Thyroglobulin antibodies: Trend over time and clinical impact in differentiated thyroid carcinoma with and without radioiodine ablation.

INTRODUCTION: Thyroglobulin antibodies (TgAb) trend may be considered a surrogate marker for thyroglobulin in differentiated thyroid carcinoma. The aim of this study is to analyse, in cases with positive TgAb, trend over time and its relationship with response to treatment. MATERIAL AND METHODS: Retrospective and descriptive study of 100 patients with differentiated thyroid carcinoma and positive TgAb (measured by electrochemoluminiscense) after thyroidectomy. Assessment of response to initial treatment was performed 6-24 months after surgery. Status at last follow-up was evaluated. RESULTS: After the first year nearly half of the patients showed a reduction in TgAb levels ≥50%, in 91% of these patients, status at last follow up was excellent response (65%) or indeterminate response due to decreasing TgAb levels (26%). At first assessment, indeterminate responses were found in 49% of cases, without significant differences among initial risk of recurrence category or whether radioiodine ablation was performed. At last evaluation (median 53.5 months), 15% of ablated low-risk patients had an indeterminate response (due to declining TgAb), vs 62% in the non-ablated low-risk group (p 0.03). Median time to negativization for post-surgical TgAb levels<100UI/ml was 11 months [3-94] vs 31 months [8-119] for patients with TgAb≥100UI/ml (p 0.0003). CONCLUSION: A reduction of ≥50% in TgAb levels during the first year correlated with favourable outcomes. Non-ablated patients and patients with higher levels of post-surgical TgAb may need a longer time to achieve negative conversion.

Métodos de tiroglobulina de primera y segunda generación: su utilidad en pacientes con cáncer diferenciado de tiroides / First and second generation thyroglobulin measurement methods: Their usefulness in patients with thyroid cancer

El cáncer diferenciado de tiroides (CDT) es el cáncer endocrinológico más frecuente y en las últimas décadas su incidencia ha aumentado. El seguimiento de la enfermedad se efectúa con la medición de tiroglobulina (Tg) sérica, ecografía cervical y barrido corporal total diagnóstico. Los métodos de Tg han evolucionado a través del tiempo. Actualmente, los ensayos inmunométricos de Tg se clasifican en 1.ª y 2.ª generación (1.ª G y 2.ª G). Comprobamos que los ensayos de 2.ª G alcanzan una precisión adecuada para medir valores del orden de 0,1 ng/ml y los de 1.ª G de 1 ng/ml. La bibliografía señala que en el caso de los pacientes de bajo riesgo, una Tg bajo levotiroxina indetectable por un método de 2.ª G puede evitar la realización de Tg estimulada, sea por la suspensión de la terapia hormonal como por el empleo de la TSH recombinante humana, debido a su mayor sensibilidad. Sin embargo, por su menor especificidad, un valor detectable no asegura la presencia de enfermedad, y debería confirmarse. Para optimizar la utilidad clínica de dicha medición se podrían emplear valores de cortes de acuerdo con la población y el método en lugar de la sensibilidad funcional o límite de cuantificación del mismo. Se señalan también otros aspectos críticos en la medición de Tg como son la discordancia entre distintas metodologías y las interferencias en su medición, principalmente por anticuerpos antitiroglobulina. En presencia de interferencias pierden utilidad los ensayos de Tg de 1.ª y 2.ª G. El seguimiento de los pacientes con Tg interferida tiene limitaciones todavía no resueltas. Es importante consensuar entre médicos y bioquímicos las dificultades técnicas y los criterios de interpretación de los valores de Tg en el seguimiento de los pacientes con CDT.

Differentiated thyroid cancer (DTC) is the most common endocrine cancer (tumour) and its incidence has risen in the past decades. Its follow-up includes measuring serum thyroglobulin (Tg), performing neck ultrasound and a diagnostic whole-body scan. Tg assays have evolved with time. At present immunoassays for Tg are classified as 1 st and 2 nd generation assays (1 st G and 2 nd G). 2 nd G assays show an adequate (good) precision at levels close to 0.1 ng/ml and 1 st G assays at levels close to 1 ng/ml. The literature shows that for low risk patients on levothyroxine treatment, who undetectable levels by 2 aG assays can avoid the stimulation test performed by thyroid hormone withdrawal or after recombinant human TSH, due to better sensitivity. However, due to lower specificity, detectable levels do not confirm the presence of disease (tumour), and should be confirmed. To optimise the clinical usefulness of the test, cut-off values specific for population and method should be used, instead of functional sensitivity or quantification limit. Critical issues for measuring Tg are discussed, such as non-harmonisation of methods, and interferences, mainly by antithyroglobulin antibodies (ATg). 1 st and 2 nd G assays are less useful in presence of ATg, and follow up of such patients is limited. Consensus between physicians and the laboratory on technical issues and interpretation criteria of Tg values is of outmost importance in the follow-up of DTC patients.

Determination of thyrotropin reference values in an adult Mexican population.

BACKGROUND AND OBJECTIVE: The upper limit of TSH reference level is controversial. The purpose of our study was to determine TSH reference values in a Mexican population in accordance with the National Academy of Clinical Biochemistry (NACB) criteria and in correlation with thyroid ultrasound (US) examination. PATIENTS AND METHODS: The study was conducted in volunteers with no known thyroid disease. We recruited 482 subjects, most of them medical or administrative staff from our hospital. They answered a questionnaire on demographic data, family history, co-morbidities, and drug use. Their thyroid hormone levels and thyroid antibodies were determined, and a complete physical examination and thyroid US were performed. The population used to establish the TSH reference intervals was selected according to the NACB criteria and their normal thyroid structural and echogenic characteristics in US examination. RESULTS: Among 482 subjects (209 males) with a median age of 26 years, prevalence rates of TPOAb and TgAb were 9.3% and 10.3% respectively. Mean TSH level in the overall population was 1.90±1.94, with a 97.5th percentile of 6.76 mIU/L. The reference population was limited to 282 subjects (41.5% were excluded) with a mean TSH of 1.86±1.63 and a 97.5th percentile of 4.88 mIU/L. No sex difference was found (p=0.287). Median urinary iodine level in the reference population was 267 µg/L IQR (161.3-482.5). CONCLUSIONS: The TSH reference interval in the reference population was 0.71 (CI 0.65-0.77) to 4.88 mIU/L (CI 4.5-5.3); these limits may be influenced by iodine nutritional status in this population.

Anticuerpos antitiroglobulina en el monitoreo del carcinoma diferenciado de tiroides en pacientes del Instituto Nacional de Enfermedades Neoplásicas. Enero - junio 2015 / Antithyroglobulin antibodies in the monitoring of differentiated thyroid cancer in patients of the National Institute of Neoplastic Diseases. January-June 2015

Introducción: el cáncer diferenciado de tiroides es la neoplasia endocrina más común, en esta neoplasia se consideran a 2 subtipos el cáncer papilar y el cáncer folicular, ambas neoplasias son de buen pronóstico, el tratamiento es la tiroidectomía y ablación con 131I, el monitoreo se realiza mediante el dosaje de tiroglobulina (Tg), que tiene como principal interferente la presencia de anticuerpos anti-tiroglobulina (Ac-Tg) que invalidan su medición. Objetivos: Detectar la presencia de Ac-Tg durante el monitoreo de pacientes del INEN con cáncer diferenciado de tiroides. Diseño: Estudio descriptivo transversal retrospectivo. Institución: Instituto Nacional de Enfermedades Neoplásicas Lima, Perú. Material: registros de las historias clínicas con monitoreo, de enero-junio 2015. Principales medidas de resultados: Presencia de Ac-Tg. Resultados: del total de 196 registros, 190 correspondieron carcinoma papilar (96,9 por ciento) y un total de 6 correspondieron al carcinoma folicular (3,1 por ciento) con una relación hombre mujer 1:6, se reportaron 35 pacientes (17,9 por ciento) con anticuerpos positivos (>115 UI/mL). Conclusiones: Con los resultados se demuestra que existe una similitud en cuanto a los datos epidemiológicos reportados; en comparación con los datos reportados en la literatura internacional, también es sugerente continuar con los estudios de los Ac-Tg como posible marcador tumoral.

Introduction: differentiated thyroid cancer is the most common endocrine malignancy, consider this neoplasia 2 subtypes papillary and follicular cancer, both neoplasms are good prognosis, treatment is thyroidectomy and 131I ablation, monitoring is performed by the dosage of thyroglobulin, whose main interfering the presence of thyroglobulin antibodies that invalidate measurement. Objectives: To detect the presence of thyroglobulin antibodies for monitoring INEN patients with differentiated thyroid cancer. Design: Retrospective cross-sectional study. Institution: National Institute of Neoplastic Diseases Lima, Peru. Material: records of medical records with monitoring, from January to June 2015. Main outcome measures: Presence of thyroglobulin antibodies. Results: total of 196 records, 190 were for papillary (96.9 per cent) carcinoma and a total of 6 corresponded to follicular carcinoma (3.1 per cent) with a male female ratio 1:6, 35 patients were reported (17.9 per cent) antibody-positive (>115 UI/mL). Conclusions: The results demonstrate that there is a similarity in terms of the epidemiological data reported; compared with data reported in the international literature, it is also suggestive continue with studies of tumor marker antithyroglobulin antibody as possible.

Interferencia de la tiroglobulina en la determinación de anticuerpos antitiroglobulina en el líquido de lavado de aguja de punción ganglionar / Thyroglobulin Interference in the Determination of Thiroglobulin Antibody in Wash-Out Fluid from Fine Needle Aspiration Biopsy of Lymph Node

La interferencia producida por los anticuerpos antitiroglobulina (aTg) en la determinación de Tiroglobulina (Tg) ha sido bien estudiada, sin embargo la interferencia que puede producir esta última sobre la determinación de los anticuerpos no está clara. Objetivo: Investigar la interferencia que la Tg puede producir sobre la determinación de los aTg en el líquido de lavado de aguja de punción ganglionar. Material y Métodos: Se estudiaron retrospectivamente las muestras provenientes de la punción de adenopatías cervicales sospechosas de 19 pacientes tiroidectomizados por Cáncer Diferenciado de Tiroides (CDT). La punción se realizó con aguja 22 G bajo guía ecográfica y luego de la preparación del extendido para el estudio citológico se procedió al lavado de la aguja con 500 µl de solución fisiológica para determinar Tg y aTg. La medición de Tg se hizo por ensayo quimioluminiscente. Los aTg se midieron utilizando dos ensayos uno no competitivo quimioluminiscente (Q) y otro competitivo electroquimioluminiscente (Eq). Se consideraron aTg negativos valores < 20 UI/ml. Se realizaron diluciones de la muestra de uno de los pacientes para el estudio de interferencia. Resultados: En todas las muestras las concentraciones de Tg mostraron valores muy elevados (rango: 15.185 -1.141.275 ng/ml). Los resultados de los aTg fueron negativos en el 100 % de las muestras cuando se midieron por el método no competitivo (Q) y francamente positivos en un rango de 106 a > 4.000 UI/ml cuando se midieron por el método competitivo (Eq), siendo estos valores proporcionales a la concentración de Tg en la muestra. Se observó una falta de linealidad cuando se realizó ensayo de dilución a muestras de concentración elevada de aTg medidas por Eq. Los aTg por Eq se negativizaron a concentraciones de Tg inferiores a 3.000 ng/ml. Los aTg medidos por Q arrojaron valores negativos en todas las diluciones. Todos estos pacientes presentaban aTg negativos en suero por Q y Eq. Conclusión: Las altas concentraciones de Tg interfieren en la medición de aTg cuando los mismos son medidos por un método competitivo. La interferencia es proporcional a las concentraciones de Tg presentes en la muestra. Se recomienda que en los líquidos de lavado de aguja de punción ganglionar los aTg sean medidos por un método no competitivo ya que no parece estar interferido por las altas concentraciones de Tg característica de los ganglios metastásicos. La detección de esta interferencia no modificó el diagnóstico ni la conducta clínica en ningún caso, sin embargo es importante conocerla con el fin de no concluir erróneamente sobre la positividad de los anticuerpos en los ganglios cuando estos son medidos por un ensayo competitivo. Rev Argent Endocrinol Metab 51:1-7, 2014 Los autores declaran no poseer conflictos de interés.

Thyroglobulin antibodies (TgAb) interference with thyroglobulin (Tg) measurements has been well studied; however, Tg interference with TgAb is unclear. Objective: To investigate how TgAb may interfere with Tg measurement in the washout fluid from lymph node fine-needle aspiration biopsy. Materials and Methods: We retrospectively studied the samples obtained by aspiration of suspicious cervical lymph nodes from 19 patients post thyroidectomy for Differentiated Thyroid Cancer (DTC). The puncture was performed with a 22 G needle under ultrasound guidance. After preparation of cytological specimens, the needle was washed with 500 ul of saline solution to determine Tg and TgAb. Tg was measured by chemilumi­nescent assay and TgAb was measured using two assays: a non-competitive chemiluminescent assay (Q) and a competitive electrochemiluminescence assay (Eq). Values of TgAb below 20 UI/ml were considered negative. Appropriate dilutions of the sample of one of the patients were performed in order to study interference. Results: In all samples tested, concentrations showed very high Tg values (range: 15.185 - 1.141.275 ng/ml). TgAb results were negative in all the samples measured by the non-competitive method. Results were clearly positive in a range of 106 to > 4.000 IU/ml when the competitive assay (Eq) was used, being proportional to Tg concentrations in the samples. A lack of linearity was observed when a dilution assay was performed in samples of high TgAb concentrations measured by Eq. When Tg concentrations were below 3.000 ng / ml, TgAb became negative when measured by Eq. TgAbs measured by Q were negative in all dilutions. TgAbs in serum were negative in all patients by the two methodologies (Q and Eq). Conclusion: High levels of Tg interfere with TgAb measurement when a competitive method is used. The interference is proportional to the concentrations of Tg. It is recommended that in the wash-out fluid from fine needle aspiration, TgAbs should be measured by a non-competitive method since there appears to be no interference from the high concentrations of Tg characteristic of metastatic nodes. The detection of this interference did not change the diagnosis or clinical management in any case; however, it is important to be aware of such interference so as not to make erroneous conclusions about the positivity of TgAbs in lymph nodes when a competitive method is used. Rev Argent Endocrinol Metab 51:1-7, 2014 No financial conflicts of interest exist.

Prevalencia de hipotiroidismo y anticuerpos antitiroglobulina en pacientes mexicanos con esclerosis sistémica / Systemic sclerosis and hypothyroidism

Objetivo: Investigar la prevalencia de hipotiroidismo y anticuerpos antitiroglobulina (AATg) en pacientes mexicanos con esclerosis sistémica (ES). Material y métodos: Se estudió la función tiroidea en pacientes con ES y controles. Se les determinaron los niveles séricos de triyodotironina, tiroxina, hormona estimulante de la tiroides (TSH) y AATg. Resultados: Fueron 110 pacientes (106 mujeres y 4 hombres), edad promedio de 48.1 ± 28.5 años, versus 80 controles (76 mujeres y 4 hombres), edad promedio 47.5 ± 28.8 años. El hipotiroidismo clínico se encontró en 19% de pacientes con ES y en 1.3% de los controles (p < 0.01). Las medianas respectivamente de triyodotironina en ES y controles fueron: 82 versus 160 ng/dl, p < 0.01; tiroxina 5.4 versus 7 ng/dl, p < 0.01; TSH 8.2 versus 1.1 μUI/ml, p < 0.001. El hipotiroidismo subclínico se observó en 35% de los pacientes con ES y en 0% de los controles. Los valores de TSH en ES y en controles fueron 7.2 versus 1.2 μUI/ml, p < 0.01; triyodotironina 116 versus 160 ng/dl, p ns; tiroxina 7 versus 7 ng/dl, p ns, respectivamente. Los AATg estuvieron presentes en 54% de los pacientes y 2.5% en el grupo control, p < 0.01. Conclusiones: Los pacientes con ES presentan elevada prevalencia de hipotiroidismo, especialmente subclínico, por lo que debe investigarse la función tiroidea para iniciar tratamiento oportuno.

OBJECTIVE: Assess the prevalence of hypothyroidism and anti-thyroglobuline antibodies (AbATg) among Mexican patients with systemic sclerosis (SSc). MATERIAL AND METHODS: Thyroid function was studied in SSs patients and controls. Triiodothyronine, thyroxine, thyroid stimulant hormone (TSH) and AbATg were measured. RESULTS: 110 SSc patients (106 women and 4 men), mean age 48.1 +/- 28.5 yrs versus 80 healthy controls (76 women and 4 men) with mean age 47.5 +/- 28.8 yrs were included. Hypothyroidism was diagnosed in 19% patients compared with 1.3% in the control group. The following results were found; triyodotironina: 82 ng/dl versus 160 ng/dl, p < 0.000; tiroxina: 5.4 ng/dl versus 7ng/dl, p < 0.01; TSH: 8.2 uUl/ mL versus 1.1 +/- 2 uUl/mL, p < 0.000. Subclinical hypothyroidism was observed in 35% patients versus 0% controls, TSH: 7.2 uUl/ml versus 1.2 +/- 1.4 uUl/ml, p < 0. 000; triyodotironina: 116 ng/dl compared with 160 ng/dl, p = ns; tiroxina: 7.0 ng/dl vs. 7.0 ng/dl, p ns; AbATg were positive in patients 54% and 2.5%, p < 0.001 in the control group. CONCLUSIONS: Our study reports a high prevalence of hypothyroidism among SSc Mexican patients, especially of the subclinical type. We need to consider hypothyroidism as a clinical entity often found among SSc patients, and start hormone replacment treatment accordingly.