Prognostic Significance of Thyroglobulin Antibodies in Differentiated Thyroid Cancer.

OBJECTIVE: To investigate whether variations in thyroglobulin autoantibodies (TgAb) are related to the recurrence or persistence of differentiated thyroid carcinoma (DTC) and may therefore be useful as surrogate tumor markers. Design and Methods. We retrospectively studied 98 subjects (83 women, 47 ± 15 years old) from an initial cohort of 1017 patients treated for DTC in five hospitals, with positive TgAb at any time during the follow-up. Patients presented five different patterns of evolution of serum TgAb concentrations: (1) stable positive TgAb, (2) de novo appearance, (3) an increase of more than 50%, (4) TgAb levels from positive to negative, and (5) a decrease of more than 50%. RESULTS: In the group of 11 patients with stable TgAb, four cases presented persistence of the disease with structural incomplete response. In the group of 22 patients with sustained increasing trend rising more than 50% or de novo detectable TgAb levels, three patients were diagnosed with structural incomplete response. There was no evidence of recurrence or persistence of the disease in any of the 65 patients who showed a significant decrease in (n = 35) or disappearance of (n = 30) TgAb. CONCLUSIONS: Our results suggest that not only the appearance of a significant increase in TgAb but also stable concentrations of TgAb should be regarded as a sufficient risk condition for an active search for recurrent or persistent disease. Conversely, a significant decrease in TgAb levels can represent a good prognostic sign.

Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population.

BACKGROUND: The glycoprotein YKL-40 is a new marker of early inflammation and endothelial dysfunction. Adiponectin is a collagen-like protein with anti-atherogenic and anti-inflammatory effects. Increased concentrations of both markers have been reported in patients with type 1 diabetes (T1D). AIM: To assess the possible role of YKL-40 and adiponectin as a marker of subclinical cardiovascular disease in asymptomatic patients with type 1 diabetes with no history of ischemic or macrovascular heart disease and its relationship with other classic inflammatory biomarkers. METHODS: Concentrations of YKL-40, adiponectin, IL-6, IL-1ß, TNF-α, hsCRP and homocysteine were determined in 150 T1D patients (58% men, age: 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution, BMI: 25.1 ± 3.6 kg/m(2); HbA1c 8.1 ± 2.3%, 4% smokers; 26% retinopathy, microalbuminuria 9%) and 50 controls age, sex and smoke condition matched. Subclinical atherosclerosis was assessed by a carotid ultrasonography and a computed tomography for evaluation of calcium artery calcification score (CACS). RESULTS: 82% of T1D patients and 92% of controls had a calcium score of 0. T1D patients showed a significantly higher mean common carotid artery intima media thickness (CIMT) compared to controls (0.55 ± 0.14 vs 0.48 ± 0.14 mm, p = 0.01). Concentrations of YKL-40 and adiponectin were significantly higher in T1D [42.6 (10.4-195.0) vs ±28.7 (11.0-51.2) ng/ml, p = 0.001 and 15.8 ± 9.1 vs. 12.4 ± 5.3 mg/ml, p = 0.008], with no differences when compared to other inflammatory parameters. In T1D patients no association was found between YKL-40 and adiponectin and screening test for subclinical arterial disease (neither CACS nor CIMT). A positive correlation was found between levels of YKL-40 and age and duration of disease (r = 0.28, p = 0.003; r = 0.35, p = 0.001). There were no differences in the YKL-40 in relation to the presence or absence of retinopathy or nephropathy. Levels of adiponectin were higher in patients with nephropathy (21.84 ± 8.15 vs. 14.88 ± 8.27 mg/ml, p = 0.008). CONCLUSIONS: Type 1 diabetes patients from a Mediterranean area with a longer disease evolution, although a lower degree of subclinical disease, showed significatively higher concentrations of YKL-40 and adiponectin compared with the controls. Therefore, we conclude that YKL-40 and adiponectin are early inflammatory markers in diabetic subjects even in the presence of a low atherosclerotic background.

High prevalence of vitamin D deficiency and lack of association with subclinical atherosclerosis in asymptomatic patients with Type 1 Diabetes Mellitus from a Mediterranean area.

AIMS: Several studies linked vitamin D deficiency with coronary artery disease (CAD). The aim of this study was to evaluate the relationship between the concentrations of 25-hydroxyvitamin D (25OHD) and the presence of early atherosclerosis in asymptomatic Type 1 Diabetes (T1D) patients with no previous history of ischemic heart disease. METHODS: One hundred and forty-five patients with T1D (age 37.8 ± 8 years, 57 % male, all Caucasian, disease duration 20.6 ± 8.3 years, HbA1c 7.6 ± 1.4 % (60.2 ± 11.1 mmol/mol), body mass index (BMI) 25.2 ± 3.5 kg/m2, 52.4 % smokers, 23 % retinopathy, 10 % nephropathy) and 48 controls matched for age, sex, BMI and smoking habit were studied. 25OHD deficiency was defined for values ≤20 ng/mL. A sun exposure questionnaire, carotid ultrasonography to determine carotid intima-media thickness (CIMT) and the presence of atheroma plaques and cardiac computed tomography for evaluation of calcium artery calcification (CACS) were performed. RESULTS: T1D subjects showed a high proportion of 25OHD deficiency (43.2 % vs. 21.7 %, p = 0.032). Of all, 82 % of T1D patients and 92 % of controls had a calcium score of 0. CIMT was greater in patients with T1D (0.55 ± 0.14 mm vs 0.48 ± 0.15, p = 0.01) compared with controls. T1D subjects showed no differences in the results of CACS or CIMT according to the vitamin D concentrations. CONCLUSIONS: T1D patients have lower concentrations and twice more prevalence of 25OHD deficiency than controls. There was no association between 25OHD concentrations and subclinical CAD.

Low prevalence of subclinical atherosclerosis in asymptomatic patients with type 1 diabetes in a European Mediterranean population.

OBJECTIVE: To evaluate the presence of early carotid and coronary atherosclerosis in asymptomatic patients with type 1 diabetes with no history of ischemic heart disease. RESEARCH DESIGN AND METHODS: One hundred and fifty patients with type 1 diabetes (58% males; 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution; HbA1c 8.1 ± 2.3%; 52% nonsmokers; 26% retinopathy; 9% microalbuminuria) and 50 nondiabetic control subjects age and sex matched were studied. Carotid ultrasonography to determine common carotid artery intima-media thickness (c-IMT) and the presence of atheroma plaques and cardiac computed tomography for calcium analysis and quantification (coronary artery calcium score [CACS]) were performed. RESULTS: Most patients with type 1 diabetes and control subjects displayed a CACS of 0 (82 vs. 92%). Patients with type 1 diabetes with CACS ≥1 were older and had higher HbA1c (44.5 ± 5.1 vs. 36.7 ± 8.1 years [P < 0.001] and 8.5 ± 1.1 vs. 7.8 ± 1.0% [P < 0.003], respectively) and longer evolution of diabetes (25.4 ± 9.2 vs. 19.3 ± 7.4 years, P < 0.005) and mean c-IMT (0.67 ± 0.18 vs. 0.53 ± 0.11 mm, P < 0.001) compared with patients with CACS of 0. Smoking (P < 0.02), nephropathy (P < 0.05), retinopathy (P < 0.05), and male sex (P < 0.03) were significantly and positively associated with CACS ≥1. Mean c-IMT was significantly higher in patients with type 1 diabetes (0.55 ± 0.14 vs. 0.48 ± 0.14 mm, P < 0.01), and 11% of them presented atheroma plaques (8% of control subjects). Multivariant logistic regression analysis showed that c-IMT was related to CACS (ß = 6.87, P < 0.001). CONCLUSIONS: A small percentage of patients with type 1 diabetes showed data suggestive of subclinical atherosclerosis. Universal screening of coronary disease in this population is not justified. Carotid ultrasonography may be useful for screening in the subset of patients with cardiovascular risk factors and long disease evolution.

Utilidad de la pulsioximetría en el cribado de la aterosclerosis carotídea en pacientes con diabetes mellitus tipo 2 / Usefulness of pulse oximetry in screening of carotid atherosclerosis in patients with type 2 diabetes mellitus

Fundamento y objetivo: La pulsioximetría se ha propuesto como método de cribado de la vasculopatía periférica. Dado que la arteriosclerosis afecta a todo el territorio vascular, estudiamos su eficacia para detectar pacientes con diabetes mellitus tipo 2 (DM2) con arteriosclerosis carotídea.Pacientes y método: Se incluyeron 105 pacientes con DM2 sin historia previa de vasculopatía periférica. Se realizó historia clínica, exploración física, medición del índice tobillo-brazo (ITB) y de la saturación de oxígeno en el pie y la mano mediante pulsioximetría, análisis sanguineo y ecografía carotídea (medición del grosor íntima-media carotídeo y de placas carotídeas [PC]). Se consideraron patológicos los valores de ITB inferiores a 0,9 y un descenso en la pulsioximetría de la saturación de oxígeno superior al 2% en los pies respecto de la mano o tras la elevación de la extremidad inferior respecto del decúbito supino. Resultados: Sesenta pacientes eran varones (edad media de 62,1 años [desviación estándar de 7,1] y hemoglobina glucosilada media del 6,9% [1,0]). Un 58,1% presentaba PC. Los datos antropométricos y analíticos fueron homogéneos entre los pacientes con y sin PC. El ITB fue inferior a 0,9 en el 49% y en el 25% de los pacientes con y sin PC, respectivamente. No hubo diferencias en la pulsioximetría en función de la presencia de PC ni del ITB patológico. Tampoco el grosor íntima-media fue diferente en función de la pulsioximetría, aunque fue mayor en los pacientes con PC y con ITB inferior a 0,9 que en aquéllos sin alteraciones. Estos resultados fueron independientes de la historia de macroangiopatía clínica (AU)

Background and objective: Pulse oximetry of the toes has been suggested in the screening of peripheral arterial disease. We studied the uselfuness of pulse oximetry in detection of type 2 diabetic patients with carotid atherosclerosis. Subjects and methods: 105 patients with type 2 diabetes mellitus (DM) without previous clinical peripheral arterial disease were enrolled. All patients had (1) ankle-brachial index (ABI) measurement, (2) pulse oximetry to measure SaO2 of their index fingers and big toes in the supine position and at elevated 30cm and (3) a carotid ultrasound [carotid artery intima-media thickness (IMT) and carotid plaques (CP) measurements]. The ABI was considered abnormal when it was <0.9 and when the pulse oximetry showed a decrease in SaO2 of >2% of the finger compared to foot or to 30cm foot elevation. Results: 60 patients were men (age of 62±7 years, HbA1c of 6.9±1.0); 58.1% had CP. There were no differences in anthropometric and biochemical results between patients with or without CP. The ABI was <0.9 in 49% and 25% of patients with and without CP, respectively. Neither were there differences in pulse oximetry in patients with CP or in those with ABI <0.9. The IMT did not change in relation to pulse oximetry, but it was higher in patients with CP and with ABI <0.9 than in patients without alterations. These results were independent of the presence of previous clinical macroangiopathy. Conclusion: Pulse oximetry is not a useful screening method of carotid atherosclerosis in type 2 DM (AU)

[Usefulness of pulse oximetry in screening of carotid atherosclerosis in patients with type 2 diabetes mellitus]. / Utilidad de la pulsioximetría en el cribado de la aterosclerosis carotídea en pacientes con diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Pulse oximetry of the toes has been suggested in the screening of peripheral arterial disease. We studied the uselfuness of pulse oximetry in detection of type 2 diabetic patients with carotid atherosclerosis. SUBJECTS AND METHODS: 105 patients with type 2 diabetes mellitus (DM) without previous clinical peripheral arterial disease were enrolled. All patients had (1) ankle-brachial index (ABI) measurement, (2) pulse oximetry to measure SaO(2) of their index fingers and big toes in the supine position and at elevated 30cm and (3) a carotid ultrasound [carotid artery intima-media thickness (IMT) and carotid plaques (CP) measurements]. The ABI was considered abnormal when it was <0.9 and when the pulse oximetry showed a decrease in SaO(2) of >2% of the finger compared to foot or to 30cm foot elevation. RESULTS: 60 patients were men (age of 62+/-7 years, HbA(1c) of 6.9+/-1.0); 58.1% had CP. There were no differences in anthropometric and biochemical results between patients with or without CP. The ABI was <0.9 in 49% and 25% of patients with and without CP, respectively. Neither were there differences in pulse oximetry in patients with CP or in those with ABI <0.9. The IMT did not change in relation to pulse oximetry, but it was higher in patients with CP and with ABI <0.9 than in patients without alterations. These results were independent of the presence of previous clinical macroangiopathy. CONCLUSION: Pulse oximetry is not a useful screening method of carotid atherosclerosis in type 2 DM.

Serum pepsinogen I: an early marker of pernicious anemia in patients with type 1 diabetes.

CONTEXT: Pernicious anemia (PA) is an autoimmune organ disease much more common in type 1 diabetic patients (DM1) than in nondiabetic subjects, but it is clinically silent until its end stage. OBJECTIVE: This study aimed to determine biochemical markers of latent PA in a population of DM1 patients attending the endocrinology outpatient clinic of a university hospital. STUDY SUBJECTS: The population studied consisted of 186 unselected patients (32.4 +/- 8.7 yr) and 118 healthy controls (30.9 +/- 9.4 yr). MEASUREMENTS AND INTERVENTIONS: Plasma gastrin and pepsinogen I were determined in patients and controls, whereas hemoglobin A1c, serum cobalamin, hemoglobin, and organ-specific antibodies were determined only in patients. Latent PA was defined as serum pepsinogen I less than 30 microg/liter. In patients with low pepsinogen I concentrations and hypergastrinemia, esophagogastroduodenoscopy (EGD) was performed. RESULTS: DM1 patients showed significantly lower pepsinogen I concentrations (P < 0.001) and higher gastrinemia than controls. Latent PA was present in 12.4% of patients vs. 0.9% of controls. Among patients, more women than men showed low plasma pepsinogen I concentrations (P = 0.002) and thyroperoxidase antibody positivity (P < 0.001). Only the highest parietal cell antibody titers (> or =1:640) identified patients with significantly higher levels of plasma gastrin (P < 0.001) and lower levels of pepsinogen I (P < 0.001). The histopathological EGD findings confirmed different degrees of gastric body mucosa atrophy in all cases. CONCLUSION: The high prevalence of latent PA found in our DM1 patients leads us to recommend its screening using serum pepsinogen I concentrations. In patients with hypergastrinemia and high parietal cell antibody titers, EGD should be considered to confirm gastric mucosa atrophy.

[Growth retardation and nutritional status in foster children]. / Retraso de crecimiento y estado nutricional en niños ingresados en una institución de acogida.

BACKGROUND: Our main objective was to determine growth retardation in children entering a foster home and catch-up growth at the end of the stay. We also analyzed the nutritional status and its relationship with growth retardation. SUBJECTS AND METHOD: Height and weight were determined in 118 children, aged between one month and fifteen years; they were examined at admission and at the time of leaving the center. In another group of 31 prepubertal children, we analized their nutritional status determining the body mass index, prealbumin, retinol binding protein, GHBP, IGF-1, IGFBP-3 and leptin at admission. RESULTS: 31 (26.2%) out of the of the 118 children group had a height deficit (height < 2 SDS) at admission. 32 (27.1%) of the overall group of children showed significant catch-up growth after their stay at the foster home, and 15 (46.8%) of them showed a catch-up growth > 0.5 SDS. Children below two years of age showed the most important growth deficit. The nutritional status study showed normal results in all parameters in the 31 children group. Significant correlations were observed between IGF-I and weight/height, IGFBP-3 and weight/height, GHBP and body mass index, and leptin and body mass index. CONCLUSIONS: An important proportion of children showed significant growth retardation at entering a foster home, although a significant catch-up growth was observed at the end of their stay. Growth failure in this population does not appear to be related to the nutritional status.

Retraso de crecimiento y estado nutricional en niños ingresados en una institución de acogida / Growth retardation and nutritional status in foster children

FUNDAMENTO: Se determinó la incidencia de retraso de crecimiento en niños con problemas sociales que ingresaban en una institución de acogida y valoramos la recuperación de dicho retraso tras su paso por el centro. En una segunda fase se analizó el estado nutriticional como posible causa del retraso de crecimiento en niños con problemas sociales. SUJETOS Y MÉTODO: Se estudiaron dos cohortes de niños ingresados en el centro de acogida Estels. Se procedió al análisis retrospectivo del peso y la talla en el momento del ingreso y del alta en el centro de la cohorte A, formada por 118 niños (47 varones y 71 niñas) de edades comprendidas entre un mes y los 15 años. Se determinaron los parámetros nutricionales albúmina, prealbúmina, proteína transportadora de retinol, y los parámetros hormonales IGF-I, IGFBP-3, GHBP y leptina en la cohorte B, compuesta por 31 niños (16 varones y 15 niñas) de 1 a 11 años de edad, a su ingreso en el centro de acogida. RESULTADOS: Grupo A. El 26,2 por ciento (31 sujetos) de los niños que ingresaron en el centro de acogida presentó una talla inferior a -2 desviaciones estándar (DE), 32 (27,1 por ciento) presentaron crecimiento recuperador tras su paso por el mismo, y 15 (46,8 por ciento) de ellos presentaron una recuperación de talla superior a 0,5 DE. Los menores de 2 años de edad fueron los más afectados; el 45 por ciento de ellos presentó talla inferior a -2 DE al ingreso. Grupo B. El estudio nutricional objetivó unos resultados hormonales (IGF-I, IGFBP-3, GHBP y leptina) dentro de la normalidad. Se observaron las siguientes correlaciones significativas entre parámetros hormonales y auxológicos: IGF-I con peso y talla IGFBP-3 con peso y talla, GHBP con IMC y leptina con IMC.CONCLUSIONES: Una proporción significativa de los niños que ingresan en una institución de acogida presenta retraso de crecimiento. En nuestro estudio se detectó crecimiento recuperador en un grupo importante de todos ellos tras su paso por el centro. La malnutrición no es una causa principal del retraso de crecimiento presentado por estos niños (AU)

Baja sensibilidad del IGF-I, la IGFBP-3 y la GH urinaria en el diagnóstico de la insuficiencia de la hormona del crecimiento en niños y adolescentes varones con talla baja y velocidad de crecimiento disminuida / Low sensitivity of IGF-I, IGFBP-3 and urinary GH in the diagnosis of growth hormone insufficiency in slowly-growing short-statured boys

FUNDAMENTO: Se estudió la utilidad del IGF-I, la IGFBP-3 y la excreción urinaria de la hormona del crecimiento (GH) en el diagnóstico del retraso de crecimiento en niños y adolescentes varones con talla baja. SUJETOS Y MÉTODO: Se enviaron a un laboratorio central las muestras de suero de dos pruebas farmacológicas de estímulo de la secreción de GH y dos muestras de orina de 24 h para determinar la GH sérica y urinaria, y las concentraciones séricas de IGF-I, IGFBP-3 y GHBP tanto en valores absolutos como estandarizados para sujetos de la misma edad y sexo (índice Z). Los niños con talla baja se clasificaron en dos grupos diagnósticos dependiendo de los resultados del pico de concentración de GH estimulada que se estableció arbitrariamente en 7,5 µg/l: deficitarios en hormona del crecimiento (DGH) (n = 25) (pico < 7,5 µg/l), y talla baja idiopática (TBI) (n = 54) (pico 7,5 µg/l). Además, se incluyó un grupo de 15 niños y adolescentes varones con crecimiento normal. RESULTADOS: La velocidad de crecimiento estandarizada fue menor, y el índice de masa corporal mayor, en el grupo de DGH respecto al de TBI. Los valores estandarizados del IGF-I presentaron diferencias significativas entre los 3 grupos (p = 0,001). El análisis de regresión lineal múltiple, considerando la velocidad de crecimiento estandarizada como variable dependiente, reveló que el IGF-I estandarizado es el mejor factor de predicción, seguido de la respuesta máxima de la GH al estímulo con clonidina y de la excreción urinaria de GH. Las curvas ROC revelaron un nivel de corte óptimo para el diagnóstico de déficit de GH (DGH) de -2,05 para el IGF-I estandarizado (32 por ciento de sensibilidad y 90 por ciento de especificidad) y de -1,14 para la IGFBP-3 estandarizada (28 por ciento de sensibilidad y 94 por ciento de especificidad). CONCLUSIONES: Las mediciones de IGF-I e IGFBP-3 estandarizadas para sujetos de la misma edad y sexo resultaron muy eficientes sólo en el diagnóstico del DGH grave, pero tuvieron escasa sensibilidad para diagnosticar el DGH idiopático aislado, definido según una baja respuesta de la GH a las pruebas de estímulo (AU)