Publications by authors named "Alicia Santos"

53 Publications

Evidence for Deleterious Antigenic Imprinting in SARS-CoV-2 Immune Response.

bioRxiv 2021 Jun 9. Epub 2021 Jun 9.

A previous report demonstrated the strong association between the presence of antibodies binding to an epitope region from SARS-CoV-2 nucleocapsid, termed Ep9, and COVID-19 disease severity. Patients with anti-Ep9 antibodies (Abs) had hallmarks of antigenic imprinting (AIM), including early IgG upregulation and cytokine-associated injury. Thus, the immunological memory of a previous infection was hypothesized to drive formation of suboptimal anti-Ep9 Abs in severe COVID-19 infections. This study identifies a putative primary antigen capable of stimulating production of cross-reactive, anti-Ep9 Abs. Binding assays with patient blood samples directly show cross-reactivity between Abs binding to Ep9 and only one bioinformatics-derived, homologous potential antigen, a sequence derived from the neuraminidase protein of H3N2 Influenza A virus. This cross-reactive binding is highly influenza strain specific and sensitive to even single amino acid changes in epitope sequence. The neuraminidase protein is not present in the influenza vaccine, and the anti-Ep9 Abs likely resulted from the widespread influenza infection in 2014. Therefore, AIM from a previous infection could underlie some cases of COVID-19 disease severity.

Importance: Infections with SARS-COV-2 result in diverse disease outcomes, ranging from asymptomatic to fatal. The mechanisms underlying different disease outcomes remain largely unexplained. Previously, our laboratory identified a strong association between the presence of an antibody and increased disease severity in a subset of COVID-19 patients. Here, we report that this severity-associated antibody cross-reacts with viral proteins from an influenza A viral strain from 2014. Therefore, we speculate that antibodies generated against previous infections, like the 2014 influenza A, play a significant role in directing some peoples’ immune responses against SARS-COV-2. Such understanding of the sources and drivers of COVID-19 disease severity can help early identification and pre-emptive treatment.
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http://dx.doi.org/10.1101/2021.05.21.445201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202420PMC
June 2021

Real-life implementation of a G6PD deficiency screening qualitative test into routine vivax malaria diagnostic units in the Brazilian Amazon (SAFEPRIM study).

PLoS Negl Trop Dis 2021 May 18;15(5):e0009415. Epub 2021 May 18.

Instituto de Pesquisa Clínica Carlos Borborema, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency greatly hinders Plasmodium vivax malaria radical cure and further elimination due to 8-aminoquinolines-associated hemolysis. Although the deleterious health effects of primaquine in G6PD deficient individuals have been known for over 50 years, G6PD testing is not routinely performed before primaquine treatment in most P. vivax endemic areas.

Method/principal Findings: The qualitative CareStart G6PD screening test was implemented in 12 malaria treatment units (MTUs) in the municipality of Rio Preto da Eva, Western Brazilian Amazon, a malaria endemic area, between February 2019 and early January 2020. Training materials were developed and validated; evaluations were conducted on the effectiveness of training health care professionals (HCPs) to perform the test, the interpretation and reliability of routine testing performed by HCPs, and perceptions of HCPs and patients. Most HCPs were unaware of G6PD deficiency and primaquine-related adverse effects. Most of 110 HCPs trained (86/110, 78%) were able to correctly perform the G6PD test after a single 4-hour training session. The test performed by HCPs during implementation showed 100.0% (4/4) sensitivity and 68.1% (62/91) specificity in identifying G6PD deficient patients as compared to a point-of-care quantitative test (Standard G6PD).

Conclusions/significance: G6PD screening using the qualitative CareStart G6PD test performed by HCPs in MTUs of an endemic area showed high sensitivity and concerning low specificity. The amount of false G6PD deficiency detected led to substantial loss of opportunities for radical cure.
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http://dx.doi.org/10.1371/journal.pntd.0009415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162658PMC
May 2021

Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score.

mSphere 2021 04 28;6(2). Epub 2021 Apr 28.

Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, USA

Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients ( = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient's comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.
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http://dx.doi.org/10.1128/mSphere.00203-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092137PMC
April 2021

Cushing "Blues".

J Clin Endocrinol Metab 2021 Jun;106(7):e2816-e2818

IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, Universitat Autónoma de Barcelona, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unit 747), ISCIII, Barcelona, Spain.

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http://dx.doi.org/10.1210/clinem/dgab239DOI Listing
June 2021

Psychological complications of Cushing's syndrome.

Curr Opin Endocrinol Diabetes Obes 2021 Jun;28(3):325-329

Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

Purpose Of Review: The aim of this article is to review and discuss recent evidence of psychological complications in Cushing's syndrome.

Recent Findings: Recent research has described the presence of depression, anxiety, posttraumatic stress disorder, mania, bipolar disorder and psychotic symptoms in patients with Cushing's syndrome. Furthermore, the perspective of patients' partners has also been emphasized.

Summary: Recent literature highlights the importance of screening for psychological alterations in Cushing's syndrome, as these alterations can be present in many patients, having a high impact in daily life. Depression is a very common symptom, although in rare cases, patients can also present mania or psychosis. Some studies highlight the importance of screening for organic disease (including Cushing's syndrome) in patients with unexpected or first onset psychiatric symptoms. Finally, the perspective of the patients' partners makes it clear that the partners can also suffer due to the disease of the patient. Intervention programmes involving patient's partners could be helpful to improve both patient and partner wellbeing.
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http://dx.doi.org/10.1097/MED.0000000000000633DOI Listing
June 2021

EndoERN patient survey on their perception of health care experience and of unmet needs for rare endocrine diseases.

Endocrine 2021 Mar 5;71(3):569-577. Epub 2021 Feb 5.

Pediatric Endocrinology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, 17176, Stockholm, Sweden.

Patients' perceptions on quality of care and gaps in diagnosis/management of rare endocrine diseases (RED) were collected in a 21-item questionnaire, answered on-line in the patients' language. There were 598 (66% females) responses from 29 countries reflecting pituitary, adrenal, thyroid, parathyroid, gonadal, genetic and autoimmune diseases. While in 36% a diagnosis was made in <1 year, in 28% it took >5 years. In 64% it took 2-7 professionals for a correct diagnosis, after which in >50% a specialist/specific treatment was available within 1 month; 60% were satisfied with current treatment. Most (59-67%) would have liked access to psychological support, social worker, dietician or physiotherapist/rehabilitation specialists. Half were satisfied with information received, treatment and health care follow-up; 87% contacted patient/support groups; 78% agreed that "The personal limitations related to the disease, impact on my everyday quality of life". Conclusion: Diagnostic delay in RED is still unsatisfactory in Europe, as well as specific needs impacting QoL.
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http://dx.doi.org/10.1007/s12020-021-02625-0DOI Listing
March 2021

Antibody Response to a Nucleocapsid Epitope as a Marker for COVID-19 Disease Severity.

bioRxiv 2020 Oct 16. Epub 2020 Oct 16.

Characterization of antibody response to SARS-CoV-2 is urgently needed to predict COVID-19 disease trajectories. Ineffective antibodies or antibody-dependent enhancement (ADE) could derail patients' immune responses, for example. ELISA and coronavirus antigen microarray (COVAM) analysis epitope-mapped plasma from 86 COVID-19 patients. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including ICU stay, requirement for ventilators, and death. Furthermore, anti-Ep9 antibodies correlate both with various comorbidities and ADE hallmarks, including increased IL-6 levels and early IgG response. Importantly, anti-Ep9 antibodies can be detected within five days post-symptom onset and sometimes within one day. The results lay the groundwork for a new type of COVID-19 diagnostic for the early prediction of disease severity to guide more effective therapeutic interventions.

One Sentence Summary: Antibodies targeting a specific location within a SARS-CoV-2 structural protein are linked to poor COVID-19 disease outcomes.
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http://dx.doi.org/10.1101/2020.10.15.341743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574261PMC
October 2020

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1, IL-12/VEGF, and IL-10/IP-10 Axis.

J Immunol Res 2020 8;2020:4585704. Epub 2020 Jan 8.

Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas (UFAM), 69077-000 Manaus, AM, Brazil.

Background: Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. . Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects.

Results: Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1, MIP-1, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers.

Conclusion: In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1, MIP-1, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1 and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile.
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http://dx.doi.org/10.1155/2020/4585704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199620PMC
March 2021

Virus Bioresistor (VBR) for Detection of Bladder Cancer Marker DJ-1 in Urine at 10 pM in One Minute.

Anal Chem 2020 05 20;92(9):6654-6666. Epub 2020 Apr 20.

Department of Chemistry, University of California, Irvine, Irvine, California 92697, United States.

DJ-1, a 20.7 kDa protein, is overexpressed in people who have bladder cancer (BC). Its elevated concentration in urine allows it to serve as a marker for BC. However, no biosensor for the detection of DJ-1 has been demonstrated. Here, we describe a virus bioresistor () capable of detecting DJ-1 in urine at a concentration of 10 pM in 1 min. The consists of a pair of millimeter-scale gold electrodes that measure the electrical impedance of an ultrathin (≈ 150-200 nm), two-layer polymeric channel. The top layer of this channel (90-105 nm in thickness) consists of an electrodeposited virus-PEDOT (PEDOT is poly(3,4-ethylenedioxythiophene)) composite containing embedded M13 virus particles that are engineered to recognize and bind to the target protein of interest, DJ-1. The bottom layer consists of spin-coated PEDOT-PSS (poly(styrenesulfonate)). Together, these two layers constitute a current divider. We demonstrate here that reducing the thickness of the bottom PEDOT-PSS layer increases its resistance and concentrates the resistance drop of the channel in the top virus-PEDOT layer, thereby increasing the sensitivity of the and enabling the detection of DJ-1. Large signal amplitudes coupled with the inherent simplicity of the sensor design result in high signal-to-noise (/ > 100) and excellent sensor-to-sensor reproducibility characterized by coefficients of variation in the range of 3-7% across the DJ-1 binding curve down to a concentration of 30 pM, near the 10 pM limit of detection (LOD), encompassing four orders of magnitude in concentration.
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http://dx.doi.org/10.1021/acs.analchem.0c00534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266010PMC
May 2020

Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits.

Proc Natl Acad Sci U S A 2020 03 11;117(12):6630-6639. Epub 2020 Mar 11.

Laboratorio de Inmunopatología. Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428, Ciudad de Buenos Aires, Argentina;

Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant ( ) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren's syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking β1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating β1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3 regulatory T cells (Tregs), and increased number of CD8 T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren's syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8 T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.
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http://dx.doi.org/10.1073/pnas.1922778117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104299PMC
March 2020

Patient-Centered Outcomes with Pituitary and Parasellar Disease.

Neuroendocrinology 2020 27;110(9-10):882-888. Epub 2020 Feb 27.

Department of Medicine/Endocrinology, IIB-Sant Pau, Hospital Sant Pau, Research Center for Pituitary Diseases, Barcelona, Spain.

Over the last 2 decades, advances in the diagnosis and management of pituitary diseases have made it possible to attain an endocrine "cure" in a large proportion of patients. In other words, tumors can be excised or controlled with drugs, mass effects of the lesion on surrounding structures can be solved, and pituitary deficiencies can be substituted with all relevant hormones. While this is considered a satisfactory outcome for health care providers, patients often suffer from an aftermath of prior endocrine dysfunction exposure, with irreversible effects, both physically and psychologically, which have a great impact on their everyday life. Diagnostic delay, often of several years, adds a negative impact on health perception. This affects their social, professional, and family domains and determines their future life. Understanding that this may occur is important, and health care providers should offer information to prepare the patient for this difficult journey, especially in the case of acromegaly, Cushing disease, or hypopituitarism. In order to maintain a good quality of life (QoL) in the long-term, patients need to adapt to this new situation, something that may be difficult, since they often cannot continue with all the activities and rhythm they used to do. Depression is often the consequence of maladaptation to the new situation, leading to impaired QoL.
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http://dx.doi.org/10.1159/000506809DOI Listing
February 2020

Quality of Life in Patients With Cushing's Disease.

Front Endocrinol (Lausanne) 2019 11;10:862. Epub 2019 Dec 11.

Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona, Barcelona, Spain.

Cushing's disease (and by extension, Cushing's syndrome) is a rare disease due to a chronic cortisol excess, which usually has an important impact on quality of life (QoL). It can lead to numerous comorbidities that can interfere with daily life, as fatigability, myopathy, bone loss and fragility, increased cardiovascular risk, depression, and cognitive alterations. Of note, psychological alterations (including depression and anxiety) occur often, and are an important determinant of impaired quality QoL. QoL scores using different questionnaires are poorer in comparison to healthy controls, other pituitary adenomas and some chronic diseases. Even if some improvements can be observed after successful treatment, recovery does not seem to be complete, and comorbidities persist. This persistent QoL impairment has been found using both generic and disease-specific QoL questionnaires, and is also reported by the patients themselves, when asked directly. Multidisciplinary teams are essential to improve patients' well-being. Clinicians should take into account the whole scope of clinical problems and address the different comorbidites associated with the disease. Screening in the psychological sphere, with further intervention if necessary, can be helpful in the management of these patients. Interventions and programs have shown promising results, although there is a need for further development of new strategies for the benefit of these patients.
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http://dx.doi.org/10.3389/fendo.2019.00862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917662PMC
December 2019

High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry.

Eur J Endocrinol 2019 Nov;181(5):461-472

Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and the Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality.

Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years.

Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment.

Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases were the commonest cause of death soon after diagnosis, emphasizing the need for careful clinical vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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http://dx.doi.org/10.1530/EJE-19-0464DOI Listing
November 2019

Quality of Life in Cushing's disease: A long term issue?

Ann Endocrinol (Paris) 2018 Jun 4;79(3):132-137. Epub 2018 Apr 4.

Endocrinology/Medicine Department, Research Center for Pituitary Diseases, Hospital Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona (UAB), Pare Claret 167, 08025 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), ISCIII, Spain. Electronic address:

The purpose of this review is to describe how quality of life (QoL) is impaired in patients with hypercortisolism due to Cushing's syndrome of any aetiology, including pituitary-dependent Cushing's disease. It is worse in active disease, but improvement after successful therapy is often incomplete, due to persistent physical and psychological co-morbidities, even years after endocrine "cure". Physical symptoms like extreme fatigability, central obesity with limb atrophy, hypertension, fractures, and different skin abnormalities severely impair the affected patients' everyday life. Psychological and cognitive problems like bad memory, difficulties to concentrate and emotional distress, often associated with anxiety and depression, make it difficult for many patients to overcome the aftermath of treated Cushing's syndrome. Recent studies have shown diffuse structural abnormalities in the central nervous system during active hypercortisolism, thought to be related to the wide distribution of glucocorticoid receptors throughout the brain. Even though they improve after treatment, normalization is often not complete. Shortening the exposure to active Cushing's syndrome by reducing the often long delay to diagnosis and promptly receiving effective treatment is highly desirable, together with preparing the patient for the difficult periods, especially after surgery. In this way they are prepared for the impairments they perceive in every day life, and live with the hope of later improvement, which can be therapeutic in many instances.
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http://dx.doi.org/10.1016/j.ando.2018.03.007DOI Listing
June 2018

Worse Health-Related Quality of Life at long-term follow-up in patients with Cushing's disease than patients with cortisol producing adenoma. Data from the ERCUSYN.

Clin Endocrinol (Oxf) 2018 06 16;88(6):787-798. Epub 2018 Apr 16.

Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and the Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Objective: Hypercortisolism in Cushing's syndrome (CS) is associated with impaired health-related quality of life (HRQoL), which may persist despite remission. We used the data entered into the European Registry on Cushing's syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS) have worse HRQoL, both before and after treatment than patients with adrenal causes (ADR-CS).

Methods: Data from 595 patients (492 women; 83%) who completed the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment were analysed.

Results: At baseline, HRQoL did not differ between PIT-CS (n = 293) and ADR-CS (n = 120) on both EuroQoL and CushingQoL. Total CushingQoL score in PIT-CS and ADR-CS was 41 ± 18 and 44 ± 20, respectively (P = .7). At long-time follow-up (>1 year after treatment) total CushingQoL score was however lower in PIT-CS than ADR-CS (56 ± 20 vs 62 ± 23; P = .045). In a regression analysis, after adjustment for baseline age, gender, remission status, duration of active CS, glucocorticoid dependency and follow-up time, no association was observed between aetiology and HRQoL. Remission was associated with better total CushingQoL score (P < .001), and older age at diagnosis with worse total score (P = .01). Depression at diagnosis was associated with worse total CushingQoL score at the last follow-up (P < .001).

Conclusion: PIT-CS patients had poorer HRQoL than ADR-CS at long-term follow-up, despite similar baseline scoring. After adjusting for remission status, no interaetiology differences in HRQoL scoring were found. Age and presence of depression at diagnosis of CS may be potential predictors of worse HRQoL regardless of CS aetiology.
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http://dx.doi.org/10.1111/cen.13600DOI Listing
June 2018

Preoperative medical treatment in Cushing's syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN.

Eur J Endocrinol 2018 Apr 12;178(4):399-409. Epub 2018 Feb 12.

Centre Hospitalier Universitaire de BordeauxBordeaux, France.

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial.

Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS).

Patients And Methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS).

Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS ( < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) ( < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol ( < 0.01) and a lower remission rate ( < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups.

Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.
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http://dx.doi.org/10.1530/EJE-17-0997DOI Listing
April 2018

Depression and Anxiety Scores Are Associated with Amygdala Volume in Cushing's Syndrome: Preliminary Study.

Biomed Res Int 2017 18;2017:2061935. Epub 2017 May 18.

Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

Introduction: Cushing's syndrome (CS) has repeatedly been associated with hippocampal volume reductions, while little information is available on the amygdala, another structure rich in glucocorticoid receptors. The aim of the study was to analyze amygdala volume in patients with CS and its relationship with anxiety, depression, and hormone levels.

Material And Methods: 39 CS patients (16 active and 23 patients in remission) and 39 healthy controls matched for age, sex, and education level completed anxiety (STAI) and depression tests (BDI-II) and underwent a 3 Tesla brain MRI and endocrine testing. Amygdala volumes were analysed with FreeSurfer software.

Results: Active CS patients had smaller right (but not left) amygdala volumes when compared to controls ( = 0.045). Left amygdala volumes negatively correlated with depression scores ( = -0.692, = 0.003) and current anxiety state scores ( = -0.617, = 0.011) in active CS patients and with anxiety trait scores ( = -0.440, = 0.036) in patients in remission. No correlations were found between current ACTH, urinary free cortisol or blood cortisol levels, and amygdala volumes in either patient group.

Conclusion: Patients with active CS have a smaller right amygdala volume in comparison to controls, while left amygdala volumes are associated with mood state in both patient groups.
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http://dx.doi.org/10.1155/2017/2061935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451775PMC
March 2018

Psychiatric Symptoms in Patients with Cushing's Syndrome: Prevalence, Diagnosis and Management.

Drugs 2017 May;77(8):829-842

Department of Endocrinology/Medicine, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER 747), Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Barcelona, Spain.

Cushing's syndrome (CS) results from chronic exposure to cortisol excess, produced by the adrenal cortex. Hypercortisolism predisposes to psychiatric and neurocognitive disorders, mainly to depression and anxiety disorders. Screening tools to identify psychiatric symptoms are available for clinicians in their daily practice, although a specific diagnosis should be performed by specialists. Even if psychiatric symptoms improve after remission of hypercortisolism, complete recovery may not be achieved. Given the burden of these symptoms, psychiatric or psychological monitoring and treatment should be offered through all phases of CS, with a multidisciplinary approach. The aim of this article is to review data on the prevalence, diagnosis and management of psychiatric symptoms seen in patients with CS and to propose therapeutic approaches that may be followed in clinical practice. The prevalence of different psychiatric disorders has been described in both the active phase and after CS remission. Patients may not talk spontaneously about psychiatric symptoms they present, thus clinicians should ask directly about them. We recommend the use of screening tools in clinical practice to detect and treat these symptoms promptly. Even if reference endocrinologists cannot perform a definite psychiatric diagnosis, it will be important to ask patients directly about the presence of symptoms and refer if necessary to a psychiatrist. Additionally, patient information and educational programmes could be useful to manage psychiatric symptoms and to improve quality of life in patients with CS.
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http://dx.doi.org/10.1007/s40265-017-0735-zDOI Listing
May 2017

Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN.

Eur J Endocrinol 2017 05;176(5):613-624

Department of EndocrinologyChristie Hospital, Manchester, UK.

Objective: To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines.

Patients And Methods: We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS).

Results: Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years ( < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years ( < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC ( < 0.05).

Conclusions: Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.
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http://dx.doi.org/10.1530/EJE-16-0967DOI Listing
May 2017

MANAGEMENT OF ENDOCRINE DISEASE: Quality of life tools for the management of pituitary disease.

Eur J Endocrinol 2017 Jul 28;177(1):R13-R26. Epub 2017 Mar 28.

Hospital Sant PauIIB-Sant Pau, Research Center for Pituitary Diseases, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), ISCIII, and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

Background: In the last few years, quality of life (QoL) has become an outcome measure in patients with pituitary diseases.

Objective: To describe the available data on QoL impairment evaluated with questionnaires in patients with pituitary diseases.

Design: Critical review of the pertinent literature and pragmatic discussion of available information.

Methods: Selection of relevant literature from PubMed and WOK, especially from the last 5 years and comprehensive analysis.

Results: QoL is impaired in all pituitary diseases, mostly in acromegaly and Cushing's disease (similar to other causes of Cushing's syndrome), but also in non-functioning pituitary adenomas and prolactinomas, especially in the active phase of the disease. Nevertheless, even after endocrine 'cure', scores tend to be below normative values, indicative of residual morbidity after hormonal control. The presence of hypopituitarism worsens subjective QoL perception, which can improve after optimal substitution therapy, including recombinant human growth hormone, when indicated.

Conclusions: To improve the long-term outcome of pituitary patients, helping them to attain the best possible health, it appears desirable to include subjective aspects captured when evaluating QoL, so that the affected dimensions are identified and if relevant treated. Additionally, being aware that treatment outcome may not always mean complete normalisation of physical and mental issues related to QoL can be a first step to adaptation and conforming to this new status.
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http://dx.doi.org/10.1530/EJE-17-0041DOI Listing
July 2017

White matter involvement on DTI-MRI in Cushing's syndrome relates to mood disturbances and processing speed: a case-control study.

Pituitary 2017 Jun;20(3):340-348

Neuroradiology Unit, Hospital Sant Pau, IIB-Sant Pau, and UAB, C/ San Antoni Maria Claret 167, 08025, Barcelona, Spain.

Purpose: Cushing's syndrome (CS) is an endocrine disorder due to prolonged exposure to cortisol. Recently, microstructural white matter (WM) alterations detected by diffusion tensor imaging (DTI) have been reported in CS patients, and related to depression, but other functional significances. remain otherwise unclear. We aimed at investigating in more depth mood symptoms in CS patients, and how these relate to cognition (information processing speed), and to WM alterations on DTI.

Methods: The sample comprised 35 CS patients and 35 healthy controls. Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, State-Trait Anxiety Inventory (STAI) to assess anxiety, and processing speed was measured by the Symbol Digit Modalities Test (SDMT). DTI studies were acquired using a 3-Tesla Philips-Achieva MR-facility. Voxelwise statistical analysis of fractional anisotropy (FA), mean, axial and radial diffusivities (MD, AD, RD) data were performed using FMRIB Software Library. Correlation analysis were obtained between mood and processing speed variables, and FA, MD, AD and RD values, taking both CS patients and healthy controls.

Results: Active, controlled and cured CS patients showed greater depression (F = 12.4, p < 0.001), anxious state (F = 4.8, p = 0.005) and anxious trait (F = 9.6, p < 0.001) scores, than controls. Using the entire sample, depression scores correlated negatively to FA and positively to RD values. Although there were no differences in processing speed between groups, SDMT scores correlated positively to both FA and AD values.

Conclusions: There were greater depressive and anxious symptoms in CS patients than in healthy controls, but no difference in processing speed. However, DTI is related to depression and information processing speed in CS.
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http://dx.doi.org/10.1007/s11102-017-0793-yDOI Listing
June 2017

Cushing's syndrome and pregnancy outcomes: a systematic review of published cases.

Endocrine 2017 Feb 4;55(2):555-563. Epub 2016 Oct 4.

Endocrinology/Medicine Departments, Hospital Sant Pau, Barcelona, Spain.

Pregnancy in Cushing's syndrome (CS) is extremely rare due to the influence of hypercortisolism on the reproductive axis. Purpose of this study is to investigate whether the etiology of CS in pregnancy determines a different impact on the fetal/newborn and maternal outcomes. We performed a systematic review of cases published in the literature from January 1952 to April 2015 including the words "Cushing AND pregnancy". We included 168 manuscripts containing 220 patients and 263 pregnancies with active CS during pregnancy and with a history of CS but treated and cured hypercortisolism at the time of gestation. Adrenal adenoma was the main cause of active CS during pregnancy (44.1 %). Women with active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003), gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs. 2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss in active CS were etiology of hypercortisolism [Odds Ratio -OR-for pregnancy-induced CS 4.7 (95 % Confidence Interval-CI 1.16-18.96), p = 0.03], publication period [OR for "1975-1994" 0.10 (95 % CI 0.03-0.40), p = 0.001] and treatment during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06-1.02), p = 0.052], [OR surgical treatment 0.34 (95 % CI 0.11-1.06), p = 0.063]). The period of diagnosis of CS (before, during or after pregnancy) was the only predictor of overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI 1.37-15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes. Diagnosis of CS during pregnancy was also associated with worse overall fetal morbimortality. Both medical treatment and surgery during pregnancy appeared to be protective in avoiding fetal loss.
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http://dx.doi.org/10.1007/s12020-016-1117-0DOI Listing
February 2017

Reduced DNA methylation of FKBP5 in Cushing's syndrome.

Endocrine 2016 Dec 23;54(3):768-777. Epub 2016 Sep 23.

Departments of Psychiatry and Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing's syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation. Thirty-two Cushing's syndrome patients and 32 matched controls underwent memory tests, 3-Tesla MRI of the brain, and DNA extraction from total leukocytes. DNA samples were bisulfite treated, PCR amplified, and pyrosequenced to assess a total of 41CpG-dinucleotides in the introns 1, 2, 5, and 7 of FKBP5. Significantly lower intronic FKBP5 DNA methylation in CS patients compared to controls was observed in ten CpG-dinucleotides. DNA methylation at these CpGs correlated with left and right HV (Intron-2-Region-2-CpG-3: LHV, r = 0.73, p = 0.02; RHV, r = 0.58, p = 0.03). Cured and active CS patients showed both lower methylation of intron 2 (92.37, 91.8, and 93.34 %, respectively, p = 0.03 for both) and of intron 7 (77.08, 73.74, and 79.71 %, respectively, p = 0.02 and p < 0.01) than controls. Twenty-two subjects had the CC genotype, 34 had the TC genotype, and eight had the TT genotype. Lower average DNA methylation in intron 7 was observed in the TT subjects compared to CC (72.5vs. 79.5 %, p = 0.02) and to TC (72.5 vs. 79.0 %, p = 0.03). Our data demonstrate, for the first time, a reduction of intronic DNA methylation of FKBP5 in CS patients.
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http://dx.doi.org/10.1007/s12020-016-1083-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391874PMC
December 2016

Cortisol Excess and the Brain.

Front Horm Res 2016 17;46:74-86. Epub 2016 May 17.

Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required.
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http://dx.doi.org/10.1159/000443868DOI Listing
September 2017

Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.

Endocrine 2016 Sep 21;53(3):848-56. Epub 2016 Apr 21.

Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), C/Sant Antoni Maria Claret n.167, 08025, Barcelona, Spain.

Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety.
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http://dx.doi.org/10.1007/s12020-016-0963-0DOI Listing
September 2016

Cardiovascular risk and white matter lesions after endocrine control of Cushing's syndrome.

Eur J Endocrinol 2015 Dec;173(6):765-75

Endocrinology/Medicine DepartmentsHospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Sant Antoni Maria Claret n. 167, 08025 Barcelona, SpainNeuroradiology UnitHospital de Sant Pau, and IIB-Sant Pau, UAB, Barcelona, SpainINNDACYTAvda. Europa, 20, planta baja puerta D 08907, Hospitalet de Llobregat, SpainEscola Universitària d'InfermeriaHospital de Sant Pau. Universitat Autònoma de Barcelona (UAB), Barcelona, SpainDepartment of Psychiatry and Clinical PsychobiologyPsychology Faculty, Institute for Brain, Cognition and Behaviour (IR3C), Universitat de Barcelona (UB), Barcelona, Spain.

Objective: Cushing's syndrome (CS) is associated with high cardiovascular risk. White matter lesions (WML) are common on brain magnetic resonance imaging (MRI) in patients with increased cardiovascular risk.

Aim: To investigate the relationship between cardiovascular risk, WML, neuropsychological performance and brain volume in CS.

Design/methods: Thirty-eight patients with CS (23 in remission, 15 active) and 38 controls sex-, age- and education-level matched underwent a neuropsychological and clinical evaluation, blood and urine tests and 3Tesla brain MRI. WML were analysed with the Scheltens scale. Ten-year cardiovascular risk (10CVR) and vascular age (VA) were calculated according to an algorithm based on the Framingham heart study.

Results: Patients in remission had a higher degree of WML than controls and active patients (P<0.001 and P=0.008 respectively), which did not correlate with cognitive performance in any group. WML severity positively correlated with diastolic blood pressure (r=0.659, P=0.001) and duration of hypertension (r=0.478, P=0.021) in patients in remission. Both patient groups (active and in remission) had higher 10CVR (P=0.030, P=0.041) and VA than controls (P=0.013, P=0.039). Neither the 10CVR nor the VA correlated with WML, although both negatively correlated with cognitive function and brain volume in patients in remission (P<0.05). Total brain volume and grey matter volume in both CS patient groups were reduced compared to controls (total volume: active P=0.006, in remission P=0.012; grey matter: active P=0.001, in remission P=0.003), with no differences in white matter volume between groups.

Conclusions: Patients in remission of Cushing's syndrome (but not active patients) have more severe white matter lesions than controls, positively correlated with diastolic pressure and duration of hypertension. Ten-year cardiovascular risk and vascular age appear to be negatively correlated with the cognitive function and brain volume in patients in remission of Cushing's syndrome.
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http://dx.doi.org/10.1530/EJE-15-0600DOI Listing
December 2015

A specific nursing educational program in patients with Cushing's syndrome.

Endocrine 2016 Jul 23;53(1):199-209. Epub 2015 Sep 23.

Universitat Autónoma de Barcelona (UAB), 08193, Bellaterra (Cerdanyola del Vallès), Spain.

Cushing's syndrome (CS) is a rare endocrine disease, due to cortisol hypersecretion. CS patients have comorbidities, often still present after biochemical cure. Specific nursing healthcare programs to address this disease and achieve improved health related quality of life (HRQoL) are lacking. Thus, an educational nursing intervention, through the development and promotion of specific educational tools, appears to be justified. The objective of this study is to assess the effectiveness of an educational nursing program in CS patients on HRQoL, clinical parameters, level of pain and physical activity, patterns of rest, and use of health resources. A prospective, randomized study was conducted in two reference hospitals for CS. Sixty-one patients (mean age 47 ± 12.7 years, 83.6 % females) were enrolled and divided into 2 groups: an "intervention" group where educational sessions were performed over 9 months and a "control" group, without these sessions. Specific questionnaires were used at the beginning and end of the study. After educational sessions, the intervention group had a better score in the CushingQoL questionnaire (p < 0.01), reduced level of pain (p < 0.05), improved physical activity (p < 0.01) and healthy lifestyle (p < 0.001) compared to the control group. A correlation between the CushingQoL score and reduced pain (r = 0.46, p < 0.05), improved physical activity (r = 0.89, p < 0.01), and sleep (r = 0.53, p = 0.01) was observed. This educational nursing program improved physical activity, healthy lifestyle, better sleep patterns, and reduced pain in CS patients, influencing HRQoL and reducing consumption of health resources. Moreover, the brief nature of the program suggests it as a good candidate to be used in CS patients.
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http://dx.doi.org/10.1007/s12020-015-0737-0DOI Listing
July 2016

Quality of life in patients with hypopituitarism.

Curr Opin Endocrinol Diabetes Obes 2015 Aug;22(4):306-12

Endocrinology/Medicine Departments, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, U 747), IIB-Sant Pau, ISCIII, Hospital Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

Purpose Of Review: Quality 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 Findings: Recent 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 Cushing's 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.

Summary: Further improvement of QoL may be possible with individualized psychosocial interventions.
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http://dx.doi.org/10.1097/MED.0000000000000169DOI Listing
August 2015

Impaired decision making and delayed memory are related with anxiety and depressive symptoms in acromegaly.

Endocrine 2015 Dec 28;50(3):756-63. Epub 2015 May 28.

Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

Evaluation of cognitive function in acromegaly has revealed contradictory findings; some studies report normal cognition in patients with long-term cured acromegaly, while others show attention and memory deficits. Moreover, the presence of affective disorders in these patients is common. Our aim was to evaluate memory and decision making in acromegalic patients and explore their relationship with affective disorders like anxiety and depressive symptoms. Thirty-one patients with acromegaly (mean age 49.5 ± 8.5 years, 14 females and 17 males) and thirty-one healthy controls participated in this study. The Iowa Gambling Task (IGT), Rey Auditory Verbal Learning Test, State-Trait Anxiety Inventory, and Beck Depression Inventory-II (BDI-II) were used to evaluate decision making, verbal memory, anxiety, and depressive symptoms, respectively. Acromegalic patients showed impairments in delayed verbal memory (p < 0.05) and more anxiety and depressive symptoms (p < 0.05) than controls. In the IGT, acromegalic patients presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (p < 0.05) and higher number of the riskier cards (p < 0.05). Moreover, multiple correlations between anxiety and depressive symptoms and performance in memory and decision making were found. Impaired delayed memory and decision making observed in acromegalic patients are related to anxiety and depressive symptoms. Providing emotional support to the patients could improve their cognitive function. A key clinical application of this research is the finding that depressive symptoms and anxiety are essentially modifiable factors.
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http://dx.doi.org/10.1007/s12020-015-0634-6DOI Listing
December 2015