Iris Crespo

Verbal and Visual Memory Performance and Hippocampal Volumes, Measured by 3-Tesla Magnetic Resonance Imaging, in Patients with Cushing's Syndrome

CONTEXT Cushings syndrome (CS) affects cognition and memory. OBJECTIVE Our objective was to evaluate memory and hippocampal volumes (HV) on 3-tesla magnetic resonance imaging (3T MRI) in CS patients and controls. PATIENTS AND METHODS Thirty-three CS patients (11 active, 22 cured) and 34 controls matched for age, sex, and education underwent Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex Figure memory tests. Gray matter and HV were calculated on 3T MRI, using FreeSurfer image analyses software. RESULTS No differences in HV were observed between active and cured CS or controls. Memory performance was worse in CS patients than controls (P < 0.04 in active; P < 0.03 in cured CS) but did not differ among CS groups, which were therefore analyzed together; they performed worse for verbal (P = 0.02) and visual memory (P = 0.04) than controls. In 12 CS patients, memory was below normative cutoff values for verbal (n = 6, cured), visual memory (n = 10, six cured) or both (n = 4); these patients with severe memory impairments showed smaller HV compared with their matched controls (P = 0.02 with verbal impairment; P = 0.03 with visual impairment). They were older (P = 0.04), had shorter education (P = 0.02), and showed a trend toward longer duration of hypercortisolism (P = 0.07) than the remaining CS patients. Total (P = 0.004) and cortical (P = 0.03) brain gray matter volumes were decreased in CS compared with controls, indicating brain atrophy, whereas subcortical gray matter (which includes HV) was reduced only in the 12 patients with severe memory impairment. CONCLUSION Verbal and visual memory is worse in CS patients than controls, even after biochemical cure. HV was decreased only in those whose memory scores were below normative cutoff values.

A reappraisal of the medical therapy with steroidogenesis inhibitors in Cushing's syndrome

To evaluate the outcome of preoperative therapy with ketoconazole (KTZ) and/or metyrapone (MTP) in previously untreated patients with Cushings syndrome (CS).

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.

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.

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.

Quality of life in Cushing’s syndrome

IntroductionCushing syndrome (CS) of any etiology (adrenal, pituitary or ectopic) impacts negatively on health-related quality of life (QoL), especially in active hypercortisolism but also after endocrine cure. Both generic questionnaires like the short-form 36 health survey -SF-36- and the derived SF-12, or the Hospital Anxiety and Depression Scale (HADS), and disease-specific measures like the CushingQoL and the Tuebingen CD-25 questionnaires have provided information on the impact of CS on patients perceived health.Materials and methodsStudies published since January 2013 until November 2014 on QoL in patients with CS were identified, reviewed and summarized.ConclusionsTreatment of CS improves patients perceived QoL, but it often takes many months and often never normalizes. In parallel to persistent QoL impairment in cured CS, brain and cerebellar volume are reduced. Depression, anxiety and cognitive dysfunction are common. Pediatric patients with CS also present worse QoL than normal children, as well as additional issues like delayed growth and pubertal development, next to abnormal body composition, psychological and cognitive maturation. Fluoxetine has been suggested as a neuroprotectant and antidepressant for patients with CS, although no prospective studies are yet available. The CushingQoL questionnaire has been mapped to well-validated instruments like SF-36 or EQ-5D, and therefore may be used in cost-utility and other health economy studies.

Health-Related Quality of Life in Pituitary Diseases

In the last 15 years, worse health-related quality of life (QoL) has been reported in patients with pituitary diseases compared with healthy individuals. Different QoL questionnaires have shown incomplete physical and psychological recovery after therapy. Residual impairments often affect QoL even long-term after successful treatment of pituitary adenomas. In this article, knowledge of factors that affect QoL in pituitary diseases is reviewed. The focus is on 5 pituitary diseases: Cushing syndrome, acromegaly, prolactinomas, nonfunctioning pituitary adenomas, and hypopituitarism.

Quality of life in patients with hypopituitarism.

Purpose of reviewQuality of life (QoL) is impaired in patients with adults with growth hormone deficiency (AGHD) of any cause, especially if additional hypopituitarism is present, and improves after replacement therapy with recombinant human growth hormone (rhGH). This review includes relevant publications since 2013. Recent findingsRecent findings confirm that most patients with AGHD who improve their QoL after rhGH therapy experience persistent effects for years, if replacement therapy is maintained. Sometimes, however, QoL may not normalize completely, especially if it is caused by a craniopharyngioma (because of concomitant neuropsychological comorbidities that affect autonomy and cognitive function), or functional pituitary tumours, i.e., in Cushings disease, in which chronic brain exposure to hypercortisolism is associated with more depression, anxiety, loss of memory and emotional distress. Another group in which QoL and energy rarely normalize despite improving after rhGH is hypopituitarism because of traumatic brain injury. Worse QoL is seen in patients who also suffer insomnia, depression, negative illness perceptions and are treated in a rural (compared with an urban) healthcare environment. Better QoL after rhGH is seen in AGHD patients who are not depressed, after successful surgery, living in Europe (rather than the USA), with poorer baseline QoL scores, less obesity and no impaired vision. SummaryFurther improvement of QoL may be possible with individualized psychosocial interventions.

Telomere length analysis in Cushing's syndrome

INTRODUCTION Hypercortisolism in Cushings syndrome (CS) is associated with increased morbidity and mortality. Hypercortisolism also occurs in chronic depressive disorders and stress, where telomere length (TL) is shorter than in controls. We hypothesized that shortening of telomere might occur in CS and contribute to premature aging and morbidity. AIM To investigate TL in CS patients compared with controls. METHODS Seventy-seven CS patients (14 males, 59 pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated longitudinally, during active disease and after remission of hypercortisolism. Leukocyte TL was measured by telomere restriction fragment-Southern technique. Clinical markers were included in a multiple linear regression analysis to investigate potential predictors of TL. RESULTS Mean TL in CS patients and controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the longitudinal evaluation, TL was shorter in active disease than after remission (7273 vs 7870, P<0.05). Age and dyslipidemia were negative predictors (P<0.05), and total leukocyte count was a positive predictor for TL (P<0.05). As expected, a negative correlation was found between TL and age (CS, R=-0.400 and controls, R=-0.292; P<0.05). No correlation was found between circulating cortisol, duration of exposure to hypercortisolism or biochemical cure and TL. CONCLUSION Even though in the cross-sectional comparison of CS and controls no difference in TL was found, in the longitudinal evaluation, patients with active CS had shorter TL than after biochemical cure of hypercortisolism. These preliminary results suggest that hypercortisolism might negatively impact telomere maintenance. Larger studies are needed to confirm these findings.