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Biomedical subjects

L Barzon

Publications and source records attributed to L Barzon.

35 records · Page 2Linked to original sources
PubMed2000

The diagnosis of Cushing's syndrome: atypical presentations and laboratory shortcomings.

In the last 3 decades, there have been several advances in understanding the pathogenesis of Cushing's syndrome and in testing for the diagnosis and differential diagnosis of its various forms. Advanced diagnostic techniques provide useful tools in discovering ectopic adrenocorticotropic hormone sources. However, the occurrence of unusual clinical presentations, laboratory shortcomings, and exogenous compound interference may lead to wrong conclusions. This article reviews the atypical presentations of hypercortisolism and some laboratory shortcomings that may confuse the diagnosis of Cushing's syndrome. Comments and suggestions are given with the aim of helping the clinician avoid diagnostic mistakes.

Cushing Syndrome↗
PubMed2000

New perspectives for gene therapy in endocrinology.

Gene therapy for endocrine diseases represents an exciting new type of molecular intervention that may be a curative one. Endocrine disorders that might be treated by gene therapy include monogenic diseases, such as GH deficiency and hypothalamic diabetes insipidus, and multifactorial diseases, such as diabetes mellitus, obesity and cancer. Premises seem promising for endocrine tumours, but many combined approaches of cell and gene therapy are foreseeable also for other endocrine disorders. This review outlines the principles of gene therapy, describes the endocrine disorders that might take advantage of gene transfer approaches, as well as the gene therapy interventions that have already been attempted, their major limitations and the problems that remain to be solved.

Animals↗
PubMed2000

Diagnosis and management of adrenal incidentalomas.

PURPOSE: The incidental discovery of adrenal masses has become a common clinical problem. We address current trends in clinical, endocrine, radiological and scintigraphic evaluation, and strategies for management of adrenal masses. A diagnostic and therapeutic algorithm is suggested. MATERIALS AND METHODS: A comprehensive review of the literature was performed using MEDLINE, bibliographies of select articles, current issues of peer reviewed general medicine, endocrinology, diagnostic imaging and surgical journals, and meeting abstracts of recent international congresses. RESULTS: Most adrenal incidentalomas are benign and nonhypersecreting but all should be evaluated to exclude from diagnosis hypersecretory syndromes or malignancy. In all cases hormonal screening for pheochromocytoma, hyperaldosteronism and subclinical hypercortisolism should be performed. Attenuation values on computerized tomography, chemical shift magnetic resonance imaging and scintigraphy reveal the nature of the mass in most cases. Fine needle aspiration biopsy should be reserved for cases suspected of extra-adrenal malignancy. CONCLUSIONS: A multidisciplinary approach, including hormonal screening, radiological evaluation and scintigraphy, is required to identify and remove adrenal masses with endocrine and oncological morbidity. Long-term morphofunctional followup is suggested for nonoperated cases.

Adrenal Gland Diseases↗
PubMed1999

Mutations in CYP11B1 gene converting 11beta-hydroxylase into an aldosterone-producing enzyme are not present in aldosterone-producing adenomas.

In the human adrenal cortex, cortisol and aldosterone are synthesized by the isozymes 11beta-hydroxylase and aldosterone synthase, respectively, encoded by the 93% identical CYP11B1 and CYP11B2 genes. In vitro mutagenesis of CYP11B1 complementary DNA, resulting in the replacement of CYP11B1 codons by those encoding the corresponding amino acid residues of CYP11B2 enzyme (exon 5, Ser288Gly; exon 6, Val320Ala), yields a complementary DNA encoding a mutant enzyme with an efficient aldosterone synthase activity. Identical somatic mutations in the CYP11B1 gene in vivo would produce a gene encoding an enzyme with C18 activity and that would preserve ACTH responsiveness due to the retained 5'-promoter in the mutated CYP11B1 gene. An ACTH-responsive aldosterone synthase activity of this type is commonly seen in patients with aldosterone-producing adenomas (APA). We examined the occurrence of mutations in exons 5 and 6 of the CYP11B1 gene in APA from 10 patients with primary aldosteronism. Patients were selected on preoperative evidence of a 50% or greater plasma aldosterone decrease after short term dexamethasone trial and no aldosterone response to upright posture. DNA from adenomas was amplified by PCR using two pairs of primers spanning the regions of CYP11B1 gene, i.e. exons 3-5 and exons 6-9, where mutations could be located. Targeted regions were screened for mutations by automated sequencing of PCR products. No point mutations of the CYP11B1 gene over the two regions examined were found in APA. This argues against involvement of mutations in the pathogenesis of ACTH-responsive APA.

Adenoma↗
PubMed1999

Risk factors and long-term follow-up of adrenal incidentalomas.

The natural course of adrenal incidentalomas and the risk that such lesions evolve toward hormonal hypersecretion or malignancy are still under evaluation. Of 246 consecutive patients with adrenal incidentaloma studied at our institution in the last 15 yr, 91 underwent surgery. Of the remaining patients, a group of 75 (52 females and 23 males; median age, 56 yr; range, 19-77 yr) with incidentally discovered asymptomatic adrenal masses (60 unilateral and 15 bilateral; median diameter, 2.5 cm; range, 1.0-5.6) was enrolled in an endocrine and morphological follow-up of at least 2 yr after diagnosis (median, 4 yr; range, 2-10). During follow-up, no patients developed malignancy; 9 showed mass enlargement, with appearance of a new mass in the contralateral gland in 2; 3 developed adrenal hyperfunction (overt Cushing's syndrome in 2, nonclinical hypercortisolism in 1); and 3 showed adrenal mass enlargement associated with adrenal hyperfunction (nonclinical hypercortisolism in 2, pheochromocytoma in 1). The estimated cumulative risks to develop mass enlargement and hyperfunction were 8% and 4%, respectively, after 1 yr, 18% and 9.5% after 5 yr, and 22.8% and 9.5% after 10 yr. Nine risk factors for adrenal mass enlargement or hyperfunction were arbitrarily selected and evaluated: sex, age, presence of obesity, hypertension, diabetes, abnormal endocrine tests, mass size, mass location, and scintigraphic uptake pattern. Three of them attained statistical significance: mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake by the mass at scintigraphy had relevance for the occurrence of adrenal hyperfunction, whereas the presence of endocrine test abnormalities at diagnosis had predictive value for mass enlargement. It is concluded that subtle hormonal abnormalities are risk factors for mass size increase, which is not a sign of malignant transformation. Both mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake, indicating higher risks of hyperfunction, should be considered to plan a more thorough endocrine follow-up.

Adolescent↗
PubMed1998

Effect of octreotide on 24-h blood pressure profile in acromegaly.

The aim of the study was to investigate the effect of octreotide, a somatostatin analog drug potentially able to inhibit growth hormone (GH), on the circadian blood pressure profile in a group of patients with acromegaly. Ten patients with GH-secreting pituitary adenoma were studied before and 6 months after treatment with subcutaneous octreotide 0.2 to 0.6 mg/day. Twenty-four hour blood pressure and heart rate were measured every 15 min at daytime (07:00 to 22:59) and every 30 min at nighttime (23:00 to 06:59) using a TM-2420 recorder. No correlation was found between GH levels and 24-h blood pressure in baseline conditions. Untreated patients had a significant nocturnal decrease of both systolic and diastolic blood pressure (P < .01), and all showed a circadian systolic or diastolic blood pressure rhythm. During octreotide treatment, 24 h as well as nighttime systolic and diastolic blood pressures significantly increased (P < .05), whereas daytime systolic and diastolic blood pressures did not change. Treated patients did not have a nocturnal decline in both systolic and diastolic blood pressures (P = NS), and eight lost their systolic or diastolic blood pressure rhythm. In conclusion, blood pressure circadian rhythm seems to be maintained in acromegaly. Octreotide treatment is associated with an increase of 24-h and nighttime blood pressure, and with loss of circadian blood pressure rhythm. Splanchnic vasoconstriction by this drug, shifting blood to peripheral vessels, may explain this phenomenon.

Acromegaly↗
PubMed1998

Zona fasciculata-like histotype and aldosterone response to upright posture are not related in aldosterone-producing adenomas.

Two distinct subtypes of patients with primary aldosteronism due to aldosterone-producing adenomas (APA), based on different aldosterone responses to angiotensin, have been identified. We evaluated the relationship between adrenal zona fasciculata-like histotype and response of plasma aldosterone to upright posture in a series of patients with APA. Twenty-five patients were retrospectively divided in two groups according to aldosterone response to posture, i.e., a first group without postural change of aldosterone (n = 19) and a second group with at least 30% aldosterone increase after standing (n = 6). The percentage of zona fasciculata-like cells was calculated at histology in all adenoma tissues removed at adrenalectomy. The two groups of patients were similar in sex, age, systolic/diastolic blood pressure, supine/upright plasma renin activity, supine/upright aldosterone, tumor size. No differences between the two groups were observed as to zona fasciculata-like (84 +/- 3% vs 71 +/- 9%, P NS) and non-zona fasciculata-like cells percentage in adenoma tissues. No inverse correlation was found in either group between the percentage change from supine to upright aldosterone and the percentage of zona fasciculata-like cells. Aldosterone and cortisol responses to ACTH testing were similar in the two groups. Our results indicate that the two subtypes of primary aldosteronism based on different postural responses of aldosterone are not due to a different prevalence of zona fasciculata-like histotype in APA.

Adenoma↗
PubMed1998

Incidentally discovered adrenal tumors: endocrine and scintigraphic correlates.

Hormonal and morphological data were investigated in 202 consecutive patients with adrenal incidentalomas (171 unilateral and 31 bilateral) in an attempt to assess subclinical hyperfunction or malignancy. In addition to the classical evaluation, scintiscan was carried out in a large number of these patients. In unilateral incidentalomas, 83% showed normal hormonal function, whereas 17% had biochemical signs of adrenal overactivity (hyperaldosteronism in 3, hypercortisolism in 17, medullary hyperfunction in 9). [75Se]Methylnorcholesterol scintigraphy depicted malignant, space-occupying lesions as decreased or absent radiotracer uptake by the mass, and cortical adenomas as increased or normal uptake. In cortical adenomas a relationship between radiocholesterol uptake and degree of functional autonomy was demonstrated. [123I]Metaiodobenzilguanidine scintiscan visualized 7 of 8 pheochromocytomas. In bilateral incidentalomas, abnormal adrenal function was more frequent, accounting for 29% of cases (hyperaldosteronism in 3, hypercortisolism in 3, adrenal insufficiency in 2, and congenital adrenal hyperplasia in 1). Malignant lesions were not scintigraphically visualized. [75Se]Methylnorcholesterol scan also provided functional information in the case of a cortisol-secreting adenoma and an aldosteronoma with a concomitant contralateral nonhypersecreting adenoma, showing the greatest uptake in the hyperfunctioning adenomas. In both unilateral and bilateral lesions, endocrine testing failed to differentiate benign from malignant tumors. Although hormonal assessment is mandatory to clarify the functional patterns, only morphofunctional examination by scintiscan seems to provide more data about the likelihood of malignancy.

17-alpha-Hydroxyprogesterone↗
PubMed1998

Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man.

A decrease in hypothalamic-pituitary-adrenal axis sensitivity to glucocorticoid feedback suppression seems to occur with aging. To investigate possible abnormalities in the inhibitory effect of glucocorticoids on ACTH secretion in the elderly, we evaluated the endogenous ACTH response to hydrocortisone (25 mg as an i.v. bolus) in 15 healthy aged (65-88 yr) and 15 healthy young (18-26 yr) men. Blood samples for ACTH and cortisol determinations were collected at -15, 0, 2, 5, 10, 15, 30, 45, 60, 90, 120, and 180 min. Hydrocortisone injection produced a rapid increase in plasma cortisol levels within the first 2 min in both groups. In old men, in concomitance with the cortisol increase, ACTH levels showed only a slight and nonsignificant decrease within the first 15 min, followed by a pronounced and significant decline thereafter. In young subjects, in concomitance with the plasma cortisol increase, a marked decrease in ACTH levels was observed within the first 15 min, followed by a less pronounced decline thereafter. The response curve of ACTH inhibition could be arbitrarily divided in two parts. The first part (from 0-60 min) showed a significant difference between old and young men, whereas the remaining part of the curve (from 60-180 min) showed no differences between the two groups. The slower response in glucocorticoid feedback inhibition of ACTH in old men supports the concept of some alteration in the central regulation by steroids in aging. Age-related vascular factors affecting cortisol penetration through the blood-brain barrier more than hippocampus-hypothalamus receptor abnormalities could be involved in the fast component of hypothalamic-pituitary-adrenal axis feedback regulation.

Adolescent↗
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↗
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↗
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↗
PubMedDate not supplied

Paclitaxel is an effective antiproliferative agent on the human NCI-H295 adrenocortical carcinoma cell line.

In view of a potential clinical use, we assessed the antiproliferative effect of paclitaxel on the human steroid-secreting NCI-H295 adrenocarcinoma cell line. By MTT, paclitaxel induced a dose-dependent inhibition of cell proliferation, with IC50 lower than blood levels of the drug achieved in patients treated for other malignancies. Cell exposure to paclitaxel for 24 h at the different IC50S produced a dose-responsive increase in DNA fragmentation, morphologically confirmed by electron microscopy. A time-dependent decrease in aldosterone, cortisol and testosterone was observed. Paclitaxel is an effective antiproliferative agent in this human adrenocortical carcinoma cell line. Apoptosis induced by the drug in involved in neoplastic cell death. A potential role of the drug in the treatment of patients with adrenocortical cancer could be considered.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Adrenocortical carcinoma: experience in 45 patients.

Forty-five patients with adrenocortical carcinoma (13 nonfunctioning and 32 functioning carcinomas) were retrospectively studied. Five-year survival rate was 29% overall; for patients at stage I-II (n = 15) it was 70%, and for patients at stage III-IV (n = 30) it was 12%. In patients given mitotane + chemotherapy survival rate was similar to that observed in patients given chemotherapy alone, and significantly longer than in patients given mitotane alone (p < 0.05). There were no differences in disease-free interval and survival between adjuvant mitotane and no treatment. Optimization of therapeutic protocols in addition to early recognition may improve prognostic aspects of this type of malignancy for which treatment outcome is still unsatisfactory.

Adolescent↗
PubMedDate not supplied

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Adrenal Gland Neoplasms↗