Respuesta a metformina en el síndrome de ovario poliquístico (SOP): rol de las variantes genéticas / Response to metformin in polycystic ovary syndrome (PCOS): role of genetic variants

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.

Compromiso de seno cavernoso como presentación de cáncer anaplásico de tiroides / Cavernous sinus involvement as presentation of anaplastic thyroid cancer

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.

Cáncer diferenciado de tiroides en tiroides lingual, presentación de un caso / Differentiated thyroid cancer in the lingual thyroid, presentation of a case

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)

Clasificación de los fenotipos de síndrome de ovario poliquístico de acuerdo a los criterios de Rotterdam: ¿una condición estática o variable? / Effects of pregnancy and changes in body weight on polycystic ovary syndrome phenotypes according to the Rotterdam criteria

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.