Protocolo asistencial clínico-psicológico para el tratamiento del tabaquismo con citisina / Clinical-psychological care protocol for the treatment of smoking with cytisine

Citisina es un tratamiento farmacológico del tabaquismo que ha sido introducido recientemente en nuestro país. Los estudios realizados con el mismo durante los últimos años muestran que es un tratamiento eficaz y seguro utilizado a dosis decrecientes durante un periodo de 25 días. Sus específicas características de dosis y tiempo de duración hacen recomendable que se diseñe un protocolo asistencial clínico-psicológico para ser desarrollado durante la utilización de citisina. Un grupo multidisciplinario de profesionales sanitarios expertos en tabaquismo han consensuado un protocolo que recomiendan para llevar a cabo en aquellos pacientes a los que se prescriba citisina como fármaco para dejar de fumar. (AU)

Cytisine is a smoking cessation medication that has appeared recently in Spain. It is effective and safe for helping smokers to quit using for 25 days. Its specific characteristicis in doses and duration recommends to desing a protocol clinical-psychological. A multidisciplinary group of health professionals experts on smoking cessation has designed a protocol to develop with patients who are receiving cytisineas medication for smoking cessation. (AU)

Disposable electrochemical sensor combined with molecularly imprinted solid-phase extraction for catabolites detection of flavan-3-ol in urine samples.

Polyphenols are bioactive substances of vegetal origin with a significant impact on human health. The assessment of polyphenol intake and excretion is therefore important. In this work, a new electrochemical approach based on molecularly imprinted polymer extraction and preconcentration, combined with a disposable carbon screen-printed sensor and adsorptive transfer differential pulse voltammetry detection has been proposed for quantifying of 4-hydroxyphenylacetic acid (4-HPA), which is a biomarker of flavan-3-ols intake, and other phenolic acids. The simple experimental performance has allowed the rapid data collection with relevant information about the profile of catabolites extracted. The method was validated over a concentration range of 10-200 mg L-1, R2 > 0.999. In the optimized conditions, the recovery value was 94% with RSD 8%. The limits of detection and quantification were 2.38 mg L-1 and 7.21 mg L-1, respectively. The method was validated by means of a chromatographic method, being the differences between the values of the 4-HPA concentrations obtained by both methods under 1%. The proposed method showed high recoveries, low detection limit, and good accuracy, providing a fast, reliable, and cheap procedure to quantify phenolic metabolites in urine, and representing therefore a good and interesting alternative method. Also, the procedure offers other advantages, including the miniaturization, the low use of organic solvents, the ability to analyse small volumes of samples, in situ analysis and simple instrumentation requirement.

The silent variants of pituitary tumors: demographic, radiological and molecular characteristics.

INTRODUCTION: Tumors of the anterior pituitary gland (PTs) are mostly benign tumors with a low prevalence, which has nevertheless increased with advances in brain radiology techniques. Nearly half of PTs are not associated with a clinical endocrine syndrome. These tumors have been indistinctly named non-functioning pituitary adenomas (NFPAs) or silent pituitary tumors (SPTs) and the mechanisms of silencing are not fully known. AIM: To study the frequency and characterize the silent variant of PTs in a large local series, and to assess their pituitary adenohypophyseal gene expression. METHODS: This observational, cross-sectional study was performed in a Pituitary Tumor Center of Excellence and involved 268 PTs. After identifying the different subtypes according to the immunohistochemical (IHC) expression of adenohypophyseal hormones, we studied their gene expression by RT-qPCR. RESULTS: We found that silent tumors were larger and more invasive, but not more proliferative than their functional counterparts. The RT-qPCR complements the IHC typification of PTs, reducing the proportion of null-cell subtype. Finally, some silent PT subtype variants showed lower specific adenohypophyseal hormone gene expression than their functional counterparts, which may contribute to the absence of endocrine manifestations. CONCLUSIONS: This paper highlights the importance of identifying the silent variant of the PTs subtypes. As expected, silent tumors were larger and more invasive than their functioning counterparts. However, there was no difference in the proliferation activity between them. Finally, the lower specific gene expression in the silent than in the functioning counterparts of some PTs subtypes gives insights into the silencing mechanisms of PTs.

Is Somatostatin Receptor and Dopamine Receptor profiling useful in the management of silent somatotroph tumors?

Silent somatotroph tumors (sSTs) are pituitary neuroendocrine tumors (PitNETs) which do not give rise to the clinical syndrome of acromegaly. Differently to their functioning counterparts, the adjuvant medical treatment with somatostatin analogues (SSAs) or dopamine receptors agonists (DAs) has been scarcely addressed in these tumors. As preliminary results of an ongoing research on silencing mechanisms involved in the pathogenesis of sSTs, we have characterized by qRT-PCR the expression of SSTRs and DRDs in a large series of 18 silent and 68 functioning STs. Although the expression of SSTR2 and SSTR5 was lower in sSTs than in functioning ones, we found a negative correlation between SSTR2 and the tumor size of the sSTs. Additionally, levels of expression of DRD2 were similar between the two subtypes suggesting a possible basis for the treatment of these tumors with SSAs and DAs.

Why don't corticotroph tumors always produce Cushing's disease?

OBJECTIVE: Silent corticotroph tumors are a pituitary neuroendocrine tumor subtype of corticotroph lineage that do not clinically express Cushing's disease. The silencing of this type of tumor is not fully understood. The aim of the present study was to delve into the lack of secretory activity, studying the post-transcriptional and post-translational regulation of POMC/ACTH in a series of molecularly identified functioning and silent corticotroph tumors. DESIGN: We analyzed 24 silent corticotroph, 23 functioning corticotroph and 25 silent gonadotroph tumors. METHODS: We used Sanger sequencing, quantitative real-time PCR and Western blot to analyze genetic alterations in POMC, gene expression of TBX19, NEUROD1, POMC, PCSK1, PCSK2, CPE and PAM and protein expression of POMC, PC1/3, PC2, CPE and PAM. RESULTS: We found different polymorphisms in the POMC gene of corticotroph tumors, some of them related to deficiency of proopiomelanocortin. Silent corticotroph tumors showed lower PC1/3 gene and protein expression than functioning ones, especially compared to micro-functioning corticotroph tumors (all P < 0.05). Moreover, we found a positive correlation between PC2 and CPE gene and protein expression (rho ≥ 0.670, P < 0.009) in silent corticotroph tumors compared with functioning ones. CONCLUSIONS: By studying the post-transcriptional and post-translational processing of POMC and ACTH, respectively, in a large series of silent and functioning corticotroph tumors, we found that the lack of secretory activity of these tumors is related to an impaired processing of POMC and a high degradation of ACTH, with the macro-functioning corticotroph tumor behaving as an intermediate state between micro-functioning and silent corticotroph tumors.

[The return of the statisticians. On the value of statistics in clinical neuropsychology]. / El regreso de los estadisticos. Sobre el valor de la estadistica en neuropsicologia clinica.

There was a time when clinicians looked down on any decision-making that did not depend on their own judgement. Statisticians laughed at such naivety, as they were fully aware of the extent to which the heuristics that guide human decisions are capable of error, even in the most highly trained individuals. More than 60 years after the beginning of this conflict, the two standpoints have still not been adopted in clinical psychology or in neuropsychology. This work defends the practical application of statistics in clinical decision-making and shows that even intuitive-type judgement is somehow based on applying the basic use of statistical concepts, without neglecting the fact that statistical instruments have sometimes been misused. To this end, this study compares the opinions offered by some clinicians in sentence form with the bibliography consulted, which spans the period from the earliest works by the clinical psychologist Paul Meehl to the present day. We have no intention whatsoever of imposing an opinion, but instead of discussing the advantage of adopting an approach that uses mathematical knowledge to support clinical decision-making. Attention is also drawn to the need for multidisciplinary teams in the special units of our hospitals.

TITLE: El regreso de los estadisticos. Sobre el valor de la estadistica en neuropsicologia clinica.Hubo un tiempo en que los clinicos despreciaban cualquier toma de decisiones que no dependiera de su propio juicio. Los estadisticos se reian de tal ingenuidad, conociendo lo falible de los heuristicos que guian las decisiones humanas, incluso en los individuos mas entrenados. Tras mas de 60 años del inicio del enfrentamiento, ambas posturas aun no se han asimilado en psicologia clinica ni en neuropsicologia. El presente trabajo respalda la aplicacion practica de la estadistica en la toma de decisiones clinica y muestra que incluso el juicio de tipo intuitivo descansa de algun modo en la aplicacion del uso basico de conceptos estadisticos, sin obviar que en ocasiones se ha hecho mal uso de las herramientas estadisticas. Para ello contrasta las opiniones ofrecidas por algunos clinicos en forma de frase con la bibliografia consultada, que se extiende desde los primeros trabajos del psicologo clinico Paul Meehl hasta la actualidad. Lejos de querer imponer una opinion, se comenta la ventaja de asumir un enfoque que aproveche los conocimientos matematicos como apoyo a la toma de decisiones clinica. Finalmente se comenta la necesidad de equipos multidisciplinares en las unidades especiales de nuestros centros hospitalarios.

Impact of circulating bacterial DNA in long-term glucose homeostasis in non-diabetic patients with HIV infection: cohort study.

In HIV-infected patients, the damage in the gut mucosal immune system is not completely restored after antiretroviral therapy (ART). It results in microbial translocation, which could influence the immune and inflammatory response. We aimed at investigating the long-term impact of bacterial-DNA translocation (bactDNA) on glucose homeostasis in an HIV population. This was a cohort study in HIV-infected patients whereby inclusion criteria were: patients with age >18 years, ART-naïve or on effective ART (<50 HIV-1 RNA copies/mL) and without diabetes or chronic hepatitis C. Primary outcome was the change in HbA1c (%). Explanatory variables at baseline were: bactDNA (qualitatively detected in blood samples by PCR [broad-range PCR] and gene 16SrRNA - prokaryote), ART exposure, HOMA-R and a dynamic test HOMA-CIGMA [continuous infusion of glucose with model assessment], hepatic steatosis (hepatic triglyceride content - 1H-MRS), visceral fat / subcutaneous ratio and inflammatory markers. Fifty-four men (age 43.2 ± 8.3 years, BMI 24.9 ± 3 kg/m2, mean duration of HIV infection of 8.1 ± 5.3 years) were included. Baseline HbA1c was 4.4 ± 0.4% and baseline presence of BactDNA in six patients. After 8.5 ± 0.5 years of follow-up, change in HbA1c was 1.5 ± 0.47% in patients with BactDNA vs 0.87 ± 0.3% in the rest of the sample p < 0.001. The change in Hba1c was also influenced by protease inhibitors exposure, but not by baseline indices of insulin resistance, body composition, hepatic steatosis, inflammatory markers or anthropometric changes. In non-diabetic patients with HIV infection, baseline bacterial translocation and PI exposure time were the only factors associated with long-term impaired glucose homeostasis.

Safety of long-term treatment with Pegvisomant: analysis of Spanish patients included in global ACROSTUDY.

PURPOSE: To evaluate the long-term safety of Pegvisomant (PEG) in the Spanish cohort of ACROSTUDY. METHODS: As of July 2013, 199 Spanish patients were included in ACROSTUDY, a global non interventional safety PEG surveillance study. Patients were observed for safety, biochemical outcome and magnetic resonance imaging evaluations. RESULTS: PEG was administered during an average period of 6.7 ± 2.1 years and a mean daily dose of 15.5 ± 7.5 mg. 48.2% of patients received PEG monotherapy. 90.9% of patients had received other medical treatment before PEG start. 195 adverse events (AEs) were reported in 88 patients (44.2%), and serious AEs were described in 31 patients (15.6%). There were no cases of liver tests >10 ULN, or permanent liver damage. Tumor size changes were locally reported in 61 cases (33.5%), with increases observed in 11 patients (6%). In acromegalic patients with diabetes mellitus a decrease in fasting serum glucose value was reported, reaching statistical significance after 1 and 4 years of treatment (-24.6 and -25.9 mg/dl, p = 0.04). After 60 months, normal or lower limit of normal (LLN) IGF-I levels were found in 67.9% of patients. 85.5% of patients showed an IGF-I normal or

Biological markers of fertility (inhibin-B) in HIV-infected men: influence of HIV infection and antiretroviral therapy.

OBJECTIVES: Inhibin B (IB) levels and the IB: follicle-stimulating hormone (FSH) ratio (IFR), biomarkers of global Sertoli cell function, show a strong relationship with male fertility. The aim of the study was to examine the prevalence of impaired fertility potential in HIV-infected men and the influence of antiretroviral therapy (ART) on fertility biomarkers. METHODS: A cross-sectional study with sequential sampling was carried out. A total of 169 clinically stable patients in a cohort of HIV-infected men undergoing regular ambulatory assessment in a tertiary hospital were included. The mean [± standard deviation (SD)] age of the patients was 42.6 ± 8.1 years, all were clinically stable, 61.5% had disease classified as Centers for Disease Control and Prevention (CDC) stage A, and were na?ve to ART or had not had any changes to ART for 6 months (91.1%). Morning baseline IB and FSH concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and an electrochemiluminescent immunoassay (ECLIA), respectively. A multivariate logistic regression model was used to identify factors associated with impaired fertility, defined as IB < 119 pg/mL or IFR < 23.5. RESULTS: The mean (± SD) IB level was 250 ± 103 pg/mL, the median [interquartile range (IQR)] FSH concentration was 5.1 (3.3-7.8) UI/L and the median (IQR) IFR was 46.1 (26.3-83.7). The prevalence of impaired fertility was 21.9% [95% confidence interval (CI) 16.3-20.7%]. Negative correlations of body mass index and waist: hip ratio with FSH and IB levels were observed (P < 0.01), while a sedentary lifestyle and previous nevirapine exposure were associated with a decreased risk of IB levels ≤ 25th percentile in multivariate analysis. Only older age, as a risk factor, and sedentary lifestyle, with a protective effect, were independently associated with impaired fertility in multivariate analysis. CONCLUSIONS: Global testicular Sertoli cell function and fertility potential, assessed indirectly through serum IB levels and IB: FSH ratio, appear to be well maintained in HIV-infected men and not damaged by ART.

Synthesis of a molecularly imprinted polymer for the isolation of 1-hydroxypyrene in human urine.

In the last decades, the assessment of polycyclic aromatic hydrocarbons' exposure has generated great interest and 1-hydroxypyrene (1-OHP) has been commonly used as a biological indicator of exposure to PAHs in many studies in environmental and occupational health. In this research, a molecularly imprinted polymer (MIP) was synthesised by precipitation polymerisation using 1-OHP as template, methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as cross-linker, and acetonitrile as porogen. MIP was used as solid-phase extraction (SPE) material for sample pretreatment and isolation of 1-OHP and posterior detection in a reversed-phase HPLC-FLD. Various parameters including washing solvent, elution solvent and volume affecting the extraction efficiency of the polymer have been evaluated to achieve the isolation of 1-OHP from urine samples and to reduce non-specific interactions. Cross-selectivity was studied in the presence of other structural analogues of the 1-OHP as hydroxyphenantrene isomers. The method was validated over a concentration range of 0.15-2.00 µg L(-1), R(2)>0.998. Recovery values were in the range of 78-90% and RSD <6.7%. The limits of detection and quantification were 0.05 µg L(-1) and 0.17 µg L(-1), respectively. In our knowledge, it is the first time that this methodology is applied for analysing urinary hydroxypyrene and it has been demonstrated that this specific MISPE-HPLC-FLD method offers a fast and simple alternative to determine 1-OHP in human urine samples.

An HPLC-DAD method for the simultaneous determination of nine ß-lactam antibiotics in ewe milk.

The presence of ß-lactam residues in foodstuffs constitutes a potential risk to the human health and undesirable effects on consumers, and nowadays these antibiotic residues are also recognised as an emerging environmental problem. In addition, these are of great concern to prestigious Manchego cheese processors (Central Spain denomination of origin) because they reduce the curdling of milk and cause improper cheese ripening, which consequently lead to an important loss of monetary income. This work describes the development of a sensitive and reliable method using liquid chromatography with UV-diode array detection (LC-DAD) for simultaneous determination of the ß-lactam antibiotics, ampicillin (AMP), benzylpenicillin (PEG), cephalexin (CFX), cefazolin (CFL), cefoperazone (CFP), cloxacillin (CLO), dicloxacillin (DCL), oxacillin (OXA) and phenoxymethylpenicillin (PEV), in Manchega ewe milk. The column, mobile phase, temperature and flow rate were optimised to provide the best resolution of these analytes. The extraction method of the antibiotic residues involves the deproteinisation of the milk sample using acetonitrile and centrifugation followed by a solid-phase extraction (SPE) clean-up. The recoveries for the studied ß-lactams ranged from 79% to 96% with relative standard deviations between 0.5% and 4.9%. The limits of quantification (LOQs) for all these compounds were in the range of 3.4-8.6µgkg(-1), which are lower than the maximum residue limits (MRLs) established by the European Union for the studied ß-lactams in milk, making the method suitable for performing routine analyses. The proposed multi-residue LC-UV-diode array detection (LC-DAD) method is a powerful and popular alternative for the determination and confirmation of antibiotic residues in small milk industries and is the first one capable of determining nine ß-lactam antibiotics in samples of Manchega ewe milk.

Impact of vitamin D insufficiency on insulin homeostasis and beta cell function in nondiabetic male HIV-infected patients.

OBJECTIVES: Vitamin D is thought to play a role in glucose homeostasis and beta cell function. Our aim was to examine the impact of plasma 25-hydroxyvitamin D [25(OH)D] upon in vivo insulin sensitivity and beta cell function in HIV-infected male patients without diabetes. METHODS: A cross-sectional study was carried out involving a cohort of HIV-infected patients undergoing regular assessment in a tertiary hospital. Eighty-nine patients [mean (± standard deviation) age 42 ± 8 years] were included in the study: 14 patients were antiretroviral therapy (ART)-naïve, while 75 were on ART. Vitamin D insufficiency (VDI) was defined as 25(OH)D < 75 nmol/L; insulin sensitivity was determined using a 2-h continuous infusion of glucose model assessment with homeostasis (CIGMA-HOMA), using the trapezoidal model to calculate the incremental insulin and glucose areas under the curve (AUCins and AUGglu, respectively). Beta cell function was assessed using the disposition index (DI). Abdominal visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) were measured by magnetic resonance imaging (MRI) and 1-H magnetic resonance spectroscopy. Multivariate linear regression analysis was performed. RESULTS: VDI was associated with insulin resistance (IR), as indicated by a higher CIGMA-HOMA index (odds ratio 1.1) [1.01-1.2]. This association was independent of the main confounders, such as age, Centers for Disease Control and Prevention (CDC) stage, ART, lipodystrophy, body mass index, VAT:subcutaneous adipose tissue ratio and HTGC, as confirmed by multivariate analysis (B = 12.3; P = 0.01; r² = 0.7). IR in patients with VDI was compensated by an increase in insulin response. However, beta cell function was lower in the VDI subpopulation (33% decrease in DI). CONCLUSIONS: VDI in nondiabetic HIV-positive male patients is associated with impaired insulin sensitivity and a decrease in pancreatic beta cell function.

Characterization of Spanish honeys with protected designation of origin "Miel de Granada" according to their mineral content.

Honey attributes such as geographical origin or specified botanical sources often command a premium price due to their organoleptic or pharmacoactive properties. "Miel de Granada" is a highly quality product with protected designation of origin (PDO) which includes six monofloral honeys and two multifloral honeys. Our objective was the characterization of "Miel de Granada" according to their metal content. Metal content was specific enough and allowed discrimination from honeys of different botanical and geographical origins and confirmed the authenticity of PDO labelling as Granada product with the determination of only five elements (K, Na, Ca, Mg and Zn). Chemometric techniques as cluster analysis and ANOVA were used to classify honeys according to their botanical and geographical origin in the metal data. Metal content marks the differences in honey samples and can be used as a tool to assess the quality of honeys. ANOVA showed significant differences among rosemary honeys from different geographical areas despite the botanical factor weight. Our research contributes to the groundwork studies to determine the geographical origin of Spanish honeys.

Development of a molecularly imprinted polymer-matrix solid-phase dispersion method for selective determination of ß-estradiol as anabolic growth promoter in goat milk.

A simple, fast, and sensitive method for determination of 17 ß-estradiol (E2) in goat milk samples has been developed by combining selective molecularly imprinted matrix solid-phase dispersion (MIP-MSPD) and liquid chromatography with diode-array detection (DAD). The molecularly imprinted polymer was synthesized by use of 17ß-estradiol as template molecule, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as crosslinker monomer, azobisisobutyronitrile as initiator, and acetonitrile as porogen, and was used as selective solid support for matrix solid-phase dispersion. The selected dispersant had high affinity for E2 in the goat milk matrix and the extract obtained was sufficiently clean for direct injection for HPLC analysis without any interferences from the matrix. The proposed MIP-MSPD method was validated for linearity, precision, accuracy, decision limit (CCα) and detection capability (CCß), in accordance with European Commission Decision 2002/657/EC criteria. Linearity ranged from 0.3-10 µg g(-1) (correlation coefficient r(2) > 0.999). Mean recovery of E2 from goat milk samples at different spiked levels was between 89.5 and 92.2%, with RSD values within 1.3-2%. CCα and CCß values were 0.36 and 0.39 µg g(-1), respectively. The developed MIP-MSPD method was successfully applied to direct determination of E2 in goat milk samples.

Customization of entropy estimation measures for human arterial hypertension records segmentation.

This paper describes a new application of the recently developed Coefficient of Sample Entropy (CosEn) measure. This entropy estimator is specially suited for cases where the length of the time series is extremely short. CosEn has already been used successfully to characterize and detect atrial fibrillation, using as few as 12 heartbeats. We have customized the methodology employed for heartbeat interval series to blood pressure hypertensive (BPHT) human records. Little can be found about BPHT records and its nonlinear regularity analysis. The method described in this paper provides a good segmentation between control and pathologic groups, based on the corresponding labeled BPHT records. The experimental dataset was drawn from the available records at the Hypertension Unit of the University Hospital of Mostoles, in Spain. The hypertension related variables studied were systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP). The hypothesis test yielded the following results in each case: acceptance probability of 0 for SBP, 0.005 for DBP and 0 for MBP. The confidence intervals for the three variables were nonoverlapping.

Characterization of detrended fluctuation analysis in the context of glycemic time series.

There is a growing interest in the analysis of hyperglycemia and its relationship with other pathologies. The level of glucose in blood is regulated by the flux/reflux and controlled by hyperglycemia hormones and hypoglycemic insulin. Glycemic profiles are characterized by a nonlinear and nonstationary behavior but also influenced by circadian rhythms and patient daily routine which introduce quasi-periodic trends into them. This type of signals are commonly analyzed by Detrended Fluctuation Analysis (DFA) which states that the control system in charge of regulating the glucose level usually holds a long-range negative correlation. But there is an inconsistency about the windowing lengths, as no standard or rules are set. This work studies the influence of the windowing length sequence, and shows that there is a need for selecting the optimal values in order to obtain a good differentiation between different groups, and these values are somehow determined by signal characteristics.

Comparative study between Sample Entropy and Detrended Fluctuation Analysis performance on EEG records under data loss.

This study compares two signal entropy measures, Sample Entropy (SampEn) and Detrended Fluctuation Analysis (DFA) over real EEG signals after a randomized sample removal. Both measures have demonstrated their ability to discern between, among others: control and pathologic EEG signals, seizure free or not, control and opened eyes EEG, and side of brain signals. Results show that SampEn behaves better when analyzing control signals, while DFA provides better segmentation results between epileptic signals, in the context of sample loss, particularly when discerning between seizure and seizure free signal intervals.

Merits and pitfalls of mifepristone in Cushing's syndrome.

OBJECTIVE: Mifepristone is the only available glucocorticoid receptor antagonist. Only few adult patients with hypercortisolism were treated to date by this drug. Our objective was to determine effectiveness and tolerability of mifepristone in Cushing's syndrome (CS). DESIGN: Retrospective study of patients treated in seven European centers. METHODS: Twenty patients with malignant (n=15, 12 with adrenocortical carcinoma, three with ectopic ACTH secretion) or benign (n=5, four with Cushing's disease, one with bilateral adrenal hyperplasia) CS were treated with mifepristone. Mifepristone was initiated with a median starting dose of 400 mg/day (200-1000). Median treatment duration was 2 months (0.25-21) for malignant CS, and 6 months (0.5-24) for benign CS. Clinical (signs of hypercortisolism, blood pressure, signs of adrenal insufficiency), and biochemical parameters (serum potassium and glucose) were evaluated. RESULTS: Treatment was stopped in one patient after 1 week due to severe uncontrolled hypokalemia. Improvement of clinical signs was observed in 11/15 patients with malignant CS (73%), and 4/5 patients with benign CS (80%). Psychiatric symptoms improved in 4/5 patients within the first week. Blood glucose levels improved in 4/7 patients. Signs of adrenal insufficiency were observed in 3/20 patients. Moderate to severe hypokalemia was observed in 11/20 patients and increased blood pressure levels in 3/20 patients. CONCLUSION: Mifepristone is a rapidly effective treatment of hypercortisolism, but requires close monitoring of potentially severe hypokalemia, hypertension, and clinical signs of adrenal insufficiency. Mifepristone provides a valuable treatment option in patients with severe CS when surgery is unsuccessful or impossible.