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BACKGROUND: There is no universal consensus regarding cut-off points for TSH in pregnancy, so concentrations of 2.5 or 4.0 mIU/L were suggested for first trimester (Endocrine Society [2012] and ATA [2017] guidelines, respectively). Yet, the impact of physiological variation in TSH secretion has not been assessed. SUBJECTS AND METHODS: We assessed baseline concentrations of free T4, free T3 and TSH at 30-minute intervals (between 7.00 and 9.00 hours) in 110 healthy pregnant women, age 30.2 ± 6.0 years, 9.9 ± 2.4 weeks of gestation, and in 19 female controls, age 28.9 ± 10.7. RESULTS: Mean TSH concentrations in pregnant women were 1.62 ± 1.26 mIU/L and on average varied by 39.5% (dispersion between the highest and the lowest TSH), with no difference in TSH variation between pregnant women and controls. Taking into account the highest TSH out of five consecutive measurements, TSH >2.5 mIU/L and TSH above 4.0 mIU/L were found in 23 (20.9%) and 10 (9.1%) pregnant women, respectively. In contrast, when the lowest TSH value was considered, then concentrations of TSH >2.5 mIU/L and >4.0 mIU/L were found in 14 (12.7%) and 4 (3.6%) women, respectively. This discrepancy was even more pronounced in aTPO-negative subjects (21 [21.2%] vs 8 [8.1%] women, for TSH >2.5 mIU/L, and six [6.06%] vs one [1.01%], for TSH >4.0 mIU/L). Furthermore, either six (5.4%) or 10 (9.1%) women had TSH concentrations below 0.1 mIU/L. CONCLUSIONS: In a significant number of patients, diagnosis of subclinical thyroid dysfunction could be erroneously made not as a result of 'disease', but as a result of physiological variation in TSH concentrations.
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Doenças da Glândula Tireoide , Tireotropina , Adulto , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Testes de Função Tireóidea , TiroxinaRESUMO
PCOS is widely accepted as associated with an increased cardiovascular risk, however, without convincing evidence of an increased cardiovascular mortality. We assessed prevalence of obesity, glucose intolerance, and dyslipidaemia in 490 women with PCOS, aged 24.75±8.05 years, diagnosed according to the Rotterdam consensus criteria. Fifty-two percent of women had BMI<26 kg/m2, 81.8% had total cholesterol<200 mg/dl, 82.8% had LDL cholesterol<130 mg/dl (48.3%<100 mg/dl), 81.4% had triglycerides<150 mg/dl, 96.08% had fasting glucose<100 mg/dl, 90.3% had glucose<140 mg/dl at 120' of OGTT. The most frequent abnormality was low HDL cholesterol, as only 33.9% had LDL>60 mg/dl. Combination of several risk factors related to dyslipidaemia was, however, relatively rare, for example, a combination of raised total cholesterol and LDL cholesterol was present only in 2.9% of subjects. An increase in BMI, total cholesterol, LDL-cholesterol, and glucose concentrations at 120' of OGTT was more pronounced in women, who had raised concentrations of at least two androgens (n=172, 35.1%), yet there was no increase in insulin resistance parameters, that is, HOMA-IR, QUICKI, McAuley, or Belfiore index. Contrary to common belief, over 50% of women with PCOS have normal body weight, and with exception of lower HDL cholesterol, most have no significant dyslipidaemia or glucose intolerance. Women with normal or borderline abnormal androgens, who form the majority of PCOS subjects, seem to have more healthy metabolic profile. This might be one of the reasons for the absence of evidence of an increased CV mortality in women with PCOS.
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Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Dislipidemias/epidemiologia , Síndrome do Ovário Policístico/fisiopatologia , Estado Pré-Diabético/epidemiologia , Adulto , Glicemia/análise , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Dislipidemias/sangue , Feminino , Seguimentos , Humanos , Resistência à Insulina , Lipídeos/sangue , Polônia/epidemiologia , Estado Pré-Diabético/sangue , Prevalência , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: Accumulating evidence supports a role for exosomes in immune regulation. In this study, we investigated the total circulating exosome transcriptome in relapsing-remitting multiple sclerosis (RRMS) patients and healthy controls (HC). METHODS: Next generation sequencing (NGS) was used to define the global RNA profile of serum exosomes in 19 RRMS patients (9 in relapse, 10 in remission) and 10 HC. We analyzed 5 million reads and >50,000 transcripts per sample, including a detailed analysis of microRNAs (miRNAs) differentially expressed in RRMS. The discovery set data were validated by quantification using digital quantitative polymerase chain reaction with an independent cohort of 63 RRMS patients (33 in relapse, 30 in remission) and 32 HC. RESULTS: Exosomal RNA NGS revealed that of 15 different classes of transcripts detected, 4 circulating exosomal sequences within the miRNA category were differentially expressed in RRMS patients versus HC: hsa-miR-122-5p, hsa-miR-196b-5p, hsa-miR-301a-3p, and hsa-miR-532-5p. Serum exosomal expression of these miRNAs was significantly decreased during relapse in RRMS. These miRNAs were also decreased in patients with a gadolinium enhancement on brain magnetic resonance imaging. In vitro secretion of these miRNAs by peripheral blood mononuclear cells was also significantly impaired in RRMS. INTERPRETATION: These data show that circulating exosomes have a distinct RNA profile in RRMS. Because putative targets for these miRNAs include the signal transducer and activator of transcription 3 and the cell cycle regulator aryl hydrocarbon receptor, the data suggest a disturbed cell-to-cell communication in this disease. Thus, exosomal miRNAs might represent a useful biomarker to distinguish multiple sclerosis relapse. Ann Neurol 2017;81:703-717.
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Exossomos/metabolismo , Perfilação da Expressão Gênica/métodos , MicroRNAs/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Adulto , Biomarcadores/sangue , Técnicas de Cultura de Células , Exossomos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNARESUMO
OBJECTIVES: to evaluate the impact of epidural analgesia (EA) on labor delivery and neonatal status. MATERIAL AND METHODS: retrospective, observational, cohort study comprising 5593 pregnant women who met the inclusion criteria (singleton pregnancy cephalic presentation, 37-42 weeks of gestation). Out of them, 2496 had EA and 3097 constituted the control group. MAIN OUTCOME MEASURES: incidence of labor complications and operativd deliveries in women who received EA, neonatal status assessed by Apgar score in 1- and 5-minute, and cord pH values. RESULTS: Labor complications were more frequently observed in the epidural group, with an almost 1.5-fold higher incidence in nulliparous (16.32% vs. 11.29%) and 1.4-fold in multiparous women (9.86% vs. 7.08%). Stepwise logistic regression confirmed that EA is a significant risk factor for labor complications in nulliparous women (OR 1.27, 95% CI 1.03-1.58) and for forceps delivery in multiparous women (5.20, 95% CI 3.31-8.177). Also, EA is an important risk factor for both, low cord arterial pH <7.10 (OR 1.98, 95% CI 1.28-3.09, p=0.0023) and low Apgar score at 7 minute (OR=4.55, 95% CI 2.35-8.80, p<0.0001). Crucially there was no difference in the incidence of a low Apgar score at 5 minutes. CONCLUSIONS: EA constitutes an independent risk factor for operative vaginal delivery in multiparous women, but has no effect on the incidence of cesarean sections, either in nulliparous or multiparous women. EA also increases the risk of labor complications, low 1-minute Apgar score and low umbilical cord pH, but is not associated with low 5-minute Apgar score.
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Analgesia Epidural/estatística & dados numéricos , Analgesia Obstétrica/estatística & dados numéricos , Cesárea/estatística & dados numéricos , Complicações do Trabalho de Parto/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Distribuição por Idade , Causalidade , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Paridade , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: We aimed to assess renin, aldosterone, and cortisol in the early stages of pregnancy-induced hypertension (PIH), i. e., at the time of diagnosis. METHODS: During the postural test, we measured aldosterone, renin [Liason DiaSorin Inc. (Italy)], as well as cortisol, sodium, potassium, and 24-h urinary sodium and potassium excretion in 62 women with newly diagnosed PIH, 70 healthy women during the 3rd trimester of pregnancy, and in 22 healthy non-pregnant women. RESULTS: In all groups, there was a significant increase in aldosterone and renin in upright versus supine posture (p<0.01). Both supine and upright aldosterone concentrations were higher in healthy pregnant women than in women with PIH and the lowest in healthy not-pregnant [supine (median±intequartile range): 25.04±18.4 ng/dL, 18.03±12.58 ng/dL, and 7.48±4.78 ng/dL, p<0.001, upright: 31.60±21.32 ng/dL, 25.11±13.15 ng/dL, and 12.4±12.4 ng/dL, p<0.001, for healthy pregnant, pregnant with PIH, and non-pregnant, respectively]. Supine renin concentrations were higher only in healthy pregnant (p<0.001), while in the upright position, there was a difference only between healthy pregnant and women with PIH (p=0.002). Both in supine and upright positions, there was no difference in the aldosterone-to-renin ratio between healthy pregnant women and women with PIH, though, in both groups, the ratio was higher than in non-pregnant women (p<0.001). Morning cortisol concentrations and 24-h urinary sodium excretion were lower in women with PIH than in healthy pregnant (p<0.001, p=0.002, respectively). CONCLUSION: Hyperaldosteronism is not involved in the etiology of PIH. In PIH, there is also a tendency towards lower sodium excretion and lower morning cortisol concentrations.
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Hipertensão Induzida pela Gravidez , Hipertensão , Humanos , Feminino , Gravidez , Renina , Aldosterona , Hidrocortisona , Sódio , Potássio , Hipertensão/etiologiaRESUMO
BACKGROUND: It has been speculated that higher concentrations of 25-hydroxy-vitamin D (25OHD) provide some protection against COVID-19. We assessed whether there is any relationship between 25OHD concentrations and the subsequent development of COVID-19 infection. MATERIALS AND METHODS: Concentrations of 25OHD were measured in March-April 2020 in 134 healthy subjects (57 males), age range 6-50, from a single urban general practice in central Poland. Data on COVID-19 infection during the subsequent 12 months (prior to the vaccination program) were obtained from the national database of COVID-19 cases. None of the subjects received any 25OHD supplements. RESULTS: The average 25OHD concentrations were 18.1 ± 7.39 ng/mL (37.3% had 25OHD above 20 ng/mL). Thirty-one (23.1%) patients developed COVID-19 infection, but an increased risk was only observed in individuals with 25OHD concentrations below 12 ng/mL (COVID-19 infection in 11 out of 25 patients (44%) with 25OHD < 12 ng/mL versus 20 out of 109 (18.3%) for those with 25OHD above 12 ng/mL, p = 0.0063). Such a relationship was no longer observed for subjects with 25OHD concentrations above 20 ng/mL (p = 0.2787). CONCLUSIONS: Although only a minority of healthy subjects had 25OHD concentrations above 20 ng/mL in spring, an increased risk of subsequent COVID-19 infection was only observed in those with severe 25OHD deficiency (<12 ng/mL).
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COVID-19 , Deficiência de Vitamina D , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Deficiência de Vitamina D/epidemiologia , COVID-19/epidemiologia , Vitamina D , Vitaminas , Suplementos NutricionaisRESUMO
Copeptin is a stable part of a vasopressin precursor that closely mirrors arginine vasopressin (AVP) secretion. It is known that AVP/copeptin is also released in response to nonosmotic stimuli, such as stress evoked during anterior pituitary dynamic testing. In order to examine the role of AVP in challenging the hypothalamo-pituitary-adrenal axis, we assessed adrenocorticotropic hormone (ACTH), cortisol, copeptin and growth hormone (GH) during a glucagon stimulation test (GST) in 10 patients with satisfactory initial cortisol concentrations (mean ± SD: 20.34 ± 5.10 µg/dL) and failure to show any further cortisol increment on stimulation. For comparison, we measured copeptin in two subjects during an insulin tolerance test (ITT). During GST, there was an increase in copeptin (p = 0.02, average individual increase of 98%, range 10% to 321%). There was a robust increase in GH (p = 0.002, average increase 3300%), a decline in cortisol (p = 0.02, average decline 21.8%) and a fall in ACTH (p = 0.06). The relative increase in copeptin during ITT (176% and 52.2%) overlapped with increments observed during GST; however, here there was an increase in cortisol (20.45â24.26 µg/dL and 4.23â29.29 µg/dL, respectively). There was a moderate correlation between copeptin and GH concentrations (r = 0.4235, p = 0.0007). These results confirm that AVP is not crucial for ACTH-cortisol stimulation, though it might be an important factor in GH secretion.
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INTRODUCTION: Both pregnancy and polycystic ovary syndrome (PCOS) constitute insulin-resistant states that are associated with an increased prevalence of glucose intolerance. Some women demonstrate significant insulin resistance (IR) and develop gestational diabetes (GDM) even in the 1st trimester. We compared surrogate IR indices in 1st-trimester pregnant women and in women with PCOS (Rotterdam consensus criteria). MATERIAL AND METHODS: We performed a 75-g oral glucose tolerance test (OGTT) with insulin measurements in 106 healthy 1st-trimester pregnant women at 9.9 ± 2.6 weeks of gestation and in 418 women with PCOS. We assessed IR (HOMA-IR, QUICKI, Matsuda, Belfiore, and Stumvoll indices) as well as the prevalence of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADSPG) and World Health Organization (WHO) (1999) criteria. RESULTS: Despite having a slightly lower BMI (p = 0.027), pregnant women had either similar (QUICKI, Belfiore index, Stumvoll0-120 min) or greater IR than women with PCOS (e.g. HOMA-IR 3.85 ± 6.11 vs. 2.64 ± 2.04, p = 0.002), while only the Matsuda index demonstrated less IR in pregnant women (p = 0.003). The correlation between IR indices in pregnant women showed marked variability, ranging from r = 0.334 (HOMA-IR vs. Belfiore index) to r = -1.0 (HOMA-IR vs. QUICKI, p < 0.001). This was accompanied by a high prevalence of GDM (14.2% and 9.4%, IADPSG and WHO criteria, respectively). Women with GDM diagnosed according to IADPSG criteria demonstrated greater IR than pregnant women without GDM. In women with GDM diagnosed according to WHO (1999) criteria these differences were visible only for OGTT-derived IR indices (Belfiore, Matsuda, and Stumvoll0-120 index). CONCLUSIONS: Depending on the choice of IR indices, healthy 1st-trimester pregnant women demonstrate either similar or greater IR than women with PCOS, and this is accompanied by a high prevalence of early GDM. It remains to be established whether GDM screening should be performed in the 1st trimester.
Assuntos
Diabetes Gestacional , Resistência à Insulina , Síndrome do Ovário Policístico , Glicemia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Insulina , Polônia/epidemiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Gravidez , PrevalênciaRESUMO
OBJECTIVE: Diagnosis of primary hyperaldosteronism in pregnancy is complicated due to lack of reference ranges for aldosterone, renin and aldosterone-to-renin ratio. We have endeavoured to establish third-trimester reference ranges for the above-mentioned parameters. DESIGN & PATIENTS: We performed postural tests for aldosterone and renin (chemiluminescence immunoassay Liason® DiaSorin Inc., Italy) in 70 healthy pregnant women (age 30.53±4.51 years), at 32.38±4.25 weeks of gestation and in 22 non-pregnant healthy women (age 33.08±8.72 years). RESULTS: Aldosterone reference ranges were 6.51-73.97 ng/dl and 12.33-86.38 ng/dl, for supine and upright positions, respectively and that for renin were 6.25-59.36 µIU/ml and 11.12-82.55 µIU/ml, respectively. Aldosterone and renin concentrations were higher in an upright position (p=0.000459 and p=0.00011, respectively). In contrast, aldosterone-to-renin ratio was not affected by posture (i. e. 0.497-3.084 ng/dl/µIU/ml versus 0.457-3.06 ng/dl/µIU/ml, p=0.12), but was higher (p=0.00081) than in non-pregnant controls. In comparison to manufacturer-provided non-pregnant reference range, supine aldosterone concentrations increased by 556% (lower cut-off) and 313% (upper cut-off), while upright aldosterone concentrations increased by 558% (lower cut-off) and 244% (upper cut-off). The reference range for supine renin concentrations increased by 223% (lower cut-off) and 48.7% (upper cut-off), while upright renin concentrations increased by 253% (lower cut-off) and 79% (upper cut-off). CONCLUSIONS: There is an upward shift in aldosterone and renin reference ranges in the third-trimester of pregnancy accompanied by an increase in an aldosterone-to-renin ratio, that is not influenced by posture. It remains to be established whether the aldosterone-to-renin ratio may be used as a screening tool for primary hyperaldosteronism in pregnancy.
Assuntos
Hiperaldosteronismo , Hipertensão , Adulto , Aldosterona , Feminino , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/etiologia , Gravidez , Terceiro Trimestre da Gravidez , Valores de Referência , Renina , Adulto JovemRESUMO
BACKGROUND: There is no consensus regarding vitamin sufficiency status with either 20 ng/mL or 30 ng/mL sufficiency cut-off. We assessed the effects of summer sunshine exposure on vitamin D status. PARTICIPANTS: We measured vitamin D concentrations, PTH, creatinine, and total calcium in 132 healthy subjects, age 29.36 ± 13.57 years, in spring and autumn. RESULTS: There was an overall increase in vitamin D concentrations from spring to autumn from 18.1 ± 7.39 ng/mL to 24.58 ± 7.72 ng/mL, (p < 0.001), accompanied by a decrease in PTH from 44.4 ± 17.76 pg/mL to 36.6 ± 14.84 pg/mL, (p < 0.001). In spring, only 5.3% of individuals were vitamin D sufficient for a 30 ng/mL cut-off, increasing to 23.2% in autumn (p < 0.001). In contrast, when a 20 ng/mL cut-off was employed, vitamin D sufficiency was found in 34.1% in spring and 66.4% individuals in autumn, respectively, (p < 0.001). In multiple regression analysis, holiday leave was the only significant determinant of vitamin D increase (p < 0.001). CONCLUSIONS: Holiday leave is the strongest determinant of an increase in vitamin D. The majority of healthy individuals fail to reach a 30 ng/mL vitamin D cut-off after summer sunshine exposure. This raises the question, whether such a cut-off is indeed suitable for the Polish population.
Assuntos
Deficiência de Vitamina D , Vitamina D , Adolescente , Adulto , Humanos , Pessoa de Meia-Idade , Hormônio Paratireóideo , Polônia , Estações do Ano , Deficiência de Vitamina D/epidemiologia , Vitaminas , Adulto JovemRESUMO
The aim of this study was to analyze stress and anxiety levels experienced by pregnant and post-partum women during the COVID-19 pandemic, as well as to indicate the social and medical factors that could contribute to stress and anxiety. A total of 210 patients were enrolled in the study. Two well-established test-tools were applied: State-Trait Anxiety Inventory (STAI) and Perceived Stress Scale (PSS-10). The study revealed that the levels of stress and anxiety experienced by the surveyed patients were moderate to high. We demonstrated that women with mental treatment history, those in the first trimester of pregnancy and the ones that are single or in an informal relationship tend to experience higher levels of psychological distress and anxiety. Such factors as age, education, parity, eventful obstetric history, comorbidities, and the number of hospital stays proved to be statistically insignificant in the analysis. Our findings could be used to identify patients at greater risk of experiencing adverse mental effects and to provide them with adequate psychological support. Further multi-center studies are warranted in order to draw final conclusions.
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Ansiedade/epidemiologia , COVID-19/psicologia , Pandemias , Período Pós-Parto/psicologia , Gestantes/psicologia , Estresse Psicológico/epidemiologia , Depressão , Feminino , Humanos , GravidezRESUMO
OBJECTIVE: The aim of the study was to estimate the effect of maternal obesity on pregnancy course, delivery and newborn well-being. MATERIAL AND METHODS: Data about women who delivered in PMMH was analyzed and obese pregnant women (pre-pregnancy BMI > or =30) were included in the study group; the rest of the mothers constituted the control group. The pregnancy course, labor and delivery, and newborn well-being were taken into consideration. RESULTS: 4648 women were found in our delivery database, among them 208 (4.48%) were classified as obese. In this group, pregnancy-associated hypertension was common, either non-proteinuric one (8.65% vs 2.39%, p=0.001) or preeclampsia (4.81% vs 1.58 %, p<0.05). There were also more cases of gestational diabetes mellitus requiring insulin therapy (9.62% vs 1.48%, p<0.001) and polyhydramniosis (4.81% vs 2.11%, p<0.05) than in case of controls. The mean gestational age at delivery and newborn general health (estimated by Apgar score, mean umbilical cord pH and the incidence of cases with pH < or =7.10) were similar in both groups. The mean birthweight (3266 g vs 3100 g, p<0.05) and the incidence of macrosomia (20.19% vs 5.69%, p<0.001) were significantly higher in the study group. The delivery mode was comparable in both groups, with the marked tendency towards higher incidence of elective cesarean sections in case of obese mothers (27.88% vs 19.90%, p=0.01). CONCLUSION: Maternal obesity is a significant perinatal risk factor; with pregnancy-associated hypertension and gestational diabetes requiring insulin therapy in obese mothers and macrosomia in newborns as most common complications.
Assuntos
Obesidade/epidemiologia , Assistência Perinatal/métodos , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Comorbidade , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido , Obesidade/prevenção & controle , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/prevenção & controle , Polônia/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/prevenção & controle , Fatores de Risco , Saúde da MulherRESUMO
BACKGROUND: Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable. SUBJECTS AND METHODS: In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices). RESULTS: There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = -0.999, HOMA-IR/McAuley index, r = -0.849 and between all OGTT-derived IR indices (e.g. r = -0.876, for IRI/Matsuda, r = -0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P < 0.001 for all), contrasting with a significant (P < 0.001), but highly variable correlation between IR indices derived from fasting vs OGTT-derived variables, ranging from r = -0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = -0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations. CONCLUSIONS: Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution.
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Preterm birth is defined as delivery before 37 completed weeks of pregnancy, and it is the leading cause of neonatal morbidity and mortality. Oxidative stress is recognized as an important factor in the pathogenesis of premature labor. We conducted this analysis to investigate the safety of administration of the tocolytic drug Atosiban-a reversible, competitive antagonist of the oxytocin receptor in the treatment of preterm birth and its impact on the level of oxidative stress in pregnant women after 48 hours of tocolytic treatment. This prospective study was conducted between March 2016 and August 2017 at the Obstetric Clinic of the Polish Mother's Memorial Hospital Research Institute. Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) values as well as 3-nitrotyrosine, carbonyl, and thiol group levels were measured using an ELISA test in serum and plasma of 56 pregnant women before and after 48 hours of continuous administration of Atosiban. We found that TAS levels decreased almost twice after the 48-hour drug administration (0.936 ± 0.360 mmol/L vs. 0.582 ± 0.305 mmol/L, P < 0.001) while TOS increased from 18.217 ± 16.093 µmol/L to 30.442 ± 30.578 µmol/L (P < 0.001). We also found a significant increase in OSI index-almost a threefold increase from 0.022 ± 0.022 to 0.075 ± 0.085, P < 0.001. In addition, statistically significant differences in the level of carbonyl groups were found. It increased from 65.358 ± 31.332 µmol/L to 97.982 ± 38.047 µmol/L (P < 0.001), which indicates increased oxidation of plasma proteins. Furthermore, patients who gave birth prematurely had higher levels of TOS after a 48-hour drug administration than the second group with labor after 37 weeks of pregnancy (42.803 ± 34.683 µmol/L vs. 25.792 ± 27.821 µmol/L, P < 0.031). The obtained results clearly indicate that pregnant women during tocolytic treatment with Atosiban are in a state of increased oxidative stress and occurrence of preterm birth can be associated with this phenomenon. This trial is registered with NCT03570294.
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Antagonistas de Hormônios/efeitos adversos , Estresse Oxidativo/fisiologia , Nascimento Prematuro/tratamento farmacológico , Vasotocina/análogos & derivados , Adulto , Feminino , Antagonistas de Hormônios/farmacologia , Antagonistas de Hormônios/uso terapêutico , Humanos , Recém-Nascido , Estudos Retrospectivos , Vasotocina/efeitos adversos , Vasotocina/farmacologia , Vasotocina/uso terapêuticoRESUMO
BACKGROUND: Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin closely reflects vasopressin release. Copeptin has been shown to subtly mirror stress potentially mediated via corticotrophin-releasing hormone. To further test a potential direct interaction of corticotrophin-releasing hormone with copeptin release, which could augment vasopressin effects on pituitary function, we investigated copeptin response to corticotrophin-releasing hormone. PATIENTS AND METHODS: Cortisol, adrenocorticotropin and copeptin were measured in 18 healthy controls and 29 subjects with a history of pituitary disease during standard corticotrophin-releasing hormone test. RESULTS: Patients with previous pituitary disease were subdivided in a group passing the test (P1, n = 20) and failing (P2, n = 9). The overall copeptin response was higher in controls than in subjects with pituitary disease (area under the curve, p = 0.04 for P1 + P2) with a maximum increase in controls from 3.84 ± 2.86 to 12.65 ± 24.87 pmol/L at 30 min, p < 0.05. In contrast, both groups of pituitary patients lacked a significant copeptin response to corticotrophin-releasing hormone, and even in P1, where adrenocorticotropin concentrations increased fourfold (mean, 21.48 vs. 91.53 pg/mL, p < 0.01), copeptin did not respond (e.g., 4.35 ± 5.81 vs. 5.36 ± 6.79 pmol/L, at 30 min, p = ns). CONCLUSIONS: Corticotrophin-releasing hormone is able to stimulate copeptin release in healthy controls suggesting a direct interaction of corticotrophin-releasing hormone and vasopressin/vasopressin. Interestingly, this relation is altered already in the group of pituitary patients who pass the standard corticotrophin-releasing hormone test indicating (1) the corticotrophin-releasing hormone-adrenocorticotropin-cortisol response is largely independent from the vasopressin system, but (2) the corticotrophin-releasing hormone-vasopressin interaction reflected by copeptin may be much more sensitive to reveal subtle alterations in the regulation of pituitary function.
Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Glicopeptídeos/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Doenças da Hipófise/metabolismo , Hipófise/metabolismo , Receptores de Hormônio Liberador da Corticotropina/agonistas , Transdução de Sinais , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/fisiopatologia , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Biomarcadores/sangue , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/farmacologia , Feminino , Glicopeptídeos/sangue , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Imunoensaio , Cinética , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/sangue , Doenças da Hipófise/fisiopatologia , Hipófise/efeitos dos fármacos , Hipófise/fisiopatologia , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Estimulação QuímicaRESUMO
Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon is a standard procedure to assess pituitary dysfunction but the pathomechanism of glucagon action remains unclear. As arginine vasopressin (AVP) may act on the release of both, GH and ACTH, we tested here the role of AVP in GST by measuring a stable precursor fragment, copeptin, which is stoichiometrically secreted with AVP in a 1:1 ratio. ACTH, cortisol, GH, and copeptin were measured at 0, 60, 90, 120, 150, and 180 min during GST in 79 subjects: healthy controls (Group 1, n = 32), subjects with pituitary disease, but with adequate cortisol and GH responses during GST (Group 2, n = 29), and those with overt hypopituitarism (Group 3, n = 18). Copeptin concentrations significantly increased over baseline 150 and 180 min following glucagon stimulation in controls and patients with intact pituitary function but not in hypopituitarism. Copeptin concentrations were stimulated over time and the maximal increment correlated with ACTH, while correlations between copeptin and GH were weaker. Interestingly, copeptin as well as GH secretion was significantly attenuated when comparing subjects within the highest to those in the lowest BMI quartile (p < 0.05). Copeptin is significantly released following glucagon stimulation. As this release is BMI-dependent, the time-dependent relation between copeptin and GH may be obscured, whereas the close relation to ACTH suggests that AVP/copeptin release might be linked to the activation of the adrenal axis.