Respuesta a cartas al editor sobre la curva de aprendizaje de punción-aspiración con aguja fina de tiroides / Reply to letters to the editor on the thyroid fine needle aspiration biopsy learning curve

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Curva de aprendizaje de la punción aspiración con aguja fina de tiroides / Learning curve of thyroid fine-needle aspiration biopsy

Introducción: La punción-aspiración con aguja fina (PAAF) es la técnica de referencia en la evaluación de los pacientes con nódulos tiroideos. Su mayor limitación son las muestras inadecuadas, que deberían ser menos del 20% de los casos. Objetivo: Analizar la curva de aprendizaje de dicha técnica de un endocrinólogo sin experiencia (endocrinólogo 2), comparando sus resultados con los obtenidos en los mismos nódulos por un colega experimentado (endocrinólogo 1). Material y métodos: Se realizaron 60 PAAF entre los meses de febrero y junio de 2016. Cada endocrinólogo realizó 2punciones de cada nódulo en un orden establecido aleatorizadamente. El orden de las punciones y el endocrinólogo que las realizaba eran datos desconocidos para la patóloga que analizó las muestras. Resultados: En el total de las PAAF, el endocrinólogo 1 tuvo un porcentaje de diagnósticos significativamente superior al endocrinólogo 2 (82 vs. 72%; p=0,015). En las primeras 20 PAAF la diferencia entre ambos fue notable y estadísticamente significativa (80 vs. 50%; p=0,047). En las siguientes 20 PAAF la diferencia se redujo y ya no tenía significación estadística (90 vs. 65%; p=0,058). Y en las últimas 20 la diferencia fue mínima y sin significación estadística (75 vs. 70%; p=0,723). Conclusiones: La curva de aprendizaje de la eco-PAAF puede completarse en un entorno adecuado haciéndola un mínimo de 60 veces. Aunque las guías recomiendan al menos 3punciones por nódulo, 2son suficientes para conseguir un porcentaje adecuado de diagnósticos (AU)

Background: Fine-needle aspiration biopsy (FNAB) is the reference procedure for thyroid nodule evaluation. Its main limitation are inadequate samples, which should be less than 20%. Objective: To analyze the learning curve of the procedure by comparing the results of a non-experienced endocrinologist (endocrinologist 2) to those of an experienced one (endocrinologist 1). Material and methods: Sixty FNABs were analyzed from February to June 2016. Each endocrinologist made 2punctures of every nodule in a random order. This order and the professional making every puncture were unknown to the pathologist who examined the samples. Results: Endocrinologist 1 had a higher percentage of diagnoses than endocrinologist 2 (82% vs. 72%, P=.015). In the first 20 FNABs, the difference between both physicians was remarkable and statistically significant (80% vs. 50%, P=.047). In the following 20 FNABs, the difference narrowed and was not statistically significant (90% vs. 65%, P=.058). In the final 20 FNABs, the difference was minimal and not statistically significant (75% vs. 70%, P=.723). Conclusions: The learning curve of ultrasound-guided FNAB may be completed in a suitable environment by performing it at least 60 times. Although the guidelines recommend at least 3punctures per nodule, 2are enough to achieve an accurate percentage of diagnoses (AU)

Learning curve of thyroid fine-needle aspiration biopsy. / Curva de aprendizaje de la punción aspiración con aguja fina de tiroides.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) is the reference procedure for thyroid nodule evaluation. Its main limitation are inadequate samples, which should be less than 20%. OBJECTIVE: To analyze the learning curve of the procedure by comparing the results of a non-experienced endocrinologist (endocrinologist 2) to those of an experienced one (endocrinologist 1). MATERIAL AND METHODS: Sixty FNABs were analyzed from February to June 2016. Each endocrinologist made 2punctures of every nodule in a random order. This order and the professional making every puncture were unknown to the pathologist who examined the samples. RESULTS: Endocrinologist 1 had a higher percentage of diagnoses than endocrinologist 2 (82% vs. 72%, P=.015). In the first 20 FNABs, the difference between both physicians was remarkable and statistically significant (80% vs. 50%, P=.047). In the following 20 FNABs, the difference narrowed and was not statistically significant (90% vs. 65%, P=.058). In the final 20 FNABs, the difference was minimal and not statistically significant (75% vs. 70%, P=.723). CONCLUSIONS: The learning curve of ultrasound-guided FNAB may be completed in a suitable environment by performing it at least 60 times. Although the guidelines recommend at least 3punctures per nodule, 2are enough to achieve an accurate percentage of diagnoses.

Tratamiento del hipotiroidismo subclínico en gestantes con una dosis fija diaria de 75 µg de tiroxina / Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 microgram

ANTECEDENTES Y OBJETIVOS: Los métodos habituales de cálculo de la dosis inicial de tiroxina en el tratamiento de gestantes hipotiroideas usan el peso de las pacientes (1 microgramo/kg/día) o la concentración plasmática de TSH. Este estudio analiza la idoneidad de tratar a estas mujeres con una dosis fija de 75 microgramo/día de la hormona. PACIENTES Y MÉTODOS: Se seleccionaron mediante un muestreo consecutivo a todas aquellas mujeres diagnosticadas de gestación en el área sanitaria de Vigo entre enero y agosto de 2012, sin antecedentes de tiroidopatía y con una concentración de TSH superior a 4,5 mUI/ml y T4L normal. Las 116 gestantes de la muestra resultante recibieron tratamiento con 75 microgramo/día de tiroxina, y se les hizo un análisis a los 2, 4 y 6 meses tras la instauración del tratamiento, modificándose la dosis de la hormona si la concentración de TSH era inferior a 0,3 o superior a 4,5 mUI/ml. RESULTADOS: Una de las pacientes tuvo, en un análisis, una concentración de TSH inferior a 0,3 mUI/ml; el descenso de la dosis de tiroxina a 50 microgramo/día permitió mantener dicha concentración en el rango deseado hasta el parto. Seis tuvieron en un análisis una concentración de TSH superior a 4,5 mUI/ml; en todas ellas el aumento de la dosis de tiroxina a 100 microgramo/día permitió mantener dicha concentración en el rango deseado hasta el parto. CONCLUSIONES: Una dosis de tiroxina 75 microgramo/día permitió conseguir los objetivos de concentración de TSH de nuestro estudio en la mayoría de las gestantes con hipotiroidismo subclínico, independientemente de su peso y de su concentración inicial de TSH

BACKGROUND AND OBJECTIVES: Treatment of hypothyroid pregnant women is usually calculated based on weight (1 microgram/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 microgram/day. PATIENTS AND METHODS: All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4.5 mUI/mL were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 microgram-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/mL. RESULTS: A woman had a TSH level less than 0.3 mUI/mL in a test; reduction of thyroxine dose to 50 microgram/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/mL in one test; in all of them, increase in thyroxine dose to 100 microgram/day allowed for maintaining the level within the desired range until delivery. CONCLUSIONS: Fixed daily doses of thyroxine 75 microgram allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level

Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 µg.

BACKGROUND AND OBJECTIVES: Treatment of hypothyroid pregnant women is usually calculated based on weight (1 µg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 µg/day. PATIENTS AND METHODS: All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 µg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. RESULTS: A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 µg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 µg/day allowed for maintaining the level within the desired range until delivery. CONCLUSIONS: Fixed daily doses of thyroxine 75 µg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level.

Influencia de la glucemia venosa en ayunas en el cálculo de la glucemia media estimada / Influence of venous blood glucose during fasting in the calculation of estimated average glucose

INTRODUCCIÓN: La glucosa media estimada (eAG) es una aproximación en mg/dl de la concentración plasmática media de glucosa durante los 60-90 días previos. OBJETIVO: Conocer el papel de la glucemia venosa en ayunas y las glucemias posprandiales en el cálculo de eAG. MATERIAL Y MÉTODOS: Se incluyó a 413 pacientes con diabetes mellitus atendidos entre enero y julio de 2012, usando como criterios de exclusión las condiciones que pueden modificar los valores de A1c. Se recogieron las glucemias venosas en ayunas y A1c pertenecientes a una misma extracción. Se calculó el valor de eAG perteneciente a cada determinación de A1c, y la diferencia entre cada glucemia venosa y la eAG de 909 parejas de valores. RESULTADOS: Edad de 64 ± 13,5 años. El 53% eran varones, y en el 95% de los casos diabéticos tipo 2. La media de A1c en la muestra analizada fue de 8,1 ± 1,6%. El valor de eAG de este porcentaje es de 186 mg/dl. La glucemia venosa en ayunas fue de 172 ± 69 mg/dl. La diferencia entre la eAG y la media de las glucemias venosas en ayunas fue de 14 mg/dl, significativa con una p < 0,01. CONCLUSIÓN: La eAG es significativamente superior a la media de las glucemias en ayunas en los pacientes con diabetes. Podemos suponer que esta diferencia es consecuencia de la influencia de las glucemias posprandiales en el cálculo de eAG, y que la contribución de la glucemia en ayunas a dicho cálculo es aproximadamente del 92%, y la de la glucemia posprandial, del 8%

INTRODUCTION: The estimated average glucose (eAG) level is an approximate calculation in mg/dL of the plasma concentration of glucose over the previous 60-90 days. OBJECTIVE: To determine the role of venous blood glucose during fasting and post-prandial levels in the calculation of eAG. MATERIAL AND METHODS: We included 413 patients with diabetes mellitus that were being treated between January and July 2012. We considered any condition that could modify the values of A1c as exclusion criteria. We measured the fasting venous blood glucose levels and A1c in the same samples. We calculated the eAG level of each A1c measurement, and the difference between each venous blood glucose level and the eAG of 909 pairs of values. RESULTS: The mean age of the patients was 64 ± 13.5 years old. From our sample, 53% were male, and 95% of these cases were suffering from type 2 diabetes. The average A1c in the sample was 8.1% ± 1.6%. The eAG level for this percentage was 186 mg/dL. The fasting venous blood glucose was 172 ± 69 mg/dL. The difference between the eAG and the average of the fasting venous glucose levels was 14 mg/dL. This was found to be significant with P < 0.01. CONCLUSION: The eAG level is significantly higher than the mean of the levels in fasting in patients with diabetes. We can assume that this difference is due to the influence of the post-prandial glucose levels in the calculation of eAG; and that the contribution of fasting blood glucose to this calculation is approximately 92%, and that of post-prandial blood glucose only 8%

¿Es necesario suspender durante 4 semanas el tratamiento con tiroxina antes de la realización de un rastreo-ablación? / Should thyroxine treatment be discontinued for four weeks before I 131 thyroid ablation?

Introducción Es frecuente que la suspensión de aporte de tiroxina como preparación para un rastreo-ablación se prolongue durante 4 semanas, en las que es habitual la aparición de clínica de hipotiroidismo. Una alternativa útil en algunos casos es utilizar TSHhr, pero sus problemas de disponibilidad durante el año 2012 limitarán su uso. Pacientes y métodos Se realizó un análisis de la concentración de TSH y T4 libre en los días 7, 14, 21 y 28 desde el momento de la realización de una tiroidectomía total (12 pacientes) o desde la suspensión del tratamiento con tiroxina (20 pacientes). Se usó el test de Mann Wittney para analizar las comparaciones de variables cuantitativas y el Chi-cuadrado para las nominales. Resultados En el día 14, la concentración plasmática de TSH fue igual o superior a (..) (AU)

Background It is a usual practice to discontinue thyroxine treatment for four weeks before 131I ablation. Symptoms of hypothyroidism usually occur during this time. Use of rhTSH is a helpful alternative in some cases, but problems of availability of this agent during 2012 will limit its use. Patients and methods Plasma TSH and FT4 levels were measured on days 7, 14, 21, and 28 after total thyroidectomy (12 patients) or discontinuation of thyroxine treatment (20 patients). A Mann-Whitney U test was used to compare quantitative variables, and a Chi-square test was used for nominal variables. Results On day 14, TSH levels were (..) (AU)

[Should thyroxine treatment be discontinued for four weeks before I(131) thyroid ablation?]. / ¿Es necesario suspender durante 4 semanas el tratamiento con tiroxina antes de la realización de un rastreo-ablación?

BACKGROUND: It is a usual practice to discontinue thyroxine treatment for four weeks before (131)I ablation. Symptoms of hypothyroidism usually occur during this time. Use of rhTSH is a helpful alternative in some cases, but problems of availability of this agent during 2012 will limit its use. PATIENTS AND METHODS: Plasma TSH and FT4 levels were measured on days 7, 14, 21, and 28 after total thyroidectomy (12 patients) or discontinuation of thyroxine treatment (20 patients). A Mann-Whitney U test was used to compare quantitative variables, and a Chi-square test was used for nominal variables. RESULTS: On day 14, TSH levels were 30µIU/mL of higher in 71% of patients (66% in the thyroidectomy group and 75% in the group discontinued thyroxine treatment). On day 21, almost all patients from both groups (91% in the thyroidectomy group and 100% in the group discontinued thyroxine treatment) had TSH levels of 30µIU/mL or higher. On day 14, most patients in both groups had FT4 levels below the normal range. CONCLUSIONS: Discontinuation of thyroxine treatment for four weeks is not required. Fourteen days is an adequate time in most patients, and 21 days are sufficient in virtually all patients.

The choice of therapy in acromegaly: results of treatment at a tertiary care hospital.

OBJECTIVE: The aim of our study was to investigate the characteristics of acromegalic patients diagnosed at a tertiary University Hospital and to evaluate the results of the recommended treatment protocols. PATIENTS AND METHODS: All our acromegalic patients were included (n=48; 27 women). Demographic, hormonal, visual and imaging data at diagnosis and during follow-up were recorded, as well as the treatments applied. RESULTS: In 73.0% of the patients, acromegaly was due to a pituitary macroadenoma. From those under periodic surveillance, 68.2% underwent surgery and 36.4% had radiotherapy. At the time of the study 88.6% of the patients were receiving medical therapy, 28.2% of them as first-line treatment. Applying current criteria, only one patient was cured by surgery. Considering normal age and sex-matched concentrations of IGF-I as a control criteria, surgery resulted in disease control in 10% of the patients who had surgery, while medical treatment controlled the disease in 76.9% (P <0.05). Of those who receive medical therapy as first-line treatment, tumour size decreased in 45.5%, while in the rest no significant changes were observed during follow-up. CONCLUSIONS: Not all centres obtain the results reported in the literature in terms of disease control and morbidity after surgical treatment of growth hormone-secreting tumours. It is possible that in some hospitals first-line medical treatment should be chosen, unless the patient has visual disturbances, as long as it is not clear that partial surgical removal of the tumour significantly improves response to medical therapy or reduces its costs.

Respuesta secretora de PYY1-36 y PYY3-36 en sujetos normales tras la ingesta de una comida mixta / PYY1-36 and PYY-36 secretory respose after a mixed meal in healthy individuals

Introducción: El péptido YY (PYY) tiene 36 aminoácidos y lo sintetizan fundamentalmente las células L del intestino. El PYY aumenta tras las comidas y alcanza su nadir tras el ayuno. Tras la ingestión se liberan dos formas: PYY1-36 yPYY3-36. Se ha demostrado que el PYY3-36 reduce la ingesta en humanos y roedores. Hay poca información sobre los valores plasmáticos de PYY, especialmente de PYY3-36, en respuesta a la ingestión y su relación con la respuesta de ghrelina. Objetivos: Estudiar la respuesta secretora de PYY1-36 y PYY3-36 en sujetos normales tras ingerir una comida mixta y su relación con la secreción de ghrelina total y acilada. Sujetos y métodos: Estudiamos a 8 sujetos sanos, 4 mujeres y 4 varones, con una mediana de edad de 53 (intervalo, 36-59) años. Tras el ayuno nocturno, recibieron en2 días diferentes y de forma aleatoria: una comida oral mixta estándar, que consistía en 400 ml de Isosource Energy (159 kcal/100 ml) o placebo por vía oral (400 ml de agua). Se obtuvieron muestras sanguíneas en los tiempos 0, 30, 45, 60 y 120 min para la determinación de PYY1-36, PYY3-36, ghrelina total y ghrelina acilada. Lasc omparaciones se realizaron mediante la prueba de Wilcoxon. Las correlaciones numéricas se analizaron mediante la prueba de correlación de Spearman. Se consideró significativo un valor de p 0,05.Resultados: Tras ingerir la comida, se produce un máximo de PYY1-36 (mediana[intervalo]) de 141,5 (81-198) pg/ml y no hay respuesta tras placebo, con un máximo de 92,5 (46-219) pg/ml (p = 0,04). Los valores del área bajo la curva (ABC) de PYY1-36tras la ingesta fueron 14.865 (8.032-19.822) pg/ml/min y tras placebo, 8.992 (4.455-21.382) pg/ml/min (p = 0,06). Tras ingerir la comida se produce un máximo de PYY3-36de 92,5 (59-135) pg/ml y no hay respuesta tras placebo, con un máximo de 46,5 (30-66) pg/ml (p = 0,02). Los valores del ABC de PYY3-36 tras la ingesta fueron 9.086(6.412-14.970) pg/ml/min y tras placebo, 4.984 (3.142-6.772) pg/ml/min (p = 0,012). El cociente nadir de ghrelina total/máximo de PYY1-36 disminuye de forma marcada trasla ingestión; los valores preprandiales son 7,44 (3,64-14,56) y los posprandiales, 3,55(1,64-7,16) (p = 0,03), mientras que no se modifica tras placebo. El cociente nadir deghrelina acilada/máximo de PYY3-36 disminuye de forma marcada tras la ingestión, ylos valores preprandiales son 2,03 (0,92-3) y los posprandiales, 0,73 (0,26-1,27) (p =0,02), mientras que no se modifican tras placebo. Conclusiones: En sujetos normales, PYY1-36 y PYY3-36 aumentan de forma paralelatras ingerir una comida mixta; simultáneamente, los valores de ghrelina total yacilada disminuyen. El cociente entre el nadir de ghrelina acilada y el máximo dePYY3-36 disminuye tras ingerir una comida mixta. Este conjunto de datos indica suposible participación en la regulación aguda del apetito tras la comida (AU)

Background: Peptide YY (PYY) is a 36 aminoacid peptide synthesized mostly by intestinalL cells. This peptide reaches its nadir during fasting and increases immediately after meals. After food intake, two molecular forms are released, PYY1-36 and PYY3-36. PYY3-36reduces food intake in both humans and rodents. There is scarce information about plasmatic concentrations of PYY, especially ofPYY3-36, after food ingestion, and their relationship to ghrelin. Objectives: To study PYY1-36 and PYY3-36secretory response after a mixed meal, and its relationship to total and acylated ghrelinsecretion in healthy subjects. Subjects and method: We studied eight healthy subjects, 4 women and 4 men, with a median age of 53 (range, 36-59) years. After an overnight fast, the subjects received either a mixed standard meal (400 ml Isosource Energy® [159 kcal/100 ml]) or placebo (400 ml of water) orally in random order on two different days. Blood samples were obtained at 0, 30, 45, 60 and 120 min for measurement of PYY1-36, PYY3-36, total ghrelin and acylated ghrelin. Comparisons were made by Wilcoxon’s test. Numerical correlations were performed using Spearman’s test. P-values 0.05 were considered significant. Results: After a mixed meal, PYY1-36 reached a peak of (median [range]) 141.5 (81-198)pg/ml. There was no response to placebo, with a peak of 92.5 (46-219) pg/ml (p = 0.04).The area under the curve (AUC) of PYY1-36levels after a mixed meal were 14,865 (8,032-19,822) pg/ml/min and after placebo were8,992 (4,455-21,382) pg/ml/min (p = 0.06).After ingestion of a mixed meal, PYY3-36reached a peak of 92.5 (59-135) pg/ml, with noresponse to placebo (46.5 [30-66] pg/ml) (p =0.02). The AUC of PYY3-36 levels after a mixed meal were 9,086 (6,412-14,970) pg/ml/min, and after placebo were 4,984 (3,142-6,772)pg/ml/min (p = 0.012). The quotient between nadir total ghrelin/peak PYY1-36 was markedly diminished after food ingestion, with preprandial values of 7.44 (3.64-14.56) and postprandial values of 3.55 (1.64-7.16) (p =0.03). The former quotient was unmodified by placebo. The quotient between nadir acylated ghrelin/peak PYY3-36 was markedly diminished after ingestion of a mixed meal, with preprandial values of 2.03 (0.92-3) and postprandial values of 0.73 (0.26-1.27) (p =0.02). This quotient was unmodified byplacebo .Conclusions: In healthy subjects, blood levels of both PYY1-36 and PYY3-36 increase after ingestion of a mixed meal. Simultaneously, total and acylated ghrelinlevels diminish. The quotient between nadiracylated ghrelin/peak PYY3-36 diminishes after a mixed meal. All these data suggest the possible contribution of these peptides to appetite regulation after ingestión (AU)

Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure.

BACKGROUND: Malnutrition is very prevalent among patients with chronic renal failure. The role of derangements in the gut-brain axis for regulation of appetite in the genesis of anorexia of these patients has not been adequately investigated. Design. Following a randomized, crossover design, we analysed plasma levels of peptide YY (PYY)(1-36) and PYY(3-36) both fasting and after a standardized oral mixed meal or intraperitoneal glucose infusion in 10 stable uraemic patients undergoing peritoneal dialysis and 8 healthy controls, matched for age, gender and body mass index. Main results. Median baseline plasma levels of PYY(1-36) in the different provocation tests oscillated between 406 and 460 pg/mL in patients, as compared with 73 and 100 pg/mL in controls (P < 0.001). Corresponding values for PYY(3-36) oscillated between 235 and 267 pg/mL in patients, versus 56 and 70 pg/mL in controls (P < 0.001). The association of high levels of PYY(3-36) and normal levels of acylated ghrelin (when compared with healthy controls) configurated a markedly pro-anorexigenic pattern in patients. Neither oral intake nor intraperitoneal glucose resulted in significant changes in plasma levels of PYY(1-36) or PYY(3-36) in subjects with renal failure, in contrast with the expected postprandial rise observed in healthy controls (41% for PYY(1-36), P = 0.04 and 32% for PYY(3-36), P = 0.02, median values). CONCLUSIONS: Baseline plasma levels of PYY(1-36) or PYY(3-36) are markedly elevated in patients with renal failure undergoing peritoneal dialysis. Provocation studies disclose a marked disregulation in the postprandial secretion of these anorexigenic peptides, when compared with healthy controls. These findings may contribute to clarify the complex pathogenesis of anorexia of chronic renal failure.

PYY(1-36) and PYY(3-36) secretory response after a mixed meal in healthy individuals.

BACKGROUND: Peptide YY (PYY) is a 36 amino acid peptide synthesized mostly by intestinal L cells. This peptide reaches its nadir during fasting and increases immediately after meals. After food intake, two molecular forms are released, PYY(1-36) and PYY(3-36). PYY(3-36) reduces food intake in both humans and rodents. There is scarce information about plasmatic concentrations of PYY, especially of PYY(3-36), after food ingestion, and their relationship to ghrelin. OBJECTIVES: To study PYY(1-36) and PYY(3-36) secretory response after a mixed meal, and its relationship to total and acylated ghrelin secretion in healthy subjects. SUBJECTS AND METHOD: We studied eight healthy subjects, 4 women and 4 men, with a median age of 53 (range, 36-59) years. After an overnight fast, the subjects received either a mixed standard meal (400ml Isosource Energy® [159kcal/100ml]) or placebo (400ml of water) orally in random order on two different days. Blood samples were obtained at 0, 30, 45, 60 and 120 min for measurement of PYY(1-36), PYY(3-36), total ghrelin and acylated ghrelin. Comparisons were made by Wilcoxon's test. Numerical correlations were performed using Spearman's test. P-values ≤ 0.05 were considered significant. RESULTS: After a mixed meal, PYY(1-36) reached a peak of (median [range]) 141.5 (81-198) pg/ml. There was no response to placebo, with a peak of 92.5 (46-219) pg/ml (p=0.04). The area under the curve (AUC) of PYY(1-36) levels after a mixed meal were 14,865 (8,032-19,822) pg/ml/min and after placebo were 8,992 (4,455-21,382) pg/ml/min (p=0.06). After ingestion of a mixed meal, PYY(3-36) reached a peak of 92.5 (59-135) pg/ml, with no response to placebo (46.5 [30-66] pg/ml) (p = 0.02). The AUC of PYY(3-36) levels after a mixed meal were 9,086 (6,412-14,970) pg/ml/min, and after placebo were 4,984 (3,142-6,772) pg/ml/min (p=0.012). The quotient between nadir total ghrelin/peak PYY(1-36) was markedly diminished after food ingestion, with preprandial values of 7.44 (3.64-14.56) and postprandial values of 3.55 (1.64-7.16) (p=0.03). The former quotient was unmodified by placebo. The quotient between nadir acylated ghrelin/peak PYY(3-36) was markedly diminished after ingestion of a mixed meal, with preprandial values of 2.03 (0.92-3) and postprandial values of 0.73 (0.26-1.27) (p=0.02). This quotient was unmodified by placebo. CONCLUSIONS: In healthy subjects, blood levels of both PYY(1-36) and PYY(3-36) increase after ingestion of a mixed meal. Simultaneously, total and acylated ghrelin levels diminish. The quotient between nadir acylated ghrelin/peak PYY(3-36) diminishes after a mixed meal. All these data suggest the possible contribution of these peptides to appetite regulation after ingestion.

Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy.

Context It has been reported that metformin might modify thyroid hormone economy. In two retrospective studies, initiation of treatment with metformin caused suppression of TSH to subnormal levels. Objective To prospectively evaluate if administration of metformin to obese, diabetic patients with primary hypothyroidism on stable thyroxine replacement doses modifies TSH levels. Patients and methods Eight obese, diabetic postmenopausal women with primary hypothyroidism participated in the study. They received 1,700 mg of metformin daily for 3 months. Weight, TSH, free T4, and free T3 levels were measured at baseline, 3 months after metformin initiation and 3 months after its withdrawal. Results After 3 months of on metformin, mean TSH was significantly lower than basal TSH (3.11 +/- 0.50 microUI/ml vs. 1.18 +/- 0.36 microUI/ml; P = 0.01). Mean TSH 3 months after metformin withdrawal was 2.21 +/- 0.37 microUI/ml, significantly higher than TSH after metformin (P = 0.05), but not different from basal TSH. Mean fT4 level increased during metformin administration (basal fT4: 1.23 +/- 0.06 ng/dl, fT4 after metformin: 1.32 +/- 0.04 ng/dl; P = ns), and decreased after its withdrawal (fT4 3 months after metformin withdrawal: 1.15 +/- 0.05 ng/dl; vs. 3 months after metformin, P = 0.04; vs. basal; P = ns). Conclusions In obese, diabetic patients with primary hypothyroidism on thyroxine replacement treatment, short-term metformin administration is associated with a significant fall in TSH.

Desaparición tumoral tras tratamiento médico primario en la acromegalia / Tumoral disappearance after primary medical treatment in acromegaly

La acromegalia es una enfermedad de evolución insidiosa y poco común, causada por la hipersecreción crónica de somatotropina (GH). La cirugía transesfenoidal es el tratamiento de elección para la mayoría de los pacientes con acromegalia. Sin embargo, el tratamiento médico primario con análogos de la somatostatina puede ser una opción en pacientes con macroadenomas que no se puede resecar completamente y no causan síntomas compresivos. Así, varios estudios han mostrado que el tratamiento primario con análogos de la somatostatina controla las concentraciones de GH y el factor de crecimiento similar a la insulina (IGF) I y reduce el tamaño tumoral en un porcentaje de pacientes significativo. Presentamos a un paciente con acromegalia tratado de forma primaria medicamente; inicialmente no responde a un análogo de la somatostatina, pero después prácticamente desaparece el adenoma hipofisario con lanreotida autogel (AU)

Acromegaly is an insidious and uncommon disorder caused by chronic growth hormone hypersecretion. Transsphenoidal surgery is the treatment of choice in most patients with acromegaly. However, primary medical treatment with somatostatin analogs can be offered to patients with macroadenomas that cannot be completely resected and do not cause compression symptoms. Several studies have shown that primary medical therapy with somatostatin analogs controls growth hormone and insulin-like growth factor-I levels and decreases tumor volume in a significant percentage of patients. We report the case of a patient with acromegaly who received primary medical treatment with a somatostatin analog without response. The treatment was changed to lanreotide autogel, producing disappearance of the pituitary adenoma (AU)

Síndrome de Cushing por receptores corticosuprarrenales aberrantes / Cushing’s syndrome caused by aberrant adrenal receptors

En investigaciones recientes se ha demostrado que la producción de cortisol en algunos casos de síndrome de Cushing no dependiente de la corticotropina (previamente descritos como "autónomos") está regulada por la existencia de receptores de membrana aberrantes que producen un estímulo crónico de las células corticosuprarrenales, no regulado de forma negativa por glucocorticoides, y que conduce a un incremento crónico de la esteroidogénesis y (posiblemente) a la proliferación celular en la glándula. Se han descrito receptores de este tipo en casos de síndrome de Cushing para varias hormonas, entre ellas el péptido inhibidor gástrico (GIP), la arginina vasopresina (AVP), las catecolaminas, la lutropina/gonadotropina coriónica humana, la serotonina y otras. Los mecanismos moleculares que conducen a la aparición de este tipo de receptores en la corteza suprarrenal todavía son desconocidos. Esta nueva variante etiológica del síndrome de Cushing no dependiente de la corticotropina dará lugar (como así está ocurriendo) a la utilización de tratamientos farmacológicos alternativos a la adrenalectomía. Son probables la identificación futura de nuevos receptores aberrantes capaces de inducir la esteroidogénesis que causa el síndrome de Cushing y la descripción de receptores aberrantes en otros órganos endocrinos y no endocrinos (AU)

Recent studies have shown that cortisol production in some cases of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (previously suspected as being "autonomous") is actually regulated by aberrant membrane receptors. These receptors produce a chronic stimulus on adrenal cells unregulated by the usual glucocorticoid negative feedback, thus increasing chronic steroidogenesis and possibly stimulating cellular hyperplasia. Receptors of this type have been described in cases of Cushing's syndrome caused by a several hormones: gastric inhibitor peptide (GIP), arginine-vasopressin (AVP), catecholamines, LH/hCG, serotonin (5-HT) and others. The molecular mechanisms leading to expression of this type of receptors in the adrenal cortex are still unknown. This new etiological variant of ACTH-independent Cushing's syndrome will lead (as is already happening) to the use of new pharmacological alternatives to adrenalectomy. Potentially, further studies will identify other aberrant receptors that induce steroidogenesis leading to Cushing's syndrome, as well as the presence of aberrant receptors in other endocrine and non-endocrine organs (AU)