[Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina]. / Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina.

INTRODUCTION: Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. METHODS: The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. RESULTS: BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. CONCLUSION: BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our population. There is a significant correlation between BRAF mutation and lymph-node metastasis.

Introducción: Se ha descrito que alteraciones moleculares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogénesis. Nuestro objetivo fue conocer la frecuencia mutacional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos: Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 muestras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados: La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspondieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la mutación, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los ganglios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión: La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina / Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina

Resumen Introducción : Se ha descrito que alteraciones molecu lares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogé nesis. Nuestro objetivo fue conocer la frecuencia muta cional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos : Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 mues tras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados : La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspon dieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la muta ción, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los gan glios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión : La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Abstract Introduction : Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. Methods : The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. Results : BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. Conclusion : BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our popu lation. There is a significant correlation between BRAF mutation and lymph-node metastasis.

Is radioiodine ablation with 1.1 GBq (30 mCi) 131I necessary in low-risk thyroid cancer patients? Results from a long-term follow-up prospective study.

BACKGROUND: In patients with low-risk differentiated thyroid cancer (DTC), remnant ablation with radioiodine (RA) after total thyroidectomy (TT) is controversial. No benefits have been demonstrated in terms of mortality or disease-free survival. Recent evidence found that RA did not improve mid-term outcomes. PURPOSE: To evaluate initial response to treatment and long-term follow-up status in low-risk DTC patients after TT vs. TT + RA with 131I 1.11 GBq (30 mCi). METHODS: Prospective multicenter non-randomized study; 174 low-risk DTC that underwent TT were recruited an divided in two groups according to RA (87 ablated and 87 non-ablated). Response to treatment was evaluated at 6-18 months after thyroidectomy and at the end of follow-up with measurements of thyroglobulin, and anti-thyroglobulin antibodies levels, and neck ultrasonography. RESULTS: Baseline characteristics of both groups were similar. Ablated patients: median age 45.5 years, 84% females, 95.4% papillary thyroid carcinoma (PTC), mean tumor size 16 mm; non-ablated: median age 45 years, 88.5% females, 96.6% PTC, mean tumor size 14 mm. Response to initial treatment was similar between both groups, with < 2% of structural incomplete response. Final status was evaluated in 139 cases (median follow-up of 60 months). Among ablated patients, 82.8% had no evidence of disease (NED), 12% had an indeterminate response (IR) and 5% a biochemical incomplete response (BIR). Non-ablated patients had NED in 90%, IR in 8.7% and BIR in 1.2%. No statistical difference was found between groups (p = 0.29). No patient had evidence of structural disease at the end of follow-up. CONCLUSIONS: Our findings support the recommendation against routine RA in low-risk DTC patients.

Unusual metastases from differentiated thyroid carcinoma: analysis of 36 cases.

PURPOSE: Metastases of differentiated thyroid cancer (DTC) in sites different from lungs and bone are unusual (UM); their impact in management and prognosis remains unknown. Our aim was to evaluate the prevalence of UM, to describe their characteristics and to analyze their impact in disease outcome and mortality. METHODS: We retrospectively reviewed the file records from 8 different centers. Those patients with DTC and UM were included. UM were diagnosed by: (i) biopsy/cytology and/or (ii) radioiodine (RAI) uptake associated to elevated thyroglobulin (Tg) levels and/or c) presence of one or more structural lesion/s with 18-FDG uptake in the PET/CT scan and elevated Tg levels. RESULTS: Thirty-six (0.9%) out of a total of 3982 DTC patients were diagnosed with UM; 75% had papillary histology. The most frequent localization was central nervous system (CNS, 31%). UM were metachronous in 75%, symptomatic in 55.6% and fulfilled RAI-refractoriness criteria in 77.8% of cases. Metastatic lesions in lung/bone and/or locoregional disease were present in 34 cases (94.4%). Diagnosis of UM changed the therapeutic approach in 72.2% of patients. After a median follow up of 13 months, 21 (58.3%) patients died from DTC related causes. In 8 of them CNS progression was the immediate cause of death. CONCLUSIONS: Prevalence of UM was low; they were frequently metachronic and RAI-refractory. Although UM were found in patients with widespread disease, their diagnosis usually led to changes in therapy. UM were associated with poor prognosis and high frequency of disease-specific mortality.

[Association between body mass index and aggressiveness of papillary thyroid carcinoma]. / Asociación entre índice de masa corporal y agresividad del carcinoma papilar de tiroides.

The aim of the study was to evaluate the association of the body mass index (BMI) with the clinical-pathological characteristics and the recurrence of papillary thyroid carcinoma. The cohort consisted of 208 patients with papillary thyroid carcinoma diagnosed in 2003-2014, in Buenos Aires, Argentina. The patients were grouped according to the BMI as follows: BMI <18.5 kg/m2 (low weight); BMI ≥ 18.5 and < 25 kg/m2 (normal weight); BMI ≥ 25 and < 30 kg/m2 (overweight); BMI ≥ 30 kg/m2 (obesity). Two experienced pathologists reviewed and cross-checked all pathology specimens to confirm diagnosis, tumor characteristics and extent of the disease. All patients were followed every 6 months for 2 years, and annually thereafter. Recurrences were searched by using diagnostic imaging and histological confi rmation when necessary. Regression analysis was applied to defi ne associations of BMI with clinical, pathological, and prognosis features of the disease. A 5-point increase in BMI was significantly associated with tumor size (OR 1.21; 95% CI 1.1-1.5; p = 0.01) and greater extranodal extension in cervical metastases (OR 1.11; 95% CI 1.06-1.21; p = 0.03). The analysis of prognostic variables showed no association between increase in BMI and risk of recurrence (HR 1.11; 95% CI 0.91-1.22). In conclusion, we found that BMI relates directly with tumor size and extranodal extension, but not with recurrence.

Asociación entre índice de masa corporal y agresividad del carcinoma papilar de tiroides / Association between body mass index and aggressiveness of papillary thyroid carcinoma

El objetivo del estudio fue evaluar la asociación del índice de masa corporal (IMC) con las características clínico-patológicas y la recurrencia del carcinoma papilar de tiroides. La cohorte consistió en 208 pacientes con carcinoma papilar de tiroides diagnosticado en 2003-2014, en Buenos Aires, Argentina. El seguimiento fue semestral los primeros 2 años y luego anual. Los pacientes fueron agrupados según el IMC de la siguiente manera: IMC < 18.5 kg/m² (bajo peso); IMC ≥ 18.5 y < 25 kg/m² (peso normal); IMC ≥ 25 y < 30 kg/m² (sobrepeso); IMC ≥ 30 kg/m² (obesidad). Dos patólogos experimentados revisaron todas las muestras para determinar las características del tumor y la extensión de la enfermedad. La recurrencia tumoral fue evaluada mediante diagnóstico por imágenes y confirmación histológica. Se utilizó un análisis de regresión para identificar la asociación del IMC con las características clínico-patológicas del tumor y con la recurrencia. El aumento de 5 puntos en el IMC se asoció significativamente con mayor tamaño tumoral (OR 1.21; IC 95% 1.1-1.5; p = 0.01) y con mayor extensión extranodal de las metástasis cervicales (OR 1.11; IC95% 1.06-1.21; p = 0.03). No se observó asociación entre el aumento del IMC y el riesgo de recurrencia (HR 1.11; IC95% 0.91-1.22). En conclusión, se demostró una asociación directa del IMC con el tamaño tumoral y la extensión extranodal pero no con la recurrencia del tumor.

The aim of the study was to evaluate the association of the body mass index (BMI) with the clinical-pathological characteristics and the recurrence of papillary thyroid carcinoma. The cohort consisted of 208 patients with papillary thyroid carcinoma diagnosed in 2003-2014, in Buenos Aires, Argentina. The patients were grouped according to the BMI as follows: BMI <18.5 kg/m² (low weight); BMI ≥ 18.5 and < 25 kg/m² (normal weight); BMI ≥ 25 and < 30 kg/m² (overweight); BMI ≥ 30 kg/m² (obesity). Two experienced pathologists reviewed and cross-checked all pathology specimens to confirm diagnosis, tumor characteristics and extent of the disease. All patients were followed every 6 months for 2 years, and annually thereafter. Recurrences were searched by using diagnostic imaging and histological confirmation when necessary. Regression analysis was applied to define associations of BMI with clinical, pathological, and prognosis features of the disease. A 5-point increase in BMI was significantly associated with tumor size (OR 1.21; 95% CI 1.1-1.5; p = 0.01) and greater extranodal extension in cervical metastases (OR 1.11; 95% CI 1.06-1.21; p = 0.03). The analysis of prognostic variables showed no association between increase in BMI and risk of recurrence (HR 1.11; 95% CI 0.91-1.22). In conclusion, we found that BMI relates directly with tumor size and extranodal extension, but not with recurrence.

Estruma ovárico asociado con enfermedad de graves / Struma ovarii associated with Graves' disease

El hipertiroidismo se define como la producción excesiva de hormonas tiroideas a partir de tejido tiroideo maduro eutópico o ectópico. La prevalencia general de hipertiroidismo es 1.2%, y la causa más frecuente es la enfermedad de Graves. El estruma ovárico representa el 1% de todos los tumores ováricos y es una causa infrecuente de hipertiroidismo ectópico. Su comportamiento es benigno en más del 90% de los casos; usualmente asintomáticos, sólo el 8% se presentan con tirotoxicosis, y es infrecuente su asociación con enfermedad de Graves. Se comunica el caso de una paciente con esta infrecuente asociación.

Hyperthyroidism is defined as an excessive production of thyroid hormones by eutopic or ectopic mature thyroid tissue. The overall prevalence of hyperthyroidism is 1.2% and the most common cause is Graves' disease. Struma ovarii represents 1% of all ovarian tumors and is an uncommon cause of ectopic hyperthyroidism. It is benign in >90% of the cases; usually asymptomatic, and only 8% are presented with thyrotoxicosis, being rare its association with Graves' disease. We report the case of a patient with this association.

[Struma ovarii associated with Graves' disease]. / Estruma ovárico asociado con enfermedad de Graves.

Hyperthyroidism is defined as an excessive production of thyroid hormones by eutopic or ectopic mature thyroid tissue. The overall prevalence of hyperthyroidism is 1.2% and the most common cause is Graves' disease. Struma ovarii represents 1% of all ovarian tumors and is an uncommon cause of ectopic hyperthyroidism. It is benign in >90% of the cases; usually asymptomatic, and only 8% are presented with thyrotoxicosis, being rare its association with Graves' disease. We report the case of a patient with this association.

Carcinoma papilar en quiste tirogloso. Propuesta de algoritmo diagnóstico y terapéutico / Papillary carcinoma in a thyroglossal duct cyst. Proposal of an algorithm for diagnosis and treatment / Carcinoma papilar em cisto tirogloso: proposta de algoritmo diagnóstico e terapêutico

Antecedentes: el carcinoma diferenciado de tiroides en quiste tirogloso (CaQT) es una entidad rara. La incidencia de CaQT es de 1 a 2%. Usualmente su forma de presentación clínica es indistinguible de una lesión benigna y el diagnóstico definitivo es postquirúrgico. No hay en la actualidad un consenso sobre la indicación de tiroidectomía total, radioablación con iodo y/o terapia supresiva con levotiroxina luego de ser extirpado quirúrgicamente...

Introduction: the development of well -differentiated thyroid carcinoma in thyroglossal duct cysts (TGDCa) is uncommon. The incidence of TGDCa lies within 1 to 2%. Usually the clinical appearance is indistinguishable from a benign thyroglossal duct cyst. The definitive diagnosis is post-operative. After the surgery of choice, the other alternative treatments such as thyroidectomy, radioiodine and L-T4 therapy are controversial...

Antecedentes: o carcinoma diferenciado de tireoide em cisto tirogloso (CaQT) é uma entidade rara. A incidência de CaQT é de 1 a 2 por cento. Em geral, a sua forma de apresentação clínica é indistinguível de uma lesão benigna e o diagnóstico definitivo é pós-cirúrgico. Não existe atualmente um consenso sobre a indicação de tiroidectomia total, radioablação com iodo e/ou terapia supressiva com levotiroxina após ser extirpado cirurgicamente...

Estimación de la Incidencia de Cáncer de Tiroides en Capital Federal y el Gran Buenos Aires (período 2003-2011) / Incidences Rates of Thyroid Cancer in Buenos Aires (2003-2011)

La incidencia del cáncer de tiroides ha aumentado significativamente en las últimas décadas en el resto del mundo. En Argentina no existe un registro nacional de cáncer por lo que la incidencia del mismo no puede establecerse. Por lo tanto, nuestro objetivo fue estimar la incidencia de cáncer de tiroides en la población de la Ciudad Autánoma de Buenos aires y Gran Buenos Aires así como la relación por género y la histología en el período de 2003 hasta 2011. Asumiendo que la población de afiliados a la Obra Social de la Policía Federal Argentina es representativa de los habitantes de Buenos Aires y el conurbano calculamos que la incidencia es de 6,51 casos/100.000 habitantes/año, con un incremento en 25 años mayor al doble, con predominio del carcinoma papilar frente al folicular.

Thyroid cancer incidence has significantly risen worldwide in the last decades. In Argentina, there is no national cancer registry; therefore its incidence can not be established. The objective of this study was to estimate the incidence of thyroid cancer in the population of Buenos Aires City and suburbs, and the relationship between gender and histology over the period 2003-2011. Assuming that the population affiliated to the Social Security of the Argentine Federal Police is representative of the inhabitants of Buenos Aires City and suburbs, we estimate an incidence of 6.51 cases/100,000 population/year, with an increasing incidence of almost double from 1981-1986 to 2003-2011. An increase in papillary thyroid cancer was mainly responsible for this rising trend. Incidence rates were higher for females (11.76/100,000 women) compared to those for males (2.65/100,000 men). Among men and women of all ages, the highest rate of incidence was for tumor size < 1 cm.

Estimación de la Incidencia de Cáncer de Tiroides en Capital Federal y el Gran Buenos Aires (período 2003-2011) / Incidences Rates of Thyroid Cancer in Buenos Aires (2003-2011)

La incidencia del cáncer de tiroides ha aumentado significativamente en las últimas décadas en el resto del mundo. En Argentina no existe un registro nacional de cáncer por lo que la incidencia del mismo no puede establecerse. Por lo tanto, nuestro objetivo fue estimar la incidencia de cáncer de tiroides en la población de la Ciudad Autánoma de Buenos aires y Gran Buenos Aires así como la relación por género y la histología en el período de 2003 hasta 2011. Asumiendo que la población de afiliados a la Obra Social de la Policía Federal Argentina es representativa de los habitantes de Buenos Aires y el conurbano calculamos que la incidencia es de 6,51 casos/100.000 habitantes/año, con un incremento en 25 años mayor al doble, con predominio del carcinoma papilar frente al folicular.(AU)

Thyroid cancer incidence has significantly risen worldwide in the last decades. In Argentina, there is no national cancer registry; therefore its incidence can not be established. The objective of this study was to estimate the incidence of thyroid cancer in the population of Buenos Aires City and suburbs, and the relationship between gender and histology over the period 2003-2011. Assuming that the population affiliated to the Social Security of the Argentine Federal Police is representative of the inhabitants of Buenos Aires City and suburbs, we estimate an incidence of 6.51 cases/100,000 population/year, with an increasing incidence of almost double from 1981-1986 to 2003-2011. An increase in papillary thyroid cancer was mainly responsible for this rising trend. Incidence rates were higher for females (11.76/100,000 women) compared to those for males (2.65/100,000 men). Among men and women of all ages, the highest rate of incidence was for tumor size < 1 cm.(AU)

Radioiodine thyroid remnant ablation after recombinant human thyrotropin or thyroid hormone withdrawal in patients with high-risk differentiated thyroid cancer.

To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 µg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. "No evidence of disease" (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. "Persistent disease" was failure to achieve NED, "recurrence," loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

Reliability of stereoscopic nonmydriatic retinography for assessment of diabetic macular edema when performed by endocrinologists.

BACKGROUND: Diabetic macular edema (DME) is the main cause of moderate vision loss in type 2 diabetes. Diagnosis is achieved by dilated fundus examination or by measuring retinal thickness. However, it can be identified in nonmydriatic retinography (NMR) with hard exudates as a surrogate marker or macular thickness under stereoscopic vision. To date, few studies have focused on interobserver reliability for DME with this technique. METHODS: Fity-three type 2 diabetes patients with known diabetic retinopathy were studied. We obtained 182 pairs of stereoscopic retinographs with a nonmydriatic camera. Photographic options were 30 degrees or 45 degrees macula-centered retinal field and spontaneous or pharmacological dilation using tropicamide. An endocrinologist with a minimum of training and another with no specific training in this kind of examination diagnosed the images. DME was assumed if retinal thickness was identified within one disc diameter around the fovea. RESULTS: The kappa index agreement between both endocrinologists for all the data was 0.16 (P = 0.02). Depending on the photographic options, all the kappa indices were below 0.25, except for the 45 degrees retinal field under spontaneous mydriasis (0.58) where the number of samples analyzed was reduced to 22. CONCLUSIONS: In our study, endocrinologists with a low level of training did not reach a suitable level of agreement regarding the reliability of stereoscopic NMR as a technique for diagnosing DME. We feel that, as NMR can be performed by various different health providers, it would be advisable to establish generally agreed upon criteria for training staff in this technique.

Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.

In order to search for sequence variants conferring risk of thyroid cancer we conducted a genome-wide association study in 192 and 37,196 Icelandic cases and controls, respectively, followed by a replication study in individuals of European descent. Here we show that two common variants, located on 9q22.33 and 14q13.3, are associated with the disease. Overall, the strongest association signals were observed for rs965513 on 9q22.33 (OR = 1.75; P = 1.7 x 10(-27)) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 x 10(-9)). The gene nearest to the 9q22.33 locus is FOXE1 (TTF2) and NKX2-1 (TTF1) is among the genes located at the 14q13.3 locus. Both variants contribute to an increased risk of both papillary and follicular thyroid cancer. Approximately 3.7% of individuals are homozygous for both variants, and their estimated risk of thyroid cancer is 5.7-fold greater than that of noncarriers. In a study on a large sample set from the general population, both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH), and the 9q22.33 allele is associated with low concentration of thyroxin (T(4)) and high concentration of triiodothyronine (T(3)).

Coste de la diabetes mellitus en España / Cost of diabetes mellitus in Spain

No disponible

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults.

OBJECTIVE: To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test. PATIENTS AND DESIGN: Seventy-three patients with adult GH deficiency and organic hypothalamic-pituitary disease were recruited, along with 46 controls. The patients were divided into five groups according to the number of associated hormone deficiencies present. MEASUREMENTS: Hypopituitary subjects underwent assessment of GH secretory status by the ITT, the glucagon test and measurement of serum IGF-I concentration. Controls underwent the glucagon test. After the ITT, glucose and GH levels were measured at baseline, 30, 60 and 90 minutes, and after glucagon at baseline, 90, 120, 150, 180, 210 and 240 minutes. RESULTS: The highest GH value after the ITT in the patient group was 3 microg/l (0.76 +/- 0.82 microg/l), and after the glucagon test the highest GH peak value was 2.9 microg/l (0.64 +/- 0.79 microg/l). A correlation was found between the GH peak and the progressive number of hormone deficiencies. After the glucagon test, the GH peak obtained in the controls at 180 minutes was 9.8 +/- 4.6 microg/l and, on an individual basis, none of the 46 controls failed to achieve peak GH levels higher than 3 microg/l. In the controls, a negative correlation was observed between the GH response to glucagon and age (r = -0.389, P = 0.0075) and body mass index (r = -0.329, P = 0.0254). The accuracy of the glucagon test for differentiating patients from controls, estimated by receiver operating characteristics (ROC) curve methodology, showed that the cut-off of 3 microg/l for the GH peak provides 100% sensitivity and 100% specificity and is a reliable decision threshold. CONCLUSIONS: The glucagon GH test is reliable and provides a clear separation between GH-deficient and normal adults. A single glucagon test with a cut-off of 3 microg/l for the GH peak is diagnostic of GH deficiency in adults and could be considered and studied as an alternative to the ITT.