Comparación de los efectos inducidos sobre la calciuria por tiazidas y diferentes dosis de sal en la dieta: implicaciones en la práctica clínica / A comparison of induced effects on urinary calcium by thiazides and different dietary salt doses: Implications in clinical practice

Introducción: La restricción de ClNa en la dieta y el tratamiento con tiazidas han sido utilizados en pacientes hipercalciúricos. Objetivos: Conocer la ingesta habitual de sal y la correlación entre natriuria y calciuria con la dieta habitual (B) y tras la modificación de la cantidad de ClNa y la administración de tiazidas. Material y métodos: Diecinueve jóvenes sanos, a los que se les sustituyó su dieta por 2 l diarios de Nutrison(R) Low Sodium (500 mg de Na) durante 2 días. Posteriormente se añadieron cada 2 días 5 g de ClNa ("5", "10" y "15") y durante los 2 últimos días 50 y 100 mg de Higrotona(R) (H50) y (H100). Se determinaron iones, ARP y aldosterona en sangre venosa, así como la natriuria y calciuria. Valoración estadística: se calcula la t de Wilcoxon y la correlación lineal de Pearson. Resultados: Natriuria (mEq/24h): 210,3 ± 87,6 ("B"); 42,7 ± 20,4 ("5"); 135,5 ± 50,6 ("10"); 225,5 ± 56,7 ("15"). Calciuria (mg/24h): 207,8 ± 93,6 ("B"); 172,8 ± 63,1 ("5"); 206,2 ± 87,7 ("10"); 227,4 ± 84,1 ("15"). Correlación positiva entre natriuria y calciuria en "10" (r = 0,47) y en "15" (r = 0,67). Tras Higrotona(R), natriuria: 232,3 ± 50,7; 377 ± 4 (H50); 341,1 ± 68,4 (H100); Ca en orina: 209,8 ± 57,4; 213,2 ± 67,6 (H50); 159,1 ± 52,2 (H100). Conclusiones: La ingesta de sal en la población estudiada es de 14,9 ± 4,9 g/día. Encontramos correlación entre natriuria y calciuria con ingestas de 11,25 y 16,25 g de sal. Con la ingesta habitual, por cada gramo de sal aumenta la calciuria 5,46 mg y con 100 mg de Higrotona(R), la calciuria disminuye 50,7 mg/24 h. Los datos podrían ser de utilidad para el manejo de pacientes con hipercalciuria excretora o hipoparatiroidismo

Introduction: Both dietary restriction of sodium chloride (NaCl) and treatment with thiazides have been used in hypercalciuric patients. Objectives: To calculate regular salt intake and investigate the correlation between natriuresis and urinary calcium with usual diet (B) and after changing the amount of NaCl intake and administration of thiazides. Material and methods: Nineteen healthy young individuals had their diet replaced by 2l of Nutrison(R) Low Sodium (500 mg sodium/day) daily for two days. Then, 5 g of NaCl were added every two days ("5", "10" and "15"), administering 50 mg (H50) and 100 mg (H100) of Higroton(R) on the last two days. Blood sodium, plasma renin activity (PRA) and aldosterone were determined in venous blood samples, as were urinary sodium and calcium. Statistical analysis: Wilcoxon t-test and the Pearson linear correlation were calculated. Results: Urinary Na (mEq/24h): 210.3 ± 87.6 ("B"); 42.7±20.4 ("5"); 135.5±50.6 ("10"); 225.5±56.7 ("15"). Urinary calcium (mg/24h): 207.8±93.6 ("B"); 172.8±63.1 ("5"); 206.2±87.7 ("10"); 227.4±84.1 ("15"). A positive correlation was observed between natriuresis and urinary calcium in "10" (r = 0.47) and "15" (r = 0.67). After Higroton(R), natriuresis: 232.3 ± 50.7; 377 ± 4 (H50); 341.1±68.4 (H100); Ca in urine: 209.8 ± 57.4; 213.2 ± 67.6 (H50); 159.1 ± 52.2 (H100). Conclusions: Salt intake in the population studied was estimated to be 14.9 ± 4.9 g/day with a positive correlation found between sodium and calcium urine output with daily intakes of 11.25 and 16.25g of salt. With the usual intake, for each gram of salt, urinary calcium increased by 5.46 mg/24 h and with 100 mg of Higroton(R) it decreased by 50.7 mg/24h. These data could be useful for the management of patients with excretory hypercalciuria or hypoparathyroidism

A comparison of induced effects on urinary calcium by thiazides and different dietary salt doses: Implications in clinical practice. / Comparación de los efectos inducidos sobre la calciuria por tiazidas y diferentes dosis de sal en la dieta: implicaciones en la práctica clínica.

INTRODUCTION: Both dietary restriction of sodium chloride (NaCl) and treatment with thiazides have been used in hypercalciuric patients. OBJECTIVES: To calculate regular salt intake and investigate the correlation between natriuresis and urinary calcium with usual diet (B) and after changing the amount of NaCl intake and administration of thiazides. MATERIAL AND METHODS: Nineteen healthy young individuals had their diet replaced by 2l of Nutrison® Low Sodium (500mg sodium/day) daily for two days. Then, 5g of NaCl were added every two days («5¼, «10¼ and «15¼), administering 50mg (H50) and 100mg (H100) of Higroton® on the last two days. Blood sodium, plasma renin activity (PRA) and aldosterone were determined in venous blood samples, as were urinary sodium and calcium. STATISTICAL ANALYSIS: Wilcoxon t-test and the Pearson linear correlation were calculated. RESULTS: Urinary Na (mEq/24h): 210.3±87.6 («B¼); 42.7±20.4 («5¼); 135.5±50.6 («10¼); 225.5±56.7 («15¼). Urinary calcium (mg/24h): 207.8±93.6 («B¼); 172.8±63.1 («5¼); 206.2±87.7 («10¼); 227.4±84.1 («15¼). A positive correlation was observed between natriuresis and urinary calcium in «10¼ (r=0.47) and «15¼ (r=0.67). After Higroton®, natriuresis: 232.3±50.7; 377±4 (H50); 341.1±68.4 (H100); Ca in urine: 209.8±57.4; 213.2±67.6 (H50); 159.1±52.2 (H100). CONCLUSIONS: Salt intake in the population studied was estimated to be 14.9±4.9g/day with a positive correlation found between sodium and calcium urine output with daily intakes of 11.25 and 16.25g of salt. With the usual intake, for each gram of salt, urinary calcium increased by 5.46 mg/24 h and with 100mg of Higroton® it decreased by 50.7mg/24h. These data could be useful for the management of patients with excretory hypercalciuria or hypoparathyroidism.

Infarto hipofisario silente de etiología infrecuente / Silent pituitary infarction of an uncommon etiology

No disponible

[Sugar and diabetes: international recommendations]. / Azúcar y diabetes: recomendaciones internacionales.

Nutrition in the diabetic patient is not just a mere nutrient but his treatment is based. In fact, international scientific societies have called "medical nutrition therapy" to give it the emphasis it deserves. Nutritional recommendations of scientific societies have been changing in recent years with evidence-based medicine. Regarding the consumption of sugar, most believe it does not affect metabolic control if it is replaced by other carbohydrates, but does not indicate a specific amount.

La nutrición en el paciente diabético no es sólo un del mero aporte de nutrientes sino que es la base su tratamiento. De hecho, las sociedades científicas internacionales lo han denominado «tratamiento médico nutricional¼ para darle el énfasis que se merece. Las recomendaciones nutricionales de las sociedades científicas han ido cambiando en los últimos años con la medicina basada en la evidencia. Respecto al consumo de azúcar, la mayoría considera que no afecta el control metabólico si éste se sustituye por otros hidratos de carbono, pero no se indica una cantidad concreta.

Are proton pump inhibitors a new antidiabetic drug? A cross sectional study.

AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A cross-sectional study of consecutive in-patients admitted to hospital in any department during the first semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS: A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was significantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to -0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION: PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies.

Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas / Clinical and molecular study of five families with resistance to thyroid hormones

Fundamento y objetivo: La resistencia a la acción de las hormonas tiroideas (SRHT) es un síndrome causado mayoritariamente por mutaciones en el gen receptor beta de las hormonas tiroideas (THRB). Se estudian cinco familias con fenotipo de SRHT. Pacientes y método: Se realizó secuenciación de THRB. Se evaluó la respuesta a triyodotironina (T3) y efecto dominante negativo de los mutantes in vitro y se estudiaron los mecanismos de resistencia en sujetos sin mutación THRB cuantificando en cultivos de fibroblastos cambios de expresión en los genes regulator of calcineurin 2 (ZAKI4) y Kruppel-like factor 9 (BTEB). Resultados: Tres casos presentaron mutaciones en THRB: R243Q, R320C, R429Q, dando lugar a receptores TRβ con menor respuesta a T3. R243Q y R320C ejercen efecto dominante negativo. Un sujeto sin mutación THRB presentó cambios de expresión en ZAKI4 y BTEB similar a R230C, mientras que el otro mostró niveles de expresión superiores a los controles. Conclusiones: Mutaciones heterocigotas en THRB causaron tres de los casos de SRHT estudiados. Uno de los casos con SRHT sin mutación se comporta a nivel molecular como los portadores de mutación, mientras que en el otro la resistencia no está mediada por TRβ (AU)

Background and objective: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. Patients and methods:THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures.Results: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. Conclusions:Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRβ independent (AU)

[Clinical and molecular study of five families with resistance to thyroid hormones]. / Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas.

BACKGROUND AND OBJECTIVE: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. PATIENTS AND METHODS: THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures. RESULTS: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. CONCLUSIONS: Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRß independent.

A family with congenital hypothyroidism caused by a combination of loss-of-function mutations in the thyrotropin receptor and adenylate cyclase-stimulating G alpha-protein subunit genes.

BACKGROUND: Resistance to thyrotropin (TSH) causes congenital hypothyroidism (CH). TSH receptor (TSHR) and adenylate cyclase-stimulating G alpha protein subunit (GNAS) loss-of-function mutations cause TSH resistance. We describe a family with TSH resistance and CH bearing a combination of inactivating mutations in TSHR and GNAS genes. We describe studies to determine the molecular mechanisms involved in TSH resistance in this family. METHODS: DNA sequencing to identify TSHR and GNAS gene mutations was performed. In vitro effects of the mutations on cAMP production and TSH binding were investigated in COS7 cells. cAMP production was evaluated by transfecting a cAMP response element (CRE)-luciferase reporter with pSVL-TSHR and pSVK3-GNAS vectors. For binding studies, cells transfected with pSVL-TSHR vectors were incubated with iodine-125 bovine TSH ((125)IbTSH). RESULTS: Family members with and without CH were heterozygous for the TSHR mutant p.E34K or the GNAS mutant c.750_751insA (=GNASMut). The propositus had CH and he was heterozygous for TSHR p.E34K; his mother, also heterozygous for TSHR p.E34K, did not have CH. The euthyroid propositus' wife was heterozygous for GNASMut. The propositus' two daughters had CH, one was heterozygous for GNASMut and the other a compound heterezygous for TSHR p.E34K and GNASMut. Albright's hereditary osteodystrophy phenotype was present in those with GNASMut mutation but only the daughters had pseudohypoparathyroidism type 1a. Cells transfected with TSHRE34K had lower TSH affinity and less CRE-luciferase response than cells transfected with TSHR wild-type (WT). Cells transfected with GNASMut did not stimulate CRE-luciferase activity, but when cells were transfected with GNASMut plus GNASWT, a similar response to GNASWT alone was observed. The combination of TSHRWT and GNASWT showed higher CRE-luciferase response than TSHRWT and TSHRE34K with either GNASWT or GNASWT plus GNASMut. CONCLUSIONS: CH was caused by loss-of-function mutations in TSHR and/or GNAS. The absence of CH in the propositus' mother argues against a role for TSHR p.E34K being the only cause of CH. The minimal thyroidal phenotypic differences between the sisters with pseudohypoparathyroidism type 1a and TSH resistance, both heterozygous for GNAS c.750_751insA but only one bearing the TSHR p.E34K mutant, suggest that the main cause for CH was preferential expression of the mutated maternal GNAS allele in the thyroid gland.

Tratamiento con levotiroxina e imatinib / Levothyroxine therapy and imatinib

Los requerimientos de levotiroxina de los pacientes con hipotiroidismo suelen ser estables y por ello se recomienda control de la función tiroidea1 o 2 veces al año. Las dosis de levotiroxina ocasionalmente pueden variar por interacciones farmacológicas. Presentamos el caso de una paciente que requirió ajuste de la dosis del evotiroxina al iniciar el tratamiento con imatinib. Mujer de 59 años en tratamiento con levotiroxina por hipotiroidismo secundario atiroidectomía subtotal con buen control clínico y analítico. Tras ser diagnosticada de leucemia mieloide crónica y ser tratada con imatinib,presentó clínica y bioquímica compatible con hipotiroidismo, que precisó un aumento de la dosis de levotiroxina para mantener la función tiroideanormal. Recientemente se ha descrito algún caso de hipotiroidismo al añadir imatinib a pacientes en tratamiento sustitutivo con levotiroxina. Este nuevo caso avala la interacción de ambos fármacos. Por lo tanto, c omentamos los posible mecanismos fisiopatológicos que contribuyen a que el imatinib induzca el hipotiroidismo en pacientes en tratamiento sustitutivo con hormona tiroidea (AU)

Levothyroxine requirements in patients with hypothyroidism are usually stable. Consequently, thyroid function is usually monitored once or twice yearly. Occasionally, the dose of levothyroxine can be changed by pharmacologicalreactions. We report the case of a 59-year-old woman who was under levothyroxine therapy for hypothyroidism secondary to subtotal thyroidectomy, with clinical and biochemical euthyroidism, who required an increased dose of levothyroxine after starting imatinib therapy. The patient was diagnosed with chronic myeloid leukemia and imatinib therapy was started. Subsequently, we observed clinical and biochemical hypothyroidism, requiring an increase in levothyroxine dose. Some cases of hypothyroidism after initiation of imatinib therapy in patients with levothyroxine replacement therapy have recently been published. Our case provides further evidence of a reaction between the two drugs. Therefore, wediscuss the most likely physiopathological mechanisms contributing to imatinibinduced hypothyroidism in patients underlevothyroxine replacement therapy (AU)

Levothyroxine therapy and imatinib.

Levothyroxine requirements in patients with hypothyroidism are usually stable. Consequently, thyroid function is usually monitored once or twice yearly. Occasionally, the dose of levothyroxine can be changed by pharmacological reactions. We report the case of a 59-year-old woman who was under levothyroxine therapy for hypothyroidism secondary to subtotal thyroidectomy, with clinical and biochemical euthyroidism, who required an increased dose of levothyroxine after starting imatinib therapy. The patient was diagnosed with chronic myeloid leukemia and imatinib therapy was started. Subsequently, we observed clinical and biochemical hypothyroidism, requiring an increase in levothyroxine dose. Some cases of hypothyroidism after initiation of imatinib therapy in patients with levothyroxine replacement therapy have recently been published. Our case provides further evidence of a reaction between the two drugs. Therefore, we discuss the most likely physiopathological mechanisms contributing to imatinib-induced hypothyroidism in patients under levothyroxine replacement therapy.

Leptina e insulinoterapia en la diabetes gestacional / Leptin and insulin therapy in gestational diabetes

Introducción: Se han publicado varios trabajos que implican a la leptina (L) en diversos procesos metabólicos, entre ellos la diabetes gestacional (DG) y otras alteraciones del embarazo como la preeclampsia y el retraso de crecimiento intrauterino. Se ha observado que la concentración de L en plasma es superior en gestantes diabéticas que en gestantes sanas. Objetivo: Valorar si la L puede ser un parámetro bioquímico de utilidad en pacientes con DG a la hora de predecir la necesidad de tratamiento insulínico desde el momento mismo del diagnóstico. Pacientes y método: Cincuenta mujeres diagnosticadas de DG entre las semanas 28 y 32 con: media ± desviación estándar de edad, 34,4 ± 4,5 años; IMC, 25,4 ± 2,14, y L, 48,5 ± 16 ng/ml. Fueron separadas en 2 grupos: uno con criterios de insulinización, formado por 24 pacientes, y otro que no precisó insulina, formado por 26. Los criterios de inclusión fueron: presentar un IMC > 22,5 y 40 ng/ml. Conclusiones: Con la cautela de precisar más estudios y con mayor número de pacientes, se puede indicar que la L es útil como parámetro bioquímico que nos ayude a predecir la necesidad de tratamiento insulínico en pacientes diagnosticadas de DG

Introduction: Various studies have implicated leptin in several metabolic processes, among them gestational diabetes (GD) and other pregnancy-associated alterations such as preeclampsia and uterine growth retardation. Plasma leptin levels have been observed to be higher in diabetic pregnant women than in healthy pregnant women. Objective: To evaluate whether leptin could be a useful biochemical marker in patients with GD to predict the need for insulin therapy at diagnosis. Patients and method: Fifty women with a diagnosis of GD between 28 and 32 weeks of pregnancy [mean age, 34.4 ± 4.5 years; body mass index (BMI), 25.4 ± 2.14, and leptin level, 48.5 ± 16 ng/ml] were studied. The women were divided into two groups: one group was composed of 24 women with criteria for insulin therapy and the other group consisted of 26 women not requiring insulin therapy. The inclusion criteria were BMI greater than 22.5 and lower than 27 and biochemical determination between weeks 28 and 32. Results: Maternal plasma leptin levels were significantly higher in the group requiring insulin. No differences were found in the mean age of the patients or in BMI. The odds ratio predicting the need for insulin therapy during pregnancy was 6 in pregnant women with a leptin level higher than 40 ng/ml. Conclusions: Leptin determination could be useful in predicting the need for insulin therapy in patients with GD. However, further studies with a larger number of patients are required to confirm our findings