RESUMO
La metformina es un hipoglicemiante ampliamente utilizado en el tratamiento de mujeres con síndrome de ovario poliquístico (SOP) por su acción como sensibilizante a la insulina, demostrando tener múltiples efectos favorables en parámetros clínicos y bioquímicos. Especial interés ha causado la variabilidad interindividual en el tratamiento con metformina, que se manifiesta con una respuesta subóptima en diversos grados o con la presencia de efectos adversos, principalmente gastrointestinales. Hasta ahora, pocos estudios han caracterizado este fenómeno en el SOP, así como los mecanismos que le subyacen. Se ha propuesto que variantes de genes envueltos en el transporte y acción de metformina podrían contribuir a la heterogeneidad de su respuesta. En este sentido, se han identificado polimorfismos de nucleótidos únicos (SNPs) en los transportadores de cationes orgánicos, en las proteínas de extrusión de múltiples fármacos y toxinas, y en proteínas quinasas; cuyas principales acciones son a nivel intestinal, hepático y renal, afectando la absorción, distribución y excreción de metformina, probablemente por modificaciones en su farmacocinética. Hasta ahora los escasos estudios disponibles en el SOP han identificado SNPs que estarían afectando la eficacia del tratamiento, sin embargo, no se ha profundizado en los efectos adversos asociados a las variantes genéticas. Es evidente que dichas variantes tienen relevancia clínica y que debieran ser consideradas al diseñar un tratamiento farmacológico, para optimizar su efectividad y minimizar reacciones adversas. El objetivo de este artículo es revisar la información sobre las variantes genéticas asociadas a la variabilidad en la respuesta del tratamiento con metformina en el SOP.
Metformin is a hypoglycemic agent widely used in the treatment of women with Polycystic Ovary Syndrome (PCOS) due to its action as an insulin sensitizer and its multiple favorable effects on clinical and biochemical parameters. There is great concern regarding the inter-individual variability in the response to metformin treatment, which may manifest as a suboptimal effect to varying degrees or by the presence of adverse effects, mainly gastrointestinal. Until now, scarce studies have characterized this phenomenon in PCOS, as well as the mechanisms that underlie it. It has been proposed that genetic variants involved in metformin transport and action could contribute to the heterogeneity of its response. In this sense, single nucleotide polymorphisms (SNPs) have been identified in organic cation transporters, in multidrug and toxin extrusion proteins, and in protein kinases; whose main actions are at the intestinal, hepatic and renal levels, affecting the absorption, distribution and excretion of metformin, probably due to modifications in the pharmacokinetics of the drug. Until now, the few studies available on PCOS have identified SNPs that may be affecting the efficacy of the treatment. However, the adverse effects associated with genetic variants have not been studied in depth. These variants may have clinical relevance and should be considered when designing a pharmacological treatment, to optimize its effectiveness and minimize adverse reactions. The objective of this article is to review the information on genetic variants associated with variability in the response to metformin treatment in PCOS.
Assuntos
Humanos , Feminino , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Variação Genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Anaplastic thyroid cancer is an uncommon malignant tumor, usually fatal, primarily affecting older adults and doesn't have effective systemic therapy. The median survival is less than 6 months from diagnosis. Brain metastases are low frequency and reach 18 percent. We present the case of a patient with papillary carcinoma of the thyroid who takes an aggressive form, becoming anaplastic carcinoma, with involvement of the central nervous system (CNS) manifested by paralysis of the cranial nerve IV, which is rare clinical condition.
Assuntos
Humanos , Neoplasias da Glândula Tireoide/diagnóstico , Carcinoma Anaplásico da Tireoide/diagnóstico , Tireoidectomia , Biópsia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Evolução Fatal , Trombose do Corpo Cavernoso/etiologia , Carcinoma Anaplásico da Tireoide/cirurgia , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/diagnóstico por imagemRESUMO
The lingual thyroid carcinoma is very uncommon neoplasia with an incidence of less than 1 percent. The papillary variant is the most frequent. Cervical MRI helps differentiate muscle from thyroid tissue. The definitive diagnosis is given by histology. Management is similar to that of orthotopic thyroid cancer. We present the case of a 23-year-old woman with hypothyroidism undergoing treatment with dysphagia and sensation of pharyngeal foreign body and malodorous oral bleeding. Nasopharyngoscopy showed a rounded mass at the base of the tongue; the biopsy was compatible with thyroid neoplasia. Image study with ultrasound confirms empty thyroid bed with presence of lingual ectopic thyroid. The team of surgeons performed surgery with Trotter Technique, they removed a tumor of 4 centimeters of diameter. The definitive biopsy concludes minimally invasive follicular carcinoma. The treatment was completed with 100 mCi of radioiodine. Systemic screening at 7 days was negative, as the post-operative thyroglobulin (Tg)
Assuntos
Humanos , Feminino , Adulto Jovem , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/patologia , Carcinoma Papilar, Variante Folicular/diagnóstico , Carcinoma Papilar, Variante Folicular/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Língua/cirurgia , Carcinoma Papilar, Variante Folicular/cirurgia , Tireoide LingualRESUMO
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is tightly associated with insulin resistance and obesity and characterized by hyperandrogenism, chronic oligo-anovulation and polycystic ovarian morphology when fully expressed. The 2003 Rotterdam consensus proposed that two or three of these features were necessary to make the diagnosis, which generated four phenotypes. Several studies have suggested that these phenotypes could differ in their metabolic and endocrine characteristics and that they could vary in the same patient when analyzed throughout life. AIM: To determine if the initial classification of PCOS phenotypes is modified by different physiological conditions. MATERIAL AND METHODS: We performed a non-concurrent prospective analysis of 88 women with PCOS according to the Rotterdam criteria. The effect of physiological conditions such as changes in body weight, pregnancy and ageing more than five years on PCOS phenotype expression was analyzed. RESULTS: Twenty four percent of women became pregnant, 37% decreased and 24% increased their body weight during follow up. These conditions modified significantly the proportion of the different phenotypes (c2 = 32.2, p < 0.001). For instance, weight reduction was associated with a change to a better phenotype (p = 0.047) and even a normalization of the PCOS condition in 27% of the patients. On the other hand, an increase in body weight modifying body mass index in one unit, conferred an 8% probability of changing to a worst phenotype. CONCLUSIONS: Pregnancy and changes in body weight significantly modify PCOS phenotypes.
Assuntos
Fatores Etários , Peso Corporal/fisiologia , Síndrome do Ovário Policístico/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Fenótipo , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
Background: Polycystic Ovary Syndrome (PCOS) is tightly associated with insulin resistance and obesity and characterized by hyperandrogenism, chronic oligo-anovulation and polycystic ovarian morphology when fully expressed. The 2003 Rotterdam consensus proposed that two or three of these features were necessary to make the diagnosis, which generated four phenotypes. Several studies have suggested that these phenotypes could differ in their metabolic and endocrine characteristics and that they could vary in the same patient when analyzed throughout life. Aim: To determine if the initial classification of PCOS phenotypes is modified by different physiological conditions. Material and Methods: We performed a non-concurrent prospective analysis of 88 women with PCOS according to the Rotterdam criteria. The effect of physiological conditions such as changes in body weight, pregnancy and ageing more than five years on PCOS phenotype expression was analyzed. Results: Twenty four percent of women became pregnant, 37% decreased and 24% increased their body weight during follow up. These conditions modified significantly the proportion of the different phenotypes (c2 = 32.2, p < 0.001). For instance, weight reduction was associated with a change to a better phenotype (p = 0.047) and even a normalization of the PCOS condition in 27% of the patients. On the other hand, an increase in body weight modifying body mass index in one unit, conferred an 8% probability of changing to a worst phenotype. Conclusions: Pregnancy and changes in body weight significantly modify PCOS phenotypes.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem , Fatores Etários , Peso Corporal/fisiologia , Síndrome do Ovário Policístico/fisiopatologia , Fenótipo , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the metabolic profile of Chilean and Argentinian women with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria. DESIGN: Observational cross-sectional study. SETTING: Academic centers. PATIENT(S): Women with PCOS, aged 18-39 years: 220 Chilean (PCOSCh) and 206 Argentinian (PCOSAr). INTERVENTION(S): Physical examination, fasting blood samples for androgens, gonadotropins, metabolic parameters, and a transvaginal ultrasound. MAIN OUTCOME MEASURE(S): Comparative analysis of the metabolic profile in both populations divided into four phenotypes. RESULT(S): The distribution of the different phenotypes was different in both populations. PCOSCh women showed a higher body mass index and a higher percentage of metabolic syndrome in all phenotypes compared with the PCOSAr women. The PCOSAr women exhibited a statistically significantly higher diastolic blood pressure in phenotypes A, B, and C and a higher percentage of hypertension in phenotypes A and D compared with the PCOSCh women. CONCLUSION(S): The data show differences in the metabolic profile of both populations. PCOSCh women presented with greater metabolic alterations such as dysglycemia and dyslipidemia and a higher prevalence of metabolic syndrome, independent of the phenotype. The PCOSAr patients showed more elevated blood pressure. Ethnic diversity associated with environmental factors are fundamental elements in the analysis of the PCOS phenotypes.
Assuntos
Etnicidade , Síndrome Metabólica/etnologia , Síndrome do Ovário Policístico/etnologia , Adolescente , Adulto , Androgênios/sangue , Argentina/epidemiologia , Biomarcadores/sangue , Índice de Massa Corporal , Chile/epidemiologia , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/etnologia , Jejum/sangue , Feminino , Gonadotropinas/sangue , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/etnologia , Hipertensão/diagnóstico , Hipertensão/etnologia , Modelos Logísticos , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Análise Multivariada , Razão de Chances , Fenótipo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico por imagem , Prevalência , Fatores de Risco , Ultrassonografia , Adulto JovemRESUMO
Background: Polycystic ovary syndrome (PCOS) is a common endocrine metabolic dysfunction closely associated with insulin resistance and obesity, which predisposes to pregnancy complications and prenatal programming of the offspring. The aim of this review is to report our experience in PCOS patients who became pregnant and were followed during the whole pregnancy. Firstly, we analyzed the effect of pregnancy on PCOS pathophysiology and secondly the role of PCOS in pregnancy outcomes. Regarding the firstpoint, during normal pregnancy a progressive insulin resistance, serum lipid changes and an increase in androgen levels is observed, which is exacerbated in the PCOS condition. This adverse intrauterine environment could have a prenatal programming effect with detrimental consequences for female or male fetuses. Regarding the second point, PCOS is associated with an increased risk for maternal complications such as gestational diabetes (GDM) and pregnancy-induced hypertension. Moreover, these adverse pregnancy outcomes are more frequently associated with an increase in low birth weight and high birth weight newborns. According to our clinical experience, PCOS patients who became pregnant and were not treated with metformin during the whole pregnancy, showed a higher prevalence of gestational diabetes and SGA newborns, which was improved with metformin treatment. In summary, pregnancy may constitute a period in which an abnormal condition is established or aggravated in the fetus of a PCOS mother. Moreover, PCOS enhanced adverse obstetric and neonatal outcomes.
Assuntos
Animais , Feminino , Humanos , Masculino , Gravidez , Síndrome do Ovário Policístico/complicações , Complicações na Gravidez , Peso ao Nascer/fisiologia , Diabetes Gestacional/etiologia , Feto/embriologia , Modelos Animais , Resultado da GravidezRESUMO
BACKGROUND: The polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder that arise from a combination of genetic and environmental factors. AIM: To assess the role of the androgen receptor (AR) CAG repeat polymorphism in the metabolic and reproductive features in daughters of women with PCOS (PCOSd). METHODS: Sixty-seven PCOSd and 60 daughters of control women (Cd) were studied in early stages of sexual development. Sex steroids, glucose, insulin and lipids were determined. The AR CAG repeat sizes and X-chromosome inactivation (XCI) were analyzed. RESULTS: PCOSd and Cd had similar mean number of CAG repeats and XCI pattern. In PCOSd and Cd, methylation-weighted biallelic means CAGn (mwCAGn) was not associated with androgen levels. In infants and pubertal PCOSd, mwCAGn was associated with a low concentration of HDL-cholesterol. CONCLUSIONS: AR CAG repeat polymorphism appears to be unrelated with serum androgen levels. However, the short mwCAGn variant may have a possible impact on the lipid profile in PCOSd.
Assuntos
Saúde da Família , Mães , Síndrome do Ovário Policístico/genética , Polimorfismo Genético , Receptores Androgênicos/genética , Repetições de Trinucleotídeos , Inativação do Cromossomo X , Adolescente , Desenvolvimento do Adolescente , Androgênios/sangue , Criança , Desenvolvimento Infantil , Pré-Escolar , Chile , HDL-Colesterol/sangue , Feminino , Estudos de Associação Genética , Humanos , Lactente , Leucócitos/metabolismo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/metabolismo , Receptores Androgênicos/metabolismoRESUMO
CONTEXT: We have previously described increased serum levels of anti-Müllerian hormone (AMH) and stimulated insulin in daughters of women with polycystic ovary syndrome (PCOS), suggesting that these girls may have an altered ovarian follicular development which may be modulated by insulin. However, the specific relationship between serum AMH and insulin levels during each Tanner stage of puberty in this cohort has not been established. OBJECTIVE: The aim of our study was to establish the relationship between AMH and poststimulated insulin serum concentrations during each stage of puberty in daughters of women with PCOS (PCOSd), compared to daughters of control women (Cd). DESIGN: We studied 135 PCOSd and 93 Cd classified according to their Tanner stage. Gonadotrophins, sex steroids, sex hormone-binding globulin (SHBG), and AMH were determined in a fasting sample. Ovarian volume was measured by pelvic ultrasound. In addition, in both groups we performed an oral glucose tolerance test with measurements of glucose and insulin. RESULTS: Anti-Müllerian hormone levels were significantly higher in PCOSd compared to Cd at all Tanner stages. Daughters of women with PCOS having AMH concentrations greater than 2 standard deviation (SD) above the mean AMH value for the Cd group showed decreased serum follicle-stimulating hormone (FSH) concentrations and increased stimulated levels of insulin during Tanner stages I, II, and III. CONCLUSIONS: Anti-Müllerian hormone levels are increased in PCOSd during all stages of puberty. We suggest that those PCOSd with the highest AMH levels probably represent a group of girls with more severe ovarian dysfunction and metabolic derangements.
Assuntos
Hormônio Antimülleriano/sangue , Insulina/sangue , Síndrome do Ovário Policístico/sangue , Puberdade/sangue , Adolescente , Androstenodiona/sangue , Glicemia/metabolismo , Criança , Estudos de Coortes , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Núcleo Familiar , Ovário/fisiologia , Síndrome do Ovário Policístico/patologia , Gravidez , Globulina de Ligação a Hormônio Sexual/análise , Estatísticas não Paramétricas , Testosterona/sangueRESUMO
OBJECTIVE: To evaluate the ovarian function during early infancy in daughters of women with polycystic ovary syndrome (PCOS) treated with metformin throughout pregnancy (PCOSd+M), as a means to reduce androgen and insulin levels, compared with daughters of nontreated PCOS women (PCOSd-M) and daughters of women who belong to a healthy comparison group (HCd). DESIGN: Descriptive and analytic study. SETTING: Unit of endocrinology and reproductive medicine. PATIENT(S): Fifteen PCOSd+M, 23 PCOSd-M, and 35 HCd were studied at 2-3 months of age. INTERVENTION(S): A GnRH analogue test was performed with determinations of gonadotropins, sex steroids, SHBG, and anti-Müllerian hormone (AMH). MAIN OUTCOME MEASURE(S): Differences in AMH levels between PCOSd+M, PCOSd-M and HCd. RESULT(S): AMH and peak E(2) concentrations were significantly higher in PCOSd-M compared with HCd, whereas PCOSd+M exhibited AMH concentrations and peak E(2) levels similar to those observed in HCd. CONCLUSION(S): The improvement of the altered endocrine-metabolic environment of PCOS mothers reduces AMH levels in their daughters, which might reflect a decrease in their follicular mass.