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1.
Cell Mol Life Sci ; 79(11): 543, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36205798

RESUMO

According to the free hormone hypothesis, biological activity of a certain hormone is best reflected by free rather than total hormone concentrations. A crucial element in this theory is the presence of binding proteins, which function as gatekeepers for steroid action. For testosterone, tissue exposure is governed by a delicate equilibrium between free and total testosterone which is determined through interaction with the binding proteins sex hormone-binding globulin and albumin. Ageing, genetics and various pathological conditions influence this equilibrium, hereby possibly modulating hormonal exposure to the target tissues. Despite ongoing controversy on the subject, strong evidence from recent in vitro, in vivo and human experiments emphasizes the relevance of free testosterone. Currently, however, clinical possibilities for free hormone diagnostics are limited. Direct immunoassays are inaccurate, while gold standard liquid chromatography with tandem mass spectrometry (LC-MS/MS) coupled equilibrium dialysis is not available for clinical routine. Calculation models for free testosterone, despite intrinsic limitations, provide a suitable alternative, of which the Vermeulen calculator is currently the preferred method. Calculated free testosterone is indeed associated with bone health, frailty and other clinical endpoints. Moreover, the added value of free testosterone in the clinical diagnosis of male hypogonadism is clearly evident. In suspected hypogonadal men in whom borderline low total testosterone and/or altered sex hormone-binding globulin levels are detected, the determination of free testosterone avoids under- and overdiagnosis, facilitating adequate prescription of hormonal replacement therapy. As such, free testosterone should be integrated as a standard biochemical parameter, on top of total testosterone, in the diagnostic workflow of male hypogonadism.


Assuntos
Hipogonadismo , Globulina de Ligação a Hormônio Sexual , Albuminas , Androgênios , Cromatografia Líquida/métodos , Humanos , Masculino , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/metabolismo , Espectrometria de Massas em Tandem/métodos , Testosterona
2.
Tijdschr Psychiatr ; 64(7): 466-469, 2022.
Artigo em Holandês | MEDLINE | ID: mdl-36040092

RESUMO

Both Cushing’s and pseudo-Cushing’s syndrome involve a state of hypercortisolism. Cushing’s syndrome is a progressive multisystemic disease, caused by either the administration of corticosteroids, or the overproduction of cortisol by a tumoral process. In pseudo-Cushing’s syndrome the HPA-axis is hyperactive due to a pathophysiological process, most frequently caused by depression. The existence of a cyclic variant of Cushing’s syndrome, characterised by intermittent hypercortisolism, complicates the diagnosis in a patient with for example depression. In case of remaining intermittent hypercortisolism after remission of the depression, extreme hypercortisolism and (suspicion of) a tumor, we have to consider a cyclic Cushing syndrome. Also, in patients with treatment resistant depression or depression with atypical features combined with intermittent hypercortisolism psychiatrists have to consider a cyclic Cushing syndrome.


Assuntos
Síndrome de Cushing , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Depressão/diagnóstico , Diagnóstico Diferencial , Humanos , Hidrocortisona
3.
Pituitary ; 24(6): 970-977, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34518998

RESUMO

PURPOSE: We present an up-to-date review of all published cases of sellar melanocytoma, a benign melanocytic neoplasm arising from melanocytes present in the leptomeninges surrounding the pituitary. METHODS: Both the Medline and Embase databases were searched for case reports or case series of patients with a sellar mass consisting of melanocytes. RESULTS: All 14 identified patients developed symptoms due to compression of the surrounding structures. Symptoms included pituitary dysfunction and visual impairment. All patients received a transsphenoidal resection as first-line treatment. The diagnosis is made on pathological examination but deciding whether a sellar melanocytic tumor is best classified as a melanocytoma or a melanoma is not straightforward. DISCUSSION: Genetic analyses can help differentiate between central nervous system origin and metastasis of a cutaneous melanoma with the presence of a GNAQ and GNA11 mutations or a BRAF mutation, respectively. First choice treatment is complete resection, and in case of incomplete resection or recurrence additional radiotherapy is advised.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanócitos , Mutação , Hipófise
4.
Maturitas ; 138: 36-41, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32631586

RESUMO

BACKGROUND: Menopause is often associated with a central accumulation of body fat. This provokes insulin resistance. The resulting hyperinsulinemia may increase the risk of diabetes, cardiovascular disease and breast cancer. Long-term studies indicate that menopausal hormone therapy (MHT) reduces insulin resistance. To broaden knowledge of the mechanisms behind the influence of MHT on glucose homeostasis we focused on the direct short-term effects of MHT with oral combined estradiol and drospirenone on glucose and insulin metabolism in healthy postmenopausal women. METHODS: This randomized, placebo-controlled study recruited 80 healthy postmenopausal women. Women were randomized to treatment with estradiol 1 mg continuously combined with drospirenone 2 mg or placebo for 6-8 weeks. All participants underwent an oral glucose tolerance test (OGTT) before and after the treatment period. Glucose, insulin, fructosamine and C-peptide levels were measured in serum before and 30, 60, 90, 120 and 150 min after a 75-gram oral glucose challenge. RESULTS: After intervention, significantly higher glucose levels at 120 min (p < 0.024) and 150 min (p < 0.030) were observed in the MHT group compared with the placebo group. These glucose levels remained within the normal range. A significantly lower insulin peak serum level (p < 0.040) and a non-significantly smaller area under the curve (AUC) for insulin levels (p = 0.192) was observed in the MHT group at the end of the study period relative to baseline. No significant change in the insulin AUC in the placebo group was observed. There were no significant differences in fructosamine, HOMA-IR and C-peptide levels between the MHT group and the placebo group. CONCLUSION: This double-blind randomized study (EC/2008/694) indicates that treating healthy, postmenopausal women with 1 mg estradiol continuously combined with 2 mg drospirenone significantly decreases peak insulin levels and increases peak glucose levels during an OGTT compared to placebo. These glucose levels remained within the normal range.


Assuntos
Androstenos/uso terapêutico , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Glucose/metabolismo , Terapia de Reposição Hormonal , Insulina/metabolismo , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Administração Oral , Glicemia/análise , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Teste de Tolerância a Glucose , Humanos , Pessoa de Meia-Idade , Pós-Menopausa
5.
Int J Obes (Lond) ; 41(8): 1207-1213, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28461687

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is strongly associated with obesity, dyslipidemia and insulin resistance. NAFLD often presents as simple steatosis (NAFL) but can progress to non-alcoholic steatohepatitis (NASH) and fibrosis. Current non-invasive biomarkers are not tailored to identify significant (⩾F2) fibrosis, although recent guidelines recommend a stringent follow-up of this patient population. We and others have reported on the role of pathological angiogenesis in the pathogenesis of NAFLD, highlighting pro-angiogenic factors as potential diagnostic markers. OBJECTIVE: To investigate the applicability of angiogenic and endothelial dysfunction markers as non-invasive diagnostic tools for NASH or NASH-associated fibrosis in obese patients. METHODS: In a prospective cross-sectional study, male patients undergoing bariatric surgery (n=61) and control patients (n=35) were recruited. Serum protein levels and visceral adipose tissue gene expression of endothelial dysfunction and angiogenic markers were analyzed by multiplex bead-based assay and quantitative RT-PCR, respectively. For validation, we recruited a second cohort of patients undergoing bariatric surgery (n=40) and a cohort of NAFLD patients from our outpatient clinic (n=30). RESULTS: We identified serum vascular cell adhesion molecule-1 (VCAM-1) as an independent predictor for ⩾F2 fibrosis (median 14.0 vs 8.7 ng ml-1 in patients with and without significant fibrosis; P<0.0001) with an area under the receiver-operating characteristics (AUROC) curve of 0.80. The cutoff point of 13.2 ng ml-1 showed a sensitivity of 80% and specificity of 83%. In line with these results, VCAM-1 visceral adipose tissue gene expression was also elevated in patients with fibrosis (P=0.030). In the bariatric surgery and clinical validation cohorts, VCAM-1 displayed similar AUROCs of 0.89 and 0.85, respectively. CONCLUSIONS: VCAM-1 levels are able to accurately predict significant (⩾F2) fibrosis in NAFLD patients.


Assuntos
Cirrose Hepática/sangue , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto , Área Sob a Curva , Cirurgia Bariátrica , Biomarcadores/sangue , Estudos Transversais , Progressão da Doença , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/fisiopatologia , Regulação da Expressão Gênica , Humanos , Resistência à Insulina , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/sangue , Obesidade/complicações , Obesidade/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Regulação para Cima
6.
Andrologia ; 49(2)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27135437

RESUMO

The prevalence of testosterone substitution as well as of androgen deprivation therapy in men is increasing. This review aims to summarise available knowledge of the effects of sex steroids on cardiac structure and function in men. MEDLINE was searched through PubMed. Original studies, systematic reviews and meta-analyses, and relevant citations were screened. A short-term hormonal intervention study in healthy young men with respect to echocardiographic parameters of structure and function was performed. Preclinical research provides sufficient evidence for the heart as a substrate for sex hormones. In animals, administration of oestradiol appears to have beneficial effects on cardiac structure and function, whereas administration of testosterone to noncastrated animals adversely affects cardiac function. However, the effects of sex steroids on cardiac function and structure appear more heterogeneous in human observational studies while comparative, prospective studies in humans are lacking. It is concluded that although effects of testosterone substitution as well as of androgen deprivation on cardiac structure and function can be expected based on pre-clinical research, there exists an important knowledge gap of the effects of hormonal intervention in men. As such, there is a need to address this question in future prospective intervention trials.


Assuntos
Androgênios/deficiência , Coração/efeitos dos fármacos , Terapia de Reposição Hormonal , Miocárdio/metabolismo , Testosterona , Função Ventricular/efeitos dos fármacos , Adulto , Fatores Etários , Animais , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/farmacologia , Ecocardiografia , Estradiol/administração & dosagem , Estradiol/farmacologia , Estrogênios/administração & dosagem , Estrogênios/farmacologia , Feminino , Coração/diagnóstico por imagem , Coração/fisiopatologia , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hipogonadismo/fisiopatologia , Letrozol , Masculino , Miocárdio/patologia , Nitrilas/administração & dosagem , Nitrilas/farmacologia , Fatores Sexuais , Testosterona/efeitos adversos , Testosterona/uso terapêutico , Triazóis/administração & dosagem , Triazóis/farmacologia , Ultrassonografia Doppler
7.
Obes Rev ; 17(1): 68-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26597657

RESUMO

The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising, as is the prevalence of obesity and type 2 diabetes. It is increasingly recognized that an impaired pattern in adipokine secretion could play a pivotal role in the development of NAFLD. We performed a systematic review to evaluate the potential link between newly described adipokines and liver histology in biopsy-proven NAFLD patients. A computerized literature search was performed in PubMed, EMBASE and Web of Science electronic databases. Thirty-one cross-sectional studies were included, resulting in a total of seven different investigated adipokines. Studies included in this review mainly had a good methodological quality. Most adipokines were suggested to be involved in the inflammatory response that develops within the context of NAFLD, either at hepatic or systemic level, and/or hepatic insulin resistance. Based on literature, clinical studies suggest that chemerin, resistin and adipocyte-fatty-acid-binding protein potentially are involved in NAFLD pathogenesis and/or progression. However, major inconsistency still exists, and there is a high need for larger studies, together with the need of standardized assays to determine adipokine levels.


Assuntos
Adipocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/sangue , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia
8.
Andrologia ; 47(1): 5-19, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25495275

RESUMO

There is a limited body of knowledge of desired and undesired effects of cross-sex hormones in transsexual people. Little attention has been given to the fact that chromosomal configurations, 46,XY in male-to-female transsexuals subjects (MtoF) and 46,XX in female-to-male transsexual subjects (FtoM), obviously, remain unchanged. These differences in their genomes cause sex differences in the functions of cells. This study reviews sex differences in metabolism/cardiovascular pathology, immune mechanisms, bone (patho)physiology and brain functions and examines whether they are, maybe partially, determined by genetic mechanisms rather than by (cross-sex) hormones. There do not appear to be major genetic impacts on the changes in bone physiology. Also immune functions are rather unaffected and the evidence for an increase of autoimmune disease in MtoF is preliminary. Brain functions of transsexuals may have differed from controls before cross-sex hormones; they do undergo shifts upon cross-sex hormone treatment, but there is no evidence for changes in sex-specific brain disease. The prevalence of cardiovascular disease is higher in MtoF receiving oestrogens than in FtoM receiving androgens. While type of oestrogen and route of administration might be significant, it is reasonable to speculate that nonhormonal/genetic factors play a role.


Assuntos
Androgênios/farmacologia , Osso e Ossos/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Estrogênios/farmacologia , Sistema Imunitário/efeitos dos fármacos , Pessoas Transgênero , Doenças Cardiovasculares/genética , Feminino , Humanos , Masculino , Osteoporose/genética , Fraturas por Osteoporose/genética , Fatores Sexuais
9.
Eur J Endocrinol ; 160(3): 397-402, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19050164

RESUMO

OBJECTIVE: To assess and compare the effects of short-term aromatase inhibition on glucose metabolism, lipid profile, and adipocytokine levels in young and elderly men. DESIGN AND METHODS: Ten elderly and nine young healthy men were randomized to receive letrozole 2.5 mg daily or placebo for 28 days in a crossover design. RESULTS: Both in young and elderly men, active treatment significantly increased serum testosterone (+128 and +99%, respectively) and decreased estradiol levels (-41 and -62%, respectively). Fasting glucose and insulin levels decreased in young men after active intervention (-7 and -37%, respectively) compared with placebo. Leptin levels fell markedly in both age groups (-24 and -25%, respectively), while adiponectin levels were not affected by the intervention. Lipid profile was slightly impaired in both groups, with increasing low density lipoprotein-cholesterol levels (+14%) in the younger age group and 10% lower levels of APOA1 in the elderly. A decline in IGF1 levels (-15%) was observed in the younger age group. No changes in weight or body mass index were observed in either young or old men. CONCLUSIONS: Short-term aromatase inhibition appears to affect glucose metabolism in young men, and lipid metabolism, including leptin secretion, in young and elderly men. Furthermore, the short period of exposure suggests that these changes might be mediated by direct effects of sex steroids rather than by changes in body composition.


Assuntos
Inibidores da Aromatase/administração & dosagem , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Leptina/sangue , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Aromatase/metabolismo , Estudos Cross-Over , Estradiol/sangue , Humanos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Letrozol , Hormônio Luteinizante/sangue , Masculino , Placebos , Testosterona/sangue , Adulto Jovem
10.
Eur J Endocrinol ; 159(4): 459-68, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18593825

RESUMO

OBJECTIVE: This study was designed to assess longitudinal changes in serum testosterone levels, explore relationships with aging, genetic-, health-, and lifestyle-related factors, and investigate predictors of changes in healthy elderly men. DESIGN: Population-based, longitudinal, 4-year observational study in 221 community-dwelling men aged 71-86 years at baseline. METHODS: Hormone levels assessed by immunoassay, anthropometry, questionnaires on general health, and genetic polymorphisms. Predictors of changes in testosterone levels explored using linear mixed-effects modeling for longitudinal analyses. RESULTS: Total testosterone (TT), free testosterone, and bioavailable testosterone (BioT) levels decreased with aging, decreases in BioT being most marked. No changes in sex hormone-binding globulin (SHBG) or estradiol (E(2)), while LH and FSH levels increased during follow-up. Subjects who gained weight displayed a greater decline in TT levels, mainly due to decreasing SHBG levels. However, baseline body composition was not predictive of subsequent changes in testosterone levels. Baseline E(2) (P=0.023 to 0.004), LH (P=0.046 to 0.005), and FSH (P<0.002) levels were independently positively associated with a faster decline in testosterone fractions, although only FSH remained significant when adjusting for baseline testosterone (P=0.041-0.035). Carriers of a 'TA' haplotype of the estrogen receptor alpha gene (ER alpha) PvuII and XbaI polymorphisms displayed a slower decline of TT and BioT (P=0.041-0.007). CONCLUSIONS: In elderly men with already low serum testosterone levels, a further decline was observed, independent of baseline age. The identification of FSH levels as a predictor of this decline appears to reflect the testicular mechanisms of aging-related changes in testosterone production, whereas associations with E(2) and ER alpha polymorphisms are suggestive of estrogen-related processes, possibly related to changes in the neuroendocrine regulation of testosterone production.


Assuntos
Envelhecimento/metabolismo , Testosterona/sangue , Testosterona/deficiência , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Aromatase/genética , Composição Corporal , Estradiol/sangue , Receptor alfa de Estrogênio/genética , Hormônio Foliculoestimulante/sangue , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Estilo de Vida , Estudos Longitudinais , Hormônio Luteinizante/sangue , Masculino , Saúde do Homem , Polimorfismo Genético , Valor Preditivo dos Testes , Características de Residência , Globulina de Ligação a Hormônio Sexual/metabolismo
11.
Eur J Endocrinol ; 156(3): 395-401, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17322500

RESUMO

OBJECTIVE: The androgen receptor (AR) gene contains a CAG repeat polymorphism coding for a polyglutamine chain, the length of which is inversely correlated with AR transcriptional activity. We explored whether this polymorphism modulates the activities of testosterone (T) related to body composition in elderly men. DESIGN: We performed cross-sectional analyses using data from a 4-year follow-up study in community-dwelling men aged 75-89 years (n=159). METHODS: Body composition was assessed by dual-energy X-ray absorptiometry and its relation with T and the AR gene CAG repeat length was assessed by multiple linear regression analyses, adjusting for confounding and exploring effect modification. RESULTS: AR gene CAG repeat length was not directly related to body composition, either with or without adjustment for confounding variables like age, weight, total T or sex hormone binding globulin (SHBG) levels. However, exploration of effect modification showed that CAG repeat length modulated the relation between T and body composition (standardized regression coefficients of interaction term: beta=0.12, P<0.01 and beta=-0.09, P<0.05 for fat-free mass and fat mass respectively). These results were confirmed using similar models and data of mean T, SHBG and weight of the 2 years' preceding body composition assessment instead of data of the same year (beta=0.09, P<0.05 and beta=-0.09, P<0.05 respectively). CONCLUSION: These findings suggest that the AR gene CAG polymorphism contributes, albeit modestly, to the between-subject variation of T action on body composition in community-dwelling elderly men.


Assuntos
Composição Corporal , Polimorfismo Genético , Receptores Androgênicos/genética , Testosterona/sangue , Repetições de Trinucleotídeos , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/genética , Análise de Variância , Estudos Transversais , Humanos , Modelos Lineares , Masculino , Globulina de Ligação a Hormônio Sexual/metabolismo , Expansão das Repetições de Trinucleotídeos
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