Is biochemical hypoglycemia necessary during an insulin tolerance test?

ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8

La esteroidogénesis en el síndrome de ovarios poliquísticos / Steroidogenesis in polycystic ovary syndrome

Resumen El síndrome de ovarios poliquísticos es la enfermedad endocrina más frecuente en la edad reproductiva; se caracteriza por alteraciones menstruales, hiperandrogenismo clínico o bioquímico e identificación ultrasonográfica de quistes ováricos. Las alteraciones neuroendocrinas y metabólicas que lo acompañan implican desensibilización del eje hipotálamo-hipófisis-ovario, esteroidogénesis e hiperandrogenismo. Recientemente se ha explorado el papel de la resistencia a la insulina. Se ha establecido que la principal causa del síndrome de ovarios poliquísticos es el hiperandrogenismo, debido a alteraciones enzimáticas en la vía esteroidogénica, por lo que existe sobreestimulación por parte de la hormona luteinizante a causa de los pulsos rápidos generados por la hormona liberadora de gonadotropinas. Diversos factores de crecimiento y citocinas inhiben la conversión de andrógenos a estrógenos. En la desregulación característica de este síndrome también están involucradas la activina y las prostaglandinas e, incluso, altos niveles de insulina.

Abstract Polycystic ovary syndrome is the most common endocrine disease in reproductive age, characterized by menstrual alterations, clinical or biochemical hyperandrogenism, and ultrasound-identified ovarian cysts. The neuroendocrine and metabolic alterations that accompany this condition involve the desensitization of the hypothalamus-pituitary-ovary axis, steroidogenesis and hyperandrogenism; recently, the role of insulin resistance has been explored. Hyperandrogenism has been established to be the main cause of polycystic ovary syndrome, due to enzymatic alterations in the steroidogenic pathway that cause luteinizing hormone over-stimulation because of quick pulses generated by gonadotropin-releasing hormones. Various growth factors of and cytokines inhibit the conversion of androgens into estrogens; activin and prostaglandins are also involved, even high levels of insulin participate in the characteristic deregulation of this syndrome.

Salivary cortisol and alpha-amylase: subclinical indicators of stress as cardiometabolic risk

Currently, the potential for cardiovascular (CV) stress-induced risk is primarily based on the theoretical (obvious) side effects of stress on the CV system. Salivary cortisol and α-amylase, produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, are still not included in the routine evaluation of CV risk and require additional and definitive validation. Therefore, this article overviews studies published between 2010 and 2015, in which salivary cortisol and α-amylase were measured as stress biomarkers to examine their associations with CV/CMR (cardiometabolic risk) clinical and subclinical indicators. A comprehensive search of PubMed, Web of Science and Scopus electronic databases was performed, and 54 key articles related to the use of salivary cortisol and α-amylase as subclinical indicators of stress and CV/CMR factors, including studies that emphasized methodological biases that could influence the accuracy of study outcomes, were ultimately identified. Overall, the biological impact of stress measured by salivary cortisol and α-amylase was associated with CV/CMR factors. Results supported the use of salivary cortisol and α-amylase as potential diagnostic tools for detecting stress-induced cardiac diseases and especially to describe the mechanisms by which stress potentially contributes to the pathogenesis and outcomes of CV diseases.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study / Desequilíbrio na proporção salivar diurna de testosterona/cortisol em homens com apneia obstrutiva do sono grave: um estudo observacional

ABSTRACT INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Resumo Introdução: A relação complexa entre os distúrbios do sono e os hormônios pode levar a alterações na produção de cortisol e testosterona em pacientes com Apneia obstrutiva do sono (AOS). Objetivo: O objetivo deste estudo foi determinar as curvas diurnas de testosterona e cortisol livres na saliva e sua proporção (razão T/C). Método: Dez indivíduos recém-diagnosticados com AOS com base na avaliação por polissonografia noturna e sonolência diurna excessiva e sete controles pareados foram recrutados, consecutivamente. Cortisol e testosterona foram medidos em amostras de saliva coletadas ao acordar, ao meio-dia e à noite. A avaliação psicométrica dos distúrbios de ansiedade/depressão e função sexual mencionados foi realizada para detectar a presença de comorbidades neuropsicológicas. Resultados: O achado principal foi que os indivíduos com AOS apresentam hipocortisolismo ao acordar e uma redução significante na concentração de testosterona à noite, em comparação com o grupo controle, que manteve a variação fisiológica diurna de testosterona e cortisol com concentrações hormonais mais elevadas pela manhã e concentrações mais baixas durante a noite. O uso de dados de várias mensurações diurnas, em vez de uma única mensuração, permitiu detectar as alterações na razão T/C de sinais opostos no início e no final do dia: os indivíduos com AOS apresentaram razão T/C maior que os controles na parte da manhã, enquanto que a razão T/C foi significantemente inferior à dos controles durante a noite. Conclusão: Os desequilíbrios no balanço anabólico-catabólico diurno sugerem que a AOS está associada a uma desregulação dos eixos hipotálamo-hipófise-adrenal e hipotálamo-hipófise-gonadal, potencialmente a causa subjacente de algumas das comorbidades neuropsicológicas observadas em pacientes com AOS.

Insuficiencia suprarrenal relativa en pacientes cirróticos / Adrenal insufficiency in cirrhotic patients

La insuficiencia suprarrenal relativa (ISR) es frecuente en pacientes cirróticos con sepsis grave, asociándose a un pobre pronóstico. Se desconoce su importancia en condiciones de enfermedad estable. El objetivo del trabajo ha sido evaluar la prevalencia de la ISR en una serie de pacientes cirróticos estables y su relación con el deterioro de la función hepática. Se determinó el impacto de la ISR en la supervivencia y se correlacionaron los niveles entre el cortisol basal en plasma y saliva en sujetos controles y cirróticos. Fueron incluidos 47 pacientes ambulatorios y 16 controles. La funcionalidad del eje hipotalámico-pituitario-suprarrenal se valoró mediante la prueba de estimulación con 250 μg de ACTH sintética EV, definiendo la ISR como delta cortisol < 9 μg/dl. Respecto al grado de deterioro de la función hepática, 22 tenían un Child-Pugh ≤ 8 y 25 pacientes = 9. La prevalencia de ISR fue de un 22%, siendo significativamente más elevada en aquellos con mayor deterioro de la función hepática (8/32 vs. 3/13, p < 0.05). Se observó correlación entre el cortisol salival y el plasmático basal (r = 0.6, p < 0.0004). Por último, la supervivencia fue más elevada en los pacientes sin ISR al año (97%) y a los tres años (91%) que aquellos que desarrollaron esta complicación (79 % y 51%, p < 0.05, respectivamente). En resumen, la prevalencia de ISR es elevada en los pacientes con cirrosis estable y se relaciona con un deterioro de la función hepática y una mayor mortalidad.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 μg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh ≤ 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with ≤ 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

La separación materna durante la lactancia altera los niveles basales del sistema neuroendocrino en ratas adolescentes y adultas / Maternal separation during nursing alters basal neuroendocrine levels in juvenile and adult rats

Introducción. En diversos modelos animales, incluido el de la separación materna durante la lactancia, se ha demostrado que las experiencias tempranas adversas, como el maltrato, el abandono materno y el estrés psicosocial, pueden favorecer el desarrollo de algunas enfermedades mentales, pero no se han descrito completamente varios de los cambios que se producen en el sistema neuroendocrino. Objetivo. Determinar si la separación materna durante la lactancia modificaba los niveles basales de neurohormonas como la corticosterona, la corticotropina (ACTH), la oxitocina y la vasopresina (ADH), en ratas jóvenes (35 días) y adultas (90 días). Materiales y métodos. Se separaron ratas Wistar de sus madres durante dos periodos de tres horas diarias a lo largo de los 21 días de lactancia. A los 35 y 90 días se tomaron muestras de los grupos de las ratas de control y de las separadas de la madre, para obtener el suero y posteriormente medir cada una de las hormonas mediante un ensayo inmunoenzimático. Resultados. Las concentraciones de corticosterona fueron mayores en las hembras adultas de control que en el resto de los grupos, y menores en los machos adultos de control. Las de ACTH fueron mayores en los machos y hembras jóvenes separadas de la madre que en los grupos de adultos. Los niveles de oxitocina fueron significativamente mayores en las hembras adultas separadas de la madre que en los otros grupos y significativamente menores en los machos adultos. En cuanto a la vasopresina, los grupos separados de la madre tuvieron concentraciones menores, en comparación con los grupos de jóvenes y adultos de control. Conclusiones. Estos resultados muestran que el estrés temprano al que fueron sometidas las ratas, produjo cambios en las respuestas del eje hipotálamo-hipófisis-suprarrenal, las cuales variaron según el sexo y la edad.

Introduction: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet. Objective: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively). Materials and methods: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones. Results: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups. Conclusions: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.

Prueba de basculación (Tilt Table Testing): Comparación de dos protocolos: isoproterenol versus nitroglicerina / Comparison of the use of isoproterenol or nitroglycerine during the Tilt test

Background: There is debate about the advantages of different protocols usefulness of tilt test for the diagnosis of vasovagal collapse. Aim: To compare the sensitivity, specificity, adverse reactions, complications and time requirements of two different Tilt test protocols. Material and Methods: A Tilt test using isoproterenol in progressive doses (2 μg for 10 min and 5 μg for 5 min posteriorly was performed in 159 patients aged 9 to 84 years (59 males). Another Tilt test using sublingual nitroglycerine in doses of 0.3 mg was performed in 201 patients aged 8 to 87 years (62 males). Also, 20 healthy volunteers were tested. Results: The positivity rates of the tests using isoproterenol and nitroglycerin were 75.5 and 77.6% respectively (NS). The figures for sensitivity were 98.4 and 99.3% (NS). The figures for specificity were 93.2 and 98.4% (NS). The test using isoproterenol requires 15 more minutes. As adverse reactions, 38% of participants experienced palpitations with isoproterenol and 22% experienced headache with nitroglycerin. Conclusions: The Tilt test with nitroglycerin is shorter, simpler, painless, with less personnel involved and has the same diagnostic accuracy than the test with isoproterenol.

Medición de cortisol y sus fracciones. Una puesta al día / [A critical analysis of cortisol measurements: an update].

Serum cortisol measurement is a very useful tool in the biochemical evaluation of adrenocortical function. Since this hormone circulates in blood mainly linked to binding globulins but is also partially free, it can be measured not only in the blood but also in urine, saliva and other biological fluids and tissues. Basal determinations as well as dynamic testing may be performed to evaluate the circadian variations, to estimate the diurnal cortisol secretion and to analyze its relations with other components of the hypothalamic-pituitary-adrenal axis. Measurements of cortisol in blood, saliva and urine may reflect the cortisol secretion at the time of sample collection or during a 24 h span. Recently, it has been proposed the determination of cortisol in tissues such as hair and nails like a means of evaluating the hormonal status during prolonged periods. The aim of this paper is to update the methodology for measuring cortisol and its usefulness for the clinical diagnosis of troubles of the hypothalamic-pituitary-adrenal axis.

Neural regulation of the stress response: glucocorticoid feedback mechanisms

The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and to restore homeostasis after the immediate challenge has subsided. Release of glucocorticoids is mediated by the hypothalamo-pituitary-adrenal (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of glucocorticoids bind to glucocorticoid receptors in multiple body compartments, including the brain, and consequently have wide-reaching actions. For this reason, glucocorticoids serve a vital function in negative feedback inhibition of their own secretion. Negative feedback inhibition is mediated by a diverse collection of mechanisms, including fast, non-genomic feedback at the level of the PVN, stress-shut-off at the level of the limbic system, and attenuation of ascending excitatory input through destabilization of mRNAs encoding neuropeptide drivers of the HPA axis. In addition, there is evidence that glucocorticoids participate in stress activation via feed-forward mechanisms at the level of the amygdala. Feedback deficits are associated with numerous disease states, underscoring the necessity for adequate control of glucocorticoid homeostasis. Thus, rather than having a single, defined feedback ‘switch’, control of the stress response requires a wide-reaching feedback ‘network’ that coordinates HPA activity to suit the overall needs of multiple body systems.

Serum levels of hypothalamic-pituitary-testicular axis hormones in men with or without prostate cancer or atypical small acinar proliferation

INTRODUCTION: Substantial controversy exists regarding the association between testosterone serum levels and prostate cancer. OBJECTIVE: To evaluate the levels of hypothalamic-pituitary-testicular axis hormones in the sera of men with prostate cancer and atypical small acinar proliferation as well as those with normal biopsies. METHODS: A study cohort of 186 men with suspected prostate cancer who had undergone transrectal prostate biopsies was used in this study. The patients were divided into the following three groups based on the histology of the biopsy samples: no neoplasia, atypical small acinar proliferation or prostate cancer. Demographic data were also collected. Levels of total testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and serum prostate-specific antigen were measured in blood samples. RESULTS: Initially, 123 men were found to be without neoplasia, 26 with atypical small acinar proliferation and 37 with prostate cancer. After a second biopsy was taken from the men diagnosed with atypical small acinar proliferation, the diagnoses were revised: 18 were diagnosed with atypical small acinar proliferation and 45 with prostate cancer. No significant differences between the groups were identified regarding age, smoking history, chronic diseases, body mass index or PSA levels (P >.0.05). The mean serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin and estradiol were similar in all of the groups (P >.0.05). Furthermore, in individuals with prostate cancer, the Gleason scores and prevalence of hypogonadism were not significantly different (P.> 0.05). CONCLUSION: The present study revealed no difference in the serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin or estradiol in men without neoplasia compared with those with atypical small acinar proliferation or prostate cancer.

Neurobiología del estrés / Neurobiology of stress

Classically stress is defined as a threatening of homeostasis to which the organism, in order to survive, responds with a large number ofadaptative responses implicating the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Acute stress response involves several brain regions (e.g. prefrontal cortex, amygdala, hippocampus, hypothalamus) where sex differences have been evidenced both in structure and function; limbic andforebrain regions are extremely sensitive to hormones released during stress, especially glucocorticoids. Chronic stress, on the other hand, causes adaptive plasticity in the brain, in which local neurotransmitters as well as systemic hormones interact to produce structural as well as functional changes. Stress-induced structural/functional changes in brain regions may contribute to the development of psychiatric disorders such as depression and post-traumatic stress disorder. It is suggested that gonadal hormone influences provide complex contributions to sex differences in vulnerabilities to stress-related diseases.

Clásicamente el estrés se define como una amenaza a la homeostasis, frente a la cual el organismo, para sobrevivir, reacciona con un gran número de respuestas adaptativas que implican la activación del sistema nervioso simpático y el eje hipotalámico-pituitario-adrenal. La respuesta al estrés agudo incluye varias regiones cerebrales (ej. cortex prefrontal, amígdala, hipocampo, hipotálamo) donde se han evidenciado las diferencias sexuales, tanto en la estructura como en la función; las regiones límbicas y cerebrales anteriores son extremadamente sensibles a las hormonas liberadas durante el estrés, especialmente los glucocorticoides. Por otra parte, el estrés crónico causa plasticidad adaptativa en el cerebro, en el cual los neurotransmisores locales, como también las hormonas sistémicas, interactúan para producir cambios estructurales y funcionales. Los cambios estructurales/funcionales en las regiones cerebrales inducidos por el estrés pueden contribuir al desarrollo de desórdenes psiquiátricos, tales como depresión y trastorno por estrés postraumático. Se ha sugerido que las influencias de la hormona gonadal proporcionan complejas contribuciones a las diferencias sexuales en las vulnerabilidades a las enfermedades relacionadas con el estrés.

Ansiedade, pânico e o eixo hipotálamo-pituitária-adrenal / Anxiety, panic and the hypothalamic-pituitary-adrenal axis

OBJETIVO: Este artigo discute a ativação diferencial do eixo hipotálamo-pituitária-adrenal no transtorno de ansiedade generalizada e no transtorno de pânico. MÉTODO: Resultados de recentes revisões da literatura são resumidos e discutidos. RESULTADOS: Os resultados de estudos experimentais que dosaram o hormônio adrenocorticotrópico, o cortisol e a prolactina mostram que ataques de pânico naturais, bem como os provocados por agentes panicogênicos seletivos - como lactato de sódio e dióxido de carbono -, não ativam o eixo hipotálamo-pituitária-adrenal. Agonistas do receptor de colecistocinina do tipo B, como o peptídeo colecistocinina-4 e a pentagastrina, elevam os hormônios de estresse, independentemente da ocorrência de um ataque de pânico, parecendo ativar diretamente o eixo hipotálamo-pituitária-adrenal. O antagonista benzodiazepínico flumazenil não eleva o nível dos hormônios de estresse; porém, este agente farmacológico não induz ataques de pânico de modo consistente. Agentes farmacológicos que aumentam a ansiedade em pacientes de pânico (cafeína, ioimbina, agonistas serotonérgicos), assim como em pessoas saudáveis, elevam o nível dos hormônios de estresse. CONCLUSÕES: Além das diferenças na sintomatologia e na resposta farmacológica, o transtorno de ansiedade generalizada e o transtorno de pânico afetam os hormônios de estresse de modo distinto. Enquanto a ansiedade antecipatória e o transtorno de ansiedade generalizada ativam tanto o eixo hipotálamo-pituitária-adrenal como o simpático-adrenal, o ataque de pânico causa acentuada ativação simpática; porém, afeta pouco o eixo hipotálamo-pituitária-adrenal.

OBJECTIVE: This article focuses on the differential activation of the hypothalamic-pituitary-adrenal axis in generalized anxiety disorder and panic disorder. METHOD: The results of recently reported reviews of the literature are summarized and discussed. RESULTS: The results of experimental studies that assayed adrenocorticotropic hormone, cortisol and prolactin show that real-life panic attacks, as well as those induced by selective panicogenic agents such as lactate and carbon dioxide, do not activate the hypothalamic-pituitary-adrenal axis. Agonists of the cholecystokinin receptor B such as the cholecystokinin-4 peptide and pentagastrin increase stress hormones regardless of the occurrence of a panic attack and, thus, seem to activate the hypothalamic-pituitary-adrenal axis directly. The benzodiazepine antagonist flumazenil does not increase stress hormones, but this agent does not reliably induce panic attacks. Pharmacological agents that increase anxiety in both normal people and panic patients (caffeine, yohimbine, serotonergic agonists) raise stress hormone levels. CONCLUSIONS: In addition to the differences in symptomatology and pharmacological response, generalized anxiety disorder and panic disorder affect stress hormones in distinct ways. While anticipatory anxiety and generalized anxiety disorder activate both the hypothalamic-pituitary-adrenal and the sympathoadrenal axes, panic attack causes major sympathetic activation, but has little effect on the hypothalamic-pituitary-adrenal axis.

Hypothalamic-Pituitary-Gut Axis Dysregulation in Irritable Bowel Syndrome: Plasma Cytokines as a Potential Biomarker? / 대한소화기학회지

No abstract availble.

Aspectos neuroendócrinos e nutricionais em atletas com overtraining / Neuroendocrine and nutritional aspects of overtraining

A síndrome de overtraining tem sido caracterizada por um excesso de treinamento responsável pelo surgimento de diversos efeitos adversos, sendo o principal deles a diminuição do desempenho. Sua incidência entre atletas de elite vem aumentando significativamente nos últimos anos, fato este responsável pelo crescente interesse de pesquisadores em buscar medidas capazes de prevenir ou tratar tal síndrome; porém, para tanto, torna-se necessário que se esclareçam os possíveis mecanismos responsáveis pelo desenvolvimento do overtraining. Diversas hipóteses têm sido propostas no intuito de desvendar esses mecanismos, tais como a maior ativação do sistema nervoso autônomo e do eixo hipotálamo-hipófise-adrenal e supressão do eixo hipotálamo-hipófise-gonadal, porém alguns estudos têm proposto que a modulação desses sistemas seria uma conseqüência da síndrome de overtraining e não necessariamente a sua causa. Desta forma, novas hipóteses relacionadas à liberação de citocinas, à fadiga central, à depleção do glicogênio muscular e hepático, e à diminuição da disponibilidade de glutamina durante a atividade física têm sido levantadas.

O eixo hipotálamo-pituitária-adrenal, a função dos receptores de glicocorticóides e sua importância na depressão / The Hypothalamic Pituitary Adrenal axis, Glucocorticoid receptor function and relevance to depression

OBJETIVO: As mudanças no eixo hipotálamo-pituitária-adrenal (HPA) são características da depressão. Devido aos efeitos dos glicocorticóides serem mediados por receptores intracelulares, como os receptores de glicocorticóides (RGs), inúmeros estudos examinaram o número e/ou função dos RGs em pacientes com depressão. MÉTODOS: Os autores fazem uma revisão das evidências científicas dos estudos que têm consistentemente demonstrado que a função dos RGs está prejudicada na depressão maior, em conseqüência da redução da resposta do eixo HPA ao feedback negativo mediado pelos RGs e a um aumento na produção e secreção de HLC em várias regiões cerebrais, sugerindo que esses mecanismos estão envolvidos na etiologia da depressão e no tratamento antidepressivo. RESULTADOS: Esta revisão faz um resumo da literatura atual sobre RG na depressão e sobre o impacto dos antidepressivos nos RGs em estudos clínicos e pré-clínicos, e dá suporte ao conceito de que a sinalização deficiente dos RGs é parte fundamental na fisiopatogenia da depressão, na ausência de evidências claras de redução na expressão dos RGs. Embora os efeitos dos antidepressivos nos hormônios glicocorticóides e seus receptores sejam relevantes para a ação terapêutica dessas drogas, os mecanismos moleculares subjacentes a esses efeitos ainda não estão esclarecidos. Estudos indicam que os antidepressivos têm efeitos diretos nos RGs, levando a uma melhora da função e a um aumento da expressão dos RGs. Nós propomos que, em humanos, os antidepressivos podem inibir os transportadores de esteróides localizados na barreira hemato-liquórica e nos neurônios, como o complexo de resistência a múltiplas drogas glicoproteína-p ("multidrug resistance p-glycoprotein"), e podem aumentar o acesso do cortisol ao cérebro e o feedback negativo mediado por glicocorticoides no eixo HPA. CONCLUSÃO: O aumento da ação do cortisol no cérebro pode ser uma abordagem eficaz para maximizar os efeitos terapêuticos dos antidepressivos. Hipóteses referentes aos mecanismos destes receptores envolvem compostos não esteróides que regulam a função dos RGs via segundos mensageiros. A pesquisa nesta área trará novos entendimentos à fisiopatologia e ao tratamento dos transtornos afetivos, em especial na depressão.

A obesidade estaria relacionada ao aumento do volume das adrenais? / Would the obesity related to the adrenal volume increases?

Vários estudos sugerem que existe uma hiperatividade do eixo hipotálamo-hipofisário-adrenal (HHA) na obesidade, com maior acúmulo de gordura na região abdominal. Estes trabalhos demonstram que, após injeções de hormônio liberador de corticotropina (CRF) ou hormônio adrenocorticotrófico (ACTH) e ainda através de testes de stress, os níveis de cortisol estão aumentados em comparação com pacientes com deposição periférica de gordura. Além do mais, alguns estudos mostram que em pacientes deprimidos, onde a hiperatividade do HHA é uma alteração endócrina importante e conhecida, o volume das adrenais está aumentado quando comparado com normais. Para investigar se o teor de gordura visceral de alguma maneira se relaciona com o volume das adrenais, 52 mulheres com idade entre 19 e 54 anos, com diferentes índices de corpulência, foram estudadas através de medidas antropométricas como peso, índice de massa corporal (IMC), cintura e relação cintura-quadril (RCQ). As áreas de gordura visceral (GV) e sub-cutânea (GSC), além do volume das adrenais, foram medidas através da tomografia computadorizada. Houve uma correlação extremamente significativa entre as medidas de distribuição de gordura (RCQ e cintura) e a GV, sendo que a RCQ não se correlacionou com a GSC. O somatório do volume das adrenais mostrou uma correlação positiva e significativa com a RCQ (r = 0,272, p = 0,02) e uma correlação positiva, mas no limite da significância com a GV (r = 0,228, p = 0,05), não mostrando qualquer correlação com a GSC. Além disso, o somatório do volume das adrenais foi maior naquelas com GV >/= 120 cm 2 quando comparado com pacientes com área de GV < 120 cm 2 (p = 0,05). Portanto, o estudo sugere que o depósito de GV parece interrelacionar-se com a hiperatividade do HHA, aqui estimada anatomicamente através do volume das adrenais, glându-la alvo deste eixo.

Influencia del tumor testicular sobre el eje de hipotálamo, hipófisis y testículo / Testicular tumor influence on the hipothalamus-hypophisis-testicle axis

El teatículo contiene en su interior a las células germinales, que pueden producir cualquier clase de tejido o susbstancia en el organismo. Cuando existe crecimiento celular desorganizado, como en el cáncer, la gónada puede producir substancias, como la gonadotropina coriónica humana (HCG) y la alfafetoproteína (AFP), que se utilizan como marcadores de actividad tumoral. Se determinaron los valores basales de hormona luteinizante (LH), hormona foliculoestimulante (FSH), HGC y AFP e cuatro pacientes con tumor testicular. En tres de ellos el informe histopatológico indicó teratocarcinoma. En estos pacientes los niveles de HGC y AFP se encontraron elevados, en tanto que las gonadotropinas hipofisarias se hallaron bajas: en un paciente con diagnóstico de atrofia testicular todas las determinaciones fueron normales. Se observó que en estos pacientes la HCG circulante inhibió la liberación de LH y FSH.