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1.
Int Immunopharmacol ; 133: 112057, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615381

RESUMO

BACKGROUND: Dehydroepiandrosterone sulfate (DHEA-S) has been associated with an immunomodulatory function. This study aims to explore the relationship between serum levels of DHEA-S and the immune responses triggered by the Oxford-AstraZeneca COVID-19 vaccine in individuals candidate for vaccination. METHODS: Serum levels of DHEA-S, cytokine release, antibody production and virus neutralization potential were assessed in 50 male and 50 female subjects before and 2 weeks after vaccination with Oxford-AstraZeneca COVID-19 vaccine. RESULTS: Level of DHEA-S before and 2 weeks after first and second dose of vaccination was not different significantly. Levels of Interleukin (IL)-2 and Interferon (IFN)-γ were significantly higher in the supernatant of peripheral blood mononuclear cells (PBMCs) obtained from subjects 2 weeks after both first and second dose of vaccination compared to before vaccination. Serum levels of IgM 2 weeks after first dose of vaccination was significantly higher compared to before first dose of vaccination. However, serum levels of IgG 2 weeks after first and second dose of vaccination were significantly higher compared to before first and second dose of vaccination. The 50 % focus reduction neutralization test (FRNT50) titer was significantly higher 2 weeks after both first and second dose of vaccination compared to before vaccination. Levels of DHEA-S did not have significant correlation with levels of IL-2, IFN-γ, IgM and IgG, and FRNT50 before and after first and second dose of vaccination. Vaccination did not result in intense unwanted clinical presentations. CONCLUSION: DHEA-S is not involved in the quality of protective immune response during Oxford-AstraZeneca COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Sulfato de Desidroepiandrosterona , SARS-CoV-2 , Humanos , Masculino , Feminino , Sulfato de Desidroepiandrosterona/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/sangue , Adulto , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Vacinação , Leucócitos Mononucleares/imunologia , Interferon gama/sangue , Imunoglobulina G/sangue , Anticorpos Neutralizantes/sangue , Citocinas/sangue
2.
Med Sci (Basel) ; 12(2)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38651412

RESUMO

Chronic Obstructive Pulmonary Disease (COPD) is a disease of the lungs characterized by chronic airflow obstruction. Individuals with preserved ratio impaired spirometry (PRISm) may be at risk for developing COPD. This study aimed to characterize PRISm and COPD patients in terms of their immune response and endocrine profile to identify differences extending beyond lung function. The participants performed the clinical assessment, pulmonary function test, and blood collection to determine serum hormone levels and concentrations of cytokine. Differences were observed in the nutritional status, lung function, and comorbidity. There were no differences in IL-6, IL-8, IL-10, IL-12, and TNF levels between PRISm and COPD groups. Both PRISm and COPD patients have lower dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. Correlation analysis of PRISm and COPD patients revealed positive correlations between serum levels of DHEA-S and DHEA, with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), which negatively correlated with IL-8 levels. The results indicated that despite differences in lung function parameters, the PRISm and COPD groups exhibited similarities in endocrine profile alterations. This study represents the first attempt to link endocrine with immune markers and lung function in individuals with PRISm.


Assuntos
Biomarcadores , Doença Pulmonar Obstrutiva Crônica , Espirometria , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Idoso , Citocinas/sangue , Desidroepiandrosterona/sangue , Inflamação/sangue , Sulfato de Desidroepiandrosterona/sangue , Capacidade Vital , Testes de Função Respiratória , Volume Expiratório Forçado
3.
Endocrine ; 84(2): 727-734, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38536547

RESUMO

PURPOSE: To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease. METHODS: This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed. RESULTS: The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0-25.1) ng/mL; T1: 7.1 (1.8-19.9) ng/mL; T2: 5.9 (2.0-20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3-2.5) ng/mL; T1: 0.3 (0.3-1.1) ng/mL; T2: 0.5 (0.3-1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis. CONCLUSIONS: our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.


Assuntos
17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congênita , Nefrolitíase , Humanos , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/epidemiologia , Masculino , Feminino , Criança , Nefrolitíase/epidemiologia , Nefrolitíase/sangue , Nefrolitíase/etiologia , Estudos Prospectivos , Pré-Escolar , 17-alfa-Hidroxiprogesterona/sangue , Incidência , Adolescente , Hormônio Adrenocorticotrópico/sangue , Sulfato de Desidroepiandrosterona/sangue , Lactente , Androstenodiona/sangue , Ultrassonografia , Fatores de Risco
4.
Occup Med (Lond) ; 74(3): 225-229, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38457425

RESUMO

BACKGROUND: The intricate interplay between work-related stress and its physiological impact has drawn extensive research attention. Dehydroepiandrosterone sulphate (DHEA-S) emerges as a potential biomarker reflecting stress-related endocrine changes. AIMS: This cross-sectional study aimed to examine the association between job demands and DHEA-S levels among healthcare workers. The study also explored potential correlations between DHEA-S levels and psychophysical symptoms commonly linked to work-related stress. METHODS: A sample of 488 healthcare workers from a local health authority participated. Job demands were measured using the Demands scale of the Health and Safety Management Standards Indicator Tool. DHEA-S levels and symptom prevalence were assessed through serum analysis and questionnaires, respectively. RESULTS: Workers exposed to high job demands exhibited significantly lower DHEA-S levels compared to those with low job demands. Psychophysical symptoms, including sleep disorders, depression, and headache, were more prevalent in the high-demands group. DHEA-S levels showed significant negative correlations with the prevalence of all considered symptoms. CONCLUSIONS: The study shows the inverse relationship between job demands and DHEA-S levels among healthcare workers, indicating that high job demands correlate with reduced DHEA-S secretion and increased symptom prevalence. The findings suggest DHEA-S as a potential biomarker for assessing the physiological consequences of work-related stress. Proactive interventions in managing job demands are crucial for promoting employee well-being and productivity in demanding work environments. By recognizing DHEA-S as a stress biomarker, organizations can effectively address stress-related health risks and implement targeted interventions for enhancing employees' overall health and work performance.


Assuntos
Biomarcadores , Sulfato de Desidroepiandrosterona , Pessoal de Saúde , Estresse Ocupacional , Humanos , Estudos Transversais , Masculino , Sulfato de Desidroepiandrosterona/sangue , Feminino , Adulto , Pessoal de Saúde/estatística & dados numéricos , Pessoal de Saúde/psicologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Biomarcadores/sangue , Carga de Trabalho/psicologia , Depressão/epidemiologia
5.
Int J Urol ; 31(5): 484-491, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38193650

RESUMO

OBJECTIVE: Adrenocortical carcinoma is a rare condition, with limited comprehensive reports from Japan. This study aimed to review Japan's data on adrenocortical carcinoma by assessing information from 46 patients-with adrenocortical carcinoma across 10 Japanese university hospitals. METHODS: We conducted a retrospective multi-institutional analysis of the clinical characteristics of adrenocortical carcinoma in Japan. We evaluated data from 46 patients across 10 university hospitals over 10 years and analyzed the relationship between clinicopathological characteristics and overall survival. RESULTS: Five- and 10-year overall survival rates were 59% and 53%, respectively. Overall survival was significantly different among the tumor-node-metastasis system for adrenocortical carcinoma of the American Joint Committee on Cancer/International Union Against Cancer, with the worst prognosis in stage IV (p = 0.0044). In our cohort, neither the Weiss score nor the Ki-67 proliferation index correlated with overall survival. Adjuvant treatment did not yield improved overall survival, whereas resection of the primary tumor in stage IV disease was significantly associated with improved overall survival (p = 0.0262). Out of the cases evaluated for plasma hormones, plasma cortisol, aldosterone, testosterone, and DHEA-S levels were measured at 23%, 42%, 29%, and 62%, respectively, demonstrating higher levels than the upper normal limits. CONCLUSION: Patients with stage IV adrenocortical carcinoma had a poor prognosis; however, resection of the primary tumor in stage IV disease was associated with prolonged survival. The results of this study are expected to contribute to future treatment of adrenocortical carcinoma in Japan.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/sangue , Masculino , Feminino , Japão/epidemiologia , Pessoa de Meia-Idade , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/sangue , Neoplasias do Córtex Suprarrenal/terapia , Estudos Retrospectivos , Idoso , Adulto , Prognóstico , Taxa de Sobrevida , Hidrocortisona/sangue , Estadiamento de Neoplasias , Adulto Jovem , Testosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Aldosterona/sangue , Adolescente , Idoso de 80 Anos ou mais
6.
Clin Chem Lab Med ; 62(6): 1080-1091, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38205643

RESUMO

OBJECTIVES: Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for dehydroepiandrosterone sulfate (DHEAS). We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification. METHODS: Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by in-house and external calibration. Intra- and inter-laboratory performances were valued. RESULTS: Intra-laboratory CVs ranged between 4.2-13.2 % for androstenedione, 1.6-10.8 % for DHEAS, and 4.3-8.7 % and 2.6-7.1 % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 %. Median inter-laboratory CV with in-house vs. external calibration were 12.0 vs. 9.6 % for androstenedione (p<0.001), 7.2 vs. 4.9 % for DHEAS (p<0.001), 6.4 vs. 7.6 % for female testosterone (p<0.001) and 6.8 and 7.4 % for male testosterone (p=0.111). Median bias vs. all laboratory median with in-house and external calibration were -13.3 to 20.5 % and -4.9 to 18.7 % for androstenedione, -10.9 to 4.8 % and -3.4 to 3.5 % for DHEAS, -2.7 to 6.5 % and -11.3 to 6.6 % for testosterone in females, and -7.0 to 8.5 % and -7.5 to 11.8 % for testosterone in males, respectively. CONCLUSIONS: Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability.


Assuntos
Androstenodiona , Sulfato de Desidroepiandrosterona , Espectrometria de Massas em Tandem , Testosterona , Androstenodiona/sangue , Androstenodiona/análise , Testosterona/sangue , Testosterona/análise , Testosterona/normas , Humanos , Espectrometria de Massas em Tandem/normas , Espectrometria de Massas em Tandem/métodos , Calibragem , Masculino , Feminino , Cromatografia Líquida/normas , Cromatografia Líquida/métodos , Sulfato de Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/análise , Sulfato de Desidroepiandrosterona/normas , Pessoa de Meia-Idade , Espectrometria de Massa com Cromatografia Líquida
7.
Front Endocrinol (Lausanne) ; 14: 1272797, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075062

RESUMO

Objective: Sex steroid hormones are associated with the advancement of metabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship between dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels and the risk of dyslipidemia in people with type 2 diabetes mellitus. Materials and Methods: The analysis included 1,927 patients with type 2 diabetes mellitus. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels were determined using lipid chromatography-tandem mass spectrometry. Multivariable analyses were performed to investigate the association between the variables and dyslipidemia. Results: The multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of dyslipidemia across DHEA tertiles were 0.39 and 0.24-0.64, respectively (p trend = 0.001). This relationship was still maintained when analyzed as a continuous variable (odds ratio, 0.96; 95% confidence interval, 0.92-0.99; P < 0.01). However, in males with type 2 diabetes mellitus, no significant correlations were found between rising levels of dehydroepiandrosterone sulfate, androstenedione, and total testosterone and the risk of dyslipidemia (all P > 0.05). Furthermore, there was no significant association between androgen precursors and total testosterone with regard to the risk of developing dyslipidemia (all P > 0.05). Conclusions: Serum dehydroepiandrosterone levels were substantially and adversely correlated with dyslipidemia in adult men with T2DM. These results indicated that dehydroepiandrosterone may have an essential role in the development of dyslipidemia. More prospective research is required to validate this link.


Assuntos
Androstenodiona , Desidroepiandrosterona , Diabetes Mellitus Tipo 2 , Dislipidemias , Adulto , Humanos , Masculino , Estudos Transversais , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Diabetes Mellitus Tipo 2/complicações , Estudos Prospectivos , Testosterona/sangue , Fatores de Risco
8.
Gynecol Endocrinol ; 38(1): 45-49, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34664527

RESUMO

OBJECTIVE: Evaluating the impact of coenzyme Q10 (CoQ10) supplementation on hormonal indices, mental health, and biomarkers of inflammatory responses and oxidative stress among female patients suffering from polycystic ovary syndrome (PCOS). METHODS: The present double-blinded, placebo-controlled randomized clinical trial consisted of 55 PCOS women (aged 18-40 years old), who were randomized into groups receiving 100 mg/day of CoQ10 (28 cases) or placebo (27 cases) for 12 weeks. RESULTS: The supplementation of CoQ10 decreased significantly the scores of Beck Depression Inventory (BDI) (p = .03) and Beck Anxiety Inventory (BAI) (p = .01) and high-sensitivity C-reactive protein (hs-CRP) level (p = .005) when comparing with the placebo group. Moreover, CoQ10 group exhibited a significant drop in total testosterone (p = .004), dehydroepiandrosterone sulfate (DHEAS) (p < .001), hirsutism (p = .002) and malondialdehyde (MDA) (p = .001) levels in the serum, and a significant rise in sex hormone-binding globulin (SHBG) (p < .001) and total antioxidant capacity (TAC) (p < .001) levels in the serum than the placebo group. CONCLUSIONS: 12-week supplementation of CoQ10 to PCOS women showed beneficial impact on BDI, BAI, hs-CRP, total testosterone, DHEAS, hirsutism, SHBG, TAC and MDA levels.


Assuntos
Saúde Mental , Metaboloma/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Ubiquinona/análogos & derivados , Adolescente , Adulto , Antioxidantes/análise , Ansiedade/epidemiologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Sulfato de Desidroepiandrosterona/sangue , Depressão/epidemiologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Hirsutismo/epidemiologia , Humanos , Inflamação/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/fisiopatologia , Síndrome do Ovário Policístico/psicologia , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Ubiquinona/administração & dosagem , Adulto Jovem
9.
J Pediatr Endocrinol Metab ; 35(1): 19-27, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-34674406

RESUMO

Pediatric adrenocortical tumors are rare and heterogeneous endocrine malignancies. OBJECTIVES: To report clinical, biochemical, and histological features, staging, and therapeutic interventions in a cohort of 28 patients treated at a single tertiary center. METHODS: A retrospective review of medical records of children with PACT (diagnosed before <18 years of age) followed between 1987-2018 at Hospital de Pediatría Garrahan, Buenos Aires, Argentina. RESULTS: Mean age at diagnosis was 4.6 years (range, 0.3-17.3 years) and median follow-up was 4.17 years (range, 0-12 years). Female to male ratio was 2.5:1. Signs and symptoms that prompted medical intervention were hormonal overproduction (57%), abdominal complaints (36%), and hypertensive encephalopathy (7%). In patients with clinically virilizing tumors (n=16) mean height standard deviation score (SDS) and bone age advance were significantly higher while body mass index (BMI) SDS was significantly lower than in those with clinical Cushing's (n=10) (p<0.05). Serum dehydroepiandrosterone sulfate (DHEAS) levels were significantly higher in stage IV than in stage I (p=0.03). Total adrenalectomy was performed in 26 patients. Eight patients (stage III-IV) received adjuvant chemotherapy. Five-year overall and disease-free survival were 100% for ST I-II, and 51% (95% CI 21-82) and 33% (95% CI 1.2-65) for ST III-IV, respectively (p=0.002). No statistical difference was found when comparing 2-year parameters with and without adjuvant chemotherapy. CONCLUSIONS: Height SDS and BMI SDS seem to mirror hormonal secretion in pediatric adrenocortical tumors. Higher DHEAS levels were found in patients with more advanced disease. Further large-scale studies are needed to validate a possible role for DHEAS as a biochemical marker of tumor stage and to draw robust conclusions on the use of adjuvant chemotherapy.


Assuntos
Neoplasias do Córtex Suprarrenal/terapia , Adolescente , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Criança , Pré-Escolar , Sulfato de Desidroepiandrosterona/sangue , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Centros de Atenção Terciária
10.
JNCI Cancer Spectr ; 5(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34805742

RESUMO

Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], P trend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.


Assuntos
Neoplasias do Colo/etiologia , Hormônios Esteroides Gonadais/sangue , Pós-Menopausa/sangue , Neoplasias Retais/etiologia , Androstenodiona/sangue , Estudos de Casos e Controles , Intervalos de Confiança , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Estrogênios/sangue , Estrona/sangue , Europa (Continente) , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Progesterona/sangue , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue
11.
Sci Rep ; 11(1): 17743, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493761

RESUMO

Androgens have been implicated in autism pathophysiology as recently, prenatal exposure to elevated androgens has been proposed as risk factor. However, published data on postnatal sex hormone levels in autistic children are controversial and the source of prenatal androgen exposure in autism remains unknown. Therefore, this study investigated postnatal sex hormone levels and dehydroepiandrosterone (DHEA) to shed light on a potential role for the adrenal gland in autism pathophysiology. A case-control study investigating estradiol (E2), DHEA, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels was conducted with 31 Saudi males with autism and 28 healthy, age-matched boys plasma. Moreover, correlation analysis with measured hormones and previously measured total testosterone (TT) and free testosterone (FT) in the same group of autism was conducted. DHEA was significantly higher (p < 0.05) in the autism group compared to controls. DHEA positively correlated with previously measured TT (r = + 0.79, p < 0.001) and FT (r = + 0.72, p < 0.001) levels in the same autism group. FSH levels were also significantly higher in the autism group than in the control group (p < 0.01). To the best of our knowledge, this is the first study to report a strong positive correlation between TT, FT and DHEA, suggesting an adrenal source for elevated androgen levels.


Assuntos
Glândulas Suprarrenais/fisiopatologia , Transtorno Autístico/fisiopatologia , Antropometria , Transtorno Autístico/sangue , Estudos de Casos e Controles , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue
12.
Front Endocrinol (Lausanne) ; 12: 652888, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531821

RESUMO

Purpose: Principal component analysis (PCA) is a mathematical model which simplifies data into new, combined variables. Optimal treatment of pediatric congenital adrenal hyperplasia (CAH) remains a challenge and requires evaluation of all biochemical and clinical markers. The aim of this study was to introduce PCA methodology as a tool to optimize management in a cohort of pediatric and adolescent patients with CAH by including adrenal steroid measurements and clinical parameters. Methods: This retrospective, longitudinal cohort of 33 children and adolescents with CAH due to 21-hydroxylase deficiency included 406 follow-up observations. PCAs were applied to serum hormone concentrations and compared to treatment efficacy evaluated by clinical parameters. Results: We provide and describe the first PCA models with hormone parameters denoted in sex- and age-adjusted standard deviation (SD) scores to comprehensibly describe the combined 'endocrine profiles' of patients with classical and non-classical CAH, respectively. Endocrine profile scores were predictive markers of treatment efficacy for classical (AUC=92%; accuracy 95%; p=1.8e-06) and non-classical CAH (AUC=80%; accuracy 91%; p=0.004). A combined PCA demonstrated clustering of patients with classical and non-classical CAH by serum 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone-sulphate (DHEAS) concentrations. Conclusion: As an example of the possibilities of PCA, endocrine profiles were successfully able to distinguish between patients with CAH according to treatment efficacy and to elucidate biochemical differences between classical and non-classical CAH.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/patologia , Biomarcadores/sangue , Sulfato de Desidroepiandrosterona/sangue , Análise de Componente Principal/métodos , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Estudos Longitudinais , Masculino , Prognóstico , Estudos Retrospectivos
13.
J Steroid Biochem Mol Biol ; 214: 106009, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34571175

RESUMO

Associations of androstenediol, which has both androgenic and estrogenic activities, with circulating reproductive hormones and stress hormone in women during the menopausal transition may be different depending on the menopausal stage. The aim of this study was to determine the changes in circulating androstenediol during the menopausal transition in Japanese women and the associations of androstenediol with estrogen, androgen and cortisol for each stage of the menopausal transition. We divided the 104 subjects into 6 stages by menstrual regularity and follicle-stimulating hormone level: mid reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause and early postmenopause. Levels of dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and cortisol were measured. Serum androstenediol concentration was measured by using liquid chromatography mass spectrometry. There were no significant differences in androstenediol levels among the 6 stages. Levels of DHEA-S and testosterone showed significant and positive correlations with androstenediol in all stages. Estradiol levels showed negative correlations with androstenediol levels in the late menopausal transition and very early postmenopause (r=-0.452, p = 0.052 and r=-0.617, p = 0.006, respectively). Cortisol levels showed significant and positive correlations with androstenediol levels in the mid and late reproductive stages (r = 0.719, p = 0.003 and r = 0.808, p < 0.001, respectively).The associations of androstenediol with estradiol and cortisol were different depending on the stage of the menopausal transition. Androstenediol may play a compensatory role for estrogen deficiency from late menopausal transition to very early postmenopause.


Assuntos
Androstenodiol/sangue , Hidrocortisona/sangue , Menopausa/sangue , Adulto , Androgênios/química , Androstenodiona/sangue , Estudos Transversais , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Estrogênios/sangue , Feminino , Humanos , Japão , Pacientes Ambulatoriais , Pós-Menopausa/sangue , Testosterona/sangue
14.
Horm Metab Res ; 53(8): 512-519, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34384108

RESUMO

The majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.


Assuntos
Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Sulfato de Desidroepiandrosterona/sangue , Glucocorticoides/metabolismo , Adenoma/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Endocr J ; 68(11): 1337-1345, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34162776

RESUMO

Serum dehydroepiandrosterone sulfate (DHEA-S) levels reflect the state of adrenocorticotropic hormone (ACTH) secretion. However, it is difficult to use serum DHEA-S to diagnose hypothalamic-pituitary-adrenal (HPA) axis insufficiency due to its non-normal and highly skewed distribution. In this study, we focused on HPA insufficiency caused by hypothalamic and/or pituitary dysfunction and evaluated the usefulness of the standard deviation score of log-transformed DHEA-S (ln DHEA-S SD score), which was calculated from the established age- and sex-specific reference values. We retrospectively reviewed the medical records of 94 patients suspected of having HPA insufficiency, in whom serum DHEA-S measurement and the rapid ACTH stimulation test were performed, and included 65 patients who met our criteria in this study. The ln DHEA-S SD scores were distributed more normally than measured DHEA-S levels and were significantly higher in patients with a peak cortisol level ≥18 µg/dL than in those below this value, suggesting that this score is a legitimate and strong indicator of adrenocortical function. The optimal cut-off value for impaired HPA function was -0.853, with a sensitivity of 70.3% and a specificity of 100%. Among the 37 patients whose peak cortisol levels were below 18 µg/dL, 11 patients with ln DHEA-S scores ≥-0.853 exhibited significantly higher basal ACTH and basal and peak cortisol levels than the 26 patients with scores <-0.853. Thus, this score plays a supportive role in evaluating HPA axis function, particularly in patients with borderline cortisol responses to ACTH.


Assuntos
Insuficiência Adrenal/diagnóstico , Sulfato de Desidroepiandrosterona/sangue , Hipopituitarismo/diagnóstico , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Insuficiência Adrenal/sangue , Insuficiência Adrenal/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipopituitarismo/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Acta Otolaryngol ; 141(7): 695-701, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34191673

RESUMO

BACKGROUND: The pathogenesis of Idiopathic sudden sensorineural hearing loss (ISSNHL) is ambiguous. Stress is commonly defined as a cause of the disease. Serum levels of stress-related hormone (cortisol, growth hormone, aldosterone, ADH, ACTH) may be elevated in patients with ISSNHL patients. OBJECTIVES: We aimed to determine whether psychological factors and stress hormones in patients are associated with the severity of hearing loss and therapeutic outcomes. We hypothesized that the stress hormone level in the disease sequence is a strong prognostic factor of ISSNHL. Additionally, we investigated whether the subjective degree of psychological stress is likely to contribute to the therapeutic prognosis of ISSNHL, as determined using questionnaires. METHODS: We conducted a prospective study of patients aged between 19 and 65 years admitted for the treatment of ISSNHL at our hospital. All patients underwent pure tone audiometry (PTA) on day 0, day 5 and 2 weeks after discharge. As an objective indicator of stress, we measured the level of HPA axis-related hormones. So, we measured serum cortisol, adrenocorticotropic hormone (ACTH), aldosterone and dehydroepiandrosterone sulfate (DHEAS) levels in the venous blood sample of patients on day 1 and day 5 after admission. In addition, for subjective stress measurements, depression and anxiety levels were assessed using self-reported questionnaires, Beck Depression Inventory (BDI), and Perceived Stress Scale (PSS) in the revised to Korean versions. RESULTS: Eighteen patients diagnosed with ISSNHL at the Department of Otorhino-laryngology were enrolled. Serum DHEAS level measured on day 1 showed a statistically significant correlation with the hearing threshold in the hearing test performed at the time of diagnosis (p = .037, correlation coefficients(r) = 0.541). Serum ACTH level was measured on day 1, and patients were classified into normal and elevated groups based on a threshold of 1.5 pg/mL; the normal group had better hearing thresholds in the first and second hearing test than the elevated group (p = .040, 0.015, respectively). In the stress-related questionnaires, the BDI score showed a statistically significant correlation with the last hearing test (p = .015, correlation coefficients(r) = 0.613). CONCLUSION: We demonstrated the possible role of stress-related hormones in the pathogenesis of ISSNHL and suggest that depressive stress response can be a strong predictor of treatment response in patients with ISSNHL. However, the impact of response to stress on the inner ear and endolymph homeostasis remains unknown. Since this is a cross-sectional study, we can only comment on the relationship between stress and ISSNHL, not a causal relationship. Further investigation is necessary to identify the mechanism of interaction between stress and hearing ability in the inner ear.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Sulfato de Desidroepiandrosterona/sangue , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/etiologia , Estresse Psicológico/complicações , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal , Prognóstico , Estudos Prospectivos , Estresse Fisiológico
17.
Chem Res Toxicol ; 34(4): 1150-1160, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33821626

RESUMO

Prophylactic antiretroviral therapy (ART) in HIV infected pregnant mothers and their newborns can dramatically reduce mother-to-child viral transmission and seroconversion in the neonate. The ritonavir-boosted lopinavir regimen, known as Kaletra, has been associated with premature birth and transient adrenal insufficiency in newborns, accompanied by increases in plasma dehydroepiandrosterone 3-sulfate (DHEA-S). In the fetus and neonates, cytochrome P450 CYP3A7 is responsible for the metabolism of DHEA-S into 16α-hydroxy DHEA-S, which plays a critical role in growth and development. In order to determine if CYP3A7 inhibition could lead to the adverse outcomes associated with Kaletra therapy, we conducted in vitro metabolic studies to determine the extent and mechanism of CYP3A7 inhibition by both ritonavir and lopinavir and the relative intrinsic clearance of lopinavir with and without ritonavir in both neonatal and adult human liver microsomes (HLMs). We identified ritonavir as a potent inhibitor of CYP3A7 oxidation of DHEA-S (IC50 = 0.0514 µM), while lopinavir is a much weaker inhibitor (IC50 = 5.88 µM). Furthermore, ritonavir is a time-dependent inhibitor of CYP3A7 with a KI of 0.392 µM and a kinact of 0.119 min-1, illustrating the potential for CYP3A mediated drug-drug interactions with Kaletra. The clearance rate of lopinavir in neonatal HLMs was much slower and comparable to the rate observed in adult HLMs in the presence of ritonavir, suggesting that the addition of ritonavir in the cocktail therapy may not be necessary to maintain effective concentrations of lopinavir in neonates. Our results suggest that several of the observed adverse outcomes of Kaletra therapy may be due to the direct inhibition of CYP3A7 by ritonavir and that the necessity for the inclusion of this drug in the therapy may be obviated by the lower rate of lopinavir clearance in the neonatal liver. These results may lead to a reconsideration of the use of ritonavir in neonatal antiretroviral therapy.


Assuntos
Antirretrovirais/farmacologia , Inibidores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP3A/metabolismo , Sulfato de Desidroepiandrosterona/antagonistas & inibidores , Lopinavir/farmacologia , Ritonavir/farmacologia , Adulto , Antirretrovirais/química , Inibidores do Citocromo P-450 CYP3A/química , Sulfato de Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/metabolismo , Combinação de Medicamentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Recém-Nascido , Lopinavir/química , Conformação Molecular , Oxirredução , Ritonavir/química
18.
Horm Metab Res ; 53(5): 341-349, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33878788

RESUMO

The hyperandrogenism in polycystic ovary syndrome (PCOS) is associated with the risk for the future development of the cardiovascular disease. The objective of the study is to verify whether different androgens have the same harmful effect. This cross-sectional study enrolled 823 women with PCOS: 627 (76.2%) with biochemical hyperandrogenism and 196 (23.8%) with normal androgen levels. The role of individual androgen was evaluated using univariate and multivariate logistic regression. In normoandrogenemic PCOS (NA-PCOS), free androgen index (FAI) predicted significant abnormality in visceral adipose index (VAI, OR=9.2, p=0.002) and dehydroepiandrosterone (DHEA) predicted against alteration in ß-cell function (OR=0.5, p=0.007). In hyperandrogenemic PCOS (HA-PCOS), FAI predicted derangements in waist triglyceride index (WTI), VAI, and lipid accumulation product (LAP) (OR ranging from 1.6 to 5.8, p<0.05). DHEA weakly predicted against VAI (OR 0.7, p=0.018), dehydroepiandrosterone sulfate (DHEAS) tended to predict against the conicity index (OR=0.7, p=0.037). After multiple regression, FAI retained significant strength to predict various anthropometric and metabolic abnormalities (OR ranging from 1.1 to 3.0, p<0.01), DHEA was kept as a protector factor against WTI, LAP, and VAI (OR ranging from 0.6 to 0.9; p<0.01) and DHEAS against the conicity index (OR=0.5, p<0.001). In conclusion, the free androgen index was the most powerful predictor of anthropometric and metabolic abnormalities of polycystic ovary syndrome. Conversely, DHEA and DHEAS demonstrated protective effects against disorders in some markers of obesity and abnormal metabolism.


Assuntos
Androgênios/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Índice de Massa Corporal , Estudos Transversais , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Feminino , Humanos , Hiperandrogenismo/sangue , Produto da Acumulação Lipídica , Triglicerídeos/sangue , Adulto Jovem
19.
Gynecol Endocrinol ; 37(7): 600-608, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33660585

RESUMO

OBJECTIVE: The diagnostic accuracy of tests in identifying virilizing tumors in postmenopausal hyperandrogenism is limited. This systematic review compares the dexamethasone suppression test against selective ovarian and adrenal vein sampling of androgens in distinguishing neoplastic from non-neoplastic causes of postmenopausal hyperandrogenism. METHODS: Diagnostic test accuracy studies on these index tests in postmenopausal women were selected based on pre-established criteria. The true positive, false positive, false negative, and true negative values were extracted and meta-analysis was conducted using the hierarchical summary receiver operator characteristics curve method. RESULTS: The summary sensitivity of the dexamethasone suppression test is 100% (95% CI 0-100%) and that for selective venous sampling is 100% (95% CI 0-100%). The summary specificity of the dexamethasone suppression test is 89.2% (95% CI 85.3-92.2%) and that for selective venous sampling is 100% (95% CI 0.3-100%). CONCLUSION: There is limited evidence for the use of dexamethasone suppression test or selective venous sampling in identifying virilizing tumors in postmenopausal hyperandrogenism.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Androgênios/sangue , Cateterismo Periférico , Técnicas de Diagnóstico Endócrino , Hiperandrogenismo/diagnóstico , Neoplasias Ovarianas/diagnóstico , Pós-Menopausa , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/complicações , Glândulas Suprarrenais/irrigação sanguínea , Sulfato de Desidroepiandrosterona/sangue , Dexametasona , Feminino , Glucocorticoides , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/etiologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/complicações , Ovário/irrigação sanguínea , Testosterona/sangue
20.
Am J Respir Crit Care Med ; 204(3): 285-293, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33779531

RESUMO

Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways.Objectives: To measure whether AR and its ligands are associated with human asthma outcomes.Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men.Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.


Assuntos
Asma/genética , Sulfato de Desidroepiandrosterona/sangue , RNA Mensageiro/metabolismo , Receptores Androgênicos/genética , Mucosa Respiratória/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/sangue , Asma/fisiopatologia , Testes Respiratórios , Broncoscopia , Feminino , Volume Expiratório Forçado , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Qualidade de Vida , Fatores Sexuais , Capacidade Vital , Adulto Jovem
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