Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

PURPOSE: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. METHODS: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. RESULTS: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. CONCLUSION: In a developing country, TL is an adequate option for appropriately selected DTC patients.

The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods.

PURPOSE: The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods. METHODS: This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates. RESULTS: All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22-710 µg/L), and 58 µg/L (range 23-148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range < 0.5-18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity. CONCLUSIONS: The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.

Chronic urticaria and thyroid pathology.

Urticaria is defined as the sudden appearance of erythematous, itchy wheals of variable size, with or without angioedema (AE) (swelling of the deeper layers of the skin). Its classification depends on time course of symptoms and the presence of eliciting factors. When it lasts less than 6 weeks it is classified as acute urticaria (AU), and if the symptoms persist for more than 6 weeks, it is classified as chronic urticaria (CU). Current International Guidelines also classify CU as chronic spontaneous urticaria (CSU) and inducible urticarial, according to the absence or presence of environmental triggering factors. CSU is defined as urticaria and/or angioedema in which there is no evidence of a specific eliciting factor. CSU is associated with autoimmunity in 30-45% of the cases, sharing some immunological mechanisms with other autoimmune diseases, and is associated with autoimmune thyroid disease (ATD) in about 4.3%-57.4% patients. Several studies suggest that adequate therapy with anti-thyroid drugs or levothyroxine in early stages of ATD and CSU, may help to remit the latter; but there is still a lack of double-blind, placebo-controlled studies that support this hypothesis in patients without abnormal thyroid hormone levels. The objective of this review is to describe the pathophysiology of chronic spontaneous urticaria and its association with autoimmune thyroid disease.

Prognostic value of change in anti-thyroglobulin antibodies after thyroidectomy in patients with papillary thyroid carcinoma.

PURPOSE: Anti-thyroglobulin antibodies (TgAb) can be used as a surrogate tumor marker in the follow-up of papillary thyroid carcinoma (PTC). We try to determine if the change in TgAb levels in the first post-operative year is a good predictor of persistence/recurrence risk in TgAb-positive PTC patients. METHODS/PATIENTS: 105 patients with PTC who underwent thyroidectomy between 1988 and 2014 were enrolled. We calculated the percentage of change in TgAb levels with the first measurement at 1-2 months after surgery and the second one at 12-14 months. RESULTS: TgAb negativization was observed in 29 patients (27.6%), a decrease of more than 50% was observed in 57 patients (54.3%), less than 50% in 12 patients (11.4%) and in 7 patients (6.7%) the TgAb level had increased. The percentage of persistence/recurrence was 0, 8.8, 16.7 and 71.4% in each group, respectively (p < 0.001). In the multivariate analysis, only the percentage of change in TgAb showed a significant association with the risk of persistence/recurrence, regardless of other factors such as age, size and TNM stages. CONCLUSIONS: Changes in TgAb levels in the first year after surgery can predict the risk of persistence/recurrence of TgAb-positive PTC patients. Patients who achieved negativization of TgAb presented an excellent prognosis.

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.

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.

Limitaciones técnicas de los métodos para cuantificar tiroglobulina sérica y su repercusión clínica: [revisión] / Technical limitations of methods to quantify the serum thyroglobulin and its clinical repercussion: [review]

La determinación de tiroglobulina sérica se emplea, sobre todo, como marcador tumoral en el seguimiento posoperatorio de pacientes con cáncer diferenciado del tiroides. Lamentablemente, los métodos de tiroglobulina sérica presentan gran variabilidad en sus cualidades analíticas y padecen problemas técnicos que repercuten sobre la utilidad clínica de esta prueba. Para cuantificar tiroglobulina sérica se emplean 2 tecnologías diferentes: los iniciales radioinmunoensayos competitivos y los mßs recientes métodos inmunométricos no competitivos. Estos últimos son más propensos a sufrir las interferencias provocadas por la presencia de autoanticuerpos tiroglobulina y anticuerpos heterofílicos, a pesar de brindar los beneficios técnicos relativos al uso de reactivos no isotópicos, menor volumen de muestra, tiempos de incubación más cortos, así como mejor sensibilidad y facilidad de automatización. Resulta esencial que los clínicos conozcan y comprendan las limitaciones técnicas inherentes a la determinación de tiroglobulina sérica y su repercusión sobre la utilidad clínica de esta, con la finalidad de hacer un uso efectivo y eficiente de esta prueba en el seguimiento posoperatorio de pacientes con cáncer diferenciado del tiroides(AU)

The serum thyroglobulin assessment is used mainly as tumor marker during the postoperative follow-up of patients presenting with thyroid differentiated cancer. Progressively, the serum thyroglobulin methods have much variability in its analytical qualities and also have technical problems affecting on the technical usefulness of this test. To quantify the serum thyroglobulin we used two different technologies: the initial competitive radioimmunoassays and the most recent non competitive inmunometrical methods. These latter are more prone to have interferences provoked by presence of thyroglobulin antibodies and heterophilic antibodies despite to offer technical beneficial relative to use of non-isotopic reagents, a lower sample volume, shorter incubation times, as well as a better sensitivity and feasibility of automation. It is essential that clinicians know and understand the technical limitations inherent of serum thyroglobulin assessment and its repercussion on its clinical usefulness to an effective and efficient use of this test during the postoperative follow-up of patients presenting thyroid differential cancer(AU)

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.