Efficacy of Low-Dose Radioiodine Ablation in Low- and Intermediate-Risk Differentiated Thyroid Cancer: A Retrospective Comparative Analysis.

(1) Background-low-dose radioiodine ablation is an accepted strategy for the treatment of low- and intermediate-risk thyroid carcinomas, although there is no international consensus. The aim of this study is to describe the clinical experience with low-dose radioiodine ablation in patients with low- and intermediate-risk thyroid cancer compared to high-dose ablation. (2) Methods-174 patients with low- and intermediate-risk thyroid cancer, 90 treated with low-dose ablation and 84 treated with high-dose ablation, were included. The primary endpoint was response to treatment one year after ablation, defined by stimulated thyroglobulin, whole body scan and ultrasound imaging. (3) Results-an excellent response rate of 79.8% in the low-dose group and 85.7% in the high-dose group was observed (p = 0.049). Stimulated thyroglobulin at the moment of ablation (p = 0.032) and positive antithyroglobulin antibodies (p < 0.001) were independent predictive factors for nonexcellent response. Young age (p = 0.023), intermediate initial recurrence risk (p < 0.001) and low-dose ablation (p = 0.004) were independent predictive factors for recurrence. (4) Conclusion-low-dose ablation seemed to be less effective than high-dose ablation, especially in those patients with positive antithyroglobulin antibodies or higher stimulated thyroglobulin levels at the moment of ablation. Low dose was associated with higher recurrence rates, and lower age and intermediate initial recurrence risk were independent risk factors for recurrence in our sample.

New molecular biomarkers in differentiated thyroid carcinoma: Impact of miR-146, miR-221 and miR-222 levels in the evolution of the disease.

OBJECTIVE: MircroRNAs (miR) are small, noncoding RNA molecules of 18-25 nucleotides. Their dysregulation has been widely studied in many human tumours including differentiated thyroid cancer (DTC). miRs more frequently associated with these kinds of tumours are miR-146, miR-221 and miR-222. Our objective was to assess the relationship among circulating miR levels and the evolution and outcomes of disease. DESIGN: We analysed a sample of 60 patients with DTC assigning them to one of three groups according to the dynamic scale of risk (excellent response, incomplete biochemical response and incomplete structural response). PATIENTS AND MEASUREMENTS: At study inclusion, we determined thyroid-stimulating hormone, thyroxine, thyroglobulin, antithyroglobulin antibodies and plasma levels of miR-146, miR-221 and miR-222. RESULTS: Male sex and advanced age at diagnosis were associated with the worst disease progression. miR-222 was twofold to threefold higher in tall cell papillary carcinomas (P = 0.038). miR-146 (P = 0.016) and miR-221 (P = 0.050) had a positive correlation with thyroglobulin at the time of sampling. In regression analysis, miR-146 (P = 0.006), miR-221 (P = 0.004) and miR-222 (P = 0.007) predicted more than 70% of the variation in thyroglobulin levels at the time of sampling. CONCLUSIONS: Elevated miR-222 and miR-146 levels are associated with poorer outcomes of the disease and may have a prognostic value in the management and follow-up of DTC.

Insulina aspart en pacientes con diabetes tipo 2 / Insulin aspart in patients with type 2 diabetes

El objetivo de la insulinización actual es mimetizar tanto la secreción basal como la secreción prandial de insulina. La insulina regular humana ha sido usada durante años para el control prandial de los pacientes con diabetes tipo 2 (DM2); sin embargo, su perfil nunca se ha considerado óptimo. La insulina aspart, por su perfil más fisiológico, ha venido sustituyendo el régimen prandial de los pacientes con DM2 en vez de la insulina regular; sin embargo, los beneficios no están del todo claros. Aunque la insulina aspart no ha demostrado descensos significativos en HbA1c, sí ha demostrado, aunque no de manera consistente, mejorar el perfil de glucemia posprandial y, al menos en poblaciones concretas, reducir la incidencia de hipoglucemias nocturnas y graves, lo cual cobra importancia en pacientes con alto riesgo de hipoglucemias

Current insulin therapy aims to mimic both basal and prandial physiological hormone secretion to achieve near-normal glycemia. Regular human insulin has been used for years for glycemic control in type 2 diabetes mellitus (DM-2). However, its pharmacokinetic and pharmacodynamic profiles have never been considered optimal. Due to its more physiological profile, insulin aspart has gradually been substituting regular human insulin in patients with DM-2 but there is ongoing debate concerning its efficacy and safety in these patients. Although insulin aspart has not been shown to produce significant decreases in HbA1c, some - but not all - studies have reported that this drug has beneficial effects in reducing postprandial hyperglycemia. Furthermore, at least in specific populations, insulin aspart may reduce the incidence of nocturnal hypoglycemic episodes and severe hypoglycemic episodes, a finding of importance in high-risk patients

Adiponectin and leptin serum levels in osteoporotic postmenopausal women treated with raloxifene or alendronate.

OBJECTIVE: Clinical studies evaluating the role of leptin and adiponectin on bone metabolism had shown conflicting results, and data about the effect of anticatabolic drugs on these adipokines are scarce. Our aims were to determine adiponectin and leptin levels in osteoporotic postmenopausal women and their relationship with bone mass and bone turnover and to analyze changes on adiponectin and leptin levels after treatment with raloxifene or alendronate. METHODS: We selected 53 women (mean ± SD age, 63 ± 7 y) with postmenopausal osteoporosis divided into two treatment groups: raloxifene (60 mg/d; n = 20) or alendronate (70 mg/wk; n = 33) during a period of 1 year. Bone mineral density by dual-energy x-ray absorptiometry and serum levels of leptin, adiponectin, and bone turnovers markers were determined at baseline and at 1 year after treatment. RESULTS: Baseline levels of leptin were correlated to body mass index (r = 0.47; P < 0.01), waist circumference (r = 0.38, P = 0.01), and estradiol (r = 0.4, P = 0.003). Adiponectin was inversely related to bone-specific alkaline phosphatase (r = -0.41, P < 0.01) and serum crosslaps (r = -0.35; P < 0.01). There was no correlation between bone mineral density, leptin, and adiponectin. After 12 months, no changes were observed in leptin and adiponectin in the alendronate group; however, a significant increase in leptin levels (973.5 ± 637.4 pM/mL vs 1,305.7 ± 793.5 pM/mL; P = 0.031) was detected in the raloxifene group, whereas adiponectin levels showed no significant changes (P = 0.46). CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene induces a significant increase in leptin levels without significant changes in adiponectin serum levels. The antiresorptive effect of raloxifene and alendronate is not substantially influenced by changes in leptin or adiponectin levels.

Experiencia clínica en una consulta de alta resolución de nódulo tiroideo / Clinical experience in a high-resolution thyroid nodule clinic

Fundamentos y objetivos El hallazgo de un nódulo tiroideo es un hecho muy frecuente en la práctica clínica habitual. El manejo del nódulo tiroideo necesita un abordaje multidisciplinar que puede ser facilitado con la creación de unidades de alta resolución de nódulo tiroideo. Describimos la experiencia clínica y los resultados obtenidos en una consulta de alta resolución y acto único de nódulo tiroideo. Material y métodos Se han evaluado todos los pacientes derivados a la consulta de nódulo tiroideo del Hospital Virgen de la Victoria (Málaga) desde el año 2005 al 2007. Se han seguido las guías de práctica clínica de nódulo tiroideo para la recomendación de punción aspirativa con aguja fina (PAAF) y cirugía tiroidea. Se realizó análisis estadístico con programa SPSS. Resultados Durante el periodo de estudio, la consulta de nódulo tiroideo atendió a 658 pacientes (edad media 48,6 años, 89,8% mujeres). Mediante ecografía se confirmó la existencia de nódulo tiroideo en el 85,5% de los pacientes. Con un diámetro medio de 1,96cm, un 74,2% de nódulos fueron sólidos, un 55,8% hipoecoicos, y un 4,7% presentaron microcalcificaciones. Se realizó la PAAF a 475 pacientes. El 76,5% de las citologías fueron benignas, el 19,1% sospechosas, el 2,1% malignas y el 2,3% insuficientes. Se derivó a cirugía al 23,3% de los pacientes (principalmente por tamaño nodular o sospecha de malignidad). Se confirmó la existencia de patología maligna (principalmente carcinoma papilar) en el 24,9% de los nódulos intervenidos. La sensibilidad/especificidad de la citología (considerando la biopsia como el gold standard) fue del 81,8 y el 94,7%, respectivamente. Conclusiones La instauración de una consulta monográfica de nódulo tiroideo permite la optimización de recursos y reduce la demora diagnóstica, obteniendo unos resultados clínicos ampliamente satisfactorios (AU)

Background and objectives: The finding of a thyroid nodule is a very common occurrence inclinical practice. Management of thyroid nodules requires a multidisciplinary approach that may be eased by a high-resolution thyroid nodule clinic. We report our clinical experience and outcomes in a high-resolution thyroid nodule clinic. Patients and methods: All patients referred to Virgen de la Victoria Hospital (Málaga) from 2005to 2007 were evaluated following thyroid nodule guidelines. Statistical analysis was performed using SPSS software. Results: In the study period, 658 patients (mean age 48.6 years, 89.8% females) were seen atthe thyroid nodule clinic. Thyroid nodules were discovered in 85.5% of patients. Mean nodule diameter was 1.96 cm. Of these nodules, 74.2% were solid, 55.8% hypoechogenic, and 4.7% showed microcalcifications. Fine needle aspiration (FNA) was performed in 475 patients (76.5% of all cytological samples were benign, 19.1% had suspected malignancy, 2.1% were malignant, and 2.3% inadequate). Referral for surgery was required in 23.3% of patients (mainly because of nodule size or suspected malignancy). Malignancy was confirmed in 24.9% of nodules. Sensitivity and specificity of cytology (considering biopsy as gold standard) were 81.8% and 94.7%respectively.Conclusions: Implementation of a high-resolution thyroid nodule clinic decreases delay in diagnosis and optimizes available resources, thus providing for satisfactory clinical outcomes (AU)

[Clinical experience in a high-resolution thyroid nodule clinic]. / Experiencia clínica en una consulta de alta resolución de nódulo tiroideo.

BACKGROUND AND OBJECTIVES: The finding of a thyroid nodule is a very common occurrence in clinical practice. Management of thyroid nodules requires a multidisciplinary approach that may be eased by a high-resolution thyroid nodule clinic. We report our clinical experience and outcomes in a high-resolution thyroid nodule clinic. PATIENTS AND METHODS: All patients referred to Virgen de la Victoria Hospital (Málaga) from 2005 to 2007 were evaluated following thyroid nodule guidelines. Statistical analysis was performed using SPSS software. RESULTS: In the study period, 658 patients (mean age 48.6 years, 89.8% females) were seen at the thyroid nodule clinic. Thyroid nodules were discovered in 85.5% of patients. Mean nodule diameter was 1.96 cm. Of these nodules, 74.2% were solid, 55.8% hypoechogenic, and 4.7% showed microcalcifications. Fine needle aspiration (FNA) was performed in 475 patients (76.5% of all cytological samples were benign, 19.1% had suspected malignancy, 2.1% were malignant, and 2.3% inadequate). Referral for surgery was required in 23.3% of patients (mainly because of nodule size or suspected malignancy). Malignancy was confirmed in 24.9% of nodules. Sensitivity and specificity of cytology (considering biopsy as gold standard) were 81.8% and 94.7% respectively. CONCLUSIONS: Implementation of a high-resolution thyroid nodule clinic decreases delay in diagnosis and optimizes available resources, thus providing for satisfactory clinical outcomes.

Dramatic response to cholestyramine in a patient with Graves' disease resistant to conventional therapy.

BACKGROUND: Resistance to the conventional treatment of hyperthyroidism with antithyroid drugs is not commonly found in clinical practice, and only few other treatment options have been reported on in detail. For example, surgery or radioiodine ablation are well-accepted interventions that must be always considered. The euthyroid state is strongly recommended before both of these as this might reduce complications. There are few studies indicating that bile acid sequestrants, when added to antithyroid drugs, produce a more rapid decline in serum thyroid hormone levels and that this effect is maintained for at least 4 weeks. Complete normalization of serum thyroid hormone levels is generally not expected, however. SUMMARY: We report a patient whose thyrotoxicosis failed to respond to conventional treatment. The patient remained persistently hyperthyroid, both clinically and biochemically, despite several months of methimazole and propranolol and the addition of iodine. Cholestyramine, a bile acid sequestrant, was then added, and a dramatic improvement was observed. CONCLUSION: We report a patient who was resistant to conventional antithyroid drugs in whom thyroid hormone levels completely normalized after 1 week of additional treatment with cholestyramine.

Diabetes neonatal: implicaciones de la genética en el tratamiento / Neonatal diabetes: genetic implications in treatment

Neonato de 2 meses de edad diagnosticado de diabetes en el que se inició cetoacidosis con anticuerpos contra antígenos del islote negativos. En el estudio genético, se detectó la mutación R201C en el gen KCNJ11. En los últimos años se ha estudiado el cuadro de diabetes neonatal permanente debido a una mutación del gen KCNJ11 que codifica la subunidad Kir6.2 del canal del potasio sensible al adenosintrifosfato (KATP). Las mutaciones de Kir6.2 producen en última instancia una hiperpolarización de la membrana y la imposibilidad de secretar insulina al mantenerse los KATP permanentemente abiertos. Estudios recientes demuestran la efectividad de las sulfonilureas en el tratamiento. Las sulfonilureas se unen a la subunidad del receptor de sulfonilureas SUR1 y cierran el canal de forma independiente del ATP, de este modo restauran la secreción de insulina. Esta indicación no está aprobada debido a la falta de estudios de seguridad a largo plazo en lactantes; sin embargo, nos hace reflexionar sobre la importancia de la genética en la etiología y las implicaciones en su tratamiento El mielolipoma adrenal es un tumor benigno, poco frecuente, compuesto por tejido adiposo maduro y elementos hematopoyéticos diversos. Su hallazgo suele ser incidental, aunque en ocasiones pueden alcanzar gran tamaño y causar dolor abdominal y otros síntomas clínicos. La ecografía y la tomografía computarizada son herramientas útiles en su diagnóstico. Los tumores pequeños (< 6 cm) y asintomáticos pueden tratarse de forma conservadora con vigilancia periódica y los > 6 cm o con síntomas pueden precisar tratamiento quirúrgico. Presentamos un caso de mielolipoma adrenal gigante y a continuación se realiza una revisión de la literatura (AU)

A 2-month-old newborn was diagnosed with diabetes mellitus presenting with ketoacidosis and negative islet antibodies. Genetic study revealed the R201C mutation of the KCNJ11 gene. In the last few years, the heterozygous activating mutation in KCNJ11 encoding the Kir6.2 subunit of the ATP-sensitive potassium (KATP) channel has been shown to cause permanent neonatal diabetes. Diabetes results from impaired insulin secretion caused by failure of the beta cell-KATP channel to close in response to increased intracellular ATP. Recent studies have demonstrated the effectiveness of oral sulfonylurea in the treatment of this disease. Sulfonylurea closes the KATP channel by an ATP-independent route. Treatment with sulfonylurea in permanent neonatal diabetes has not yet been approved due to the lack of long-term studies in infants. However, the present case illustrates the importance of genetics to identify patients who may benefit from treatment (AU)

Neonatal diabetes: genetic implications in treatment.

A 2-month-old newborn was diagnosed with diabetes mellitus presenting with ketoacidosis and negative islet antibodies. Genetic study revealed the R201C mutation of the KCNJ11 gene. In the last few years, the heterozygous activating mutation in KCNJ11 encoding the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel has been shown to cause permanent neonatal diabetes. Diabetes results from impaired insulin secretion caused by failure of the beta cell-K(ATP) channel to close in response to increased intracellular ATP. Recent studies have demonstrated the effectiveness of oral sulfonylurea in the treatment of this disease. Sulfonylurea closes the K(ATP) channel by an ATP-independent route. Treatment with sulfonylurea in permanent neonatal diabetes has not yet been approved due to the lack of long-term studies in infants. However, the present case illustrates the importance of genetics to identify patients who may benefit from treatment.