RESUMO
Congenital adrenal hyperplasia is a group of autosomal recessive disorders leading to multiple complex hormonal imbalances caused by various enzyme deficiencies in the adrenal steroidogenic pathway. The most common type of congenital adrenal hyperplasia is due to steroid 21-hydroxylase (21-OHase, henceforth 21OH) deficiency. The rare, classic (severe) form caused by 21OH deficiency is characterised by life-threatening adrenal crises and is the most common cause of atypical genitalia in neonates with 46,XX karyotype. After the introduction of life-saving hormone replacement therapy in the 1950s and neonatal screening programmes in many countries, nowadays neonatal survival rates in patients with congenital adrenal hyperplasia are high. However, disease-related mortality is increased and therapeutic management remains challenging, with multiple long-term complications related to treatment and disease affecting growth and development, metabolic and cardiovascular health, and fertility. Non-classic (mild) forms of congenital adrenal hyperplasia caused by 21OH deficiency are more common than the classic ones; they are detected clinically and primarily identified in female patients with hirsutism or impaired fertility. Novel treatment approaches are emerging with the aim of mimicking physiological circadian cortisol rhythm or to reduce adrenal hyperandrogenism independent of the suppressive effect of glucocorticoids.
Assuntos
Hiperplasia Suprarrenal Congênita , Recém-Nascido , Humanos , Feminino , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Glucocorticoides/uso terapêutico , Hidrocortisona/uso terapêutico , Terapia de Reposição Hormonal , Triagem NeonatalRESUMO
BACKGROUND: OpenAI's ChatGPT is a pioneering artificial intelligence (AI) in the field of natural language processing, and it holds significant potential in medicine for providing treatment advice. Additionally, recent studies have demonstrated promising results using ChatGPT for emergency medicine triage. However, its diagnostic accuracy in the emergency department (ED) has not yet been evaluated. OBJECTIVE: This study compares the diagnostic accuracy of ChatGPT with GPT-3.5 and GPT-4 and primary treating resident physicians in an ED setting. METHODS: Among 100 adults admitted to our ED in January 2023 with internal medicine issues, the diagnostic accuracy was assessed by comparing the diagnoses made by ED resident physicians and those made by ChatGPT with GPT-3.5 or GPT-4 against the final hospital discharge diagnosis, using a point system for grading accuracy. RESULTS: The study enrolled 100 patients with a median age of 72 (IQR 58.5-82.0) years who were admitted to our internal medicine ED primarily for cardiovascular, endocrine, gastrointestinal, or infectious diseases. GPT-4 outperformed both GPT-3.5 (P<.001) and ED resident physicians (P=.01) in diagnostic accuracy for internal medicine emergencies. Furthermore, across various disease subgroups, GPT-4 consistently outperformed GPT-3.5 and resident physicians. It demonstrated significant superiority in cardiovascular (GPT-4 vs ED physicians: P=.03) and endocrine or gastrointestinal diseases (GPT-4 vs GPT-3.5: P=.01). However, in other categories, the differences were not statistically significant. CONCLUSIONS: In this study, which compared the diagnostic accuracy of GPT-3.5, GPT-4, and ED resident physicians against a discharge diagnosis gold standard, GPT-4 outperformed both the resident physicians and its predecessor, GPT-3.5. Despite the retrospective design of the study and its limited sample size, the results underscore the potential of AI as a supportive diagnostic tool in ED settings.
Assuntos
Serviço Hospitalar de Emergência , Humanos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Estudos Retrospectivos , Idoso , Feminino , Pessoa de Meia-Idade , Masculino , Idoso de 80 Anos ou mais , Inteligência Artificial , Médicos/estatística & dados numéricos , Processamento de Linguagem Natural , Triagem/métodosRESUMO
INTRODUCTION: To evaluate scalp hair steroid concentrations as a monitoring tool for androgen control and metabolic outcomes in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. METHODS: 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, cortisol, cortisone, progesterone, prednisolone, and prednisone concentrations were measured in scalp hair by means of LC-MS/MS in 27 women and 15 men with CAH and controls (37 women, 42 men). RESULTS: In CAH men and women, 17-OHP levels in hair showed a significant positive correlation with corresponding levels in serum (ρ = 0.654; p = 0.01; ρ = 0.553, p = 0.003 respectively), while total testosterone levels were only significantly correlated in CAH men (ρ = 0.543; p = 0.036). Androstenedione levels did not show a significant correlation. Receiver-operating characteristic (ROC) curve analysis indicated that a cutoff value of 21.7 pg/mg for 17-OHP in hair provided a sensitivity of 100% and a specificity of 88.9% for identifying men with elevated serum androstenedione. Hair 17-OHP in women showed a poorer performance in terms of identifying those with elevated androstenedione serum levels. However, when applying a cutoff value of 5.5 for the free androgen index as a marker of significant hyperandrogenism in CAH women, 17-OHP >27.6 pg/mg in hair provided a sensitivity of 100% and a specificity of 95.8% (AUC 0.986, 95% CI 0.945-1.000; p < 0.001). Neither hair cortisol nor markers of adrenal androgen control in hair showed significant associations with cardiometabolic outcome or bone health. CONCLUSION: This study shows that scalp hair 17-OHP concentrations may be a promising noninvasive long-term parameter for treatment monitoring in adult patients with CAH.
Assuntos
17-alfa-Hidroxiprogesterona/metabolismo , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/metabolismo , Cabelo/metabolismo , 17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/sangue , Adulto , Androstenodiona/sangue , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: One of the most prominent etiological theories of gender incongruence in trans women proposes a paraphilic erotic target location error (ie, autogynephilia) as a causal factor in gynephilic (ie, exclusively gynephilic and bisexual) trans women. We hypothesized that a paraphilic erotic target location should manifest itself in various aspects of sexual behavior, solitary and dyadic sexual desire, and psychosexual experience. AIM: To compare sexual behavior, sexual desire, and psychosexual experience of exclusively gynephilic and bisexual trans women with that of androphilic trans women to explore whether their sexuality differs substantially. METHODS: Trans women diagnosed with gender dysphoria (Diagnostic and Statistical Manual of Mental Disorders-5) were recruited at 4 transgender healthcare centers in Germany. The present study analyzed items on sexual behavior, desire, and experience of a self-report questionnaire, collected as part of a cross-sectional multicenter study. MAIN OUTCOMES: Multiple aspects of sexuality were examined using self-constructed items. Sexual desire was measured using the Sexual Desire Inventory and psychosexual experience using the Multidimensional Sexuality Questionnaire. RESULTS: Significantly more exclusively gynephilic than androphilic trans women reported a history of sexual arousal in relation to cross-dressing. However, little evidence was found that gynephilic and androphilic sexual desire, behavior, and psychosexual experience differ profoundly. Interestingly, a statistically non-significant trend indicated that gynephilic trans women who had not yet undergone gender affirming surgery showed the highest levels of sexual desire (solitary and dyadic), whereas the opposite was the case for androphilic trans women. CLINICAL TRANSLATION: Data of this study indicate that sexual orientation does not appear to be a good predicator for sexual behavior, desire, and psychosexual experience in trans women. STRENGTHS AND LIMITATIONS: We investigated sexual desire and experience using standardized and evaluated measures such as the Sexual Desire Inventory and Multidimensional Sexuality Questionnaire. Future studies with a larger sample size should investigate how different gender affirming medical intervention might have diverging influences on sexual behavior, desire, and experience. CONCLUSION: Ultimately, this study found little evidence for the hypothesis that sexual behavior, sexual desire, and psychosexual experience differ substantially in gynephilic (exclusively gynephilic and bisexual) and androphilic trans women. Laube JS, Auer M, Biedermann SV, et al. Sexual Behavior, Desire, and Psychosexual Experience in Gynephilic and Androphilic Trans Women: A Cross-Sectional Multicenter Study. J Sex Med 2020;17:1182-1194.
Assuntos
Comportamento Sexual , Transexualidade , Estudos Transversais , Feminino , Identidade de Gênero , Alemanha , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
PURPOSE: Patients with non-functioning pituitary adenomas (NFPA) suffer from pronounced impairments in physical and mental measures that result in an impairment of health-related quality of life (HRQOL). The role of secondary adrenal insufficiency (SAI) and especially the one of the hydrocortisone (HC) replacement dose on the HRQOL seems to be conflicting. The primary aim of this study is to assess the HRQOL in patients with NFPA in terms of presence of SAI and in patients without SAI and the secondary to explore the impact of treatment parameters such as daily HC dose. DESIGN/METHODS: In a cross-sectional study we evaluated parameters of HRQOL in 95 patients with NFPA of the Endocrine Outpatient Unit of the Max Planck Institute of Psychiatry in Munich using standardized questionnaires like Short Form (SF-36), Beck's Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and a self-constructed questionnaire about medical history. RESULTS: We could not find any significant difference between patients with and without SAI in the standardized questionnaires in terms of HRQOL. We could show that higher doses of HC were negatively correlated with HRQOL measured by SF-36 global health score regardless of using BDI or STAI in the block (ß = - 0.397; p = 0.021, ß = - 0.390; p = 0.016, respectively). CONCLUSIONS: NFPA patients with SAI do not have a worse HRQOL than patients with NFPA and intact corticotropic axis. We could show that higher doses of HC are associated with an impaired HRQOL measured by SF-36 global and physical health score, whereas mental health score is not significantly influenced by the HC dose.
Assuntos
Adenoma/tratamento farmacológico , Adenoma/psicologia , Hidrocortisona/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/psicologia , Qualidade de Vida/psicologia , Estudos Transversais , Feminino , Humanos , Hidrocortisona/farmacologia , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
PURPOSE: To develop a multidimensional and integrated clinical scoring instrument, that encompasses, summarizes and weights appropriately the desired clinical benefits of a treatment for Cushing's disease (CD). METHODS: A panel of 42 variables potentially relevant to the clinical course of CD was predefined by endocrinology experts taking into account relevant literature. Variables as well as biochemical disease activity assessed as urinary free cortisol (UFC) levels were evaluated at baseline and at least after 12 months in patients treated between 2012 and 2016 in two Munich-based academic centres of the German Cushing's Registry. The primary endpoint was the identification of variables whose changes from baseline to follow-up visit(s) could characterize well biochemical cured from not cured patients after 12 months. RESULTS: Ninety nine patients with at least two consecutive visits were enrolled. Biochemical data were available for 138 visit-pairs among which UFC was not controlled in 48 (34.8%) and controlled in 90 (65.2%) first visits. In 41 (29.7%) consecutive visits (visit-pairs) changes in biochemical activity categories was observed between visits; concretely: in 17 (12.3%) consecutive visits changing from previously controlled to not controlled, and in 24 (17.4%) from uncontrolled to controlled biochemical activity. Multivariate statistical analyses (especially analyses of variance) based on data of the 138 visit-pairs were performed in order to proof possible effects of biochemical activity on clinical benefits. However, in none of the considered 42 variables corresponding to quality of life-dimensions, laboratory, anthropometric, musculo-skeletal or other clinical areas any statistically significant differences between different categories of biochemical activity were observed. CONCLUSION: It was not possible to provide clinical key parameters in our population of patients with CD discriminating biochemical cured from non-cured patients and to construct a clinical scoring system reflecting clinical treatment benefits.
Assuntos
Síndrome de Cushing/diagnóstico , Hipersecreção Hipofisária de ACTH/diagnóstico , Síndrome de Cushing/urina , Feminino , Humanos , Hidrocortisona/urina , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hipersecreção Hipofisária de ACTH/urina , Qualidade de Vida , Sistema de Registros/estatística & dados numéricosRESUMO
BACKGROUND: Many trans individuals undergo medical interventions that result in irreversible loss of fertility. Little is known about their desire to have children and attitudes toward fertility preservation options. AIM: To study how the desire for children and the use of fertility preservation options varies among trans women and trans men in different transitioning stages in Germany. METHODS: In this cross-sectional multi-center study, N = 99 trans women and N = 90 trans men were included. Of these, 26 of each sex were just about to start medical treatment. OUTCOMES: Outcome parameter were the prevalence and determinants of a desire to have children in trans persons. RESULTS: Before treatment, a desire for children was significantly higher in trans men compared to trans women (P = .016). In contrast, in those who had already started treatment, a current desire to have children was equally present in about one fourth of participants of both genders while the interest in having children in the future was significantly higher in trans women (69.9%) than in trans men (46.9%; P = .034). Although 76.1% of trans women and 76.6% of trans men indicated that they had at least thought about preserving germ cells before starting medical transition, only 9.6% of trans women and 3.1% of trans men had put this idea into practice. Most trans men in both groups indicated that insemination of a female partner with sperm from an unrelated donor was a suitable option to fulfill their child wish, potentially explaining their low interest in preserving their own germ cells. Finally, a logistic regression analysis accounting for potential confounders revealed that overall trans women were more than twice as likely to have a current desire to have children (odds ratio 2.58), and this wish was on average 5.3% lower with each year of increasing age. CLINICAL TRANSLATION: A low level of fertility preservation among trans persons is contrasted by a high level of desire for children. This highlights the importance of counseling trans individuals regarding fertility preservation options. CONCLUSIONS: To our knowledge, this is the first study that addresses desire to have children in a clinical sample of trans women. It is also the first that investigates this issue among trans men who have not started medical treatment, and the first comparison of both genders. A limitation for the generalization of our results is the special legal context in Germany that forbids oocyte donation for reciprocal in vitro fertilization. Reproductive desire is high among trans individuals, but the use of reproductive options is surprisingly low. Auer MK, Fuss J, Nieder TO, et al. Desire to Have Children Among Transgender People in Germany: A Cross-Sectional Multi-Center Study. J Sex Med 2018;15:757-767.
Assuntos
Características da Família , Pessoas Transgênero/psicologia , Adulto , Aconselhamento , Estudos Transversais , Feminino , Preservação da Fertilidade , Fertilização in vitro , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Exercise is rewarding, and long-distance runners have described a runner's high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both ß-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner's high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.
Assuntos
Condicionamento Físico Animal , Receptor CB1 de Canabinoide/fisiologia , Receptor CB2 de Canabinoide/fisiologia , Corrida , Animais , Comportamento Animal , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. METHODS: Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level. RESULTS: Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants' with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants' acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. CONCLUSION: These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.
Assuntos
Ansiedade/psicologia , Aprendizagem da Esquiva , Adulto , Ansiedade/diagnóstico , Aprendizagem da Esquiva/efeitos dos fármacos , Feminino , GABAérgicos/farmacologia , Humanos , Masculino , Aprendizagem em Labirinto , Pessoa de Meia-Idade , Realidade VirtualRESUMO
BACKGROUND: Endocannabinoids are critical for rewarding behaviors such as eating, physical exercise, and social interaction. The role of endocannabinoids in mammalian sexual behavior has been suggested because of the influence of cannabinoid receptor agonists and antagonists on rodent sexual activity. However, the involvement of endocannabinoids in human sexual behavior has not been studied. AIM: To investigate plasma endocannabinoid levels before and after masturbation in healthy male and female volunteers. OUTCOMES: Plasma levels of the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide, the endocannabinoid-like lipids oleoyl ethanolamide and palmitoyl ethanolamide, arachidonic acid, and cortisol before and after masturbation to orgasm. METHODS: In study 1, endocannabinoid and cortisol levels were measured before and after masturbation to orgasm. In study 2, masturbation to orgasm was compared with a control condition using a single-blinded, randomized, 2-session crossover design. RESULTS: In study 1, masturbation to orgasm significantly increased plasma levels of the endocannabinoid 2-AG, whereas anandamide, oleoyl ethanolamide, palmitoyl ethanolamide, arachidonic acid, and cortisol levels were not altered. In study 2, only masturbation to orgasm, not the control condition, led to a significant increase in 2-AG levels. Interestingly, we also found a significant increase of oleoyl ethanolamide after masturbation to orgasm in study 2. CLINICAL TRANSLATION: Endocannabinoids might play an important role in the sexual response cycle, leading to possible implications for the understanding and treatment of sexual dysfunctions. STRENGTHS AND LIMITATIONS: We found an increase of 2-AG through masturbation to orgasm in 2 studies including a single-blinded randomized design. The exact role of endocannabinoid release as part of the sexual response cycle and the biological significance of the finding should be studied further. Cannabis and other drug use and the attainment of orgasm were self-reported in the present study. CONCLUSION: Our data indicate that the endocannabinoid 2-AG is involved in the human sexual response cycle and we hypothesize that 2-AG release plays a role in the rewarding consequences of sexual arousal and orgasm. Fuss J, Bindila L, Wiedemann K, et al. Masturbation to Orgasm Stimulates the Release of the Endocannabinoid 2-Arachidonoylglycerol in Humans. J Sex Med 2017;14:1372-1379.
Assuntos
Agonistas de Receptores de Canabinoides/metabolismo , Endocanabinoides/metabolismo , Ácidos Araquidônicos/metabolismo , Moduladores de Receptores de Canabinoides , Feminino , Glicerídeos/metabolismo , Humanos , Masculino , Masturbação , Ácidos Oleicos/metabolismo , Orgasmo , Alcamidas Poli-Insaturadas/metabolismoRESUMO
OBJECTIVE: There is a paucity of studies on adherence to growth hormone treatment in growth hormone deficient (GHD) adults. Therefore, this study reports on adherence to GH-replacement therapy in adults with GHD, with a special focus on the course and potential predictors of nonadherence. DESIGN: Retrospective single-centre cohort study. PATIENTS: From the local patient database, 179 suitable patients with GHD were identified. MEASUREMENTS: The primary outcome was adherence assessed by calculating the percentage of available prescription data in comparison with recommended GH dosages over a mean follow-up period of 92·4 months. Patients were categorized into five adherence categories ranging from <20% to >80%. RESULTS: Mean overall adherence was 74·0%, with 52·9% of patients falling into the adherence group of >80% and 8·8% of <20%. There was a significant drop in adherence (9·8%) between the first and second years of treatment (P < 0·001). Patients with childhood-onset GHD were significantly less adherent to GH treatment than patients with adult-onset GHD (62·0% vs 77·0%, P = 0·012); however, this finding was no longer significant after including age as a covariate. Frequency of IGF-1 levels lying outside the age- and sex-specific reference range was not a good indicator for adherence. CONCLUSION: Although overall adherence was relatively high in our study sample, there is a significant amount of patients who should be regarded as nonadherent. This applies in particular to younger patients. Treating physicians should be aware of the fact that IGF-1 levels do not seem to be a good indicator for adherence.
Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Fator de Crescimento Insulin-Like I/análise , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Coortes , Feminino , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Adulto JovemRESUMO
Beneficial effects of voluntary wheel running on hippocampal neurogenesis, morphology and hippocampal-dependent behavior have widely been studied in rodents, but also serious side effects and similarities to stereotypy have been reported. Some mouse strains run excessively when equipped with running wheels, complicating the comparability to human exercise regimes. Here, we investigated how exercise restriction to 6h/day affects hippocampal morphology and metabolism, stereotypic and basal behaviors, as well as the endocannabinoid system in wheel running C57BL/6 mice; the strain most commonly used for behavioral analyses and psychiatric disease models. Restricted and unrestricted wheel running had similar effects on immature hippocampal neuron numbers, thermoregulatory nest building and basal home-cage behaviors. Surprisingly, hippocampal gray matter volume, assessed with magnetic resonance (MR) imaging at 9.4 Tesla, was only increased in unrestricted but not in restricted runners. Moreover, unrestricted runners showed less stereotypic behavior than restricted runners did. However, after blockage of running wheels for 24h stereotypic behavior also increased in unrestricted runners, arguing against a long-term effect of wheel running on stereotypic behavior. Stereotypic behaviors correlated with frontal glutamate and glucose levels assessed by 1H-MR spectroscopy. While acute running increased plasma levels of the endocannabinoid anandamide in former studies in mice and humans, we found an inverse correlation of anandamide with the daily running distance after long-term running. In conclusion, although there are some diverging effects of restricted and unrestricted running on brain and behavior, restricted running does not per se seem to be a better animal model for aerobic exercise in mice.
Assuntos
Comportamento Animal/fisiologia , Encéfalo/fisiologia , Endocanabinoides/metabolismo , Atividade Motora/fisiologia , Corrida/fisiologia , Animais , Hipocampo/metabolismo , Hipocampo/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/fisiologia , Condicionamento Físico Animal/fisiologia , Comportamento Estereotipado/fisiologiaRESUMO
PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a hallmark of the metabolic syndrome and has been shown to be an independent predictor of cardiovascular mortality. Although glucocorticoids and growth hormone are known to be implicated in its pathophysiology, it has only rarely been investigated in the context of patients with pituitary insufficiency or former cortisol excess. METHODS: Case-control study in patients with biochemically controlled Cushing's disease (CD; N = 33) and non-functioning pituitary adenomas (NFPA; N = 79). NAFLD was estimated by calculating the fatty liver index (FLI) including BMI, waist circumference, GGT and triglyceride levels. RESULTS: Although there was no difference in FLI between patients with NFPA and CD, we identified average daily hydrocortisone (HC) intake in those with adrenal insufficiency to be an independent predictor of FLI (ß = 1.124; p = 0.017), even after adjusting for BMI and waist circumference. In line, those with a FLI > 60 were also taking in average significantly more HC per day than those with a score <60 (21.05 mg ± 5.9 vs. 17.9 mg ± 4.4; p = 0.01). FLI was also the best independent predictor for HbA1c and fasting glucose levels (both p = 0.001). Growth hormone deficiency and replacement therapy were not associated with FLI in either group. CONCLUSIONS: While HC dosage affects FLI as an estimate of NFLD in patients with CD and NFPA, the benefit of GH replacement still needs to be determined. In contrast to reports in CD patients with active disease, NAFLD in those with biochemical control was not different from NFPA patients.
Assuntos
Adenoma/complicações , Hormônio do Crescimento/deficiência , Hidrocortisona/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hipersecreção Hipofisária de ACTH/complicações , Neoplasias Hipofisárias/complicações , Adenoma/sangue , Insuficiência Adrenal/complicações , Adulto , Idoso , Doenças Cardiovasculares/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hipersecreção Hipofisária de ACTH/sangue , Neoplasias Hipofisárias/sangue , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach.
Assuntos
Estimulação Encefálica Profunda/métodos , Transtornos Parafílicos/terapia , Estimulação Encefálica Profunda/ética , Humanos , Motivação/fisiologia , Transtornos Parafílicos/fisiopatologia , Delitos Sexuais/ética , Delitos Sexuais/prevenção & controle , Comportamento Sexual/fisiologiaRESUMO
Recently, a larger hippocampus was found in exercising mice and men. Here we studied the morphological underpinnings in wheel running mice by longitudinal magnetic resonance imaging. Voxel-based morphometry revealed that running increases hippocampal volume by inhibiting an early age-related gray matter loss. Disruption of neurogenesis-related neuroplasticity by focalized irradiation is sufficient to block positive effects of exercise on macroscopic brain morphology.
Assuntos
Envelhecimento/patologia , Hipocampo/patologia , Condicionamento Físico Animal/fisiologia , Animais , Irradiação Craniana/efeitos adversos , Hipocampo/efeitos da radiação , Imageamento Tridimensional , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , CorridaRESUMO
Estradiol (E2) has been implicated in sexual functioning in both sexes. E2 levels change distinctively over the menstrual cycle, peaking around ovulation. Data on short-term effects of fluctuating E2 levels on sexual desire are however sparse and mostly based on observational studies. To fill this gap, we ran a double-blind, randomized, placebo-controlled study (N = 126) to investigate the effects of a short-term increase in E2 on sexual desire and orgasm frequency in healthy, young men and women. Circulating E2 levels were elevated through estradiol valerate (E2V) administered over two consecutive days to simulate the rise in E2 levels around ovulation. E2V had no effect on orgasm frequency and only minor effects on sexual desire. On average, the administered E2V dampened change in sexual desire compared to untreated participants with comparable baseline sexual desire in such a way that sexual desire was slightly reduced even in those with higher baseline sexual desire. These findings suggest that short-term increases in E2 have little effect on sexual function and are unlikely to explain the increase in sexual desire around ovulation.
Assuntos
Libido , Orgasmo , Masculino , Humanos , Feminino , Estradiol/farmacologia , Comportamento Sexual , Método Duplo-CegoRESUMO
OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement, including stress dosing (SD). This study prospectively assessed adrenal crisis (AC) incidence, frequency, and details of SD and disease knowledge in adult and paediatric patients and their parents. DESIGN: Prospective, observational study. METHODS: Data on AC and SD were collected via a patient diary. In case of AC, medical records were reviewed and patient interviews conducted. Adherence to sick day rules of the German Society of Endocrinology (DGE) and disease knowledge using the German version of the CAH knowledge assessment questionnaire (CAHKAQ) were assessed. RESULTS: In 187 adult patients, the AC incidence was 8.4 per 100 patient years (py) and 5.1 in 100â py in 38 children. In adults, 195.4 SD episodes per 100â py were recorded, in children 169.7 per 100â py. In children 72.3% and in adults 34.8%, SD was performed according to the recommendations. Children scored higher on the CAHKAQ than adults (18.0 [1.0] vs 16.0 [4.0]; P = .001). In adults, there was a positive correlation of the frequency of SD and the incidence of AC (r = .235, P = .011) and CAHKAQ score (r = .233, P = .014), and between the incidence of AC and CAHKAQ (r = .193, P = .026). CONCLUSION: The AC incidence and frequency of SD in children and adults with CAH are high. In contrast to the paediatric cohort, the majority of SD in adults was not in accordance with the DGE recommendations, underlining the need for structured and repeated education of patients with particular focus on transition.
Assuntos
Hiperplasia Suprarrenal Congênita , Insuficiência Adrenal , Adulto , Criança , Humanos , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/complicações , Estudos Prospectivos , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Glucocorticoides/uso terapêutico , Doença AgudaRESUMO
It has been postulated that in patients with congenital adrenal hyperplasia (CAH) with salt wasting (SW), fludrocortisone needs might be higher in those on synthetic glucocorticoid replacement therapy in comparison to conventional hydrocortisone due to the lower mineralocorticoid activity. Here we report the results of a cross-sectional single center study comparing mineralocorticoid needs between patients taking synthetic glucocorticoids (S-GC) (N = 24) and those on conventional hydrocortisone (HC) (N = 16). We could show that while both groups took comparable HC-equivalent dosages, there was no significant difference in FC dosage (GC: 0.075 mg; IQR 0.05-0.1; HC: 0.1 mg; IQR 0.05-0.1; p = 0.713). Although there was a trend for higher renin levels in the S-GC group (67.1 µU/ml; IQR 40.5-113.9 vs. 40.4 IQR 14.2-73.1; p = 0.066), this failed to reach significance. With regard to blood pressure, those taking S-GC had even significantly elevated mean systolic (125.0 mmHg, IQR 117.5-130.0 vs 116.5 mmHg IQR 111.8-124.8; p = 0.036) and diastolic (78.0 mmHg, IQR 74.3-83.8 vs 74.5mmHG, IQR 69.3-76.0; p = 0.044) during the day. Systolic dipping was however more pronounced in those on GC in comparison to those taking HC (11.3%; IQR 8.7-14.6 vs. 6.4 IQR 3.4-12.7; p = 0.031). In conclusion, we could show in this small, albeit well-balanced cohort that mineralocorticoid dosage does not significantly differ between patients receiving synthetic glucocorticoids or conventional hydrocortisone. Higher blood pressure values despite the tendency for higher renin levels in those on S-GC support the notion that the assessment of MR adequacy should be guided by the clinical picture and blood pressure on a regular basis.
Assuntos
Hiperplasia Suprarrenal Congênita , Glucocorticoides , Humanos , Adulto , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Hidrocortisona/uso terapêutico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Mineralocorticoides/uso terapêutico , Renina , Estudos TransversaisRESUMO
Purpose: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism. Methods: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47. Results: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30 min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission. Conclusion: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as dyslipidemia.
Assuntos
Síndrome de Cushing , Glucocorticoides , Animais , Feminino , Humanos , Camundongos , Hormônio Adrenocorticotrópico/metabolismo , Colesterol , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hidrocortisona , Metabolismo dos Lipídeos/genética , Estudos Prospectivos , RNA Mensageiro/metabolismoRESUMO
First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in girls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up research is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DEX may avoid unnecessary treatment and improve treatment safety.