually evident in vivo.

Adrenal Gland Diseases↗

PubMed1995

Adrenocortical carcinoma: epidemiology and natural history.

Information about epidemiology, natural history and prognostic factors of adrenocortical carcinoma in Italy is extremely scarce. We report here 35 patients of adult age who were referred to our institution in the last two decades. Nine patients had non functioning, and 26 had functioning tumors. In non-functional tumors initial symptoms were abdominal pain in 90% of cases, fever, weakness, malaise, weight loss in 30%. Only one patient was asymptomatic. Of patients with functioning tumors, 18 presented with Cushing's syndrome, 6 with Cushing's syndrome and virilization, 1 with Cushing's syndrome and feminilization and 1 with hyperaldosteronism. Twenty-two of all cases (63%) had metastases at diagnosis; most frequent sites were lung, liver and distant lymph nodes. The results of tumor staging, according to MacFarlane system, were: stage I, 1 patient (3%); stage II, 10 patients (28%); stage III-IV, 24 patients (69%). Twenty-six out of 35 patients underwent removal of the mass with complete adrenalectomy. Twelve patients received mitotane alone; 8 mitotane and chemotherapy; 5 chemotherapy alone; 2 radiotherapy associated with mitotane or chemotherapy; 1 anthalgic radiotherapy. Survival time ranged from 1 to 108 months. One-year survival rate was 60%, and 5-year survival rate was 10%. Lower survival rate compared with that reported from other countries is probably related to the referring of patients at very advanced stages of disease. Early recognition and referral, in addition to optimization of therapeutic protocols by multicenter studies, may improve prognostic aspects.

Actuarial Analysis↗

PubMed1994

Disseminated nocardiosis in a patient with Cushing's syndrome.

Nocardia Asteroides infection may occur in corticosteroid treated patients. However, nocardiosis in the presence of endogenous Cushing's syndrome has been previously reported in rare cases. We report a patient with Cushing's syndrome from bilateral nodular adrenal hyperplasia, in whom a disseminated form of nocardiosis complicated his hypercortisolism.

Adult↗

PubMed1994

24-hour blood pressure profile in Addison's disease.

The purpose of this study was to evaluate the circadian blood pressure rhythmicity in patients with primary adrenal insufficiency. Ten newly diagnosed and untreated patients with Addison's disease, 17 addisonian patients (including the previous 10) following an adequate regimen of corticosteroid replacement therapy, and 15 healthy subjects as a control group were studied. Twenty-four-hour ambulatory blood pressure and heart rate were measured automatically every 30 min using a Takeda TM-2420 recorder. The runs test, used for detecting blood pressure diurnal rhythm, was compatible with a rhythm in 2 of 10 patients with untreated Addison's disease, in 13 of 17 patients with treated Addison's disease, and in 13 of 15 normals. Six of eight addisonian patients showing no evidence of blood pressure rhythm in the untreated state acquired circadian periodicity during therapy. An analysis of blood pressure readings by Fourier series with four harmonics showed that blood pressure mesor was lower in untreated than in treated addisonian and normal subjects (P < .05). The nocturnal fall was smaller for systolic and diastolic blood pressure in untreated than in treated addisonian and normal subjects (P < .05). Adrenocortical insufficiency is often characterized by loss of circadian blood pressure rhythm, and normal rhythm can be reestablished by replacement therapy. Lack of cortisol rhythm or persistent activation of the renin-angiotensin system and sympathetic tone may play a role in this phenomenon.

Addison Disease↗

PubMed1994

Patterns of ACTH response to oCRH in Cushing's disease: correlation with histological/immunocytochemical findings.

The most common lesion in Cushing's disease is an anterior pituitary adenoma. However, normal or hyperplastic corticotropic pituitary tissue has also been found in some cases. In an attempt to distinguish the patterns of ACTH response to oCRH in different forms of anterior pituitary hypersecretion, 17 patients with pituitary adenoma and 17 without pathological evidence of adenoma were studied. These patients underwent transsphenoidal pituitary surgery by the same surgeon and were retrospectively evaluated. The diagnosis of pituitary lesions was confirmed by microscopical and immunohistochemical studies. Patients without pituitary adenoma showed a higher and more prolonged mean plasma ACTH response than that observed in patients with pituitary tumors. In patients with pituitary adenoma, the peak ACTH response was observed within 30 min after oCRH administration, and was followed by a gradual decrease to basal levels in the following 30 min. In those cases in whom no pituitary adenoma was found, oCRH injection produced a marked increase in plasma ACTH levels during the first 60 min with a slower decline at the subsequent time points. The mean response curves of the two groups, analyzed by Beherens-Fischer nonparametric ANOVA, showed significant differences, either when they were compared globally (p < 0.01), or at single time points. Differences in ACTH response to oCRH stimulation support the hypothesis of different pathogenetic mechanisms leading to ACTH hypersecretion in Cushing's disease with and without pituitary adenoma.

Adenoma↗

PubMed1994

Early adrenal hypofunction in patients with organ-specific autoantibodies and no clinical adrenal insufficiency.

Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.

17-alpha-Hydroxyprogesterone↗

PubMed1994

Abnormality of aldosterone and cortisol late pathways in glucocorticoid-remediable aldosteronism.

Patients with glucocorticoid-remediable aldosteronism (GRA) possess a chimeric gene resulting from fusion of the genes encoding steroid aldosterone synthase and 11 beta-hydroxylase. In the adrenal zona fasciculata, this may lead to ectopic expression under ACTH control of aldosterone synthase activity and increased formation of cortisol C18 oxidation products. We assessed mineralocorticoid and glucocorticoid pathways in three patients with GRA. Baseline plasma progesterone, 17 alpha-hydroxyprogesterone, corticosterone, and cortisol were normal in all patients, whereas 11-deoxycorticosterone, aldosterone, and 11-deoxycortisol were above normal. The ratios of both corticosterone/11-deoxycorticosterone and cortisol/11-deoxycortisol were abnormally low, and decreased further 60 min after administration of ACTH-(1-24) (250 micrograms) as an i.v. bolus. A low corticosterone/11-deoxycorticosterone ratio is consistent with an increased aldosterone synthase activity forming aldosterone by corticosterone. Similarly, a decreased cortisol/11-deoxycortisol ratio could reflect enhanced cortisol C18 oxidation. Our findings are in agreement with a hyperfunction of the 11 beta-hydroxylase/aldosterone synthase complex in the adrenal zona fasciculata of GRA induced by the new chimeric gene.

Adrenocorticotropic Hormone↗

PubMed1994

Juxtaglomerular cell tumor of the kidney.

A juxtaglomerular cell tumor (JGCT) was found in a 40 year old woman. For 5 years she had mild hypertension, responding to classical anti-hypertensive treatment, then she became severely hypertensive. Two renal angiographies and a CT scan were reported as normal. A second CT scan and third selective renal angiography were diagnostic, associated with lateralization of renin in renal vein measurement. Light, electron microscopy and immunohistochemistry of the resected tumor confirmed the diagnosis of renin-secreting juxtaglomerular cell tumor of the kidney.

Adult↗

PubMed1994

Left ventricular structural characteristics in Cushing's syndrome.

The aim of the present study was to assess structural characteristics of the left ventricle by echocardiography in a group of patients with Cushing's syndrome compared with a control population. Eighteen patients with Cushing's syndrome and 18 controls, matched for sex, age, body weight, body surface area, blood pressure (BP) and duration of hypertension were investigated by M-mode (2-D derived) echocardiography. In each of the two groups, 11 of 18 subjects were hypertensive. Relative wall thickness (RWT) was above normal (> 0.45) in 11 (five normotensive and six hypertensive) of 18 patients with Cushing's syndrome and in two (hypertensive) of 18 controls. Left ventricular mass index was abnormal in three (one normotensive and two hypertensive) patients with Cushing's syndrome and in four hypertensive controls. All other systolic function indices were within normal and similar in both groups. No correlation was found between RWT and BP as well as between RWT and urinary cortisol levels in patients with Cushing's syndrome. A significant correlation was found between RWT and duration of disease. Echocardiography after successful surgery showed normalisation of RWT in five of six patients in whom it was previously abnormal. Our data suggest that time factor, i.e. long-lasting exposure to increased cortisol, rather than hormone or BP levels is the most relevant determinant of left ventricular concentric remodeling in patients with Cushing's syndrome.

Adolescent↗

PubMed1993

Response of hypertension to conventional antihypertensive treatment and/or steroidogenesis inhibitors in Cushing's syndrome.

OBJECTIVES: To evaluate the effect of conventional antihypertensive drugs and/or inhibitors of steroid production in the management of hypertension in Cushing's syndrome. DESIGN: A retrospective open clinical study with pre- and post-treatment assessment. SETTING: A university hospital, where patients were initially admitted and then followed-up in an ambulatory clinic over a period of 6 years. SUBJECTS: Forty consecutive hypertensive patients with Cushing's syndrome. INTERVENTIONS: Patients were divided into two groups according to the different management of hypertension. The first group (group 1) of 28 patients included those treated with antihypertensive drugs at full dose (diuretics, calcium antagonists, angiotensin converting enzyme [ACE] inhibitors, as single agents or in combination). The second group (group 2) of 12 patients received ketoconazole alone. MAIN OUTCOME MEASURES: Blood pressure variations compared to pre-treatment levels. RESULTS: Blood pressure normalization was obtained in four of the 28 patients of group 1. In 12 of the remaining patients, ketoconazole, an inhibitor of steroid production, was subsequently added and this normalized blood pressure in all but the one in whom cortisol was not decreased. In the 12 patients of group 2, ketoconazole alone lowered blood pressure within normal limits in all but one who had long-standing hypertension. CONCLUSIONS: In hypertensive patients with Cushing's syndrome, conventional antihypertensive therapy is mostly ineffective. Blood pressure response is satisfactory only after the restoration of normal cortisol levels, indicating the need for a specific treatment for hypertension in this disorder.

Adult↗

PubMed1993

Life events in the pathogenesis of Graves' disease. A controlled study.

Contradictory findings have been reported about a possible causal relationship of life stress to Graves' disease. We evaluated this issue by investigating the occurrence of stressful life events in the year before the first signs of disease onset, using methods that have been found to be valid and reliable in psychosomatic research. Seventy consecutive patients with Graves' disease and a control group of 70 healthy subjects, matched for sociodemographic variables, were studied. Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered to patients, not during the acute phase of illness but while on remission, by antithyroid drug treatment. Patients with Graves' disease reported significantly more life events compared to controls (p < 0.001). They also had more independent events (p < 0.001) and events that had an objective negative impact (p < 0.001) according to an independent rater, unaware whether the events had occurred in patients or controls. All categories of events were found to be significantly more frequent in patients suffering from Graves' disease than in controls. By rigorous methods (inclusion of patients with Graves' disease only, careful dating of the onset of symptoms, accurate event definition, delay of the interview upon disease remission, use of a blind rater for judging independence and objective negative impact), our results support the concept of an excess of life events in Graves' disease. Stressful life events may affect the regulatory mechanisms of immune function in a number of ways. Within the extreme complexity of the phenomena implicated in the pathogenesis of autoimmune thyroid hyperfunction, our findings emphasize the role of emotional stress.

Adolescent↗