The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Morning serum cortisol role in the adrenal insufficiency diagnosis with modern cortisol assays.

PURPOSE: To investigate the accuracy of cutoff values of the morning serum cortisol (MSC) using the cortisol stimulus test (CST) insulin tolerance test (ITT) and 250 mcg short Synacthen test (SST) as the reference standard tests, to better define its clinical role as a tool in the diagnostic investigation of adrenal insufficiency (AI) AI. METHODS: An observational study was conducted with a retrospective analysis of MSC in adult patients who had been submitted to a CST to investigate AI between January 2014 and December 2020. The normal cortisol response (NR) to stimulation was defined based on the cortisol assay. RESULTS: 371 patients underwent CST for suspected AI, 121/371 patients (32.6%) were diagnosed with AI. ROC curve analysis showed an area under the curve (AUC) for MSC of 0.75 (95% CI 0.69 - 0.80). The best MSC cutoff values to confirm AI were < 3.65, < 2.35 and < 1.5 mcg/dL with specificity of 98%, 99%, and 100%, respectively. MSC > 12.35, > 14.2 and > 14.5 mcg/dL had sensitivity of 98%, 99%, and 100%, respectively, being the best cutoff values to exclude AI. Almost 25% of patients undergoing CST for possible AI had MSC values between < 3.65 mcg/dL (6.7% of patients) and > 12.35 mcg/dL (17.5% of patients), making the formal CST testing unnecessary if we consider these cutoff values. CONCLUSION: With the most modern cortisol assays, MSC could be used as a diagnostic tool, with high accuracy to confirm or exclude AI, avoiding unnecessary CST; thus, reducing expenses and safety risks during AI investigation.

Serum cortisol in mules intended for agricultural work.

Cortisol is a hormone secreted by the adrenal glands that is stimulated by physiological and pathological factors and has been studied widely in equids, but not in mules. The objectives of this study were to obtain a reference value for serum cortisol in mules destined for agricultural activities and to identify age- and gender-related differences in the value. The concentration was obtained in blood samples using a commercial sandwich ELISA specific for cortisol. The concentration was 96.3 ± 40.6 ng/ml and similar between age groups and genders.

Correlation Between Size and Function of Unilateral and Bilateral Adrenocortical Nodules: An Observational Study.

OBJECTIVE. Adrenal incidentalomas occur in 5% of adults and can produce autonomous cortisol secretion that increases the risk of metabolic syndrome and cardiovascular disease. The objective of our study was to evaluate the relationship between adrenal nodule size measured on CT and autonomous cortisol secretion. SUBJECTS AND METHODS. In a prospective study of 73 patients 22-87 years old with incidentalomas, unilateral in 52 patients and bilateral in 21 patients, we measured maximum nodule diameter on CT and serum cortisol levels at 8:00 am, 60 minutes after the adrenocorticotropic hormone stimulation test, and after the dexamethasone suppression test. We also studied 34 age-, sex-, and body mass index-matched control subjects. Statistics used were Spearman correlation coefficients, t tests, ANOVA test, and multivariate analysis. RESULTS. The mean maximum diameter of unilateral nodules measured on CT was larger on the right (2.47 ± 0.98 [SD] cm) than on the left (2.04 ± 0.86 cm) (p = 0.01). In the bilateral cases, the mean diameter of the right nodules was 2.69 ± 0.93 cm compared with 2.13 ± 0.89 cm on the left (p = 0.06). Mean baseline serum cortisol level was significantly higher in the patients with incidentalomas (bilateral, 13.1 ± 4.5 mcg/dL [p < 0.001]; unilateral, 9.7 ± 3.2 mcg/dL [p = 0.019]) than in the control subjects (7.5 ± 3.6 mcg/dL). After dexamethasone suppression test, serum cortisol levels were suppressed to less than 1.8 mcg/dL in 100% of control subjects, 33% of patients with bilateral incidentalomas, and 62% of patients with unilateral incidentalomas (p < 0.001). There were significant correlations between maximum nodule diameter on CT and serum cortisol levels after the dexamethasone suppression test (ρ = 0.500; p < 0.001) and at baseline (ρ = 0.373; p = 0.003). CONCLUSION. Increasing size of adrenal nodules is associated with more severe hyper-cortisolism and less dexamethasone suppression; these cases need further evaluation and possibly surgery because of increased risks of metabolic syndrome and cardiovascular mortality.

Uso de corticoide inalado e sua implicação no nível de eosinófilos periféricos / Inhaled corticosteroid use and its implications for peripheral blood eosinophil levels

Introdução: Um dos efeitos do corticoide sistêmico é a redução do número e da ação dos eosinófilos. O objetivo deste estudo foi avaliar a ação do corticoide inalatório (CI) sobre os eosinófilos periféricos (EoP). Métodos: Trata-se de um estudo retrospectivo de prontuários eletrônicos de pacientes adultos com asma grave, steps 4 e 5 da GINA 2019, acompanhados em um centro terciário de referência. Os pacientes em uso recente ou atual de corticoide oral foram excluídos. Foram avaliados dados demográficos, dose de budesonida inalada, sensibilização a aeroalérgenos, IgE total, cortisol sérico e EoP, no período de 2010 a 2019. Resultados: Foram avaliados 58 pacientes, sendo 81,0% do sexo feminino, com médias de idade de 61,0 anos, de início da asma aos 17,4 anos e de tempo de doença de 43,6 anos. A média de CI foi de 1682,8 µg/dia, e a média de IgE sérica total do grupo foi de 398,9 UI/mL. A IgE específica para aeroalérgenos estava positiva em 40 pacientes (69%), sendo 85% destes pacientes sensibilizados para ácaros. A média do cortisol sérico foi de 5,6 µg/dL, e dos EoP de 252,1 cel/mm3. Neste estudo não foi observada correlação entre a dose de CI e o cortisol sérico. Entretanto, 41,4% dos pacientes apresentaram EoP < 150 cel/mm3, e houve uma correlação inversa significante entre as doses de CI e os níveis de EoP, (p = 0,011 r2 = 0,11), ou seja, quanto maior a dose de CI, menor o nível de EoP. Conclusões: A GINA 2019 recomenda o uso de anticorpos monoclonais (mAbs), no step 5, direcionados pelo fenótipo de asma. Alguns destes mAbs incluem como critério de tratamento os EoP acima de 150 ou 300 cel/mm³. Neste estudo, o CI em doses elevadas estava relacionado a níveis mais baixos de EoP, portanto, alguns pacientes em uso de doses elevadas de CI poderiam apresentar EoP reduzida pelo uso de CI, interferindo na recomendação de alguns mAbs.

Introduction: One of the effects of systemic corticosteroids is to reduce the number and action of eosinophils. The aim of this study was to evaluate the action of inhaled corticosteroids (ICS) on peripheral blood eosinophils (PBE). Methods: We retrospectively reviewed the medical records of adult patients with severe asthma, steps 4-5 (GINA 2019), treated at a tertiary referral center. Patients on current or recent oral corticosteroid therapy were excluded. Data on demographics, ICS dose, sensitization to aeroallergens, total serum IgE, serum cortisol, and PBE counts were evaluated for the period from 2010 to 2019. Results: Fifty-eight patients were evaluated, 81% were women. Mean age was 61 years, with the onset of asthma at 17.4 years of age and disease duration of 43.6 years. The mean ICS dose was 1682.8 µg/day, and the mean total serum IgE was 398.9 IU/mL. Specific IgE for aeroallergens was positive in 40 patients (69%); of these, 85% were sensitized to mites. The mean serum cortisol level was 5.6 µg/dL, and the mean PBE count was 252.1 cells/mm3. There was no correlation between ICS dose and serum cortisol, but 41.4% of patients had PBE counts <150 cells/mm3. There was a significant inverse correlation between ICS doses and PBE counts (p=0.011, r2=0.11), i.e., the higher the ICS dose, the lower the PBE count. Conclusions: GINA 2019 recommends the use of monoclonal antibodies (mAbs) in asthma step 5, directed by phenotype. Some of these mAbs have as a treatment criterion PBE count above 150 or above 300 cells/mm3. In this study, high-dose ICS was correlated with lower PBE levels. Therefore, patients using high-dose ICSs could have their PBE levels reduced by ICS use, interfering with the recommendation of some mAbs.

Niveles de cortisol en la saliva y séricos en recién nacidos / Salivary and serum cortisol levels in newborn infants

Introducción. Dada la dificultad en la interpretación de los valores de cortisol sérico en recién nacidos (RN), el objetivo de este estudio fue correlacionar los niveles basales de cortisol en el suero y la saliva, y describir las concentraciones de cortisol salival durante el primer mes de vida. Población y métodos. Estudio descriptivo, prospectivo, longitudinal y de correlación. Se seleccionaron RN de término del Servicio de Neonatología del Hospital Nacional Profesor Alejandro Posadas en 2014. En la saliva, se determinó cortisol; en la sangre, cortisol, globulina tansportadora de cortisol y albúmina. Se utilizó la correlación lineal para relacionar cortisol sérico y salival; el test de Friedman para comparar el cortisol durante el primer mes de vida y la diferencia para analizar el comportamiento de valores iguales o inferiores al primer cuartil. Resultados. Se evaluaron 55 RN. Cortisol sérico: 7,65 (1,0-18,1 gg/dl); cortisol salival: 35,88 (5,52107,64 nmol/L); globulina transportadora de cortisol: 22,07 (16,5-33,0 gg/µL), expresados como mediana y rango. El coeficiente de correlación entre el cortisol sérico y salival fue de 0,54; P= 0,001. El comportamiento del cortisol durante el primer mes de vida no mostró diferencias estadísticamente significativas y la diferencia entre la segunda y la primera muestra de valores iguales o inferiores al primer cuartil aumentó en 10 de 12 pacientes. Conclusión. La determinación de cortisol en la saliva refleja la concentración de cortisol sérico en RN normales. Algunos pacientes presentaron niveles bajos de cortisol a las 36 h de vida y mostraron una tendencia a incrementarse espontáneamente durante el primer mes de vida.

Introduction. Given that serum cortisol level interpretation in newborn infants (NBIs) is hard, the objective of this study was to correlate baseline salivary and serum cortisol levels and to describe salivary cortisol levels in the first month of life. Population and Methods. Descriptive, prospective, longitudinal, and correlational study. Term NBIs were selected from the Division of Neonatology of Hospital Nacional Profesor Alejandro Posadas in 2014. Cortisol was measured in saliva specimens while cortisol, cortisol-binding globulin, and albumin were measured in blood specimens. A linear correlation was performed to relate serum and salivary cortisol levels; Friedman test was conducted to compare cortisol levels during the first month of life, and the difference was used to analyze the performance of values equal to or lower than the first quartile. Results. Fifty-five NBIs were studied. Serum cortisol: 7.65 (1.0-18.1 gg/dL); salivary cortisol: 35.88 (5.52-107.64 mmol/L); cortisol-binding globulin: 22.07 (16.5-33.0 gg/µL), expressed as median and range. The correlation coefficient between serum and salivary cortisol was 0.54, P = 0.001. Cortisol performance during the first month of life showed no statistically significant differences, and the difference between the second and the first specimen of values equal to or lower than the first quartile increased in 10 out of 12 patients. Conclusion. The measurement of cortisol in saliva reflects serum cortisol levels in normal NBIs. Some patients had low levels of cortisol at 36 hours of life and showed a trend towards a spontaneous increase during the first month of life.

Salivary and serum cortisol levels in newborn infants. / Niveles de cortisol en la saliva y séricos en recién nacidos.

INTRODUCTION: Given that serum cortisol level interpretation in newborn infants (NBIs) is hard, the objective of this study was to correlate baseline salivary and serum cortisol levels and to describe salivary cortisol levels in the first month of life. POPULATION AND METHODS: Descriptive, prospective, longitudinal, and correlational study. Term NBIs were selected from the Division of Neonatology of Hospital Nacional Profesor Alejandro Posadas in 2014. Cortisol was measured in saliva specimens while cortisol, cortisol-binding globulin, and albumin were measured in blood specimens. A linear correlation was performed to relate serum and salivary cortisol levels; Friedman test was conducted to compare cortisol levels during the first month of life, and the difference was used to analyze the performance of values equal to or lower than the first quartile. RESULTS: Fifty-five NBIs were studied. Serum cortisol: 7.65 (1.0-18.1 gg/dL); salivary cortisol: 35.88 (5.52-107.64 mmol/L); cortisol-binding globulin: 22.07 (16.5-33.0 gg/mL), expressed as median and range. The correlation coefficient between serum and salivary cortisol was 0.54, P = 0.001. Cortisol performance during the first month of life showed no statistically significant differences, and the difference between the second and the first specimen of values equal to or lower than the first quartile increased in 10 out of 12 patients. CONCLUSION: The measurement of cortisol in saliva reflects serum cortisol levels in normal NBIs. Some patients had low levels of cortisol at 36 hours of life and showed a trend towards a spontaneous increase during the first month of life.

INTRODUCCIÓN: Dada la dificultad en la interpretación de los valores de cortisol sérico en recién nacidos (RN), el objetivo de este estudio fue correlacionar los niveles basales de cortisol en el suero y la saliva, y describir las concentraciones de cortisol salival durante el primer mes de vida. POBLACIÓN Y MÉTODOS: Estudio descriptivo, prospectivo, longitudinal y de correlación. Se seleccionaron RN de término del Servicio de Neonatología del Hospital Nacional Profesor Alejandro Posadas en 2014. En la saliva, se determinó cortisol; en la sangre, cortisol, globulina tansportadora de cortisol y albúmina. Se utilizó la correlación lineal para relacionar cortisol sérico y salival; el test de Friedman para comparar el cortisol durante el primer mes de vida y la diferencia para analizar el comportamiento de valores iguales o inferiores al primer cuartil. RESULTADOS: Se evaluaron 55 RN. Cortisol sérico: 7,65 (1,0-18,1 gg/dl); cortisol salival: 35,88 (5,52107,64 nmol/L); globulina transportadora de cortisol: 22,07 (16,5-33,0 gg/ml), expresados como mediana y rango. El coeficiente de correlación entre el cortisol sérico y salival fue de 0,54; P= 0,001. El comportamiento del cortisol durante el primer mes de vida no mostró diferencias estadísticamente significativas y la diferencia entre la segunda y la primera muestra de valores iguales o inferiores al primer cuartil aumentó en 10 de 12 pacientes. CONCLUSIÓN: La determinación de cortisol en la saliva refleja la concentración de cortisol sérico en RN normales. Algunos pacientes presentaron niveles bajos de cortisol a las 36 h de vida y mostraron una tendencia a incrementarse espontáneamente durante el primer mes de vida.

Life events are positively associated with luteinizing hormone in middle age adult men: role of cortisol as a third variable.

Previous studies have tested the relationship between chronic stress and sex hormones, but inconsistent results have been found. One possibility is that this association may depend on other biological factors. This study examined the relationship between stressful life events (LE) and sex hormones in men, and whether cortisol is involved in this relationship. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 139 healthy men (mean ± SD age, 57.8 ± 5.7 years) were included in this study. Participants were assessed with the Holmes and Rahe questionnaire in relation to their experience of LE during the previous 1-5 years. Salivary and serum cortisol was measured at 08:00-09:00 h, as well as luteinizing hormone (LH), total testosterone, epinephrine (E) and norepinephrine (NE). LE weight sum and LE number positively correlated with LH (r = 0.293, p = 0.004; r = 0.220, p = 0.031, respectively). In a multiple regression analysis, LE-sum explained an additional and significant 10.4% of the variance in LH levels, after statistically controlling for the effects of age, waist circumference (WC) and BMI (F(1,90) = 6.61, p < 0.05). Importantly, cortisol interacted with LE in relation to total testosterone. In men with high cortisol values (≥15.4 µg/dl), there was a statistically significant positive relationship between LE number and total testosterone levels (p = 0.05), while LE were unrelated to total testosterone in men with low cortisol. LE correlated with sex hormones, predicting LH values, and in men with high cortisol levels shows a possible moderator effect of cortisol on the relationship between LE and total testosterone.

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

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.

[Metabolic abnormalities in young offsprings of parents with essential hypertension]. / Alteraciones metabólicas en hijos de padres con hipertensión arterial.

The familiar history of hypertension in healthy young offsprings is associated with hyperinsulinemia, which could lead to increased serum cortisol, resulting in renal endothelial damage and the presence of microalbuminuria. The aim of this study was to evaluate, in healthy young offsprings of hypertensive parents, association between insulin levels, serum cortisol and microalbuminuria attending to its relationship with increased cardiovascular risk. We performed a cross-sectional correlational study in Santa Fe, Argentina, including 145 healthy individuals aged over 18 years, allocated to two groups: those with a history of essential hypertensive parents (study group) and those without such history (control group). We evaluated fasting serum insulin, cortisol, and microalbuminuria levels in the first morning urine. The mean age was 20 ± 2.9 years, and 58% were women. The study group included 48% (n = 69) of the sample. 4.8% had insulin resistance, microalbuminuria 13.8% and 52% hipercortisolinemia, with no significant differences in serum insulin, cortisol, or microalbuminuria between groups. No correlation was found between these variables. In this study there was no association between a history of first degree hypertension and impaired insulin or cortisol homoeostasis.

Alteraciones metabólicas en hijos de padres con hipertensión arterial / Metabolic abnormalities in young offsprings of parents with essential hypertension

El antecedente familiar de hipertensión arterial en jóvenes sanos se ha asociado a hiperinsulinemia, que a su vez produciría aumento en el cortisol sérico, confluyendo ambos mecanismos en daño endotelial renal con la presencia de microalbuminuria. El objetivo del estudio consistió en evaluar en jóvenes sanos, hijos de hipertensos, la asociación entre los niveles de insulinemia, cortisol sérico y microalbuminuria, debido a su relación con mayor riesgo cardiovascular. Se realizó un trabajo transeccional y correlacional en la ciudad de Santa Fe, incluyendo 145 jóvenes sanos mayores de 18 años de edad, que se asignaron a dos grupos: aquellos con antecedente de primer grado de hipertensión arterial esencial (grupo de estudio) y sin dicho antecedente (grupo control). Se valoraron las concentraciones séricas en ayunas de insulina, cortisol, y los niveles de microalbuminuria en primera orina matutina. La media de edad fue de 20 ± 2.9 años, siendo el 58% mujeres. El grupo de estudio incluyó el 48% (n = 69). El 4.8% presentó insulino-resistencia, 13.8% microalbuminuria y el 52% hipercortisolinemia, no encontrándose diferencias significativas de los niveles séricos de insulina y cortisol, ni de microalbuminuria entre los grupos, así como tampoco correlación entre estas variables. No se encontró asociación entre el antecedente de 1er grado de hipertensión arterial y alteraciones de la homeostasis de insulina o cortisol así como tampoco evidencia de daño endotelial con presencia de microalbuminuria.

The familiar history of hypertension in healthy young offsprings is associated with hyperinsulinemia, which could lead to increased serum cortisol, resulting in renal endothelial damage and the presence of microalbuminuria. The aim of this study was to evaluate, in healthy young offsprings of hypertensive parents, association between insulin levels, serum cortisol and microalbuminuria attending to its relationship with increased cardiovascular risk. We performed a cross-sectional correlational study in Santa Fe, Argentina, including 145 healthy individuals aged over 18 years, allocated to two groups: those with a history of essential hypertensive parents (study group) and those without such history (control group). We evaluated fasting serum insulin, cortisol, and microalbuminuria levels in the first morning urine. The mean age was 20 ± 2.9 years, and 58% were women. The study group included 48% (n = 69) of the sample. 4.8% had insulin resistance, microalbuminuria 13.8% and 52% hipercortisolinemia, with no significant differences in serum insulin, cortisol, or microalbuminuria between groups. No correlation was found between these variables. In this study there was no association between a history of first degree hypertension and impaired insulin or cortisol homoeostasis.

Alteraciones metabólicas en hijos de padres con hipertensión arterial / Metabolic abnormalities in young offsprings of parents with essential hypertension

El antecedente familiar de hipertensión arterial en jóvenes sanos se ha asociado a hiperinsulinemia, que a su vez produciría aumento en el cortisol sérico, confluyendo ambos mecanismos en daño endotelial renal con la presencia de microalbuminuria. El objetivo del estudio consistió en evaluar en jóvenes sanos, hijos de hipertensos, la asociación entre los niveles de insulinemia, cortisol sérico y microalbuminuria, debido a su relación con mayor riesgo cardiovascular. Se realizó un trabajo transeccional y correlacional en la ciudad de Santa Fe, incluyendo 145 jóvenes sanos mayores de 18 años de edad, que se asignaron a dos grupos: aquellos con antecedente de primer grado de hipertensión arterial esencial (grupo de estudio) y sin dicho antecedente (grupo control). Se valoraron las concentraciones séricas en ayunas de insulina, cortisol, y los niveles de microalbuminuria en primera orina matutina. La media de edad fue de 20 ± 2.9 años, siendo el 58% mujeres. El grupo de estudio incluyó el 48% (n = 69). El 4.8% presentó insulino-resistencia, 13.8% microalbuminuria y el 52% hipercortisolinemia, no encontrándose diferencias significativas de los niveles séricos de insulina y cortisol, ni de microalbuminuria entre los grupos, así como tampoco correlación entre estas variables. No se encontró asociación entre el antecedente de 1er grado de hipertensión arterial y alteraciones de la homeostasis de insulina o cortisol así como tampoco evidencia de daño endotelial con presencia de microalbuminuria.(AU)

The familiar history of hypertension in healthy young offsprings is associated with hyperinsulinemia, which could lead to increased serum cortisol, resulting in renal endothelial damage and the presence of microalbuminuria. The aim of this study was to evaluate, in healthy young offsprings of hypertensive parents, association between insulin levels, serum cortisol and microalbuminuria attending to its relationship with increased cardiovascular risk. We performed a cross-sectional correlational study in Santa Fe, Argentina, including 145 healthy individuals aged over 18 years, allocated to two groups: those with a history of essential hypertensive parents (study group) and those without such history (control group). We evaluated fasting serum insulin, cortisol, and microalbuminuria levels in the first morning urine. The mean age was 20 ± 2.9 years, and 58% were women. The study group included 48% (n = 69) of the sample. 4.8% had insulin resistance, microalbuminuria 13.8% and 52% hipercortisolinemia, with no significant differences in serum insulin, cortisol, or microalbuminuria between groups. No correlation was found between these variables. In this study there was no association between a history of first degree hypertension and impaired insulin or cortisol homoeostasis.(AU)

Avaliação do eixo hipotálamo-hipófise adrenal no diagnóstico e na remissão da doença de Cushing / Assessment of the hypothalamic-pituitary-adrenal axis in Cushing's disease diagnosis and remission

A doença de Cushing (DC) permanece um desafio médico com muitas questões ainda não respondidas. O sucesso terapêutico dos pacientes com DC está ligado à correta investigação do diagnóstico síndrômico e etiológico, além da experiência e talento do neurocirurgião. A adenomectomia hipofisária transesfenoidal constitui-se no tratamento de escolha para a DC. A avaliação da remissão da doença no pós-operatório e da recorrência em longo prazo constitui um desafio ainda maior. Especial destaque deve ser dado para o cortisol sérico no pós-operatório como marcador de remissão. Adicionalmente, o uso de corticoide exógeno no pós-operatório apenas em vigência de insuficiência adrenal tem sido sugerido por alguns autores como requisito essencial para permitir a correta interpretação do cortisol sérico nesse cenário. Neste artigo, revisamos as formas de avaliação da atividade da DC e os marcadores de remissão e recidiva da DC após a realização da cirurgia transesfenoidal.

Cushing's disease (CD) remains a medical challenge, with many questions still unanswered. Successful treatment of CD patients is closely related to correct approach to syndromic and etiological diagnosis, besides the experience and talent of the neurosurgeon. Pituitary transsphenoidal adenomectomy is the treatment of choice for DC. Assessment of remission after surgery and recurrence in the long term is an even greater challenge. In this regard, special attention should be paid to the role of postoperative serum cortisol as a marker of CD remission. Additionally, the postoperative use of exogenous glucocorticoids only in cases of adrenal insufficiency has been suggested by some authors as an essential practice to enable the use of serum cortisol in this scenario. In this article, we review the forms of evaluation of DC activity, and markers of remission and relapse of CD after transsphenoidal surgery.

Systolic blood pressure of dogs at hospital and domestic environment

The measurement of blood pressure (BP) is an important assessment of the cardiovascular system, being influenced by physical and pathological conditions. Certain situations of stress and anxiety during BP measurement can lead to elevated values in small animals, known in medicine as "white coat effect". The aim of this research was to compare systolic blood pressure (SBP) measurement using Doppler ultrasonography in 45 adult healthy dogs in two environments, at a veterinary hospital and at home. Comparison of heart rate, serum concentrations of cortisol and glucose intended to help the evaluation of the stress level of the animals. The mean of SBP at the veterinary hospital was 154.7mmHg and it was significantly (P 0.01) higher than at home (136.3mmHg). It was also observed that HR (mean=122.7bpm), and serum cortisol (median=4.5µg dL-1) and glucose (mean=95.9mg dL-1) concentrations were significantly higher (P 0.01) at the hospital, when compared with values obtained at home (109.6bpm; 1.5µg dL-1 and 85.5mg dL-1, respectively). In conclusion, the environment can influence SBP in dogs, due to factors related to stress.

A medida da pressão arterial constitui uma importante avaliação do sistema cardiovascular, sendo influenciada por condições físicas e patológicas. Situações de estresse e ansiedade no momento da aferição podem causar valores de pressão sanguínea elevados, o que é conhecido na medicina humana como "efeito jaleco branco". O objetivo deste trabalho foi comparar os valores da pressão arterial sistólica (PAS) pelo método Doppler em 45 cães em dois ambientes, o doméstico e o hospitalar. Além disso, foram comparadas as frequências cardíacas e concentrações séricas de glicose e cortisol nos dois ambientes, com o objetivo de auxiliar a avaliação o nível de estresse dos animais. A média de PAS observada no hospital foi de 154,7mmHg e foi significativamente superior que a observada em casa (136,3mmHg). Também foi observado que os valores de FC (média=122,7bpm) e concentrações séricas de cortisol (mediana=4,5µg dL-1) e glicose (média=95,9mg dL-1) foram superiores (P 0,01) no ambiente hospitalar, quando comparados com os valores obtidos no lar dos animais (109,6bpm; 1,5µg dL-1 e 85,5mg dL-1, respectivamente). Assim, condições ambientais podem influenciar a PAS em cães, devido a fatores relacionados ao estresse.

Systolic blood pressure of dogs at hospital and domestic environment

The measurement of blood pressure (BP) is an important assessment of the cardiovascular system, being influenced by physical and pathological conditions. Certain situations of stress and anxiety during BP measurement can lead to elevated values in small animals, known in medicine as "white coat effect". The aim of this research was to compare systolic blood pressure (SBP) measurement using Doppler ultrasonography in 45 adult healthy dogs in two environments, at a veterinary hospital and at home. Comparison of heart rate, serum concentrations of cortisol and glucose intended to help the evaluation of the stress level of the animals. The mean of SBP at the veterinary hospital was 154.7mmHg and it was significantly (P 0.01) higher than at home (136.3mmHg). It was also observed that HR (mean=122.7bpm), and serum cortisol (median=4.5µg dL-1) and glucose (mean=95.9mg dL-1) concentrations were significantly higher (P 0.01) at the hospital, when compared with values obtained at home (109.6bpm; 1.5µg dL-1 and 85.5mg dL-1, respectively). In conclusion, the environment can influence SBP in dogs, due to factors related to stress.

A medida da pressão arterial constitui uma importante avaliação do sistema cardiovascular, sendo influenciada por condições físicas e patológicas. Situações de estresse e ansiedade no momento da aferição podem causar valores de pressão sanguínea elevados, o que é conhecido na medicina humana como "efeito jaleco branco". O objetivo deste trabalho foi comparar os valores da pressão arterial sistólica (PAS) pelo método Doppler em 45 cães em dois ambientes, o doméstico e o hospitalar. Além disso, foram comparadas as frequências cardíacas e concentrações séricas de glicose e cortisol nos dois ambientes, com o objetivo de auxiliar a avaliação o nível de estresse dos animais. A média de PAS observada no hospital foi de 154,7mmHg e foi significativamente superior que a observada em casa (136,3mmHg). Também foi observado que os valores de FC (média=122,7bpm) e concentrações séricas de cortisol (mediana=4,5µg dL-1) e glicose (média=95,9mg dL-1) foram superiores (P 0,01) no ambiente hospitalar, quando comparados com os valores obtidos no lar dos animais (109,6bpm; 1,5µg dL-1 e 85,5mg dL-1, respectivamente). Assim, condições ambientais podem influenciar a PAS em cães, devido a fatores relacionados ao estresse.

Systolic blood pressure of dogs at hospital and domestic environment

The measurement of blood pressure (BP) is an important assessment of the cardiovascular system, being influenced by physical and pathological conditions. Certain situations of stress and anxiety during BP measurement can lead to elevated values in small animals, known in medicine as "white coat effect". The aim of this research was to compare systolic blood pressure (SBP) measurement using Doppler ultrasonography in 45 adult healthy dogs in two environments, at a veterinary hospital and at home. Comparison of heart rate, serum concentrations of cortisol and glucose intended to help the evaluation of the stress level of the animals. The mean of SBP at the veterinary hospital was 154.7mmHg and it was significantly (P 0.01) higher than at home (136.3mmHg). It was also observed that HR (mean=122.7bpm), and serum cortisol (median=4.5µg dL-1) and glucose (mean=95.9mg dL-1) concentrations were significantly higher (P 0.01) at the hospital, when compared with values obtained at home (109.6bpm; 1.5µg dL-1 and 85.5mg dL-1, respectively). In conclusion, the environment can influence SBP in dogs, due to factors related to stress.

A medida da pressão arterial constitui uma importante avaliação do sistema cardiovascular, sendo influenciada por condições físicas e patológicas. Situações de estresse e ansiedade no momento da aferição podem causar valores de pressão sanguínea elevados, o que é conhecido na medicina humana como "efeito jaleco branco". O objetivo deste trabalho foi comparar os valores da pressão arterial sistólica (PAS) pelo método Doppler em 45 cães em dois ambientes, o doméstico e o hospitalar. Além disso, foram comparadas as frequências cardíacas e concentrações séricas de glicose e cortisol nos dois ambientes, com o objetivo de auxiliar a avaliação o nível de estresse dos animais. A média de PAS observada no hospital foi de 154,7mmHg e foi significativamente superior que a observada em casa (136,3mmHg). Também foi observado que os valores de FC (média=122,7bpm) e concentrações séricas de cortisol (mediana=4,5µg dL-1) e glicose (média=95,9mg dL-1) foram superiores (P 0,01) no ambiente hospitalar, quando comparados com os valores obtidos no lar dos animais (109,6bpm; 1,5µg dL-1 e 85,5mg dL-1, respectivamente). Assim, condições ambientais podem influenciar a PAS em cães, devido a fatores relacionados ao estresse.

Pitfalls in the diagnosis of Cushing's syndrome: [review]

Among endocrine disorders, Cushing's syndrome (CS) is certainly one of the most challenging to endocrinologists due to the difficulties that often appear during investigation. The diagnosis of CS involves two steps: confirmation of hypercortisolism and determination of its etiology. Biochemical confirmation of the hypercortisolaemic state must be established before any attempt at differential diagnosis. Failure to do so will result in misdiagnosis, inappropriate treatment, and poor management. It should also be kept in mind that hypercortisolism may occur in some patients with depression, alcoholism, anorexia nervosa, generalized resistance to glucocorticoids, and in late pregnancy. Moreover, exogenous or iatrogenic hypercortisolism should always be excluded. The three most useful tests to confirm hypercortisolism are the measurement of 24-h urinary free cortisol levels, low-dose dexamethasone-suppression tests, and determination of midnight serum cortisol or late-night salivary cortisol. However, none of these tests is perfect, each one has different sensitivities and specificities, and several are usually needed to provide a better diagnostic accuracy. The greatest challenge in the investigation of CS involves the differentiation between Cushing's disease and ectopic ACTH syndrome. This task requires the measurement of plasma ACTH levels, non-invasive dynamic tests (high-dose dexamethasone suppression test and stimulation tests with CRH or desmopressin), and imaging studies. None of these tests had 100 percent specificity and their use in combination is usually necessary. Bilateral inferior petrosal sinus sampling is mainly indicated when non-invasive tests do not allow a diagnostic definition. In the present paper, the most important pitfalls in the investigation of CS are reviewed.

Entre as doenças endócrinas, a síndrome de Cushing (SC) é certamente uma das mais desafiadoras para o endocrinologista, devido às dificuldades que comumente surgem durante a investigação. O diagnóstico de SC envolve dois passos: a confirmação do hipercortisolismo e a determinação de sua etiologia. A confirmação bioquímica do excesso de cortisol precisa ser estabelecida antes de qualquer tentativa de diagnóstico diferencial; caso contrário, poderá resultar em diagnóstico incorreto, tratamento impróprio e manejo insuficiente. Deve também ser lembrado que hipercortisolismo pode ocorrer em certos pacientes com depressão, alcoolismo, anorexia nervosa, resistência generalizada aos glicocorticóides e no final da gravidez. Além disso, hipercortisolismo exógeno ou iatrogênico deverá ser sempre excluído. Os três testes mais úteis para a confirmação do hipercortisolismo são: a medida do cortisol livre em urina de 24 h, os testes de supressão com dexametasona (TSD) em doses baixas e a determinação do cortisol sérico à meia-noite ou do cortisol salivar no final da noite. Contudo, nenhum deles é perfeito, cada um com sua sensibilidade e especificidade, sendo vários deles usualmente necessários para fornecer uma melhor acurácia diagnóstica. O maior desafio na investigação da SC envolve a diferenciação entre a doença de Cushing e a síndrome do ACTH ectópico. Esta tarefa requer a medida dos níveis plasmáticos de ACTH, testes dinâmicos não-invasivos (TSD com doses altas e testes de estímulo com CRH ou desmopressina) e estudos de imagem. Nenhum desses testes tem 100 por cento de especificidade e muitas vezes é necessário seu uso combinado. Amostragem venosa do seio petroso inferior está indicada principalmente quando os testes não-invasivos não permitem uma definição diagnóstica. Neste artigo, revisaremos as mais importantes armadilhas na investigação da SC.

Cortisol sérico e glicemia em cadelas tratadas com tramadol e submetidas à ovário-histerectomia

Tramadol is an opiate analgesic used in veterinary medicine, although few studies exist on this drug. The objective of this work was to evaluate the analgesic effect promoted by the administration of tramadol, determined the serum cortisol and blood glucose concentrations of female dogs. For that, 15 animals were used, submitted to the ovaryhysterectomy under general anesthesia with isofluorane. The animals were assigned into three groups. Group 1 (Tep): received epidural tramadol (1.0mg kg-1 diluted in bi-distilled water at 3.0mL final volume), followed by 3.0mL of bi-distilled water applied intravenously fifteen minutes later. Group 2: (Tiv) 3.0mL of bi-distilled water applied via epidural, following intravenous tramadol (1.0mg kg-1 diluted in bi-distilled water at 3.0mL final volume) applied fifteen minutes later. Group 3 (CT): 3.0mL of bi-distilled water applied via epidural, followed by 3.0mL of bi-distilled water applied intravenously fifteen minutes later. The efficacy of each analgesia regimen was evaluated for 12 hours after epidural. There were no significant differences among the experimental groups to the studied variables (P(0.05). Significant differences were observed in each treatment. In the Tep group, there was a serum cortisol increase in the 25 minutes of the transoperatory (M3), in relation to the obtained value right after the anesthesia induction (M2) (P 0.05). In the Tiv and CT groups, we could check an elevation of the variables two (M4) and four (M5) hours of the epidural injection, when compared to the pretreatment (M1) (P 0.05). In these periods, the variables that were studied in the Tep treatment were statistically similar to the pretreatment (M1). According to the results it can be concluded that 1) used methods were sensitive to determine the most stressful surgical moments as well as and, 2) epidural tramadol seems to produce longer analgesia when compared to the intravenous administration.

O tramadol é um analgésico opióide usado em medicina veterinária, embora existam poucos estudos sobre este fármaco. O objetivo deste trabalho foi avaliar o efeito analgésico promovido pela administração do tramadol, mensurando o cortisol sérico e a glicemia de cadelas. Para isso, foram utilizadas 15 fêmeas, submetidas a ovário-histerectomia sob anestesia geral com isofluorano. Os animais foram divididos em três grupos. Grupo 1 (Tep) receberam tramadol pela via epidural (1,0mg kg-1 diluído em água bidestilada ao volume final de 3,0mL) e, após 15 minutos, 3,0mL de água bidestilada pela via intravenosa. No grupo 2 (Tiv), foi administrado 3,0mL de água bidestilada pela via epidural e, após 15 minutos, tramadol pela via intravenosa (1,0mg kg-1 diluído em água bidestilada ao volume final de 3,0mL). No grupo 3 (CT), os animais receberam 3,0mL de água bidestilada pela via epidural e, após 15 minutos, 3,0mL de água bidestilada pela via intravenosa. A eficácia de cada regime analgésico foi avaliada durante 12 horas após a administração da injeção epidural. Não houve diferença significativa entre os grupos experimentais para as variáveis estudadas (P>0,05). Foram observadas diferenças significativas dentro de cada tratamento. No grupo Tep houve aumento do cortisol sérico aos 25 minutos do trans-operatório (M3), em relação ao valor obtido imediatamente após a indução anestésica (M2) (P>0,05). Nos tratamentos Tiv e CT, verificou-se elevação das variáveis, duas (M4) e quatro (M5) horas da injeção epidural (P 0,05), quando comparadas ao pré-tratamento (M1). Nesses períodos, as variáveis estudadas no tratamento Tep foram estatisticamente semelhantes ao pré-tratamento (M1). Com base nos resultados, conclui-se que: 1) a metodologia empregada foi sensível para determinar os momentos de maior estresse cirúrgico, dentre os estudados e 2) o tramadol por via epidural produz analgesia mais duradoura quando comparado à administração intravenosa.

Cortisol sérico e glicemia em cadelas tratadas com tramadol e submetidas à ovário-histerectomia

Tramadol is an opiate analgesic used in veterinary medicine, although few studies exist on this drug. The objective of this work was to evaluate the analgesic effect promoted by the administration of tramadol, determined the serum cortisol and blood glucose concentrations of female dogs. For that, 15 animals were used, submitted to the ovaryhysterectomy under general anesthesia with isofluorane. The animals were assigned into three groups. Group 1 (Tep): received epidural tramadol (1.0mg kg-1 diluted in bi-distilled water at 3.0mL final volume), followed by 3.0mL of bi-distilled water applied intravenously fifteen minutes later. Group 2: (Tiv) 3.0mL of bi-distilled water applied via epidural, following intravenous tramadol (1.0mg kg-1 diluted in bi-distilled water at 3.0mL final volume) applied fifteen minutes later. Group 3 (CT): 3.0mL of bi-distilled water applied via epidural, followed by 3.0mL of bi-distilled water applied intravenously fifteen minutes later. The efficacy of each analgesia regimen was evaluated for 12 hours after epidural. There were no significant differences among the experimental groups to the studied variables (P(0.05). Significant differences were observed in each treatment. In the Tep group, there was a serum cortisol increase in the 25 minutes of the transoperatory (M3), in relation to the obtained value right after the anesthesia induction (M2) (P 0.05). In the Tiv and CT groups, we could check an elevation of the variables two (M4) and four (M5) hours of the epidural injection, when compared to the pretreatment (M1) (P 0.05). In these periods, the variables that were studied in the Tep treatment were statistically similar to the pretreatment (M1). According to the results it can be concluded that 1) used methods were sensitive to determine the most stressful surgical moments as well as and, 2) epidural tramadol seems to produce longer analgesia when compared to the intravenous administration.

O tramadol é um analgésico opióide usado em medicina veterinária, embora existam poucos estudos sobre este fármaco. O objetivo deste trabalho foi avaliar o efeito analgésico promovido pela administração do tramadol, mensurando o cortisol sérico e a glicemia de cadelas. Para isso, foram utilizadas 15 fêmeas, submetidas a ovário-histerectomia sob anestesia geral com isofluorano. Os animais foram divididos em três grupos. Grupo 1 (Tep) receberam tramadol pela via epidural (1,0mg kg-1 diluído em água bidestilada ao volume final de 3,0mL) e, após 15 minutos, 3,0mL de água bidestilada pela via intravenosa. No grupo 2 (Tiv), foi administrado 3,0mL de água bidestilada pela via epidural e, após 15 minutos, tramadol pela via intravenosa (1,0mg kg-1 diluído em água bidestilada ao volume final de 3,0mL). No grupo 3 (CT), os animais receberam 3,0mL de água bidestilada pela via epidural e, após 15 minutos, 3,0mL de água bidestilada pela via intravenosa. A eficácia de cada regime analgésico foi avaliada durante 12 horas após a administração da injeção epidural. Não houve diferença significativa entre os grupos experimentais para as variáveis estudadas (P>0,05). Foram observadas diferenças significativas dentro de cada tratamento. No grupo Tep houve aumento do cortisol sérico aos 25 minutos do trans-operatório (M3), em relação ao valor obtido imediatamente após a indução anestésica (M2) (P>0,05). Nos tratamentos Tiv e CT, verificou-se elevação das variáveis, duas (M4) e quatro (M5) horas da injeção epidural (P 0,05), quando comparadas ao pré-tratamento (M1). Nesses períodos, as variáveis estudadas no tratamento Tep foram estatisticamente semelhantes ao pré-tratamento (M1). Com base nos resultados, conclui-se que: 1) a metodologia empregada foi sensível para determinar os momentos de maior estresse cirúrgico, dentre os estudados e 2) o tramadol por via epidural produz analgesia mais duradoura quando comparado à administração intravenosa.