Endocrine Abstracts

Background: Mitotane (o,p’DDD) is the reference therapy for adrenocortical carcinoma (ACC) and should undergo metabolization in o,p’DDE and o,p’DDA to exert its anti-proliferative activity. We have previously shown that there is a link between RRM1 gene expression and o,p’DDD activity in an adjuvant setting. Aim of this study was to assess whether RRM1 gene expression is correlated to the bioavailability and cytotoxic activity of o,p’DDD and its metabo...

Purpose: Mitotane is the reference systemic therapy for adrenocortical carcinoma (ACC), but its mechanism of action and possible predictors of treatment response remain poorly defined. Our aim was to evaluate the gene expression of ribonucleotide reductase large subunit 1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) in ACC as potential biomarkers for clinical outcome and response to mitotane.Experimental design: Forty-five and 47 tiss...

The effects of glucocorticoids are mediated by the glucocorticoid receptors (GR) and some single nucleotide polymorphisms (SNPs) have been associated to enhanced sensitivity (N363S, BclI) or reduced sensitivity (ER22/23EK) to glucocorticoids.Aim of the present study was: 1) to assess the frequency of N363S, BclI and ER22/23EK in 46 patients with Cushing’s syndrome (CS) and 73 patients with adrenal incidentaloma (AI) compared to 186 healthy subjects;...

Diagnosis of primary aldosteronism (PA) is made by screening, confirmation testing and subtype diagnosis (CT scan and adrenal vein sampling, AVS). However, some tests are costly and unavailable in most hospitals. We evaluated the role of serum 18-hydroxycorticosterone (s18OHB) and urinary and serum 18-hydroxycortisol (u and s18OHF) and 18-oxocortisol (u and s18oxoF) in the diagnosis of PA and its subtypes, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (...

A thorough pre-operative hormonal workup is advised following the recommendations of the European Network for the Study of Adrenal Tumors. Demonstration of endocrine activity may serve to the following purposes: i) prove adrenocortical origin of the mass; ii) suggest malignancy, in the event of androgen hypersecretion; iii) provide tumor markers whose assessment may be exploited during follow-up to detect tumor residual or recurrence after surgery; iv) avoid life-threatening p...

Mitotane (o,p’DDD) is commonly used for the treatment of adrenocortical carcinoma (ACC), both for advanced disease and in the adjuvant setting. Mitotane induces adrenal insufficiency but specific effects on steroidogenic enzymes are unknown.We investigated 24-h urinary steroid metabolite excretion in ACC patients on adjuvant mitotane (AD) or mitotane for metastatic disease (MET). We compared samples collected before mitotane treatment (BEFORE; MET <...

This study presents epidemiological data of 1512 Italian acromegalic patients who had been diagnosed from 1980 to 2002 and followed-up for more than 10 years, retrospectively collected by 24 tertiary referral centers. Data on co-morbidities and mortality were compared to those of the general Italian population obtained by the Italian National Institute of Statistic. At diagnosis median age of patients (41% M, 59% F) was 46 years, GH (mean±S.D.) 31±37 m...

The aim of the present study was to compare the assessment of BMD measured either by DEXA or by QUS in patients with AI. We evaluated 40 patients with AI, who underwent an evaluation of hypothalamic-pituitary-adrenal (HPA) axis function and bone densitometry measured either by DEXA (Hologic QDR 4500 W) at lumbar spine and at femur or QUS (Achilles Express) at the right foot. Subclinical Cushing’s syndrome (SCS) was defined as abnormal response to at least 2 standard tests...

N363S polymorphism of the human glucocorticoid receptor gene has been detected in the heterozygous state in approximately 3–9% of general European population. This variant has been associated with increased sensitivity to glicocorticoids, increased insulin response to dexamethasone, a tendency towards lower bone mineral density, increased body mass index, and unstable angina. However, other reports found no associations with these pathological conditions. We assessed the ...