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1.
Eur J Endocrinol ; 182(1): 11-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31652416

RESUMO

Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.

2.
Eur J Endocrinol ; 182(1): G1-G32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855556

RESUMO

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.


Assuntos
Índice de Massa Corporal , Hipotireoidismo/diagnóstico , Obesidade/diagnóstico , Comorbidade , Endocrinologia , Humanos , Hipotireoidismo/epidemiologia , Obesidade/epidemiologia , Prevalência , Testes de Função Tireóidea
3.
Nutr Metab Cardiovasc Dis ; 29(3): 279-289, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30718143

RESUMO

BACKGROUND AND AIMS: Excess body weight (EBW) is the most prevalent nutritional disorder among adolescents worldwide. Identifying determinants of EBW may help find new intervention strategies. Behavioral, socio-economic, educational and demographic correlates of EBW were examined in a population of Italian adolescents, separately for males and females. METHODS AND RESULTS: As many as 1039 male and 2052 female students (aged 16-19 ys) attending the last three years of different types of high-school of the Emilia-Romagna region in Italy were offered participation, with 552 males and 841 females being finally evaluated. The prevalence of EBW was 21.0% in males and 14.1% in females. Step-wise multivariate logistic regression analyses were performed showing that EBW was negatively related to energy intake in males (odds ratio for 100 kcal/day (OR) = 0.94, 95% confidence interval (CI): 0.89 to 0.98; P = 0.008), and to father's educational attainment (OR = 0.70, 95% CI: 0.52 to 0.95; P = 0.020), but positively related to parental obesity (OR = 2.80, 95% CI: 1.65 to 4.76; P < 0.001). In females, EBW was positively related to parental obesity (OR = 1.94, 95% CI: 1.15 to 3.29; P = 0.013), but negatively to mother's educational attainment (OR = 0.66, 95% CI: 0.45 to 0.97; P = 0.034) and type of attended school (OR = 0.66, 95% CI: 0.49 to 0.89; P = 0.007). Mother's occupation was also an independent determinant of EBW status in females (OR = 0.39, 95% CI: 0.18 to 0.85; P = 0.018 for being unemployed vs blue-collar). CONCLUSION: Parental obesity is associated with EBW in male and female adolescents. Importantly, we found sex differences in socio-economic and educational factors impacting on EBW, supporting possible distinct area of investigation.


Assuntos
Comportamento do Adolescente , Escolaridade , Comportamentos Relacionados com a Saúde , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/psicologia , Determinantes Sociais da Saúde , Meio Social , Ganho de Peso , Adolescente , Fatores Etários , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos Epidemiológicos , Humanos , Itália/epidemiologia , Estilo de Vida , Masculino , Pais/psicologia , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/fisiopatologia , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , Adulto Jovem
4.
J Endocrinol Invest ; 41(10): 1123-1135, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29363047

RESUMO

BACKGROUND: There is a growing debate on the opportunity of improving the understanding in the diagnosis and management of polycystic ovary syndrome (PCOS). OBJECTIVE: This review article summarizes recent research related to the definition of polycystic ovary syndrome (PCOS). METHODS: Review of the recent literature on the topic. RESULTS: New ideas on the definition of hyperandrogenism, based on new scientific data and clinical perspectives are presented. (i) In fact, recent studies have pointed out the need to improve the concept of androgen excess by using a larger androgen profile, rather than simply measuring the testosterone blood levels. (ii) Due to the poor correlation between androgen blood levels and the degree of hirsutism, it is proposed that the definition of hyperandrogenism should be based on the presence of blood androgen excess and hirsutism, considered separately, because their pathophysiological mechanisms may differ according to the different phenotypes of PCOS. (iii) The potential role of obesity in favoring the development of PCOS during adolescence is also discussed and the concept of "PCOS secondary to obesity" is developed. (iv) Finally, the need for greater appropriateness in the evaluation of possible coexistence is highlighted, in patients with PCOS who have fasting or glucose-stimulated very high insulin levels, or severe insulin-resistant states. CONCLUSIONS: Based on what was discussed in this review, we believe that there are margins for modifying some of the current criteria that define the various PCOS phenotypes.


Assuntos
Gerenciamento Clínico , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Feminino , Hirsutismo/diagnóstico , Hirsutismo/fisiopatologia , Hirsutismo/terapia , Humanos , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/fisiopatologia , Hiperandrogenismo/terapia , Obesidade/diagnóstico , Obesidade/fisiopatologia , Obesidade/terapia , Síndrome do Ovário Policístico/fisiopatologia
5.
J Endocrinol Invest ; 40(8): 841-850, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28326509

RESUMO

PURPOSE: Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. METHODS: A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. RESULTS: 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). CONCLUSIONS: Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Hormônios Esteroides Gonadais/sangue , Imunoensaio/métodos , Síndrome de Klinefelter/sangue , Espectrometria de Massas em Tandem/métodos , 17-alfa-Hidroxiprogesterona/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Humanos , Hidrocortisona/sangue , Síndrome de Klinefelter/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Progesterona/sangue , Estudos Prospectivos , Testosterona/sangue , Adulto Jovem
6.
Eur J Endocrinol ; 174(6): 801-11, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27188454

RESUMO

BACKGROUND: Men with Klinefelter syndrome (KS) show hypergonadotropic hypogonadism, but the pathogenesis of hypotestosteronemia remains unclear. Testicular steroidogenesis in KS men was evaluated over three decades ago after human chorionic gonadotropin (hCG) stimulation, but inconclusive results were obtained. Intriguingly, some recent studies show increased intratesticular testosterone concentrations in men with KS. OBJECTIVE: To analyze serum steroid profile, as a proxy of testicular steroidogenesis, after hCG stimulation in KS compared with control men. DESIGN: A prospective, longitudinal, case-control, clinical trial. METHODS: Thirteen KS patients (36±9 years) not receiving testosterone (TS) replacement therapy and 12 eugonadic controls (32±8 years) were enrolled. Serum steroids were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and for five consecutive days after intramuscular injection of 5000IU hCG. RESULTS: Progesterone (P), 17-hydroxyprogesterone (17OHP), TS, and estradiol (E2) showed a significant increase (P<0.001) after hCG stimulation in both groups. On the contrary, androstenedione (AS) and dehydroepiandrosterone did not increase after hCG stimulation. The 17OHP/P ratio increased in both groups (P<0.001), the TS/AS ratio (17ß-hydroxysteroid dehydrogenase type 3 (17ßHSD3) activity) did not increase after hCG in any group, and the E2/TS ratio (aromatase activity) increased significantly in both groups (P=0.009 in KS and P<0.001 in controls). Luteinizing hormone decreased after hCG in both groups (P=0.014 in KS and P<0.001 in controls), whereas follicle-stimulating hormone decreased only in control men (P<0.001). CONCLUSION: This study demonstrates for the first time using LC-MS/MS that Leydig cells of KS men are able to respond to hCG stimulation and that the first steps of steroidogenesis are fully functional. However, the TS production in KS men is impaired, possibly related to reduced hydroxysteroid deydrogenase activity due to an unfavorable intratesticular metabolic state.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Síndrome de Klinefelter/tratamento farmacológico , Testículo/efeitos dos fármacos , Testosterona/sangue , 17-Hidroxiesteroide Desidrogenases/sangue , Adulto , Gonadotropina Coriônica/farmacologia , Cromatografia Líquida , Estradiol/sangue , Humanos , Síndrome de Klinefelter/sangue , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Progesterona/sangue , Estudos Prospectivos , Espectrometria de Massas em Tandem , Resultado do Tratamento
7.
J Endocrinol Invest ; 39(8): 837-47, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26951056

RESUMO

Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.


Assuntos
Glândulas Endócrinas/fisiopatologia , Predisposição Genética para Doença , Hemocromatose/etiologia , Animais , Humanos
8.
J Endocrinol Invest ; 39(3): 291-5, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26280318

RESUMO

PURPOSE: 11ß-Hydroxylase deficiency (11OHD) represents the second most common cause of congenital adrenal hyperplasia. It is caused by mutations in the CYP11B1 gene localized about 40 kb from the CYP11B2 gene with which it shares a homology of 95 %. The asymmetric recombination of these two genes is involved both in 11OHD and in glucocorticoid-remediable aldosteronism (GRA). Our objective was to set up an easy and rapid method to detect these hybrid genes and other kinds of deletions, to improve the molecular diagnosis of 11OHD. METHODS: A set of 8 specific probes for both the CYP11B1 and the CYP11B2 genes to be used for multiplex ligation-dependent probe amplification (MLPA) analysis was designed to detect rearrangements of these genes. RESULTS: The method developed was tested on 15 healthy controls and was proved to be specific and reliable; it led us to identify a novel chimeric CYP11B2/CYP11B1 gene in one patient that carried the known A306V mutation on the other allele. Specific amplification and sequencing of the hybrid gene confirmed the breakpoint localization in the second intron. CONCLUSIONS: The MLPA kit developed enables the detection of deletions, duplications or chimeric genes and represents an optimal supplement to DNA sequence analysis in patients with 11OHD. In addition, it can also be used to show the presence of the opposite chimaera associated with GRA.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Citocromo P-450 CYP11B2/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Mutação/genética , Esteroide 11-beta-Hidroxilase/genética , Esteroide 11-beta-Hidroxilase/metabolismo , Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Prognóstico , Análise de Sequência de DNA , Adulto Jovem
10.
Prog Urol ; 24(2): 102-7, 2014 Feb.
Artigo em Francês | MEDLINE | ID: mdl-24485079

RESUMO

OBJECTIVE: To establish MRI's performances for the detection of extracapsular progression of prostate carcinoma, in a single center, analyzing the correlation between MRI imaging and histological analysis of prostate specimen. METHODS: From February 2008 to June 2012, all the patients selected for prostatectomy had a pre-operative MRI. Diffusion, T2 and dynamic T1 with gadolinium injection sequences were realized on a 1.5T-MRI with external antenna. All imaging data was analyzed by a specialized radiologist. Prostate specimens were histologically analyzed throughout large blades for utmost topographic comparison. The histological TNM was compared to the MRI data. MRI's capacity in determining the existence and the size of extracapsular progression was studied. RESULTS: One hundred and fifty-eight patients (median age 62 years old, mean PSA 8.6 ng/mL) were included, among which 45% of d'Amico low risk and 55% of intermediate and high risk. Histological results were 63% of pT2 and 37% of pT3. MRI's sensibility and specificity for detecting extracapsular progression were 0.30 and 0.85 respectively (PPV 0.54; NPV 0.67), with a 65% accuracy. In the low risk group, sensibility equaled to 0.16. CONCLUSION: In our experience, MRI results were not reliable to influence the choice of treatment. It should be executed by expert radiologists, who are still very few.


Assuntos
Imagem por Ressonância Magnética , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Prospectivos
11.
J. clin. endocrinol. metab ; 98(12): 4565-4592, dec. 2013.
Artigo em Inglês | BIGG | ID: biblio-965265

RESUMO

"OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS). PARTICIPANTS: An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer developed the guideline. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. CONCLUSIONS: We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries). Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women. Hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women. Evaluation of women with PCOS should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease. Hormonal contraceptives are the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. Clomiphene is currently the first-line therapy for infertility; metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irregularities, but it has limited or no benefit in treating hirsutism, acne, or infertility. Hormonal contraceptives and metformin are the treatment options in adolescents with PCOS. The role of weight loss in improving PCOS status per se is uncertain, but lifestyle intervention is beneficial in overweight/obese patients for other health benefits. Thiazolidinediones have an unfavorable risk-benefit ratio overall, and statins require further study."


Assuntos
Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Fatores Etários
12.
J Endocrinol Invest ; 36(8): 648-53, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24105073

RESUMO

The polycystic ovary syndrome (PCOS), the most common hyperandrogenic disorder affecting 4-7% of women, is often associated with metabolic alterations, chiefly insulin resistance and obesity. Based on available scientific evidence, PCOS should be regarded as an independent risk for the development of glucose intolerance states. This short review summarizes the available literature on the prevalence and incidence of impaired glucose tolerance and Type 2 diabetes in this disorder. In addition, some insights on potential factors responsible for individual susceptibility are discussed. Targeted intervention studies focused on prevention and treatment of glucose intolerance states in PCOS are warranted.


Assuntos
Intolerância à Glucose/etiologia , Síndrome do Ovário Policístico/complicações , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Feminino , Intolerância à Glucose/epidemiologia , Humanos , Incidência , Resistência à Insulina , Obesidade/genética , Síndrome do Ovário Policístico/genética , Prevalência , Proteínas/genética , Globulina de Ligação a Hormônio Sexual/genética
13.
Clin Obes ; 3(5): 132-40, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25586628

RESUMO

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Obesity is an increasingly prevalent metabolic disorder and it is associated with a large number of comorbidities, including cardiovascular diseases. Adipose tissue is an active endocrine organ and its ectopic depots and distribution have different metabolic meanings on risks for health; as a matter of fact, epicardial fat seems to play a specific role in cardiovascular diseases. The use of dual-energy X-ray absorptiometry (DXA) to evaluate and follow-up patients affected by obesity is becoming a very important point in the management of the disease. WHAT THIS STUDY ADDS: An investigation of the association between epicardial fat and regional adiposity by DXA in female obese patients. The total amount of central (trunk) fat mass is more strongly correlated than android visceral fat mass to epicardial thickness in obese women. In the interpretation of whole-body DXA data, physician should consider trunk fat mass for good and independent predictivity on epicardial fat depots. Our aim was to analyse in a population of obese women the relationship between the amount of epicardial fat as measured by transthoracic echocardiography (US) and the parameters of regional adiposity by dual-energy X-ray absorptiometry (DXA), with particular reference to a new software for visceral fat assessment and to a new 'heart-suited' regions of interests (ROIs). Sixty patients who satisfied technical inclusion criteria underwent whole-body DXA scan and US on the same day. Total and android fat mass (FM) and FM percentage (FM%) were considered as well as visceral fat (VAT) subcompartment in the android region; moreover, six new ROIs were designed on whole-body DXA images for the investigation of adiposity parameters at heart level. US provided epicardial fat thickness (EPI-thickness) and area (EPI-area), as measured following previously validated methods. Body mass index (BMI), gynoid and lower limbs (FM and FM%) were found not statistically correlated with EPI-thickness. The highest correlation was achieved by trunk FM (and FM%, with r = 0.544 and 0.480 respectively, P < 0.001), followed by ROI-1 FM (ROI-1 was drawn following thoroughly the cardiac profile), and android FM. Multivariate analysis including age, weight, BMI, trunk FM and the new ROIs (added one by one), retained in the final model trunk FM. Correlations of DXA with EPI-area were superimposable. In obese women, VAT or other new-designed ROIs are not better correlated than traditional ROIs (i.e. trunk) with epicardial fat amount.

14.
Hum Reprod ; 27(10): 3057-66, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22786777

RESUMO

STUDY QUESTION: Do different dosages of metformin account for different clinical and biochemical outcomes in women with polycystic ovary syndrome (PCOS) and do basal anthropometric and metabolic characteristics of the patients provide any indications regarding the dose required to reach the target effect? SUMMARY ANSWER: Different doses of metformin exerted the same effects on clinical, biochemical and metabolic parameters in patients affected by PCOS. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Since the insulin-sensitizing agents came into use in the management of PCOS, metformin has shown a positive benefits-risks ratio. Nonetheless, therapeutic schedules are not well standardized. This is the first study which systematically analyses the effect of different doses of metformin on clinical, hormonal and metabolic features of PCOS. On the basis of our results, higher doses are no more effective than lower doses. DESIGN: A multicentric cohort prospective study. A total of 250 PCOS women were enrolled, 49 lost to follow-up. Menstrual cyclicity, hormonal assays, oral glucose tolerance test, lipid profile and ultrasonographic pelvic examination were evaluated at the baseline and after 6 months of metformin treatment at different doses (1000, 1500 and 1700 mg). PARTICIPANTS AND SETTING: A total of 201 PCOS patients completed the study without protocol violations in three university hospitals: seventy-three patients from Centre A (treated with metformin 500 mg twice a day), 60 patients from Centre B (treated with metformin 500 mg three times a day) and 68 patients from Centre C (treated with metformin 850 mg twice a day). MAIN RESULTS AND THE ROLE OF CHANCE: Metformin exerted an overall positive effect on the clinical and endocrine-metabolic features of PCOS. The degree of these effects was independent of the administered dosage in every range of basal body mass index (BMI). When patients were stratified according to their insulinaemic status, scattered inter-doses differences were found in some of the outcome measures. Patients who exhibited an increase of >2 menstrual cycles/year were considered as responders to treatment. Responders had a higher basal BMI than non-responders and showed a greater reduction in plasma testosterone levels after metformin treatment, but other outcome measures did not differ significantly. Total insulin secretion in the 180 min following the glucose tolerance test before metformin treatment (basal AUC-I) was significantly correlated with the decrease in insulin secretion induced by metformin in both the whole group and in responders, but only correlated with the variation in the number of cycles in responders. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The different doses were administered in different centres, and between-centre variation is a potential confounding factor. GENERALIZABILITY TO OTHER POPULATIONS: The paradigm of using the minimum effective dose of metformin could be pursued in other pathological conditions characterized by insulin resistance. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests to declare.


Assuntos
Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Índice de Massa Corporal , Relação Dose-Resposta a Droga , Feminino , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Ciclo Menstrual/efeitos dos fármacos , Metformina/uso terapêutico , Resultado do Tratamento
17.
J Endocrinol Invest ; 34(9): 685-91, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21586896

RESUMO

AIM: The aims of the study were to understand the association between insulin-like factor 3 (INSL3) and functional ovarian hyperandrogenism (FOH) in PCOS and the regulatory role played by LH. SUBJECTS AND METHODS: Fifteen PCOS women were classified as FOH (FOH-PCOS, no.=8) and non-FOH (NFOH-PCOS, no.=7) according to the response of 17OH-progesterone to buserelin (a GnRH analogue) with respect to 15 controls. FOH-PCOS and NFOH-PCOS were compared for basal INSL3 levels. In addition, the effect of buserelin on INSL3 concentrations and the relationship between basal and buserelin-stimulated LH and 17OH-progesterone and INSL3 were evaluated. RESULTS: Basal INSL3 levels were higher in FOH-PCOS than NFOH-PCOS (p=0.001) and controls (p=0.001), whereas they did not differ between NFOHPCOS and controls. In addition, FOH-PCOS had a higher response of LH to buserelin with respect to NFOH-PCOS. Within all PCOS women the levels of INSL3 positively correlated with free testosterone (p=0.022) and negatively with SHBG (r= p=0.031). Moreover, positive correlations with the absolute increase of 17OH-progesterone (p<0.001) and with the LH area under the curve (p=0.001) after buserelin administration were found. In the multiple regression analysis INSL3 persisted significantly correlated only with 17OH-progesterone response to buserelin. Finally, INSL3 was not significantly modified after buserelin administration either in FOHPCOS or in NFOH-PCOS. CONCLUSIONS: These data suggest that INSL3 is related to FOH in PCOS women, but this association seems not to be mediated by LH, further reinforcing the concept that a pathophysiological heterogeneity for ovarian hyperandrogenism in PCOS exists.


Assuntos
Hiperandrogenismo/sangue , Hiperandrogenismo/fisiopatologia , Insulina/sangue , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , 17-alfa-Hidroxiprogesterona/metabolismo , Adolescente , Adulto , Índice de Massa Corporal , Busserrelina/metabolismo , Feminino , Fármacos para a Fertilidade Feminina/metabolismo , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Hormônio Luteinizante/metabolismo , Pessoa de Meia-Idade , Ovário/anatomia & histologia , Síndrome do Ovário Policístico/sangue , Proteínas , Adulto Jovem
18.
Int J Androl ; 34(6 Pt 1): 548-55, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21087288

RESUMO

Testosterone administered alone or in combination with progestogens in male contraception induces reversible oligo-azoospermia, but its effects on body composition and metabolism are less known. We analysed anthropometric and metabolic parameters in five groups of 10 males: four receiving testosterone undecanoate (TU: 1000 mg) plus norethisterone enanthate (NETE: 200 mg) at different intervals (every 8 weeks: NETE-8; every 12 weeks: NETE-12; every 6 weeks for 12 weeks and then every 12 weeks: NETE-6/12; every 6 weeks for 12 weeks and then TU plus placebo every 12 weeks: NETE-6/12/0) and one placebo (NETE-0/0) for a total of 48 weeks. Body mass index (BMI) and waist circumference did not change in any groups except for the NETE-8 in which BMI increased significantly (p = 0.02) at the end of the treatment period. Lean body mass (MAMC or AMA) increased significantly in the highest hormonal dose groups (p = 0.04, NETE-6/12; p = 0.004, NETE-8). No differences were observed in glucose levels, insulin sensitivity index and lipid profile as well as in biochemical and cell count parameters in any groups. In conclusion, NETE and TU for 48 weeks were not accompanied by any metabolic changes and any adverse effects. The weight gain of the highest NETE plus TU dosage was mainly because of gain in muscle mass.


Assuntos
Antropometria , Noretindrona/análogos & derivados , Testosterona/análogos & derivados , Adulto , Índice de Massa Corporal , Humanos , Masculino , Noretindrona/administração & dosagem , Noretindrona/uso terapêutico , Placebos , Testosterona/administração & dosagem , Testosterona/uso terapêutico
19.
J Radiol ; 91(11 Pt 1): 1121-8, 2010 Nov.
Artigo em Francês | MEDLINE | ID: mdl-21178875

RESUMO

AIM: Evaluate diffusion MRI in the multiparametric assessment of prostate cancer before needle biopsy. MATERIALS AND METHODS: One hundred eleven patients with suspected prostate cancer (mean age: 63 years old, median PSA: 7 ng/mL) were examined before undergoing needle biopsy (59 patients with a history of a negative biopsy and 52 without a history of biopsy). A diffusion sequence type SS SE-EPI (TR/TE: 5357/58, fEPI: 73, b 0 and 1000 s/mm², axial) with a qualitative analysis of the ADC map was performed in addition to T2 and T1 gadolinium enhanced sequences on 3 T MRI with an endorectal coil. The histological correlations were obtained by ultrasound guided needle biopsy (85 patients) or radical prostatectomy (26 patients). RESULTS: The correlation of the results of the diffusion sequence in the series of the 111 patients and the biopsies of the entire prostate or the hemiprostate had a sensitivity of: 92%, 77%; a specificity of: 55%, 70%; a positive predictive value of: 77%, 62%; a negative predictive value of: 84%, 80% and an efficacy of 78%, 75% respectively. The agreement of the three sequences had a specificity of 84.3%. CONCLUSION: The sensitivity of diffusion MRI is high for the detection of cancer of the prostate. Specificity of sequences is good. The results of simple visual assessment of the ADC map are good.


Assuntos
Biópsia por Agulha , Imagem de Difusão por Ressonância Magnética , Processamento de Imagem Assistida por Computador , Neoplasias da Próstata/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Estudos de Coortes , Meios de Contraste/administração & dosagem , Endossonografia , Gadolínio , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Próstata/patologia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Sensibilidade e Especificidade , Ultrassonografia de Intervenção
20.
J Radiol ; 91(11 Pt 1): 1135-42, 2010 Nov.
Artigo em Francês | MEDLINE | ID: mdl-21178877

RESUMO

AIMS: Study the incidence, type and outcome of traumatic ischemic arterial lesions of the kidney in multiple trauma patients. MATERIALS AND METHODS: Retrospective study of 500 multiple trauma patients who underwent whole body 64 slice CT Scan (mean age 34 years old, sex ratio 4M/1W, mean ISS 29). RESULTS: There were seven cases of vascular lesions of the left kidney 1.4% of patients (men, median age 25 years old, mean ISS43.9). These were closed traumas with sudden deceleration and dissection of the renal artery trunk in three cases and injury to its branches in four cases with preserved excretion. Three patients died of associated injuries, including one patient who received a stent on D0. One patient underwent a nephrectomy and the three other patients were not treated which did not affect renal function or pressure (follow-up 19 months). CONCLUSION: We found a high incidence of traumatic renal dissection in multiple trauma patients. Multidetector scan appears to provide the best results for the diagnosis of these lesions as well as the many associated lesions resulting in a very poor prognosis for these patients. Treatment is not well defined and management of these lesions is often of secondary importance because of the severity of associated injuries.


Assuntos
Aneurisma Dissecante/diagnóstico por imagem , Angiografia , Processamento de Imagem Assistida por Computador , Imagem Tridimensional , Isquemia/diagnóstico por imagem , Rim/irrigação sanguínea , Traumatismo Múltiplo/diagnóstico por imagem , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/epidemiologia , Artéria Renal/lesões , Tomografia Computadorizada Espiral , Imagem Corporal Total , Ferimentos não Penetrantes/diagnóstico por imagem , Adulto , Idoso , Aneurisma Dissecante/epidemiologia , Aneurisma Dissecante/terapia , Estudos de Coortes , Meios de Contraste/administração & dosagem , Estudos Transversais , Humanos , Incidência , Isquemia/epidemiologia , Isquemia/terapia , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/epidemiologia , Traumatismo Múltiplo/terapia , Nefrectomia , Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/terapia , Estudos Retrospectivos , Stents , Ferimentos não Penetrantes/epidemiologia , Adulto Jovem
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