Alicia Santos

The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics

OBJECTIVE The European Registry on Cushings syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushings syndrome (CS). DESIGN AND METHODS Baseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%). RESULTS Proportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups. CONCLUSIONS The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.

MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies

BACKGROUND Cushings syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. OBJECTIVE To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). METHODS Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. RESULTS Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). CONCLUSION Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.

Relationship Between Adiponectin and Left Atrium Size in Uncomplicated Obese Patients: Adiponectin, a Link Between Fat and Heart

BackgroundIt is well known that obesity is a risk factor for severe cardiovascular complications, such as coronary heart disease, heart failure, stroke, venous thromboembolic disease, and atrial fibrillation. Left ventricle (LV) and left atrium (LA) enlargement is a characteristic feature of these patients with the consequent cardiovascular risk. Factors other than hemodynamic may influence LA remodeling. The aim of the study is to evaluate the relationship between adiponectin and LA size in uncomplicated obese patients.MethodsSeventy-four asymptomatic obese patients and an age- and sex-matched control group (N = 70) were recruited. A detailed clinical, echocardiographic, and analytical study was performed. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-IR) method. Insulin sensitivity was assessed measuring serum total adiponectin concentrations.ResultsAdiponectin levels were lower in the obese group (P < 0.001) and particularly so in those obese participants with enlarged LA (32%; P < 0.0005). LA sizes were higher in the obese group (P < 0.0005). Adiponectin displayed significant correlations with body mass index, glucose, insulin, high-density lipoprotein cholesterol, and triglyceride concentrations as well as HOMA-IR (P < 0.001 for all). Adiponectin displayed significant correlations with LV mass and LA size, diastolic and systolic cardiac volumes and diameters, and cardiac output (P < 0.001 for all). Adiponectin correlations with LA size (r = −0.429; P < 0.001) persisted after adjustment for HOMA-IR, age, sex, and LV mass.ConclusionsA novel inverse relationship between adiponectin and LA size independent of age, sex, insulin resistance, and LV mass appears in our series. Adiponectin could be a link between adipose tissue and the heart, having an influence on cardiac remodeling.

Hippocampal dysfunction in cured Cushing's syndrome patients, detected by 1H-MR-spectroscopy

Proton magnetic resonance spectroscopy (1H‐MRS) is a sensitive, noninvasive imaging technique capable of measuring brain metabolites in vivo. Chronic exposure to endogenous hypercortisolism in Cushings syndrome (CS) is associated with negative effects on memory and hippocampal volumes, even after biochemical cure.

Effects of illness duration and treatment resistance on grey matter abnormalities in major depression

BACKGROUND Findings of brain structural changes in major depressive disorder are still inconsistent, partly because some crucial clinical variables have not been taken into account. AIMS To investigate the effect of major depressive disorder on grey matter volumes. METHOD Voxel-based morphometry was used to compare 66 patients with depression at different illness stages (22 each with first-episode, remitted-recurrent and treatment resistant/chronic depression) with 32 healthy controls. Brain volumes were correlated with clinical variables. RESULTS Voxel-based morphometry showed a significant group effect in right superior frontal gyrus, left medial frontal gyrus and left cingulate gyrus (P<0.05, family wise error-corrected). Patients whose condition was treatment resistant/chronic exhibited the smallest volumes in frontotemporal areas. Longer illness duration was negatively correlated with decreases in right medial frontal cortex and left insula. CONCLUSIONS Frontotemporolimbic areas are smaller in the patients with severe depression and are associated with duration of illness, but not with medication patterns, suggesting negative effects of long-lasting major depressive disorder on grey matter.

Small cerebellar cortex volume in patients with active Cushing's syndrome

OBJECTIVE Cushings syndrome (CS) is associated with neuropsychological deficits. As the cerebellum plays a key role in neuropsychological functions it may be affected in CS. The aim of this study was to investigate whether patients with CS have a smaller cerebellar volume than healthy controls, and to analyse whether cerebellar volume is associated with neuropsychological performance and clinical parameters. DESIGN A cross-sectional study was performed. METHODS Thirty-six CS patients (15 with active CS and 21 with CS in remission) and 36 controls matched for age, sex, and education underwent neuropsychological testing, quality of life assessment, clinical evaluation, and magnetic resonance imaging brain scan. Cerebellar volumes (white matter and cortex, bilateral) were calculated using FreeSurfer Software. RESULTS Patients with active CS showed smaller bilateral cerebellar cortex volumes than controls (left, P=0.035 and right, P=0.034), as well as a trend toward smaller right cerebellar cortex volumes than patients in remission CS (P=0.051). No differences were observed in the volume of cerebellar white matter between the three groups. Both right and left cerebellar cortex volumes correlated negatively with triglyceride levels (right: r=-0.358, P=0.002 and left: r=-0.317, P=0.005) and age at diagnosis (right: r=-0.433, P=0.008 and left: r=-0.457, P=0.005). Left cerebellar cortex volume also correlated positively with visual memory performance (r=0.245, P=0.038). Right cerebellar cortex volume positively correlated with quality-of-life scores (r=0.468, P=0.004). CONCLUSIONS The cerebellar cortex volume is smaller in active CS patients than in controls. This finding is associated with poor visual memory and quality of life and is mostly pronounced in patients with higher triglyceride levels and older age at diagnosis.

Impaired decision‐making and selective cortical frontal thinning in Cushing's syndrome

Cushings syndrome (CS) is caused by a glucocorticoid excess. This hypercortisolism can damage the prefrontal cortex, known to be important in decision‐making. Our aim was to evaluate decision‐making in CS and to explore cortical thickness.

Body composition after endogenous (Cushing's syndrome) and exogenous (rheumatoid arthritis) exposure to glucocorticoids.

Exposure to chronic glucocorticoid (GC) excess determines changes in body composition. The aim of the study was to compare body composition in women exposed to endogenous hypercortisolism (Cushings syndrome, CS), exogenous glucocorticoid treatment (rheumatoid arthritis, RA) and controls. Fifty-one CS women, 26 RA women treated with low-dose prednisone (5 mg/day or 10 mg/2 days), and 78 female controls were included. Fourteen CS patients were hypercortisolemic, 37 in remission (10 required hydrocortisone substitution after surgery). Body composition parameters were measured by dual-energy X-ray absorptiometry scanning (DEXA). RA patients had a greater waist-hip ratio (WHR) (p<0.01), less lean body mass (LBM) (p<0.01), and lumbar bone mineral density (BMD) (p<0.01) than controls. CS patients, globally and those with cured disease, had more total fat (both percentage and kg) and trunk fat percentage, and less whole body-BMD than RA patients (p<0.05, p<0.01, p<0.05, respectively). Active CS patients had less whole body-BMD and more LBM than RA patients (p<0.05, p=0.01, respectively). Cured CS patients not taking hydrocortisone had more total fat [both percentage (p<0.05) and kg (p<0.05)], trunk fat percentage (p<0.05), lumbar BMD (p<0.01) than RA patients. Cured CS patients requiring hydrocortisone only differed from RA patients by smaller WHR (p<0.01). All the differences in BMD disappeared when the data were reanalyzed including only the estrogen-deficient groups. Hypercortisoliof CS determines an irreversible increase in body fat, greater than in RA. Endogenous and exogenous exposure to GC negatively affects body composition by increasing the WHR. There appears to be no additional effect on BMD in estrogen-deficient women.

Differences in attention and impulsivity between borderline personality disorder and bipolar disorder

This study aims at investigating attention and impulsivity differences between borderline personality disorder and bipolar disorder, as both diseases may share neuropsychological deficits. Differential cognitive outcomes on the Continuous Performance Test-II were observed between disorders, and also when compared to healthy controls.

No clinically significant valvular regurgitation in long-term cabergoline treatment for prolactinoma.

An association between treatment for Parkinsons disease with certain dopaminergic drugs and development of cardiac valve impairment has been reported. Recent studies in hyperprolactinaemic patients treated with cabergoline (CAB) have shown either no significant findings or mild tricuspid regurgitation.