Hair cortisol in polycystic ovary syndrome.

The aim of the study was to evaluate adrenal axis hyperactivation measuring hair cortisol levels, and its influence on the relationship among metabolic parameters, inflammation markers and androgens in adult women with PCOS. 44 women (18-34 years) with PCOS diagnosis and a control group of 49 healthy women (19-35 years) were included. In both gropus body mass index (BMI) was calculated and waist circumference (WC) was measured. Hair cortisol, total serum testosterone (TT), serum cortisol, 25 OH vitamin D (25OHD), insulin, high sensitivity C-reactive protein (hsCRP), triglycerides (TG), HDL cholesterol (HDL), glucose and leptin were measured. Bioavailable testosterone (bioT) was calculated. Hair cortisol concentration was higher and significantly different in PCOS patients compared to the control group (130 vs 63 pg/mg of hair, p < 0.001). Subsequently, patients with PCOS were divided into two groups according to hair cortisol levels: group 1 with normal hair cortisol concentration and group 2 with levels above the upper limit of the reference values (128 pg/mg of hair). In group 2, TT significantly correlated with 25OHD, hsCRP, TG/HDL index, BMI, WC, insulin and HOMA (p < 0.05); bioT correlated with hsCRP and leptin (p < 0.05). Finally, 25OHD was inversely correlated with leptin and with TG/HDL index (p < 0.05). High hair cortisol concentration in patients with PCOS confirmed hyperactivation of the HPA axis. The associations observed were only found in patients with PCOS with high hair cortisol levels (> 128 pg/mg of hair), showing a possible effect of HPA axis in these associations.

Thyroid hormones in ovarian follicular fluid: Association with oocyte retrieval in women undergoing assisted fertilization procedures.

OBJECTIVE: Our aim was to analyze the role of thyroid hormones in follicular fluid (FF) in relation to the number of oocytes retrieved in women recruited for an assisted fertilization procedure. METHODS: Retrospective cohort study of 51 women 37.5±3.3 years, range 29-42, evaluated after a controlled ovarian stimulation protocol in a University Hospital. FF was sampled by transvaginal ultrasound-guided aspiration after ovarian hyperstimulation and we measured T3 (T3f), T4 (T4f), TSH (TSHf) and free T4 (T4ff). The oocyte maturation rate was calculated as: Number of metaphase II oocytes/Number of oocytes retrieved x 100. Statistical analysis was performed using the SPSS-19 software. RESULTS: Hormone levels in FF were: TSHf 1.3µIU/ml (0.4 - 2.7), T3f: 1.52±0.46 nmol/L, T4f 88.8±30.9nmol/L and T4ff: 15.44±2.57pmol/L. The number of oocytes recovered was dependent onT4f following the equation: Log (oocyte) = 0.379+0.042*T4f (r:0.352, p=0.012). After a logistic regression model analysis, T3f showed a tendency to be associated with the OMR: OR (95 % CI)= 0.977 (0.954 to 1.001), p=0.057. CONCLUSIONS: The correlation found between thyroid hormones and the number of oocytes retrieved suggests an interaction between thyroid and gonadal axes in relation to follicular development.

Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection.

An estimated one third of the world's population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.

Métodos de tiroglobulina de primera y segunda generación: su utilidad en pacientes con cáncer diferenciado de tiroides / First and second generation thyroglobulin measurement methods: Their usefulness in patients with thyroid cancer

El cáncer diferenciado de tiroides (CDT) es el cáncer endocrinológico más frecuente y en las últimas décadas su incidencia ha aumentado. El seguimiento de la enfermedad se efectúa con la medición de tiroglobulina (Tg) sérica, ecografía cervical y barrido corporal total diagnóstico. Los métodos de Tg han evolucionado a través del tiempo. Actualmente, los ensayos inmunométricos de Tg se clasifican en 1.ª y 2.ª generación (1.ª G y 2.ª G). Comprobamos que los ensayos de 2.ª G alcanzan una precisión adecuada para medir valores del orden de 0,1 ng/ml y los de 1.ª G de 1 ng/ml. La bibliografía señala que en el caso de los pacientes de bajo riesgo, una Tg bajo levotiroxina indetectable por un método de 2.ª G puede evitar la realización de Tg estimulada, sea por la suspensión de la terapia hormonal como por el empleo de la TSH recombinante humana, debido a su mayor sensibilidad. Sin embargo, por su menor especificidad, un valor detectable no asegura la presencia de enfermedad, y debería confirmarse. Para optimizar la utilidad clínica de dicha medición se podrían emplear valores de cortes de acuerdo con la población y el método en lugar de la sensibilidad funcional o límite de cuantificación del mismo. Se señalan también otros aspectos críticos en la medición de Tg como son la discordancia entre distintas metodologías y las interferencias en su medición, principalmente por anticuerpos antitiroglobulina. En presencia de interferencias pierden utilidad los ensayos de Tg de 1.ª y 2.ª G. El seguimiento de los pacientes con Tg interferida tiene limitaciones todavía no resueltas. Es importante consensuar entre médicos y bioquímicos las dificultades técnicas y los criterios de interpretación de los valores de Tg en el seguimiento de los pacientes con CDT.

Differentiated thyroid cancer (DTC) is the most common endocrine cancer (tumour) and its incidence has risen in the past decades. Its follow-up includes measuring serum thyroglobulin (Tg), performing neck ultrasound and a diagnostic whole-body scan. Tg assays have evolved with time. At present immunoassays for Tg are classified as 1 st and 2 nd generation assays (1 st G and 2 nd G). 2 nd G assays show an adequate (good) precision at levels close to 0.1 ng/ml and 1 st G assays at levels close to 1 ng/ml. The literature shows that for low risk patients on levothyroxine treatment, who undetectable levels by 2 aG assays can avoid the stimulation test performed by thyroid hormone withdrawal or after recombinant human TSH, due to better sensitivity. However, due to lower specificity, detectable levels do not confirm the presence of disease (tumour), and should be confirmed. To optimise the clinical usefulness of the test, cut-off values specific for population and method should be used, instead of functional sensitivity or quantification limit. Critical issues for measuring Tg are discussed, such as non-harmonisation of methods, and interferences, mainly by antithyroglobulin antibodies (ATg). 1 st and 2 nd G assays are less useful in presence of ATg, and follow up of such patients is limited. Consensus between physicians and the laboratory on technical issues and interpretation criteria of Tg values is of outmost importance in the follow-up of DTC patients.

Prevalencia de enfermedades tiroideas en una población del área metropolitana de Buenos Aires / Prevalence of thyroid diseases in a population of the metropolitan area of Buenos Aires

La prevalencia de alteraciones morfológicas palpables tiroideas no supera el 8% en la población adulta. En el Hospital de Clínicas de la Universidad de Buenos Aires se llevó a cabo un programa gratuito para la detección de enfermedades tiroideas, convocándose a sujetos que desconocieran antecedentes tiroideos. Nuestro objetivo fue establecer la frecuencia de patología morfológica palpable tiroidea, en una población seleccionada de pacientes, y comparar dichos resultados con los hallazgos de un programa de detección similar, realizado en el año 2001¹. Adicionalmente, evaluar la prevalencia de alteraciones funcionales y de autoinmunidad tiroidea. Los individuos que concurrieron se dividieron en 3 grupos: Grupo 1 (n = 186) pacientes con antecedentes personales de enfermedad tiroidea conocida (excluidos del análisis); Grupo 2 (n = 184) sujetos con antecedentes familiares, otras enfermedades autoinmunes, o sintomatología que pudiera atribuirse a alteración de la función tiroidea (grupo inducido), y Grupo 3 (n = 288) sujetos que consultaron por mera curiosidad (grupo random). La función y autoinmunidad tiroidea se evaluó en 144 participantes del Grupo 3, citados al azar. En el grupo random, la prevalencia de alteraciones morfológicas tiroideas, detectadas por palpación, fue del 11,09%. Al comparar estos resultados con los obtenidos 12 años atrás en un estudio similar, realizado en nuestro hospital, no se encontraron diferencias estadísticamente significativas (8,7 vs. 11,09%; p = 0,25). En cuanto a la función tiroidea, se halló hipotiroidismo subclínico en el 6,25%, hipertiroidismo subclínico en el 0,7% y autoinmunidad en el 11% de los sujetos evaluados. En conclusión, la prevalencia de alteraciones palpables de la glándula tiroides no cambió en laúltima década. Esta investigación realizada en una población correctamente seleccionada constituye una herramienta útil para referencias futuras como población control en Argentina.

The prevalence of palpable thyroid morphological abnormalities does not exceed 8% in the adult population. A free program was conducted in the Hospital de Clínicas (University of Buenos Aires) for the detection of thyroid diseases, inviting subjects who were unaware of a history of these diseases. The aim was to establish the frequency of goitre in the selected population, as well as to evaluate the prevalence of functional disorders and thyroid autoimmunity, and to compare these results with the findings of a similar study performed in 2001¹. The subjects were divided into three groups: Group 1 (n = 186) patients with a history of previously known thyroid disorders (excluded subjects); Group 2 (n = 184) subjects with a family history of thyroid disease, other autoimmune diseases, or symptoms that could be attributed to changes in thyroid function (Induced Group), and Group 3 (n = 288) subjects who participated in this program due to mere curiosity (Random Group). Autoimmunity and thyroid function was assessed in 144 randomly selected participants in Group 3. In Group 3, the prevalence of morphological alterations of the thyroid gland was 11.09%. Comparing these results with those obtained 12 years ago in a similar study performed in our hospital, no statistically significant differences were found when the prevalence of morphological thyroid alterations were compared (8.7% vs 11.09%, p=.25). As for thyroid function, subclinical hypothyroidism was found in 6.25%, subclinical hyperthyroidism in 0.7%, and autoimmunity in 11% of subjects evaluated. It was concluded that the prevalence of palpable thyroid abnormalities had not change in the last decade. This study, made in a correctly selected population, is a useful tool for future reference as a control population in Argentina.

Hair cortisol: A new tool for evaluating stress in programs of stress management.

AIMS: Longitudinal and experimental studies have shown that chronic stress contributes to the onset and progression of different diseases. Although it is not possible to eliminate stress completely, people can learn to manage it by participating in different kinds of stress management interventions. This study examined the effectiveness of stress management interventions on neuroendocrine responses in stressed students and health professionals, by measuring hair cortisol in comparison to salivary cortisol. MAIN METHODS: Salivary and hair cortisol measurements were performed in 37 subjects (31women, 6 men; mean age 34.0±10.6) who attended to a Coping Stress and Quality of Care Program at the University of Buenos Aires. Cortisol was measured at the beginning and at the end of the program. The State-Trait Anxiety Inventory STAI was used to evaluate state and trait anxiety. KEY FINDINGS: In subjects who completed the program, no differences were observed in salivary cortisol levels between the first and the last session. However, in these subjects, hair cortisol obtained in the last session was significantly lower than hair cortisol in the first session. SIGNIFICANCE: Hair cortisol appears to be a better biomarker than salivary cortisol for evaluation of the effectiveness of a stress reduction program and it seems to be a better indicator of stress system dysregulation as well.

HIV-TB coinfection impairs CD8(+) T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses.

Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8(+) T cells, and their modulation by DHEA during HIV-TB coinfection. CD8(+) T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8(+) T cells. Notably, CD8(+) T cells from HIV-TB patients displayed higher Terminal Effector (TTE ) CD45RA(dim) proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8(+) T cells from HIV-TB patients increased although restricted to the CD27(+) population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8(+) T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8(+) T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8(+) T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8(+) T-cell functions during HIV-TB coinfection.

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.

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.

Relationship between cortisol, life events and metabolic syndrome in men.

Psychological factors and stressful life events (LE) are considered to play a role in the onset of the metabolic syndrome (MS). We tested the association between LE and cortisol, a marker of chronic stress, with the risk of developing MS and their interaction. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 149 healthy men (mean ± SD age, 58.6 ± 7.7 years) were included in this study. Participants were assessed by the Holmes and Rahe questionnaire about their experience of LE during the previous 1-5 years. MS was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III (ATP-III) and International Diabetes Federation (IDF) criteria. Serum cortisol was measured at 08:00-09:00 h. Participants with MS (IDF criteria) reported significantly more past LE (p = 0.009) and greater summed weight of LE (p = 0.049) than those without MS. Furthermore, LE interacted with cortisol in relation to MS: in men with increased serum cortisol levels ( ≥ 13.7 µg/dl), number of LE significantly predicted MS-status (relative risk (RR) = 1.16, p = 0.03), whereas in men with low cortisol, LE were unrelated to MS (p = 0.52). We conclude that LE were significantly more prevalent in men with the MS than without the MS, according to IDF criteria, independent of the effects of age and body mass index, especially in men with increased serum cortisol levels.

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.

Lipoproteins, sex hormones and inflammatory markers in association with prostate cancer.

OBJECTIVE: To evaluate lipoprotein profile and sex hormones in patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their possible associations with some inflammatory markers linked to PCa. METHODS: A total of 150 men (50-65 years), matched by age and body mass index (BMI), included in this study and divided into three groups according to total prostate specific antigen (PSA), digital rectal examination and prostate biopsy: 50 PCa, 50 BPH and 50 controls. Total cholesterol (Chol), HDL-chol, LDL-chol, triglycerides (TG), total testosterone (T), free T (FT), bioavailable T (BioT), estradiol and SHBG were measured. The free androgen index (FAI) and TG/HDL-chol were calculated. In 25 PCa and 25 controls, C-reactive protein (hs-CRP), adiponectin and insulin were determined. RESULTS: Patients with PCa showed higher TG/HDL-chol and diminished HDL-chol than Controls and BPH. PSA correlated inversely with HDL-chol and directly with TG/HDL-chol. FAI, FT, BioT and estradiol levels were higher, and SHBG and adiponectin were lower in PCa than in Controls. No differences were found in androgens between BPH and PCa. CONCLUSION: Our most novel findings are that the patients with PCa presented lower total Chol and HDL-chol and higher TG/HDL-chol than BPH and Controls. Patients with PCa showed higher androgens and lower adiponectin than Controls.

La saliva y su utilidad en la evaluación de la función endocrinológica / Saliva, its utility in the evaluation of the endocrinological function

Los procedimientos habituales de diagnóstico en el laboratorio clínico implican el análisis de los componentes celulares y químicos de la sangre. Otros líquidos biológicos también se utilizan para el diagnóstico de distintas patologías, entre los cuales la saliva ofrece algunas ventajas distintivas. Constituye una muestra biológica que se puede obtener fácilmente por una técnica no invasiva, indolora y de bajo costo. La muestra de saliva para el diagnóstico de diferentes enfermedades es particularmente útil en pacientes pediátricos y en individuos añosos. Además, el análisis de la saliva puede proporcionar un método apropiado para la investigación de grandes poblcaciones, como lo avalan numerosos trabajos en los que se usa el análisis de este fluido, no solo para el diagnósticos, sino también para el monitoreo de la salud general. En los últimos años, se ha difundido el uso de muestras de saliva para el diagnóstico de diversas entidades clínicas por ser un fluido corporal que puede ser empleado para detecgtar la presencia y determinar concentraciones de una amplia variedad de anticuerpos, drogas, hormonas y marcadores tumorales. (AU)

La saliva y su utilidad en la evaluación de la función endocrinológica / Saliva, its utility in the evaluation of the endocrinological function

Los procedimientos habituales de diagnóstico en el laboratorio clínico implican el análisis de los componentes celulares y químicos de la sangre. Otros líquidos biológicos también se utilizan para el diagnóstico de distintas patologías, entre los cuales la saliva ofrece algunas ventajas distintivas. Constituye una muestra biológica que se puede obtener fácilmente por una técnica no invasiva, indolora y de bajo costo. La muestra de saliva para el diagnóstico de diferentes enfermedades es particularmente útil en pacientes pediátricos y en individuos añosos. Además, el análisis de la saliva puede proporcionar un método apropiado para la investigación de grandes poblcaciones, como lo avalan numerosos trabajos en los que se usa el análisis de este fluido, no solo para el diagnósticos, sino también para el monitoreo de la salud general. En los últimos años, se ha difundido el uso de muestras de saliva para el diagnóstico de diversas entidades clínicas por ser un fluido corporal que puede ser empleado para detecgtar la presencia y determinar concentraciones de una amplia variedad de anticuerpos, drogas, hormonas y marcadores tumorales.