Normocalcemic hyperparathyroidism after successful parathyroidectomy for single parathyroid adenoma: Prevalence, etiological factors, predictive markers, treatment and evolution.

BACKGROUND AND OBJECTIVE: Postparathyroidectomy normocalcemic hyperparathyroidism (PPNCHPPT) is a frequent situation for which we have no information in our country. The objective is to know our prevalence of PPNCHPPT, the associated etiological factors, the predictive markers, the treatment administered and the evolution. PATIENTS AND METHOD: Retrospective observational cross-sectional study on 42 patients. Twelve patients with PPNCHPPT and 30 without PPNCHPPT are compared. RESULTS: HPPTNCPP prevalence: 28.6%. Etiological factors: vitamin D deficiency: 75%; bone remineralization: 16.7%; renal failure: 16.7%; hypercalciruria: 8.3%. No change in the set point of calcium-mediated parathormone (PTH) secretion was observed, but an increase in the preoperative PTH/albumin-corrected calcium (ACC) ratio was observed. Predictive markers: PTH/ACC ratio (AUC 0.947; sensitivity 100%, specificity 78.9%) and PTH (AUC 0.914; sensitivity 100%, specificity 73.7%) one week postparathyroidectomy. EVOLUTION: follow-up 30 ±â€¯16.3 months: 50% normalized PTH and 8.3% had recurrence of hyperparathyroidism. Patients with PPNCHPPT less frequently received preoperative treatment with bisphosphonates and postoperative treatment with calcium salts. CONCLUSIONS: This is the first study in our country that demonstrates a mean prevalence of PPNCHPPT, mainly related to a vitamin D deficiency and a probable resistance to the action of PTH, which can be predicted by the PTH/ACC ratio and PTH a week post-intervention and often evolves normalizing the PTH. We disagree with the etiological effect of hypercalciuria and the change in the PTH/calcemia regulation set point, and we acknowledge the scant treatment administered with calcium salts in the postoperative period.

Evaluation of an early detection protocol, intensive treatment and control of post-surgical hypoparathyroidism in the first month after total thyroidectomy.

BACKGROUND AND OBJECTIVE: Hypoparathyroidism is the most common complication of total thyroidectomy and usually requires monitoring of calcaemia, whereby it is one of the factors that most contributes to hospital stay. The objective of the study is to evaluate the clinical usefulness of the application of our protocol for early detection, intensive treatment and control of hypoparathyroidism in the first month after thyroidectomy. PATIENTS AND METHOD: Retrospective observational cross-sectional study of 79 patients who underwent total thyroidectomy in whom parathormone (PTH) and calcemia determinations were performed at 6-8 h and 18-24 h post-surgery. When the PTH value was lower than inferior limit of the reference (15 pg/ml), oral treatment was started with 1000 mg of calcium and 0.25 µg of calcitriol every 8 h followed by calcemia controls. RESULTS: Twenty-six cases (32.9%) of normocalcemic hypoparathyroidism were detected in whom treatment prevented their progression to hypocalcaemia, except for 3 cases that had an episode of mild asymptomatic hypocalcaemia. There were no cases of moderate/severe hypocalcaemia and only one case of asymptomatic mild hypercalcaemia. There were no readmissions due to calcium abnormalities. No case with PTH > 15 pg/ml had hypocalcaemia. The protocol allowed a hospital stay of 24 h. The prevalence of permanent hypoparathyroidism was 5.1%. CONCLUSIONS: The application of our protocol during the first month after thyroidectomy is very useful because it avoids the appearance of moderate/severe hypocalcaemia and hypercalcaemia, allows a short hospital stay and is associated with a low prevalence of permanent hypoparathyroidism.

Clinical usefulness of thyroid ultrasonography in patients with primary hypothyroidism.

BACKGROUND AND OBJECTIVE: Despite the value of ultrasonography in the detection of chronic thyroiditis (CT) as well as in nodular goitre, it is often only indicated in patients with hypothyroidism if a palpable goitre or a thyroid mass is identified. The objective of the study is to evaluate the clinical usefulness of thyroid ultrasonography in patients with primary hypothyroidism without clinical suspicion of nodular goitre. And more specifically, to analyse its value in the aetiological diagnosis of hypothyroidism, and to evaluate its contribution in the detection and characterisation of coexisting subclinical thyroid nodular disease. PATIENTS AND METHOD: Prospective cross-sectional observational study of 114 patients with primary hypothyroidism of CT or idiopathic aetiology, without symptoms or cervical palpation suspected of nodular goitre, who underwent a thyroid function test, a serological study of antithyroid antibodies, a thyroid ultrasonound and, when appropriate, a cytological study of the nodules found. RESULTS: Ultrasonound allowed CT to be recognised as the cause of hypothyroidism in 19% of patients who had a negative serological study, and detected nodules larger than 9mm in 22 patients (16 with antithyroid antibodies). A cytological study was performed in 18 of the cases. Five patients underwent surgery, with carcinoma found in two of them. CONCLUSIONS: Thyroid ultrasound is useful in the aetiological diagnosis of primary hypothyroidism as well as in the detection of a coexisting, unsuspected, but clinically relevant nodular goitre, so this examination should be indicated in the initial study of patients with primary hypothyroidism.

Rate of non-invasive follicular thyroid neoplasms with papillary-like nuclear features depends on pathologist's criteria: a multicentre retrospective Southern European study with prolonged follow-up.

PURPOSE: To determine the rate of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in a multi-institutional series from the Iberian Peninsula and describing this NIFTP cohort. METHODS: Retrospective study of papillary thyroid carcinoma (PTC) or well-differentiated tumours of uncertain malignant potential (WDT-UMP) diagnosed between 2005 and 2015 and measuring ≥5 mm in adult patients from 17 hospitals. Pathological reports were reviewed to determine the cases that fulfil the original criteria of NIFTP and histology was reassessed. Rates were correlated with the number of PTC and its follicular variant (FVPTC) of each institution. Demographic data, histology, management, and follow-up of the reclassified NIFTP cohort were recorded. RESULTS: A total of 182 cases with NIFTP criteria were identified: 174/3372 PTC (rate: 5.2%; range: 0-12.1%) and 8/19 WDT-UMP (42.1%). NIFTP rate showed linear correlation with total PTC (p: 0.03) and FVPTC (p: 0.007) identified at each centre. Ultrasound findings were non-suspicious in 60.1%. Fine-needle cytology or core biopsy diagnoses were undetermined in 49.7%. Most patients were treated with total thyroidectomy. No case had nodal disease. Among patients with total thyroidectomy, 89.7% had an excellent response evaluated 1 year after surgery. There were no structural persistence or relapses. Five patients showed residual thyroglobulin after 90 months of mean follow-up. CONCLUSIONS: NIFTP rate is low but highly variable in neighbouring institutions of the Iberian Peninsula. This study suggests pathologist's interpretation of nuclear alterations as the main cause of these differences. Patients disclosed an excellent outcome, even without using the strictest criteria.

Is it time to change the management of permanent postsurgical hypoparathyroidism? / ¿Es hora de cambiar el tratamiento del hipoparatiroidismo posquirúrgico permanente?

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Punción-aspiración con aguja fina ecoguiada de nódulos tiroideos con valoración citológica in situ: eficacia diagnóstica, prevalencia y factores predictores de los resultados de categoría Bethesda I / Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination: Diagnostic efficacy, prevalence, and factors predicting for Bethesda category I results

Antecedentes y objetivo: El procedimiento de punción-aspiración con aguja fina ecoguiada de nódulos tiroideos con examen citológico in situ del material extraído puede reducir el número de citologías obtenidas de categoría Bethesda I. El objetivo del estudio ha sido evaluar nuestra experiencia del segundo año en dicha técnica para analizar la eficacia diagnóstica, la prevalencia y los factores predictores de los resultados de categoría Bethesda I. Pacientes y método: Estudio retrospectivo sobre 279 nódulos en 233 pacientes. La punción-aspiración se realizó según los criterios de 2015 de la American Thyroid Association. Una muestra de cada punción se fijó al aire y se procesó in situ mediante tinción con Diff-Quik y examen microscópico para valorar su idoneidad; en caso contrario, se repitió la punción hasta un total de 5veces. La eficacia diagnóstica se valoró en base a la sensibilidad y a la especificidad sobre las categorías citológicas Bethesda II y Bethesda VI. Resultados: La sensibilidad y la especificidad diagnóstica fueron del 100% en ambos casos. Obtuvimos un 5,4% de resultados de categoría Bethesda I y las variables independientemente asociadas fueron la edad (incremento del 4,7% por cada año de vida) y el volumen del nódulo (incremento del 2,3% por cada 1ml de volumen). Conclusiones: La punción-aspiración ecoguiada con aguja fina y examen citológico in situ del material extraído permite obtener una elevada eficacia diagnóstica y demuestra ser un procedimiento de gran validez por conseguir una tasa muy baja de resultados citológicos de categoría Bethesda I, cuyo riesgo ha sido superior en sujetos de mayor edad y en nódulos de mayor tamaño

Background and objective: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination may decrease the number of Bethesda category I cytologies. The study objective was to evaluate our second-year experience with this procedure to analyze diagnostic efficacy, prevalence, and factors predicting for Bethesda category I results. Patients and method: A retrospective study was conducted of 279 nodules from 233 patients. Ultrasound -guided fine needle aspiration was performed according to the 2015 criteria of the American Thyroid Association. A specimen of each aspiration was air-fixed on site before Diff-Quik staining and microscopic examination to assess its suitability; otherwise, nodule aspiration was repeated up to 5 times. Diagnostic efficacy was assessed based on sensitivity and specificity on the cytological categories Bethesda II and Bethesda VI. Results: Diagnostic sensitivity and specificity were both 100%, 5.4% Bethesda category I results were obtained, and variables independently associated were age (4.7% increase per year of life) and nodule volume (2.3% increase per each 1mL of volume). Conclusions: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination allows for a high diagnostic efficacy and has been shown to be a highly relevant procedure because it has a very low rate of cytological results of Bethesda category I, whose risk has been higher in older subjects and with larger nodules

Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination: Diagnostic efficacy, prevalence, and factors predicting for Bethesda category I results. / Punción-aspiración con aguja fina ecoguiada de nódulos tiroideos con valoración citológica in situ: eficacia diagnóstica, prevalencia y factores predictores de los resultados de categoría Bethesda I.

BACKGROUND AND OBJECTIVE: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination may decrease the number of Bethesda categoryI cytologies. The study objective was to evaluate our second-year experience with this procedure to analyze diagnostic efficacy, prevalence, and factors predicting for Bethesda categoryI results. PATIENTS AND METHOD: A retrospective study was conducted of 279 nodules from 233 patients. Ultrasound -guided fine needle aspiration was performed according to the 2015 criteria of the American Thyroid Association. A specimen of each aspiration was air-fixed on site before Diff-Quik staining and microscopic examination to assess its suitability; otherwise, nodule aspiration was repeated up to 5times. Diagnostic efficacy was assessed based on sensitivity and specificity on the cytological categories BethesdaII and BethesdaVI. RESULTS: Diagnostic sensitivity and specificity were both 100%, 5.4% Bethesda categoryI results were obtained, and variables independently associated were age (4.7% increase per year of life) and nodule volume (2.3% increase per each 1mL of volume). CONCLUSIONS: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination allows for a high diagnostic efficacy and has been shown to be a highly relevant procedure because it has a very low rate of cytological results of Bethesda categoryI, whose risk has been higher in older subjects and with larger nodules.

Prevalencia y malignidad asociada de las citologías de categoría Bethesda III de nódulos tiroideos según el grupo «atipia citológica» o «atipia arquitectónica» / Prevalence and associated malignancy of Bethesda category III cytologies of thyroid nodules assigned to the "cytological atypia" or "architectural atypia" groups

Objetivo: Conocer la prevalencia de citologías de categoría Bethesda III, su tasa de malignidad y analizar si existen diferencias en la segunda citología, tasa de malignidad, tipo de carcinoma y estadio TNM entre los grupos atipia citológica (AC) y atipia arquitectónica (AA). Pacientes y método: Estudio retrospectivo de 973 citologías. Las de categoría Bethesda III se agruparon en AC cuando se apreció atipia nuclear pero no diagnóstica o sospechosa de malignidad, y en AA cuando se trató de extensiones con poca celularidad, pero con un patrón predominantemente microfolicular y con coloide mínimo o ausente. Se correlacionaron los resultados citológicos y anatomopatológicos. Resultados: Hallamos 87 (8,9%) citologías de categoría Bethesda III (34 AC, 53 AA). Se realizó una segunda citología en 23 casos (16 AC, 7 AA) con resultado benigno en el 68,7% de los AC y 71,4% de los AA. Fueron intervenidos quirúrgicamente 64 casos (23 AC, 41 AA) y 15 (23,4%) resultaron malignos: 39,1% AC vs 14,6% AA (p=0,029). Hubo un falso negativo en la segunda citología. El carcinoma papilar variante folicular fue el más frecuente (60%). No hubo diferencias entre AC y AA respecto al tipo de neoplasia ni estadio TNM. Conclusiones: Nuestra prevalencia de citologías de categoría Bethesda III está dentro de lo recomendado. La tasa de malignidad es significativamente superior en el grupo AC, pero sin diferencias en el resultado de la segunda citología, tipo de carcinoma hallado ni estadio TNM. La división de la categoría Bethesda III es útil para proporcionar una mejor estratificación del riesgo de malignidad

Objective: To ascertain the prevalence of Bethesda category III cytologies and their malignancy rate, and to analyze differences in the second cytology, malignancy rate, type of carcinoma, and TNM stage between the cytological atypia (CA) and architectural atypia (AA) groups. Patients and method: A retrospective study of 973 biopsies. Bethesda category III cytologies were classified as CA when nuclear atypia was seen but they were not diagnostic or suspicious of malignancy, and as AA when smears had few cells but had a predominantly microfollicular pattern and minimal or absent colloid. The cytological and pathological results were correlated. Results: There were 87 (8.9%) Bethesda category III cytologies (34 CC, 53 AA). Second cytologies were performed in 23 patients (16 with CA, 7 with AA), and a benign result was found in 68.7% of CA and 71.4% of the AA group. Sixty-four patients (23 CA, 41 AA) underwent surgery and 15 of these (23.4%) had a malignant disease: 39.1% CA vs 14.6% AA (P=.029). There was a false negative result in the CA group. The follicular variant of papillary thyroid carcinoma was the most common malignancy (60%). There were no differences in type of carcinoma or TNM stage between CA and AA patients. Conclusions: The reported prevalence of Bethesda category III cytologies was as expected. The malignancy rate was significantly higher in the CA group, but there were no differences in the result of the second cytology, type of carcinoma found, or TNM stage. The division of Bethesda category III cytologies is useful to provide a better stratification of the risk of malignancy

Prevalence and associated malignancy of Bethesda category III cytologies of thyroid nodules assigned to the "cytological atypia" or "architectural atypia" groups. / Prevalencia y malignidad asociada de las citologías de categoría Bethesda III de nódulos tiroideos según el grupo «atipia citológica¼ o «atipia arquitectónica¼.

OBJECTIVE: To ascertain the prevalence of Bethesda category III cytologies and their malignancy rate, and to analyze differences in the second cytology, malignancy rate, type of carcinoma, and TNM stage between the cytological atypia (CA) and architectural atypia (AA) groups. PATIENTS AND METHOD: A retrospective study of 973 biopsies. Bethesda category III cytologies were classified as CA when nuclear atypia was seen but they were not diagnostic or suspicious of malignancy, and as AA when smears had few cells but had a predominantly microfollicular pattern and minimal or absent colloid. The cytological and pathological results were correlated. RESULTS: There were 87 (8.9%) Bethesda category III cytologies (34 CC, 53 AA). Second cytologies were performed in 23 patients (16 with CA, 7 with AA), and a benign result was found in 68.7% of CA and 71.4% of the AA group. Sixty-four patients (23 CA, 41 AA) underwent surgery and 15 of these (23.4%) had a malignant disease: 39.1% CA vs 14.6% AA (P=.029). There was a false negative result in the CA group. The follicular variant of papillary thyroid carcinoma was the most common malignancy (60%). There were no differences in type of carcinoma or TNM stage between CA and AA patients. CONCLUSIONS: The reported prevalence of Bethesda category III cytologies was as expected. The malignancy rate was significantly higher in the CA group, but there were no differences in the result of the second cytology, type of carcinoma found, or TNM stage. The division of Bethesda category III cytologies is useful to provide a better stratification of the risk of malignancy.

Serum 1,25-Dihydroxyvitamin D as a Biomarker of the Absence of Hypercalciuria in Postsurgical Hypoparathyroidism.

Context: Hypercalciuria is an adverse event of postsurgical hypoparathyroidism treatment that can lead to renal complications. The collection of 24-hour urine to detect hypercalciuria is often considered unreliable. Objective: The purpose of this study was to find useful predictive biomarkers of hypercalciuria in patients with permanent postsurgical hypoparathyroidism receiving treatment with oral calcium and calcitriol supplements. Design and Setting: The investigation was designed as a prospective cross-sectional study. An outpatient hospital clinic served as the study setting. Patients: Fifty-four consecutive observations were made of 34 stable outpatients with postsurgical hypoparathyroidism taking oral calcium and calcitriol supplements, and 17 adult controls without hypoparathyroidism. Intervention: There were no interventions. Main Outcome Measure: Hypercalciuria was defined as 24-hour urine calcium >300 mg. Results: Patients without hypercalciuria (n = 21) vs those with hypercalciuria (n = 33) had lower levels of serum 1,25-dihydroxyvitamin D (33.5 ± 11.9 pg/mL vs 45.8 ± 9.5 pg/mL; P < 0.001), similar albumin-corrected serum calcium (8.3 ± 0.5 vs 8.6 ± 0.5 mg/dL; P = nonsignificant), and serum parathyroid hormone (12.5 ± 5.7 vs 10.7 ± 6.8 pg/mL; P = nonsignificant). Multiple linear regression analysis showed an independent relationship between 1,25-dihydroxyvitamin D and urinary calcium excretion (B = 6.2 ± 1.423; P < 0.001). A cutoff value of 33.5 pg/mL for serum 1,25-dihydroxyvitamin D to predict the absence of hypercalciuria had 100% sensitivity and 63.6% specificity, and the area under the receiver operating characteristic curve was 0.797. No patients with serum 1,25-dihydroxyvitamin D levels of <33.5 pg/mL presented with hypercalciuria, regardless of the level of albumin-corrected serum calcium. Conclusions: Routine measurement of serum 1,25-dihydroxyvitamin D may be useful as a biomarker to predict the absence of hypercalciuria in patients with permanent postsurgical hypoparathyroidism who are receiving treatment with oral calcium and calcitriol supplements.

Estudio descriptivo de las características del cáncer diferenciado de tiroides en Cataluña en el periodo 1998-2012. Registro CECaT / A descriptive study of the characteristics of differentiated thyroid cancer in Catalonia during the period 1998-2012. The CECaT registry

INTRODUCCIÓN: Recientemente, se ha constituido en Cataluña el Consorcio para el Estudio de Cáncer de Tiroides (CECaT). Se trata de una plataforma que reúne 20 hospitales y un instituto de investigación de la comunidad. Una de sus iniciativas ha sido la realización de un estudio retrospectivo de las características de pacientes tratados de cáncer diferenciado de tiroides (CDT). MATERIAL Y MÉTODOS: Se incluyeron 1.855 pacientes de 11 hospitales tratados en el periodo (1998-2012). RESULTADOS: Del total, 1.470 (79,2%) eran mujeres. La edad media al diagnóstico fue de 47,7 (15,7) años, siendo significativamente mayor en los varones que en las mujeres, 49,3 (15) versus 47,3 (15,8); p = 0,02. El 88,9% eran carcinomas papilares. El tamaño del tumor fue de 21,5 (16) mm, siendo significativamente menor en las mujeres que en los hombres, 20,1 (14,5) mm y 26,6 (20,3) mm, respectivamente (p < 0,001). Tras un seguimiento de 5,5 (3,8) años, se disponía de la situación final en 1.355 pacientes. De ellos, 1.065 (78,6%) se encontraban libres de enfermedad, 239 (17,6%) mantenían enfermedad activa y 51 (3,8%) habían fallecido. El riesgo de no estar libre de enfermedad se relacionaba de forma significativa con: mayor edad al diagnóstico, sexo masculino, mayor tamaño del tumor, metástasis linfáticas iniciales, ausencia de signos de tiroiditis en el resto de la glándula, y presencia de invasión vascular y/o extraglandular del tumor. CONCLUSIONES: Los resultados muestran que las características del CDT de la cohorte son similares a las descritas en otros ámbitos geográficos

INTRODUCTION: The consortium for the study of thyroid cancer (CECaT), including 20 hospitals and one research institute, was recently created in Catalonia (Spain). One of the first initiatives of the group was to perform a descriptive analysis of the characteristics of patients with differentiated thyroid carcinoma (DTC). PATIENTS AND METHODS: The cohort included 1,855 patients from 11 hospitals treated over a period of 15 years (1998-2012). RESULTS: In this series, 1.470 (79.2%) patients were women. Mean age was 47.7 (15.7) years old. Age was significantly higher in male than in female patients, 49.3 (15) versus 47.3 (15.8); p = 0.02. Papillary thyroid carcinoma accounted for 88.9% of cases. Mean tumor size was 21.5 (16) mm, and was significantly lower in females than in males, 20.1 (14.5) mm and 26.6 (20.3) mm respectively (p < 0.001). After a follow-up period of 5.5 (3.7) years, information was available for 1,355 patient, of whom 1065 (78.6%) were free of disease, 239 (17.6%) had no tumor persistence, and 51 (3.8) % had died. The risk of persistent or recurrent disease was significantly associated to older age at diagnosis, male gender, larger tumor size, lymph node metastases at surgery, no signs of thyroiditis in the remaining thyroid tissue, and presence of vascular and/or extraglandular invasion. CONCLUSIONS: Patient characteristics analyzed are similar to those reported in other parts of the world

A descriptive study of the characteristics of differentiated thyroid cancer in Catalonia during the period 1998-2012. The CECaT registry.

INTRODUCTION: The consortium for the study of thyroid cancer (CECaT), including 20 hospitals and one research institute, was recently created in Catalonia (Spain). One of the first initiatives of the group was to perform a descriptive analysis of the characteristics of patients with differentiated thyroid carcinoma (DTC). PATIENTS AND METHODS: The cohort included 1,855 patients from 11 hospitals treated over a period of 15 years (1998-2012). RESULTS: In this series, 1.470 (79.2%) patients were women. Mean age was 47.7 (15.7) years old. Age was significantly higher in male than in female patients, 49.3 (15) versus 47.3 (15.8); p=0.02. Papillary thyroid carcinoma accounted for 88.9% of cases. Mean tumor size was 21.5 (16) mm, and was significantly lower in females than in males, 20.1 (14.5) mm and 26.6 (20.3) mm respectively (p<0.001). After a follow-up period of 5.5 (3.7) years, information was available for 1,355 patient, of whom 1065 (78.6%) were free of disease, 239 (17.6%) had no tumor persistence, and 51 (3.8) % had died. The risk of persistent or recurrent disease was significantly associated to older age at diagnosis, male gender, larger tumor size, lymph node metastases at surgery, no signs of thyroiditis in the remaining thyroid tissue, and presence of vascular and/or extraglandular invasion. CONCLUSIONS: Patient characteristics analyzed are similar to those reported in other parts of the world.

Identification of new pathogenic candidates for diabetic macular edema using fluorescence-based difference gel electrophoresis analysis.

BACKGROUND: Diabetic macular edema is the main cause of visual impairment in diabetic patients. The aim of the present study was to explore the differential proteomic pattern of the vitreous fluid from diabetic macular edema patients by means of fluorescence-based difference gel electrophoresis (DIGE). METHODS: Samples of vitreous from eight type 2 diabetic patients [four with diabetic macular edema without proliferative diabetic retinopathy and four with proliferative diabetic retinopathy without diabetic macular edema), and eight from non-diabetic subjects with idiopathic macular hole (control group) were selected from our vitreous bank for proteomic analysis. To further confirm the potential candidates identified by DIGE, 18 additional samples (six proliferative diabetic retinopathy, six diabetic macular edema and six macular hole, matched by age) were analysed by enzyme-linked immuno sorbent assay (ELISA). RESULTS: Selecting an abundance ratio of 1.5-fold, p < 0.05, as the threshold for the study, four proteins were specifically associated with diabetic macular edema. Hemopexin was significantly higher in the vitreous fluid of patients with diabetic macular edema in comparison with both control subjects and proliferative diabetic retinopathy patients. By contrast, clusterin, transthyretin and crystallin S were significantly decreased in the vitreous of patients with diabetic macular edema. The differential production of hemopexin, clusterin and transthyretin was further confirmed by ELISA. CONCLUSIONS: Proteomic analysis by DIGE was useful in identifying new potential candidates involved in the pathogenesis of diabetic macular edema. These results could open up new strategies in the treatment of diabetic macular edema.

Prognostic factors and follow-up of patients with differentiated thyroid carcinoma with false negative or nondiagnostic FNAC before surgery. Comparison with a control group.

Since the clinical implementation of fine needle aspiration cytology (FNAC) to diagnose thyroid carcinoma, few patients remain misdiagnosed and little is known about their clinical outcomes. An observational retrospective study was carried out to analyse prognostic factors and follow-up of patients with differentiated thyroid carcinoma (DTC) not disclosed by FNAC before surgery, compared to a control group. From October 2003 to July 2010, 308 patients underwent surgery as treatment for nodular goitre and 53 had DTC. Cases were 12 subjects with DTC and benign (n = 7) or nondiagnostic (n = 5) FNAC. Controls were 39 subjects with DTC and suspicious (n = 19) or malignant (n = 20) FNAC. Prognostic factors, recurrence and survival rates were compared. Cases had longer time from FNAC to surgery than the control group (86.8 ± 74.1 vs. 16.4 ± 23.8 weeks; P < 0.001), higher prevalence of follicular carcinoma (33.3 vs. 2.6%; P = 0.009), and of two-time total thyroidectomy (75 vs. 30.8%; P = 0.016). Average follow-up was 42.7 ± 25.3 months (2-86 months). There were no deaths. Disease-free survival for cases was 66.9 ± 5.8 months, and for controls 78.7 ± 3.9 months (P: ns). In patients with DTC, the result of the FNAC performed before surgery was not an independent predictor of recurrences or mortality in the first 7 years of follow-up. Thus, false negative or nondiagnostic FNAC in a patient with DTC does not seem to be a primary prognostic factor, but it may reveal other adverse prognostic factors such as longer time to therapy and higher prevalence of follicular carcinoma that may influence long-term outcomes.

Complex thyroid nodules with nondiagnostic fine needle aspiration cytology: histopathologic outcomes and comparison of the cytologic variants (cystic vs. acellular).

Management of complex thyroid nodules (CTN) is a common dilemma due to their high prevalence and frequent nondiagnostic fine needle aspiration cytology (FNAC). In order to know the rate of malignancy, we reviewed our experience about histopathologic diagnosis of CTN with nondiagnostic FNAC, and we analyzed if cytological variants of nondiagnostic FNAC indicated different histopathologic outcomes. We conducted a review of 927 consecutive aspirations performed between 2003 and 2008. We selected patients without history of radiation, with echographic CTN, and nondiagnostic FNAC, who underwent surgery. We analyzed histopathologic results and compared patients with benign and malignant nodules, and searched for differences between patients with cystic changes in FNAC (C-FNAC), and patients with acellular or only bloody FNAC (A-FNAC). Thirty-six patients were included (mean age 45.7 ± 13 years; 30 females). Four patients had malignant nodules; all were papillary carcinomas. Patients with benign nodules had a similar profile to patients with malignant nodules. Patients with C-FNAC (n = 21) were younger (41.3 ± 12.6 vs. 51.8 ± 11.2 years; P < 0.02), had more lymphocytic thyroiditis (33.3 vs. 0%; P < 0.02), a slightly higher rate of carcinoma in the nodule (14.3 vs. 6.6%; P: ns), and also of papillary microcarcinoma outside the nodule (9.6 vs. 0%; P: ns) than patients with A-FNAC. In conclusion, we report an 11.1% malignancy rate in CTN with nondiagnostic FNAC. Nodules with C-FNAC variant had a slightly higher rate of malignancy than A-FNAC, which may be in relation with younger age and higher prevalence of lymphocytic thyroiditis in this group of patients.

Parathyroid carcinoma in multiple endocrine neoplasia type 1. Case report and review of the literature.

Parathyroid carcinoma is an infrequent cause of primary hyperparathyroidism. Although hyperparathyroidism in multiple endocrine neoplasia 1 (MEN1) syndrome is the most common manifestation, parathyroid carcinoma is rare. We report a male patient who was diagnosed at 44 years of age with parathyroid carcinoma in the context of MEN1 syndrome coincident with a malignant gastrinoma and non-functioning adrenal adenomas. A genetic analysis revealed the mutation W183C in exon 3 of the MEN1 gene. The diagnosis of carcinoma was made after parathyroid surgery; there had been no clinical suspicion prior to surgery, as the patient had presented only moderate hypercalcemia. Our review of the few published cases of parathyroid carcinoma in MEN1 syndrome reported in the literature indicates that MEN1 gene mutations do not confer a greater risk for parathyroid carcinoma and do not appear to differ from sporadic parathyroid carcinoma.

Lipopolysaccharide-binding protein and soluble CD14 in the vitreous fluid of patients with proliferative diabetic retinopathy.

PURPOSE: The purpose of this study was to compare intravitreous levels of lipopolysaccharide-binding protein and soluble CD14 (sCD14) between patients with proliferative diabetic retinopathy (PDR) and nondiabetic subjects. METHODS: This study included 19 consecutive Type 2 diabetic patients with PDR in whom a vitrectomy was performed. Sixteen vitreous humors from nondiabetic patients matched by age, with idiopathic macular holes, were selected from our vitreous bank and used as a control group. Lipopolysaccharide-binding protein was assessed by enzyme-linked immunosorbent assay and sCD14 by a solid-phase enzyme-amplified sensitive immunoassay. RESULTS: Lipopolysaccharide-binding protein and sCD14 levels were significantly higher in patients with PDR than in the control group (lipopolysaccharide-binding protein, P < 0.001; sCD14, P < 0.01). After correcting for vitreal proteins, the results remained significantly higher in patients with PDR. No differences in serum levels were observed, and we did not find any correlation between serum and vitreous levels. A direct correlation between lipopolysaccharide-binding protein and sCD14 was detected in the vitreous fluid (r = 0.57; P < 0.001) but not in the plasma. Finally, a significant correlation between intravitreal levels of both lipopolysaccharide-binding protein and sCD14 and interleukin-8 and monocyte chemotactic protein-1 was also detected. CONCLUSION: Lipopolysaccharide-binding protein and sCD14 are elevated in the vitreous fluid of patients with PDR and thus may play a role in the innate immune response triggered by the inflammatory injury characteristic of PDR.