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1.
Int J Mol Sci ; 20(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533319

RESUMO

Induced by a bacterial infection, an immune/inflammatory challenge is a potent negative regulator of the reproduction process in females. The reduction of the synthesis of pro-inflammatory cytokine is considered as an effective strategy in the treatment of inflammatory induced neuroendocrine disorders. Therefore, the effect of direct administration of acetylcholinesterase inhibitor-neostigmine-into the third ventricle of the brain on the gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretions under basal and immune stress conditions was evaluated in this study. In the study, 24 adult, 2-years-old Blackhead ewes during the follicular phase of their estrous cycle were used. Immune stress was induced by the intravenous injection of LPS Escherichia coli in a dose of 400 ng/kg. Animals received an intracerebroventricular injection of neostigmine (1 mg/animal) 0.5 h before LPS/saline treatment. It was shown that central administration of neostigmine might prevent the inflammatory-dependent decrease of GnRH/LH secretion in ewes and it had a stimulatory effect on LH release. This central action of neostigmine is connected with its inhibitory action on local pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)α synthesis in the hypothalamus, which indicates the importance of this mediator in the inhibition of GnRH secretion during acute inflammation.


Assuntos
Inibidores da Colinesterase/administração & dosagem , Endotoxinas/efeitos adversos , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Hormônio Liberador de Gonadotropina/biossíntese , Hormônio Luteinizante/biossíntese , Neostigmina/administração & dosagem , Fase Folicular/efeitos dos fármacos , Fase Folicular/metabolismo , Hidrocortisona/biossíntese , Hipotálamo/metabolismo , Lipopolissacarídeos/efeitos adversos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-31540542

RESUMO

Abstract: Recent evidences suggest that non-arousal mechanisms can restore and stabilize breathing in sleeping patients with obstructive sleep apnea. This possibility can be examined under deep sedation which increases the cortical arousal threshold. We examined incidences of cortical arousal at termination of apneas and hypopneas in elderly patients receiving propofol sedation which increases the cortical arousal threshold. Ten elderly patients undergoing advanced endoscopic procedures under propofol-sedation were recruited. Standard polysomnographic measurements were performed to assess nature of breathing, consciousness, and occurrence of arousal at recovery from apneas and hypopneas. A total of 245 periodic apneas and hypopneas were identified during propofol-induced sleep state. Cortical arousal only occurred in 55 apneas and hypopneas (22.5%), and apneas and hypopneas without arousal and desaturation were most commonly observed (65.7%) regardless of the types of disordered breathing. Chi-square test indicated that incidence of no cortical arousal was significantly associated with occurrence of no desaturation. Higher dose of propofol was associated with a higher apnea hypopnea index (r = 0.673, p = 0.033). In conclusion, even under deep propofol sedation, apneas and hypopneas can be terminated without cortical arousal. However, extensive suppression of the arousal threshold can lead to critical hypoxemia suggesting careful respiratory monitoring.


Assuntos
Nível de Alerta/fisiologia , Hidrocortisona/biossíntese , Propofol/farmacologia , Síndromes da Apneia do Sono/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Propofol/administração & dosagem , Estudos Prospectivos , Respiração
3.
Medicine (Baltimore) ; 98(30): e16610, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348308

RESUMO

The purpose of this study was to investigate the influences of varied anesthetic methods and depths on inflammatory cytokines and stress hormone levels in radical operation among colon cancer patients during perioperative period.A total of 120 patients were collected in the study and randomly divided into 4 groups, A: general anesthesia + Narcotrend D1, B: general anesthesia + Narcotrend D2, C: general anesthesia + epidural anesthesia + Narcotrend D1, D: general anesthesia + epidural anesthesia + Narcotrend D2. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, cortisol (Cor), adrenocorticotropic hormone (ACTH), and endothelin-1 (ET-1) were measured adopting commercial kits before anesthesia (T0), 4 hours after surgery (T1), 24 hours after surgery (T2), and 72 hours after surgery (T3).There was no significant difference in basic clinical characteristics among the groups. In comparison with group A, B and C, group D showed significantly lower levels of TNF-α, IL-6, IL-10, Cor, ACTH, and ET-1 at T1 and T2 (all, P < .05). Significantly higher levels of TNF-α, IL-6, IL-10, Cor, and ACTH were detected at T1 and T2 than those at T0 (all, P < .05), whereas, at T3, the levels of inflammatory cytokines and stress hormones were all decreased near to preoperation ones.General anesthesia combined with epidural anesthesia at Narcotrend D2 depth plays an important role in reducing immune and stress response in patients with colon cancer from surgery to 24 hours after surgery.


Assuntos
Anestesia Epidural/métodos , Anestesia Geral/métodos , Neoplasias do Colo/cirurgia , Citocinas/biossíntese , Mediadores da Inflamação/metabolismo , Hormônio Adrenocorticotrópico/biossíntese , Citocinas/sangue , Quimioterapia Combinada , Endotelina-1/biossíntese , Feminino , Humanos , Hidrocortisona/biossíntese , Mediadores da Inflamação/sangue , Interleucinas/biossíntese , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossíntese
4.
Endocrinology ; 160(9): 2137-2142, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31305910

RESUMO

Owing to the prevalence of depression during childbearing, mothers can be prescribed multiple antidepressants; however, little is known about the risk and consequences to the offspring or subsequent generations. Fluoxetine (FLX) is usually the first-line of pharmacological treatment for affective disorders in pregnant women, with venlafaxine (VEN) used as secondary treatment. Given that FLX and VEN readily cross the placenta, a fetus from a treated pregnant woman is potentially at risk of the endocrine disruptive effects of these chemicals. Pharmaceutical agents, including FLX and VEN, reach aquatic ecosystems through sewage release; thus, fish could also be inadvertently affected. We report the results from a 6-day FLX exposure during early zebrafish development to an environmentally relevant level (0.54 µg/L in water) and a concentration detected in the cord blood of FLX-treated pregnant women (54 µg/L in water). The FLX exposure reduced the stress response (arithmetic difference between the stress-induced and unstressed whole-body cortisol levels) in the adult female and male zebrafish, an effect that persisted for four generations. To model the possibility of a second antidepressant exposure, filial generation 4 was exposed to VEN (5 µg/L). We found that FLX exposure sensitized these descendants to VEN. VEN treatment further suppressed cortisol production in females and decreased spawning rates in adult pairs. This is an important demonstration that in an animal model, a brief ancestral exposure of great-great-grandparents to the selective serotonin reuptake inhibitor FLX will shape the physiological responses of future generations to the serotonin and norepinephrine reuptake inhibitor VEN.


Assuntos
Fluoxetina/farmacologia , Hidrocortisona/biossíntese , Inibidores de Captação de Serotonina/farmacologia , Cloridrato de Venlafaxina/farmacologia , Peixe-Zebra/fisiologia , Animais , Feminino , Masculino , Exposição Materna/efeitos adversos
5.
Medicina (Kaunas) ; 55(5)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137861

RESUMO

Background and objective: Cortisol, as the main human glucocorticoid, is considered to be a biological marker of stress and anxiety. Since it is known that oral lichen planus (OLP) can appear and worsen during stressful events, cortisol levels have been previously studied in OLP patients. The present meta-analysis aims to assess the salivary concentration of cortisol in OLP patients compared to healthy controls. Materials and methods: Web of Science, PubMed, Cochrane Library, and Scopus databases were searched up to October 2018. The RevMan 5.3 software was used with the mean difference (MD) and 95% confidence intervals (CIs). The CMA 2.0 Software was used to evaluate the publication bias, sensitivity analysis, and meta-regression as possible sources of heterogeneity. Results: 10 studies were analyzed and a total of 269 OLP patients and 268 controls were included. The pooled MD of the salivary levels of cortisol in OLP patients compared with controls was 4.27 ng/mL (95% CI: 2.33, 6.21; P < 0.0001), thus, the salivary level of cortisol in OLP patients was significantly higher than in controls. In Indian-based population studies, a significant difference in the salivary cortisol levels in OLP patients compared with controls was detected (MD = 5.62 ng/mL; 95% CI: 2.67, 8.56; P = 0.0002). In addition, a significant difference in the salivary cortisol levels in the OLP patients compared with the controls was obtained in studies performed with enzyme-linked immunosorbent assay (ELISA) method (MD = 5.33 ng/mL; 95% CI: 2.72, 7.93; P < 0.0001). Conclusion: We suggest that supportive psychological treatment together with the conventional therapy could increase patients' capability to prevent stress, anxiety, and depression.


Assuntos
Hidrocortisona/análise , Líquen Plano Bucal/complicações , Saliva/química , Biomarcadores/análise , Humanos , Hidrocortisona/biossíntese , Líquen Plano Bucal/induzido quimicamente
6.
Drugs ; 79(9): 935-956, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31098899

RESUMO

Endogenous Cushing's syndrome is a chronic disease associated with increased morbidity and mortality if not appropriately treated. Recurrence and/or persistence of hypercortisolemia after surgical treatment, especially for Cushing's disease, are high, and long-term medical treatment is used to decrease cortisol levels and risk of metabolic comorbidities. Medical treatment is also often required while waiting for radiation effects to take place. In some cases, severe or life-threatening hypercortisolism must be urgently and medically treated, via intravenous medications or with combination therapy, before patients can undergo surgery. In the last decade, medical treatment has progressed from a few steroidogenesis inhibitors to three novel drug groups: new inhibitors for steroidogenic enzymes with possibly fewer side effects, pituitary-directed drugs that aim to inhibit the pathophysiological pathways of Cushing's disease, and glucocorticoid receptor antagonists that block cortisol's action. Understanding the pathophysiology of Cushing's syndrome has also led to the identification of potential targets that may decrease adrenocorticotrophic hormone and/or cortisol excess, and/or decrease tumor cell proliferation, and induce senescence or apoptosis. We provide here a review of current and near-future medical options to treat Cushing's syndrome, and discuss updates on clinical trials and the efficacy and safety of novel or in-development drugs, as well as future potential targets.


Assuntos
Hormônio Adrenocorticotrópico/antagonistas & inibidores , Síndrome de Cushing/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Hidrocortisona/biossíntese , Receptores de Glucocorticoides/antagonistas & inibidores , Ensaios Clínicos como Assunto , Síndrome de Cushing/metabolismo , Quimioterapia Combinada , Endocrinologia/métodos , Endocrinologia/tendências , Inibidores Enzimáticos/farmacologia , Humanos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Receptores de Glucocorticoides/metabolismo , Resultado do Tratamento
7.
Immunol Res ; 67(2-3): 176-181, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31011985

RESUMO

It has been documented that cortisol release in response to acute stressors is reduced in patients with atopic dermatitis, allergic rhinitis, and other atopic diseases compared to that in healthy subjects. We aimed to test the hypothesis that atopic patients exert reduced salivary cortisol awakening response (CAR) in comparison with healthy subjects. The hypothesis was tested on a stressful and a relax day selected subjectively. Moreover, we evaluated the impact of trait anxiety. The sample consisted of 60 subjects, out of which 28 were patients with atopy and 32 healthy volunteers of both sexes. Saliva samples were collected in the morning to evaluate CAR as well as in the early afternoon and evening to look at cortisol concentrations during the rest of the day. The results showed reduced CAR in atopic patients compared to that in healthy subjects. This effect was modulated by sex with a significant difference observed in males. While CAR was reduced, atopic patients had unchanged cortisol concentrations throughout the day. The evening cortisol was even higher in atopic patients. If the subjects were stratified according to the trait anxiety, no significant differences in CAR between high and low anxiety were observed. No differences in cortisol variables including CAR were observed between the stressful and relax day. In conclusion, this study presents evidence on reduced CAR suggesting an insufficient HPA axis reactivity in atopy. Furthermore, the data in atopic patients demonstrate that reduced HPA axis reactivity does not necessarily mean lower cortisol concentrations throughout the day. This might be of relevance to immune system function and the course of the disease.


Assuntos
Hidrocortisona/biossíntese , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Adolescente , Adulto , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Estresse Fisiológico , Estresse Psicológico , Fatores de Tempo , Adulto Jovem
8.
Hypertension ; 73(6): 1283-1290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31006333

RESUMO

Peripheral 18-oxocortisol (18oxoF) level could contribute to the detection of aldosterone-producing adenoma (APA) in patients with primary aldosteronism. However, peripheral 18oxoF varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of APA, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters about peripheral 18oxoF. Peripheral 18oxoF concentration ranged widely from 0.50 to 183.13 ng/dL and correlated positively with intratumoral areas stained positively for steroidogenic enzymes ( P<0.0001). The peripheral 18oxoF level also correlated significantly with that of circulating aldosterone ( P<0.0001) but not with that of cortisol, a precursor of 18oxoF. However, a significant correlation was detected between peripheral 18oxoF and intratumoral glucocorticoids ( P<0.05). In addition, peripheral 18oxoF correlated positively with the number of hybrid cells double positive for 11ß-hydroxylase and aldosterone synthase ( P<0.0001). Comparing between the cases with and those without KCNJ5 mutation, the KCNJ5-mutated group demonstrated a significantly higher concentration of peripheral 18oxoF (28.4±5.6 versus 3.0±0.9 ng/dL, P<0.0001) and a larger intratumoral environment including the hybrid cells ( P<0.001), possibly representing a deviation from normal aldosterone biosynthesis. After multivariate analysis, KCNJ5 mutation status turned out to be the most associated factor involved in 18oxoF synthesis in APA ( P<0.0001). Results of our present study first revealed that enhanced 18oxoF synthesis in APA could come from a functional deviation of aldosterone biosynthesis from the normal zona glomerulosa and the utility of peripheral 18oxoF measurement could be influenced by the prevalence of KCNJ5 mutation in an APA.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Aldosterona/metabolismo , DNA de Neoplasias/genética , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hidrocortisona/análogos & derivados , Mutação/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/metabolismo , Análise Mutacional de DNA , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo , Humanos , Hidrocortisona/biossíntese , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 98(5): e14037, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702561

RESUMO

Enhanced inflammation response was increasingly reported in association with postoperative cognitive dysfunction (POCD). Glucocorticoid receptor (GR) signal plays a key role in suppression of inflammation. This prospective cohort study aimed to evaluate GR signaling in elderly patients undergoing selective operation.One hundred twenty-six elderly patients were scheduled for hip fracture surgery with general anesthesia. Plasma cortisol levels and the expression levels of GR and FK506 binding protein 51 (FKBP51) in leukocytes were determined at 1 day preoperatively and 7 days. Postoperatively postoperative pain was assessed following surgery using visual analog pain scale (VAS). Neuropsychological tests were performed before surgery and 1 week postoperation. A decline of 1 or more standard deviations in 2 or more tests was considered to reflect POCD.POCD incidence in participants was 28.3% at 1 week after surgery. POCD patients presented significantly higher cortisol and FKBP51 levels compared with non-POCD patients (P < .05). Compared with non-POCD patients, VAS scores at 12 hours after surgery were higher in POCD patients (P < .05). No significant difference in expression levels of GR was found between groups POCD and non-POCD patients.High expression of FKBP51 in leukocytes and glucocorticoid resistance were associated with POCD in aged patients following hip fracture surgery.


Assuntos
Artroplastia de Quadril/efeitos adversos , Disfunção Cognitiva/epidemiologia , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/epidemiologia , Proteínas de Ligação a Tacrolimo/biossíntese , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrocortisona/biossíntese , Masculino , Testes Neuropsicológicos , Dor Pós-Operatória , Estudos Prospectivos , Receptores de Glucocorticoides/biossíntese
10.
Neuropsychobiology ; 77(1): 1-7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30110692

RESUMO

INTRODUCTION: The aim of this study was to expand on this field of work by examining, within a cohort of pregnant women with diagnosed clinical anxiety, the mRNA expression of a panel of genes associated with the cortisol pathway and comparing them to controls. METHODS: Placental samples were obtained from 24 pregnant women, 12 with a diagnosed anxiety disorder and 12 with no psychiatric history, within 30 min of delivery. Differential expression analysis of 85 genes known to be involved in glucocorticoid synthesis, metabolism or signalling was conducted for the: (1) full sample, (2) those at term without labour (5 cases, 7 controls) and (3) those at term with labour (7 cases, 5 controls). Correlation analyses between gene expression and measures of anxiety and depressive symptom severity were also conducted. RESULTS: No robust difference in placental gene expression between pregnant women with and without anxiety disorder was found nor did we detect robust differences by labour status. However, correlational analyses putatively showed a decrease in PER1 expression was associated with an increase in anxiety symptom severity, explaining up to 32% of the variance in anxiety symptom severity. DISCUSSION: Overall, the strongest correlation was found between a decrease in placental PER1 expression and increased anxiety scores. Labour status was found to have a profound effect on mRNA expression. The placental samples obtained from women following labour produced greater numbers of significant differences in mRNA species expression suggesting that in long-standing anxiety the placenta may respond differently under conditions of chronic stress.


Assuntos
Ansiedade/genética , Ansiedade/metabolismo , Expressão Gênica , Hidrocortisona/biossíntese , Placenta/metabolismo , Transdução de Sinais , Adulto , Estudos de Casos e Controles , Depressão/metabolismo , Feminino , Humanos , Trabalho de Parto/metabolismo , Proteínas Circadianas Period/biossíntese , Proteínas Circadianas Period/genética , Gravidez , Adulto Jovem
11.
Intern Med ; 58(3): 405-409, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30210105

RESUMO

We herein present the case of a 27-year-old woman with clinical and biochemical features of virilism. Imaging studies revealed the presence of a bilateral adrenal tumor. Although the secretion of androgens was remarkable, the autonomous production of cortisol was also evident because of a loss of circadian rhythm and the absence of cortisol suppression by dexamethasone. The surgical excision of both adrenal tumors was performed, and the histological examination showed no malignancy. We also report the successful pregnancy and delivery of the patient who showed evolving adrenocortical insufficiency along with virilization and Cushing's syndrome and who continued to receive glucocorticoid replacement therapy during pregnancy.


Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Adenoma Adrenocortical/complicações , Síndrome de Cushing/complicações , Virilismo/complicações , Neoplasias do Córtex Suprarrenal/cirurgia , Adulto , Ritmo Circadiano , Feminino , Humanos , Hidrocortisona/biossíntese , Gravidez
12.
Artigo em Inglês | MEDLINE | ID: mdl-30096932

RESUMO

The effect of horticultural therapy (HT) on immune and endocrine biomarkers remains largely unknown. We designed a waitlist-control randomized controlled trial to investigate the effectiveness of HT in improving mental well-being and modulating biomarker levels. A total of 59 older adults was recruited, with 29 randomly assigned to the HT intervention and 30 to the waitlist control group. The participants attended weekly intervention sessions for the first 3 months and monthly sessions for the subsequent 3 months. Biological and psychosocial data were collected. Biomarkers included IL-1ß, IL-6, sgp-130, CXCL12/SDF-1α, CCL-5/RANTES, BDNF (brain-derived neurotrophic factor), hs-CRP, cortisol and DHEA (dehydroepiandrosterone). Psychosocial measures examined cognitive functions, depression, anxiety, psychological well-being, social connectedness and satisfaction with life. A significant reduction in plasma IL-6 level (p = 0.02) was observed in the HT intervention group. For the waitlist control group, significant reductions in plasma CXCL12 (SDF-1α) (p = 0.003), CXCL5 (RANTES) (p = 0.05) and BDNF (p = 0.003) were observed. A significant improvement in social connectedness was also observed in the HT group (p = 0.01). CONCLUSION: HT, in reducing plasma IL-6, may prevent inflammatory disorders and through maintaining plasma CXCL12 (SDF-1α), may maintain hematopoietic support to the brain. HT may be applied in communal gardening to enhance the well-being of older adults.


Assuntos
Grupo com Ancestrais do Continente Asiático , Horticultura Terapêutica/métodos , Saúde Mental , Idoso , Ansiedade/epidemiologia , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Quimiocina CXCL12/biossíntese , Cognição , Desidroepiandrosterona/biossíntese , Depressão/epidemiologia , Feminino , Humanos , Hidrocortisona/biossíntese , Interleucinas/biossíntese , Relações Interpessoais , Masculino , Pessoa de Meia-Idade
13.
Eur J Endocrinol ; 179(3): R125-R141, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29880708

RESUMO

Congenital adrenal hyperplasia (CAH) is a group of genetic disorders of adrenal steroidogenesis that impair cortisol synthesis, with compensatory increases in ACTH leading to hyperplastic adrenals. The term 'CAH' is generally used to mean 'steroid 21-hydroxylase deficiency' (21OHD) as 21OHD accounts for about 95% of CAH in most populations; the incidences of the rare forms of CAH vary with ethnicity and geography. These forms of CAH are easily understood on the basis of the biochemistry of steroidogenesis. Defects in the steroidogenic acute regulatory protein, StAR, disrupt all steroidogenesis and are the second-most common form of CAH in Japan and Korea; very rare defects in the cholesterol side-chain cleavage enzyme, P450scc, are clinically indistinguishable from StAR defects. Defects in 3ß-hydroxysteroid dehydrogenase, which also causes disordered sexual development, were once thought to be fairly common, but genetic analyses show that steroid measurements are generally unreliable for this disorder. Defects in 17-hydroxylase/17,20-lyase ablate synthesis of sex steroids and also cause mineralocorticoid hypertension; these are common in Brazil and in China. Isolated 17,20-lyase deficiency can be caused by rare mutations in at least three different proteins. P450 oxidoreductase (POR) is a co-factor used by 21-hydroxylase, 17-hydroxylase/17,20-lyase and aromatase; various POR defects, found in different populations, affect these enzymes differently. 11-Hydroxylase deficiency is the second-most common form of CAH in European populations but the retention of aldosterone synthesis distinguishes it from 21OHD. Aldosterone synthase deficiency is a rare salt-losing disorder. Mild, 'non-classic' defects in all of these factors have been described. Both the severe and non-classic disorders can be treated if recognized.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Esteroides/biossíntese , Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/metabolismo , Brasil/epidemiologia , China/epidemiologia , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Humanos , Hidrocortisona/biossíntese , Japão/epidemiologia , Mutação , Fosfoproteínas/genética , República da Coreia/epidemiologia , Esteroide 17-alfa-Hidroxilase/genética
14.
Curr Opin Endocrinol Diabetes Obes ; 25(3): 178-184, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29718004

RESUMO

PURPOSE OF REVIEW: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a relatively common inherited disorder of cortisol biosynthesis that can be fatal if untreated. RECENT FINDINGS: The basic biochemistry and genetics of CAH have been known for decades but continue to be refined by the discoveries of an alternative 'backdoor' metabolic pathway for adrenal androgen synthesis and the secretion of 11-hydroxy and 11-keto analogs of known androgens, by the elucidation of hundreds of new mutations, and by the application of high-throughput sequencing techniques to noninvasive prenatal diagnosis. Although hydrocortisone is a mainstay of treatment, overtreatment may have adverse effects on growth, risk of obesity, and cardiovascular disease; conversely, undertreatment may increase risk of testicular adrenal rest tumors in affected men. SUMMARY: Refinements to screening techniques may improve the positive predictive value of newborn screening programs. Alternative dosing forms of hydrocortisone and additional therapeutic modalities are under study. Although surgical treatment of virilized female genitalia is widely accepted by families and patients, it is not without complications or controversy, and some families choose to defer it.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/terapia , Glândulas Suprarrenais/metabolismo , Hiperplasia Suprarrenal Congênita/complicações , Androgênios/biossíntese , Feminino , Humanos , Hidrocortisona/biossíntese , Hidrocortisona/uso terapêutico , Recém-Nascido , Masculino , Triagem Neonatal , Gravidez , Diagnóstico Pré-Natal , Virilismo/etiologia , Virilismo/cirurgia
15.
Neth J Med ; 76(3): 129-131, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29667589

RESUMO

Adrenocortical carcinoma is a rare and highly malignant disease which can cause hypercortisolism leading to dysregulation of blood pressure and glucose levels. Most patients present with advanced disease. We describe the classic presentation of a functional adrenocortical carcinoma in a patient with metabolic syndrome.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Síndrome de Cushing/etiologia , Síndrome Metabólica/etiologia , Neoplasias do Córtex Suprarrenal/sangue , Neoplasias do Córtex Suprarrenal/complicações , Carcinoma Adrenocortical/sangue , Carcinoma Adrenocortical/complicações , Idoso , Síndrome de Cushing/sangue , Feminino , Humanos , Hidrocortisona/biossíntese , Hidrocortisona/sangue , Síndrome Metabólica/sangue
16.
Mol Diagn Ther ; 22(3): 261-280, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29450859

RESUMO

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders caused by complete or partial defects in one of the several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 95-99% of all cases of CAH are caused by deficiency of steroid 21-hydroxylase, an enzyme encoded by the CYP21A2 gene. Currently, CYP21A2 genotyping is considered a valuable complement to biochemical investigations in the diagnosis of 21-hydroxylase deficiency. More than 200 mutations have been described in literature reports, and much energy is still focused on the clinical classification of new variants. In this review, we focus on molecular genetic features of 21-hydroxylase deficiency, performing an extensive survey of all clinical pathogenic variants modifying the whole sequence of the CYP21A2 gene. Our aim is to offer a very useful tool for clinical and genetic specialists in order to ease clinical diagnosis and genetic counseling.


Assuntos
Glândulas Suprarrenais/enzimologia , Hiperplasia Suprarrenal Congênita/genética , Mutação , Polimorfismo Genético , Esteroide 21-Hidroxilase/genética , Glândulas Suprarrenais/patologia , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/patologia , Alelos , Colesterol/metabolismo , Expressão Gênica , Genótipo , Humanos , Hidrocortisona/biossíntese , Hidrocortisona/deficiência , Fenótipo , Esteroide 21-Hidroxilase/metabolismo , Terminologia como Assunto
17.
Horm Metab Res ; 50(2): 168-174, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29065432

RESUMO

The main treatment algorithm for adrenal insufficiency is hormonal replacement, however, inadequate hormone substitution often leads to severe side effects. Adrenal cell transplantation could be a more effective alternative but would require life-long immune suppressive therapy. PreImplantation Factor (PIF) is an endogenous peptide secreted by viable human embryos that leads to maternal tolerance without immunosuppression. PIF could be effective for xenogeneic cell transplantation such as of bovine adrenocortical cells (BAC), which are used for bioartificial adrenal gland development that may more effectively restore complex adrenal functions. We report here that PIF exerts a dual regulatory effect on BAC by targeting mostly hyper-activated cells to specifically reduce adrenocorticotropic hormone (ACTH)-stimulated cortisol secretion. Reverse transcription real time PCR analysis revealed that PIF modulates the expression of two genes in the cortisol synthesis pathway, Steroidogenic Factor 1 (SF1), an activator of steroidogenesis, and the downstream steroidogenic enzyme Cytochrome P450 17A1 (CYP17A1). PIF increased basal expression of SF1 and CYP17A1 regardless of the activation level of the adrenocortical cells. In contrast, following ACTH stimulation, PIF reduced SF1 expression and induced expression of the immune suppressing anti-inflammatory cytokine IL10 only in the hyper-activated cells, suggesting both a protective and immune tolerant function. In conclusion, PIF regulates stress-induced adrenal steroidogenesis and immune tolerance in BAC, supporting a potential clinical application to reduce rejection by the host's immune response following xenotransplantation.


Assuntos
Glândulas Suprarrenais/transplante , Anti-Inflamatórios/metabolismo , Órgãos Bioartificiais , Citocinas/metabolismo , Peptídeos/farmacologia , Esteroides/biossíntese , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Sequência de Aminoácidos , Animais , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Bovinos , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrocortisona/biossíntese , Interleucina-10/metabolismo , Peptídeos/química
18.
Horm Metab Res ; 49(11): 847-853, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29069700

RESUMO

Aldosterone-producing adenoma (APA) is sometimes accompanied with subclinical hypercortisolism. We investigated the ability of cortisol production in APA, both clinically and pathologically. A retrospective cohort study was conducted at Yokohama Rosai Hospital from 2009 to 2016. Thirty patients with APA and serum cortisol levels during the 1 mg dexamethasone suppression test (F-DST)<3.0 µg/dl were included. We evaluated the 1) difference between pre-adrenalectomy F-DST (pre-F-DST) and post-adrenalectomy F-DST (ΔF-DST), 2) correlation between ∆F-DST and pre-F-DST, tumour size determined by CT, and type of adrenalectomy (total or partial), and 3) relationship between the ratio of F-DST divided by tumour size (ΔF-DST/pre-F-DST/mm) and immunoreactivity of CYP17A1, CYP11B1, and CYP11B2. The median [interquartile range] age was 48 [38-58] years. We found a significant decrease in F-DST after adrenalectomy [before: 1.4 (1.1-1.8); after: 0.9 (0.6-1.2); p<0.001]. Additionally, a significant correlation was found for ΔF-DST and both pre-F-DST (Spearman, ρ=-0.68, p<0.001) and tumour size (ρ=-0.51, p 0.005). No significant difference was found in ΔF-DST between total and partial adrenalectomy. CYP17A1 and CYP11B1 were positive in 21 (100%) and 17 (81%) adenomas, respectively. CYP17A1 immunoreactivity in the tumour was significantly related with ΔF-DST/pre-F-DST/mm (p 0.049). F-DST significantly decreased after adrenalectomy, and most of the adenomas were immunohistochemically positive for CYP17A1 and CYP11B1 as well as CYP11B2. We should consider the possibility of autonomous cortisol production as well as hyperaldosteronism in the evaluation and treatment of APA patients.


Assuntos
Adenoma/metabolismo , Neoplasias do Córtex Suprarrenal/metabolismo , Aldosterona/biossíntese , Hidrocortisona/biossíntese , Adenoma/patologia , Adenoma/fisiopatologia , Adenoma/cirurgia , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/fisiopatologia , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adulto , Citocromo P-450 CYP11B2/metabolismo , Dexametasona , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esteroide 11-beta-Hidroxilase/metabolismo , Esteroide 17-alfa-Hidroxilase/metabolismo
19.
Biochem J ; 474(23): 3985-3999, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29074640

RESUMO

The 18 kDa translocator protein (TSPO) is a ubiquitous conserved outer mitochondrial membrane protein implicated in numerous cell and tissue functions, including steroid hormone biosynthesis, respiration, cell proliferation, and apoptosis. TSPO binds with high affinity to cholesterol and numerous compounds, is expressed at high levels in steroid-synthesizing tissues, and mediates cholesterol import into mitochondria, which is the rate-limiting step in steroid formation. In humans, the rs6971 polymorphism on the TSPO gene leads to an amino acid substitution in the fifth transmembrane loop of the protein, which is where the cholesterol-binding domain of TSPO is located, and this polymorphism has been associated with anxiety-related disorders. However, recent knockout mouse models have provided inconsistent conclusions of whether TSPO is directly involved in steroid synthesis. In this report, we show that TSPO deletion mutations in rat and its corresponding rs6971 polymorphism in humans alter adrenocorticotropic hormone-induced plasma corticosteroid concentrations. Rat tissues examined show increased cholesteryl ester accumulation, and neurosteroid formation was undetectable in homozygous rats. These results also support a role for TSPO ligands in diseases with steroid-dependent stress and anxiety elements.


Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Proteínas de Transporte/genética , Hidrocortisona/sangue , Polimorfismo de Nucleotídeo Único , Receptores de GABA-A/genética , Receptores de GABA/genética , Adolescente , Adulto , Animais , Sequência de Bases , Proteínas de Transporte/metabolismo , Ésteres do Colesterol/biossíntese , Ésteres do Colesterol/sangue , Gonadotropina Coriônica/farmacologia , Clonagem Molecular , Corticosterona/biossíntese , Corticosterona/sangue , Embrião de Mamíferos , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Hidrocortisona/biossíntese , Masculino , Plasmídeos/química , Plasmídeos/metabolismo , Pregnanolona/biossíntese , Pregnanolona/sangue , Ratos , Ratos Transgênicos , Receptores de GABA/metabolismo , Receptores de GABA-A/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Testosterona/biossíntese , Testosterona/sangue , Dedos de Zinco , Zigoto/efeitos dos fármacos , Zigoto/crescimento & desenvolvimento , Zigoto/metabolismo
20.
Medicine (Baltimore) ; 96(37): e7998, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28906379

RESUMO

RATIONALE: An accessory ovary is a rare structure containing normal ovarian tissue, which has a direct or ligamentous connection with a normal and eutopic ovary. PATIENT CONCERNS: In the study, we reported a 46-year-old woman presented with secondary amenorrhea and virilization symptoms for 1 year. DIAGNOSES: Endocrine evaluation revealed slightly elevated serum cortisol, extremely elevated 24-hour urinary-free cortisol and serum testosterone. Clinical assessment exhibited a large solid mass with heterogeneous enhancement in the left adnexauteri compounded with hypercortisolism and hyperandrogenemia. An accessory ovarian tumor attached to the infundibulum of the left fallopian tube was found, and a separate normal ovary was present on the same side. INTERVENTIONS: The patient underwent a left adnexectomy. OUTCOMES: During surgery, a 12 cm × 8 cm, gray-red, and well-circumscribed solid mass was be identified. The tumor had ligamentous attachment with the infundibulum of left fallopian tube. The sectioned surface was gray-brown, lobulated and did not exhibit either significant necrosis or hemorrhage. Pathological findings demonstrated that tumor cells had small round nuclei, mild atypia, no mitosis were arranged in a diffuse pattern of columns or nests separated by a rich vascular network and no crystals of Reinke were found. It was diagnosis ovarian steroid cell tumor (NOS) without malignant behavior by immunohistochemical staining. The patient was finally diagnosed as accessory ovarian steroid. The patient was discharged from the hospital on the seventeenth day after surgery. During postoperative follow-up, the first postoperative menstrual flow recovered and blood pressure regained 1 month after surgery. Furthermore, her Cushing syndrome regressed and hirsutism disappeared completely 4 months after surgery cell tumor. LESSONS: It is vitally important to establish a final diagnosis according to the clinical manifestations and laboratory values in addition to imaging studies and laparoscopic examination of a rare coexistence of hyperandrogenemia and Cushing syndrome based on the accessory ovarian pathology.


Assuntos
Hidrocortisona/biossíntese , Neoplasias Ovarianas/metabolismo , Ovário/anormalidades , Tumores do Estroma Gonadal e dos Cordões Sexuais/metabolismo , Testosterona/biossíntese , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Tumores do Estroma Gonadal e dos Cordões Sexuais/complicações
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