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1.
J Endocrinol Invest ; 45(6): 1255-1263, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35237949

RESUMO

PURPOSE: Girls affected with Turner syndrome (TS) present with low bone mineral density (BMD) and osteopenia/osteoporosis. Thus, they have an increased risk to develop fractures compared to normal population. The aim of this study was to deepen the pathophysiology of skeletal fragility in TS subjects by evaluating the serum levels of Dickkopf-1 (DKK-1) and sclerostin, main regulators of bone mass, as well as the percentage of circulating osteoblast precursors (OCPs). METHODS: Thirty-four TS girls and 24 controls were recruited. All subjects underwent anthropometric measures (height, weight, body mass index-BMI). A peripheral venous blood sample was collected to determine serum levels of active intact parathyroid hormone (PTH), 25-OH vitamin D, calcium, phosphorus, bone alkaline phosphatase (bALP), osteocalcin, sclerostin, DKK-1, RANKL and OPG. OCPs were detected by flow cytometry. In TS subjects bone mineralization was measured at lumbar spine by dual energy X-ray absorptiometry (DXA). RESULTS: bALP, 25-OH Vitamin D, and osteocalcin levels were significant lower in TS subjects than in the controls. Statistically significant higher levels of sclerostin, DKK-1 and RANKL were measured in patients compared with the controls. The percentage of OCPs did not show significant differences between patients and controls. Sclerostin and DKK-1 levels were related with anthropometric parameters, bone metabolism markers, HRT, rhGH therapy, RANKL and lumbar BMAD-Z-score. CONCLUSION: TS patients showed higher levels of sclerostin and DKK-1 than controls which can be related to HRT, and to reduced bone formation markers as well as the increased bone resorption activity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Peptídeos e Proteínas de Sinalização Intercelular , Osteoporose , Síndrome de Turner , Via de Sinalização Wnt , Proteínas Adaptadoras de Transdução de Sinal/sangue , Fosfatase Alcalina/sangue , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Densidade Óssea , Feminino , Marcadores Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Osteocalcina/metabolismo , Osteoporose/sangue , Osteoporose/metabolismo , Osteoporose/patologia , Síndrome de Turner/sangue , Síndrome de Turner/metabolismo , Síndrome de Turner/patologia , Vitamina D/sangue
2.
Clin Endocrinol (Oxf) ; 91(1): 148-155, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30954026

RESUMO

OBJECTIVES: We studied cardiac autonomic changes in relation to metabolic factors, body composition and 24-hour ambulatory blood pressure measurements in Turner syndrome patients without known hypertension. DESIGN: Cross sectional. PATIENTS: Participants were 48 TS women and 24 healthy female controls aged over 18 years. METHODS: Short-term power spectral analysis was obtained in supine-standing-supine position. Bedside tests included three conventional cardiovascular reflex tests of heart rate response to standing up, heart rate response to deep breathing and blood pressure response to standing up. Mean heart rate during the last 2 minutes of work was used to calculate the maximal aerobic power (VO2max ). RESULTS: We found a significantly higher mean reciprocal of the heart rate per second (RR) in TS. Testing for interaction between position and status (TS or control), there were highly significant differences between TS and controls in high-frequency (HF) power, the coefficient of component variation (square root of HF power/mean RR) and low-frequency (LF): HF ratio, with a dampened decline in vagal activity among TS during standing. Bedside test showed TS had a significantly higher diastolic BP in the supine position compared to controls, and the adaptive rise in BP, when changing to upright position was reduced. VO2max and self-reported level of physical activity were significantly correlated to systolic ambulatory blood pressure both 24-hour and night diastolic ambulatory blood pressure. CONCLUSION: Vagal tone and modulation of the sympathovagal balance during alteration in body position are impaired in TS. These changes can be risk factors for cardiovascular disease.


Assuntos
Pressão Sanguínea/fisiologia , Tolerância ao Exercício/fisiologia , Síndrome de Turner/fisiopatologia , Adulto , Sistema Nervoso Autônomo/metabolismo , Sistema Nervoso Autônomo/fisiologia , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Turner/metabolismo
3.
Cytokine ; 113: 139-143, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29983357

RESUMO

OBJECTIVE: The following study investigated the serum adiponectin, chemerin and vaspin levels and their relationship with body mass index (BMI), glucose and lipid metabolism in girls with Turner Syndrome (TS). METHODS: A total of 64 girls with TS (mean age, 12.22 ±â€¯3.98 years; mean BMI, 18.90 ±â€¯3.45 kg/m2) were ascertained by chromosome analysis. Height, weight, waist circumference, hip circumference and blood pressure were measured, as well as the levels of fasting plasma glucose (FPG), fasting plasma insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG). The BMI, BMI standard deviation score (SDS), waist to hip ratio, waist to height ratio and insulin resistance index (HOMA-IR) were calculated. The TS group and the control group were subdivided into non-puberty or puberty subgroup. RESULTS: The TS group had higher waist to hip ratio and waist to height ratio compared to the control group. There was no significant difference in FPG, fasting plasma insulin, HOMA-IR, blood lipid and blood pressure between the two groups. Significantly higher serum levels of adioponectin (12.51 ±â€¯4.58 µg/ml) and chemerin (173.71 ±â€¯37.88 ng/ml) and significantly lower levels of vaspin (0.67 ±â€¯0.47 ng/ml) were found in the TS group compared to the control group (9.30 ±â€¯3.17 µg/ml, 159.43 ±â€¯23.19 ng/ml and 1.06 ±â€¯0.49 ng/ml, respectively) (all P < 0.05). In the TS group, adiponectin levels were negatively correlated with age, BMI and TG (r = -0.251, -0.247, -0.294, P < 0.05 for all). In the control group, adiponectin levels were negatively correlated with BMI and BMI SDS (r = -0.416 and -0.315, P < 0.05 for both), while vaspin levels were positively correlated with age, fasting plasma insulin and HOMA-IR (r = 0.257, 0.273 and 0.282, P < 0.05 for all). In addition, significantly higher levels of adiponectin were found in the non-puberty subgroup (13.88 ±â€¯4.49) µg/ml compared to puberty subgroup (9.72 ±â€¯3.39) µg/ml (P < 0.05), while no significant differences in chemerin and vaspin were found between the two TS subgroups. CONCLUSIONS: Elevated adiponectin and chemerin levels and significantly reduced vaspin were found in girls with TS. Puberty or estrogen replacement therapy may reduce adiponectin in girls with TS.


Assuntos
Adipocinas/sangue , Síndrome de Turner/sangue , Síndrome de Turner/metabolismo , Adolescente , Glicemia/fisiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Quimiocinas/sangue , Criança , Pré-Escolar , Feminino , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Lipídeos/sangue , Obesidade/sangue , Serpinas/sangue , Triglicerídeos/sangue , Síndrome de Turner/fisiopatologia , Circunferência da Cintura/fisiologia , Relação Cintura-Quadril/métodos
4.
BMC Endocr Disord ; 19(1): 9, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30658614

RESUMO

BACKGROUND: Data on adrenarche and pubarche in girls with Turner syndrome (TS) are inconsistent in the literature. METHODS: The cohort consisted of 94 girls and young women with TS born between 1971 and 2001 (age range: 3.1-23.2 yrs.), who were treated with human growth hormone and regularly presented at our outpatient clinic every 4 to 6 months.The longitudinal data of all patients were ascertained retrospectively from patient charts. The data collection ended in January 2016. Adrenarche was assessed by serum DHEAS levels and pubertal status by Tanner stages. Pubarche was defined as the appearance of pubic hair (PH2), whereas spontaneous puberty was defined as Tanner stage B2. The patients were retrospectively subdivided in two groups with regard to pubertal development: group 1 (n = 21) with spontaneous puberty and group 2 (n = 70) with induced puberty. Since blood samples were not taken at every visit, we generated seven groups according to the age of the children at which the blood samples were taken: 3-5, 5-7, 7-9, 9-11, 11-13, 13-15, and 15-17 yrs. Serum DHEAS and follicle-stimulating hormone (FSH) levels were measured by chemiluminescence immunoassay and compared with those of a control group of healthy girls. RESULTS: Adrenarche started in TS girls between 5 and 7 years. TS girls had higher DHEAS levels than the control group, with statistically significant differences in the age groups 7 to 17 years. No differences were determined between the TS girls with spontaneous puberty and those with POI. TS girls in group 2 reached the Tanner stages PH2 (p < 0.04), PH3 (p < 0.01), PH4 and PH5 (p < 0.001) markedly later than TS girls in group 1. CONCLUSIONS: The onset of adrenarche in girls with TS undergoing GH therapy does not differ from that in healthy girls. However, adrenarche is more pronounced in girls with TS. There is no difference in DHEAS levels between the TS girls with spontaneous puberty and the TS girls with primary ovarian insufficiency (POI), while the tempo of pubarche is markedly slower in the girls with POI.


Assuntos
Adrenarca/efeitos dos fármacos , Hormônio do Crescimento Humano/uso terapêutico , Maturidade Sexual/efeitos dos fármacos , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/fisiopatologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Sulfato de Desidroepiandrosterona/sangue , Feminino , Terapia de Reposição Hormonal , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Síndrome de Turner/sangue , Síndrome de Turner/metabolismo , Adulto Jovem
5.
Clin Endocrinol (Oxf) ; 89(5): 667-676, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29992593

RESUMO

OBJECTIVE: Abnormal liver function tests (LFTs) are frequent in Turner syndrome (TS). The causes and clinical significance are unclear. AIMS: To investigate the prevalence of elevated LFTs in adult TS; secondly, to analyse the associations between elevated LFTs, TS-karyotypes and TS-related conditions; and thirdly, to evaluate liver stiffness and histological assessment. METHODS: A total of 125 TS women were retrospectively studied. Karyotypes, clinical and biochemical details and aortic measurements were recorded. Fibroscan and liver biopsy results were noted. RESULTS: Elevated LFTs were found in 49.6%: gamma-glutamyltransferase (GGT) in 88.7%, ALK in 45.2%, ALT in 40.3% and AST in 29%. A FIB-4 index >1.3 was found in 11.8%. Women with isochromosome of the X long arm, iso[X](q), had a higher prevalence of elevated LFTs. A lower prevalence of abnormal GGT was found in patients with 45,X/46,XX, 45,X/47,XXX or 45,X/46,XX/47,XXX. Subjects with raised GGT were older, shorter and more likely to have higher triglyceride levels. There was no association with HRT duration after adjusting for age. Among patients with elevated aminotransferases, no differences were noted, except for higher HDL-cholesterol levels. The sinuses and ascending aorta diameter were greater in the elevated LFTs group. Fibroscan was suggestive of significant liver fibrosis in 38.1%. Among 11 biopsies, liver architectural changes were reported in 45.4%, including two with cirrhosis. CONCLUSIONS: Elevated LFTs in TS are common and important to detect given the possible progression towards severe liver disease. An association between raised LFTs and karyotype iso[X]q was demonstrated. We have also shown a new association between abnormal LFTs and aortic dilatation.


Assuntos
Hepatopatias/metabolismo , Fígado/metabolismo , Síndrome de Turner/metabolismo , Adolescente , Adulto , Idoso , Biópsia , Feminino , Humanos , Cariótipo , Cariotipagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
Ter Arkh ; 89(10): 48-53, 2017.
Artigo em Russo | MEDLINE | ID: mdl-29171470

RESUMO

AIM: To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT. SUBJECTS AND METHODS: From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data. RESULTS: 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF. CONCLUSION: By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.


Assuntos
Determinação da Pressão Arterial , Doenças Cardiovasculares , Endotélio Vascular/efeitos dos fármacos , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Síndrome de Turner , Adulto , Algoritmos , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Estrogênios/administração & dosagem , Feminino , Humanos , Conduta do Tratamento Medicamentoso , Avaliação de Processos e Resultados em Cuidados de Saúde , Federação Russa/epidemiologia , Síndrome de Turner/diagnóstico , Síndrome de Turner/metabolismo , Síndrome de Turner/terapia , Rigidez Vascular/efeitos dos fármacos
7.
Clin Endocrinol (Oxf) ; 83(1): 133-40, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25645325

RESUMO

BACKGROUND: An unfavourable cardiovascular and metabolic phenotype causes threefold excess mortality in Turner syndrome (TS), and perturbed cardiac substrate metabolism is increasingly recognized as a common component of cardiovascular and metabolic diseases. We therefore hypothesized that myocardial glucose uptake (MGU) is reduced in TS and that growth hormone (GH) treatment improves MGU. To this end, this controlled trial elucidates MGU in TS and the impact of 6 months of growth hormone treatment on MGU. METHODS AND RESULTS: Women with TS (n = 9) were examined at baseline, sequentially treated with either Norditropin(®) SimpleXx or placebo and re-examined after 6 months. MGU and myocardial blood flow (MBF) were measured using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) during a hyperinsulinaemic euglycaemic clamp (at baseline and 6 months). Blood pressure measurement, blood sampling, echocardiography and dual energy X-ray absorptiometry scan were also performed. Age-matched female controls (n = 9) were examined once. Baseline MGU was reduced in TS (0.24 ± 0.08 vs. 0.36 ± 0.13 µmol/g/min in controls; P = 0.036) despite similar insulin sensitivity (whole body glucose uptake (M-value): 9.69 ± 1.86 vs. 9.86 ± 2.58 mg/(min*kg) in controls; P = 0.9). Six months of GH carried no impact on MGU (0.25 ± 0.08 vs. 0.26 ± 0.12 µmol/g/min in the placebo group; P = 0.8). Plasma glucose, low-density cholesterol and triglycerides increased, while M-value and exercise capacity decreased during 6 months of GH treatment. CONCLUSION: MGU is reduced in TS despite normal insulin sensitivity. GH treatment does not alter MGU despite decreased whole body insulin sensitivity. A perturbed cardiac glucose uptake appears to be a feature of TS.


Assuntos
Glicemia/metabolismo , Coração/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Resistência à Insulina , Músculo Esquelético/efeitos dos fármacos , Miocárdio/metabolismo , Síndrome de Turner/metabolismo , Adulto , Estudos de Casos e Controles , Método Duplo-Cego , Feminino , Fluordesoxiglucose F18 , Técnica Clamp de Glucose , Coração/diagnóstico por imagem , Humanos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Imagem de Perfusão do Miocárdio , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Síndrome de Turner/diagnóstico por imagem , Adulto Jovem
8.
Prenat Diagn ; 35(3): 289-93, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25449554

RESUMO

OBJECTIVE: The proportion of circulating cell free DNA derived from the feto-placental unit (fetal fraction or FF) correlates with test success and interpretation reliability. Some fetal disorders are associated with systematically lower FF, sometimes resulting in noninformative results. METHODS: We analyzed results from pregnancies tested in a nested case/control study derived from a cohort of 4664 high-risk pregnancies. Low FF was defined before and after adjusting for maternal weight and gestational age. RESULTS: Compared with euploid pregnancies, the median FF was significantly higher in Down syndrome pregnancies (ratio 1.17) and significantly lower in trisomy 18 and triploid pregnancies (ratios 0.71 and 0.19, respectively). Among 2157 pregnancies tested, 13 (0.6%) had FF <3.0% (all noninformative), including three trisomy 18 and three triploidy fetuses. After adjustment, 16 pregnancies (0.7%) had FF <0.3 multiples of the median (six informative), including one trisomy 18 and three triploidy fetuses. Modeled positive predictive values for low and high-risk populations were 7% and 30%, respectively. CONCLUSION: Among women with noninformative results attributable to low FF, trisomy 18 and/or triploidy risk are sufficiently high to warrant offering additional assessments (e.g. ultrasound). If the testing indication is ultrasound abnormality, amniocentesis and karyotype/microarray should be considered. © 2014 John Wiley & Sons, Ltd.


Assuntos
DNA/metabolismo , Síndrome de Down/metabolismo , Feto/metabolismo , Síndrome de Turner/metabolismo , Adulto , Amniocentese , Estudos de Casos e Controles , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 18/metabolismo , Estudos de Coortes , DNA/genética , Síndrome de Down/genética , Feminino , Humanos , Cariotipagem , Masculino , Gravidez , Gravidez de Alto Risco , Diagnóstico Pré-Natal , Trissomia/genética , Síndrome da Trissomía do Cromossomo 18 , Síndrome de Turner/genética
9.
J Endocrinol Invest ; 38(3): 345-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25304095

RESUMO

PURPOSE: An increased risk of insulin resistance, hypertension and liver dysfunction is related to obesity (Ob), but may be also present in normal-weight Turner syndrome (TS) patients. The aim of the study was to compare metabolic risk in adolescents with TS and Ob. METHODS: The study included 21 non-obese with TS (all receiving human recombinant growth hormone, 17/21 estrogen/estrogen-progesterone), and 21 age-matched Ob girls (mean age 13.9 years). Glucose and serum insulin levels were assessed fasting and in 120' of standard oral glucose tolerance test. Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, alanine aminotransferase (ALT), FGF19, FGF21 and FGF23 levels were measured fasting. RESULTS: Mean BMI SDS was significantly lower in TS patients (0.1 vs 4.8 SD, p < 0.001). The mean systolic and diastolic blood pressure was significantly lower in TS patients (102.6 vs 124.2 mmHg, p < 0.001 and 67.1 vs 76.5 mmHg, p = 0.02). There were no differences concerning mean fasting, and post-load glucose (4.5 vs 4.3, 5.1 vs 5.8 mmol/L), and insulin (14.97 vs 17.19 and 69.3 vs 98.78 µIU/mL) levels, HOMA-IR (3.02 vs 3.4), TC (4.05 vs 4.4 mmol/L), TG (1.25 vs 1.37 mmol/L), ALT (26.9 vs 28.3 IU/L), FGF19 (232.8 vs 182.7 pg/mL), and FGF23 (12.3 vs 17.5 pg/mL) levels. Mean LDL (2.05 vs 2.7 mmol/L, p = 0.003) and FGF21 (293.9 vs 514.7 pg/mL, p = 0.007) levels were significantly lower, and HDL (1.7 vs 1.2 mmol/L, p < 0.001) level higher in TS group. CONCLUSIONS: Insulin resistance in adolescents with TS on growth hormone treatment is comparable to Ob patients, but overall metabolic risk factors seem to be lower.


Assuntos
Glicemia/metabolismo , Resistência à Insulina/fisiologia , Insulina/sangue , Obesidade/metabolismo , Síndrome de Turner/metabolismo , Adolescente , Criança , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Teste de Tolerância a Glucose , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Lipídeos/sangue , Obesidade/sangue , Fatores de Risco , Síndrome de Turner/sangue , Síndrome de Turner/tratamento farmacológico
10.
Gynecol Endocrinol ; 31(7): 526-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25826153

RESUMO

BACKGROUND: Turner syndrome (TS) is a gonadal dysgenesis related to partial or total lack of one of the X chromosomes. It this report we describe a young patient presenting some somatic features of TS, who underwent spontaneous puberty and was eumenoorheic up to the age of 23. METHODS: Using fluorescent in situ hybridization (FISH) mosaic karyotype (45X[131]/47XXX[9]) of TS and triple X syndrome was found. RESULTS: She presented uncommon for TS somatic hemihypotrophy and underwent growth hormone and surgical therapy. The patient was diagnosed with premature ovarian failure when she was 23, with absent follicular reserve. Clinical features of this case and a few published cases will be reviewed briefly.


Assuntos
Mosaicismo , Insuficiência Ovariana Primária/etiologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Trissomia/diagnóstico , Síndrome de Turner/diagnóstico , Adulto , Cromossomos Humanos X/metabolismo , Feminino , Humanos , Cariótipo , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/complicações , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/metabolismo , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/fisiopatologia , Trissomia/fisiopatologia , Síndrome de Turner/complicações , Síndrome de Turner/metabolismo , Síndrome de Turner/fisiopatologia , Adulto Jovem
11.
Lik Sprava ; (12): 69-76, 2014 Dec.
Artigo em Ucraniano | MEDLINE | ID: mdl-26638471

RESUMO

The article presents the treatment outcome in 86 children with short stature associated with different endocrine pathology and saved growth hormone secretion (congenital adrenal hyperplasia chondrodystrophy, Turner syndrome, idiopathic short stature, syndrome biologically inactive growth hormone and other genetically determined pathology). This study extends prior knowledge about the outcomes of the treatment with recombinant growth hormone and luteinizing hormone--releasing hormone analogue (alone or in combination) in short patients with poor prognosis of final height.


Assuntos
Nanismo Hipofisário/tratamento farmacológico , Nanismo/tratamento farmacológico , Hormônio Liberador de Gonadotropina/uso terapêutico , Hormônio do Crescimento/uso terapêutico , Osteocondrodisplasias/tratamento farmacológico , Síndrome de Turner/tratamento farmacológico , Adolescente , Estatura/efeitos dos fármacos , Criança , Nanismo/metabolismo , Nanismo/fisiopatologia , Nanismo Hipofisário/metabolismo , Nanismo Hipofisário/fisiopatologia , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Masculino , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/fisiopatologia , Hipófise/efeitos dos fármacos , Hipófise/fisiologia , Resultado do Tratamento , Síndrome de Turner/metabolismo , Síndrome de Turner/fisiopatologia
12.
Hum Reprod ; 27(3): 854-60, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22258659

RESUMO

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by ovarian granulosa cells and its serum levels reflect ovarian follicle reserve. The main objective of this study was to test the use of AMH assay in identifying women with primary amenorrhea (PA) and existing follicles and to study follicle phase dependent AMH secretion. METHODS: Serum levels of AMH were measured in subjects with FSH-resistant ovaries (FSHRO, n= 12), primary ovarian insufficiency (POI) with PA (n= 11) or secondary amenorrhea (SA n= 20) of unknown etiology, and controls (n= 23), and in Turner syndrome (TS) [45,X (n= 18), mosaicism (n= 7), structural X chromosome abnormalities (SCA, n= 10)], and healthy controls (n= 34). RESULTS: Serum levels of AMH in women with FSHRO were comparable with those in control women (2.76 ± 2.37 versus 3.77 ± 2.36 ng/ml) and significantly higher than in women with PA (0.05 ± 0.04 ng/ml; P < 0.001) or SA of unknown origin (0.12 ± 0.20 ng/ml; P < 0.001). TS girls/women with 45,X or SCA had low serum AMH levels (0.13 ± 0.09 and 0.27 ± 0.19 ng/ml) compared with their controls (3.34 ± 2.23 ng/ml) or subjects with mosaicism (2.33 ± 2.81 ng/ml). AMH expression was detected in granulosa cells of women with FSHRO but not in any of the 45,X fetal ovarian specimens. CONCLUSIONS: A serum AMH assay could be used to identify patients with decreasing ovarian reserves and POI. Moreover, our results support the notion that AMH is secreted mainly by small non-selected follicles, since follicular granulosa cells were AMH-positive and serum AMH levels were normal/low normal in women with FSHRO, who lack follicle development beyond the small antral stage.


Assuntos
Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/farmacologia , Folículo Ovariano/fisiologia , Adolescente , Adulto , Amenorreia/sangue , Amenorreia/metabolismo , Hormônio Antimülleriano/metabolismo , Criança , Cromossomos Humanos X , Feminino , Humanos , Mosaicismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Aberrações dos Cromossomos Sexuais , Síndrome de Turner/sangue , Síndrome de Turner/metabolismo
13.
J Pediatr Endocrinol Metab ; 25(9-10): 823-33, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23426807

RESUMO

Low bone mineral density (BMD) in patients with Turner syndrome (TS) has been reported in a considerable number of previous studies. Cortical and trabecular bone have been involved. Osteoporosis can be overdiagnosed in TS patients with a short stature unless BMD measurements are adjusted for body size. Optimization of bone health in girls with TS requires a healthy active lifestyle, including adequate calcium, vitamin D, and hormonal replacement therapy, according to consensus guidelines.


Assuntos
Densidade Óssea , Síndrome de Turner/metabolismo , Adolescente , Densidade Óssea/efeitos dos fármacos , Criança , Exercício Físico , Feminino , Fraturas Ósseas/etiologia , Hormônio do Crescimento Humano/farmacologia , Humanos , Puberdade/fisiologia , Receptores de Calcitriol/genética
14.
J Pediatr Endocrinol Metab ; 25(7-8): 669-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23155691

RESUMO

BACKGROUND: Turner syndrome (TS) patients usually have low bone mineral density (BMD) and increased risk of osteoporotic fractures. We have previously demonstrated an association of bb (BsmI polymorphic site) and ff (FokI polymorphic site) vitamin D receptor (VDR) genotypes with reduced BMD in TS patients. AIM: To analyze the relationship between VDR-Cdx2 polymorphism and BMD as well as bone metabolic variables in TS patients. METHODS: Fifty-five TS patients and 59 control women were studied. VDR-Cdx2 genotypes were determined using TaqMan probes in a real time thermocycler. Lumbar and femoral BMD were determined by dual-energy X-ray absorptiometry (DEXA) and serum intact parathyroid hormone, osteocalcin and beta3-CrossLaps were determined by electrochemiluminescence. RESULTS: Patients with genotype GG had higher levels of both osteocalcin and beta-CrossLaps as compared to patients with genotype GA (p < 0.01 and p < 0.05, respectively). CONCLUSION: Patients carrying genotype GG have higher levels of bone formation and resorption markers. This indicates a more active bone turnover that could impact on their future bone mineral density.


Assuntos
Densidade Óssea/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Síndrome de Turner/genética , Absorciometria de Fóton , Adolescente , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Fraturas Ósseas/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/fisiologia , Regiões Promotoras Genéticas/genética , Síndrome de Turner/metabolismo , Síndrome de Turner/fisiopatologia , Adulto Jovem
15.
Horm Res Paediatr ; 95(5): 465-475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35970147

RESUMO

BACKGROUND: In Turner syndrome (TS), fluorescent in situ hybridization (FISH) karyotyping offers an alternative to classical karyotyping. OBJECTIVE: We tested the added value of FISH karyotyping from lymphocytes (mesodermal origin), buccal cells (ectodermal origin), and a rear-tongue smear (endodermal origin) to determine the 45,X cell line fraction and its impact on patient phenotype. DESIGN AND PATIENTS: Classical karyotyping and three FISH assays were done in 153 girls and women previously diagnosed with TS in four university hospitals. The 45,X cell line fraction was determined for each method and correlated with the major phenotypic signs. RESULTS: Classical karyotyping identified 45,X/46,XX mosaicism in 77/153 subjects (50%), 45,X monosomy in 52/153 (34%), and other karyotypes in 24/153 (16%). FISH from lymphocytes verified 45,X in 47/52 original cases, whereas 4/52 had 45,X/46,XX and 1/52 45,X/47,XYY mosaicism. The 45,X cell line fraction was higher in FISH from lymphocytes compared to classical karyotyping (median 86.4% vs. 70.0%; p < 0.001), while there was no difference for FISH from buccal or rear-tongue smear cells. The mean 45,X cell line fraction was more abundant in patients with several of the characteristic phenotypic signs compared to patients without them (p < 0.01), but the predictive power was insufficient. CONCLUSION: FISH analysis confirmed the findings of classical karyotyping; only a few 45,X monosomy cases were reclassified as mosaics. The 45,X cell line fraction did not show clinically meaningful prediction of the phenotype. FISH analysis of buccal or rear-tongue epithelial cells may be a non-inferior, less invasive alternative to classical karyotyping.


Assuntos
Síndrome de Turner , Feminino , Humanos , Síndrome de Turner/metabolismo , Hibridização in Situ Fluorescente , Mucosa Bucal , Cariotipagem , Mosaicismo , Monossomia , Linfócitos/metabolismo , Células Epiteliais
16.
Front Endocrinol (Lausanne) ; 13: 897897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769084

RESUMO

Background: The methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed. Objective: This study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied. Design: This was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples. Results: Basal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment. Conclusions: This study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted.


Assuntos
Metilação de DNA , Hormônio do Crescimento Humano , Fator de Crescimento Insulin-Like I , Síndrome de Turner , Estatura/genética , Criança , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Regiões Promotoras Genéticas , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/genética , Síndrome de Turner/metabolismo
17.
Clin Endocrinol (Oxf) ; 74(4): 445-52, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21138463

RESUMO

OBJECTIVE: An increased rate of fractures has been reported in patients with Turner syndrome (TS). We aimed to assess bone geometry and volumetric bone mineral density (vBMD) at the radius in girls with TS and to evaluate the relationships between bone parameters and fracture history. METHODS AND DESIGN: Sixty-seven girls with TS aged 6-19 years treated currently or in the past with growth hormone (GH) and/or oestrogens were examined using peripheral quantitative computed tomography. Results were compared to reference data. RESULTS: Cortical area and cortical thickness were low in all age groups (all P<0·001). Height-adjusted total bone area at the diaphysis was increased in prepubertal and postpubertal girls (mean Z-score 1·0, P<0·05 for both) and normal in the pubertal group (mean Z-score 0·1). Cortical vBMD was decreased (mean age-specific Z-scores -2·0, -1·6 and -1·0 for prepubertal, pubertal and postpubertal groups, respectively, P<0·01 for all groups). Height- , age- and cortical thickness-adjusted cortical vBMD was positively correlated to the duration of GH therapy (P=0·012) and to oestrogen administration (P=0·047). Girls with a history of fractures had lower total vBMD at the metaphysis compared to nonfractured TS girls (mean Z-scores -1·7 vs-0·9, P=0·04). CONCLUSIONS: There is a cortical bone deficit in girls with TS characterized by low cortical area, thin cortex and probably decreased cortical vBMD. Early commencement of GH therapy, as well as oestrogen replacement, is associated with higher cortical vBMD. Further studies should investigate the potential causality of this relation.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/anatomia & histologia , Síndrome de Turner/metabolismo , Adolescente , Adulto , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Criança , Estrogênios/uso terapêutico , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Puberdade/fisiologia , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/fisiopatologia , Adulto Jovem
18.
Pediatr Res ; 70(1): 25-30, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21430600

RESUMO

Girls with Turner syndrome (TS) are treated with supraphysiological doses of growth hormone (GH) to improve final height; however in some girls, the growth response can be poor. This may reflect aberrations in GH and/or IGF-I actions at the cellular level, and thus this study compared the response of skin fibroblasts from normal children (n = 5) and girls with TS (n = 8) to GH, IGF-I, or a combination, by assessing the IGF binding protein (IGFBP) profile of conditioned medium harvested over 7 d. The two cell types had a comparable IGFBP profile; IGFBP-3 and IGFBP-4 were the most abundant species. TS fibroblasts produced more IGFBP-3 (d 7, 51.4 ± 45 ng/mL versus 20 ± 22 ng/mL; p < 0.05) than control cells; levels of IGFBP-4 were similar (21 ± 12 ng/mL versus 30 ± 21 ng/mL). GH did not influence IGFBP production. IGF-I treatment did not affect IGFBP-4 levels but enhanced the production of IGFBP-3 by both cell types (p < 0.05). However, the response of TS fibroblasts to IGF-I was approximately half that observed in normal cells (p < 0.05). Altered IGF-I activity, because of reduced bioavailability and/or reduced sensitivity, could contribute to the need for high GH doses in TS and for the poor response to GH in some girls with TS.


Assuntos
Fibroblastos/efeitos dos fármacos , Hormônio do Crescimento/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Pele/efeitos dos fármacos , Síndrome de Turner/tratamento farmacológico , Análise de Variância , Células Cultivadas , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Janus Quinase 2/metabolismo , Fosforilação , Pele/metabolismo , Pele/patologia , Fatores de Tempo , Síndrome de Turner/metabolismo , Síndrome de Turner/patologia
19.
Int J Immunopathol Pharmacol ; 24(3): 789-92, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21978710

RESUMO

Turner's syndrome (TS) is a genetic disorder caused by numeric and/or structural abnormalities of the X chromosome. In a previous study it was observed that acne is less frequent in TS than in the general population. Since the onset of acne in pre-pubertal or pubertal age is related to sebum production, this study evaluates sebum secretion in TS patients, comparing the results with those of a control group of age-matched healthy female subjects. A total of 22 patients affected by TS (mean age 26.56±7.89 years) and a control group of 23 age-matched healthy females were studied. Sebum production was measured using a Sebumeter SM810. Mean sebum secretion in TS subjects was significantly lower than in the control group (81.35±66.44 UA vs 147.09±33.62 UA, p<0.001) and this significant difference was found in every facial zone. The reduction of sebum secretion may explain, using a simple and non-invasive method, the absence or the low incidence of acne in TS patients.


Assuntos
Sebo/metabolismo , Síndrome de Turner/metabolismo , Acne Vulgar/epidemiologia , Adolescente , Adulto , Mama/crescimento & desenvolvimento , Criança , Face , Feminino , Hormônio do Crescimento/uso terapêutico , Humanos , Cariotipagem , Puberdade/fisiologia , Síndrome de Turner/epidemiologia , Síndrome de Turner/genética , Adulto Jovem
20.
J Pediatr Endocrinol Metab ; 24(5-6): 307-12, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21823528

RESUMO

BACKGROUND: Turner syndrome (TS) patients present low bone mineral density (BMD) and increased fracture risk, probably due to a genetic defect aggravated by hormonal deficiency. AIM: To study the relationship between vitamin D receptor (VDR) gene polymorphisms and BMD and bone parameters in TS patients. METHODS: DNA from 65 TS patients and 110 controls was amplified by PCR and digested with FokI, BsmI and ApaI restrictases. Lumbar and femoral BMD were determined by DEXA and serum intact parathyroid hormone, osteocalcin and beta-CrossLaps by electrochemiluminescence. RESULTS: Genotype distribution within the ApaI site was different in both groups: genotype Aa was more abundant in TS (63.8% vs. 41.3%; p<0.01), whereas AA predominated in controls (33.9% vs. 15.5%; p<0.01). Patients carrying genotype bb (BsmI) or ff (FokI) had lower BMD than those with other genotypes (p<0.01 and p<0.05, respectively). CONCLUSION: BsmI and FokI polymorphic sites of VDR could be genetic determinants of BMD in TS patients.


Assuntos
Densidade Óssea/genética , Receptores de Calcitriol/genética , Síndrome de Turner/genética , Síndrome de Turner/metabolismo , Adolescente , Alelos , Sequência de Bases , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Estudos de Casos e Controles , Primers do DNA/genética , Estradiol/uso terapêutico , Feminino , Frequência do Gene , Estudos de Associação Genética , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Cariotipagem , Mosaicismo , Polimorfismo de Fragmento de Restrição , Proteínas Recombinantes/uso terapêutico , Síndrome de Turner/complicações , Síndrome de Turner/tratamento farmacológico
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