Active Surveillance of Small Metastatic Lymph Nodes as an Alternative to Surgery in Selected Patients with Low-Risk Papillary Thyroid Cancer: A Retrospective Cohort Study.

Background: It has been suggested that small metastatic lymph nodes (LNs) detected after initial surgery in patients with differentiated thyroid cancer (DTC) can be managed with active surveillance (AS). However, there is still concern regarding the clinical outcomes of these patients. The main aims of our study were as follows: (1) to assess the frequency of growth and the need of additional treatment in a group of patients with LN recurrences selected for AS, and (2) to determine predictive factors of LN progression. Methods: We retrospectively reviewed 856 clinical records from our DTC patient's database (May 2010 to January 2022). Eighty patients had suspicious cervical LNs on consecutive ultrasound (US) after initial surgery, but we included 50 patients with cytological confirmation of metastatic disease and at least 12 months follow-up. Exclusion criteria were as follows: any LN ≥2 cm or multiple LNs ≥1.5 cm in size, proximity to vital structures, PET-positive disease (standard uptake value ≥5), aggressive histology, and distant metastasis. Patients were followed with thyroglobulin (Tg) and thyroglobulin antibodies measurements on suppressive therapy and neck US every 6-12 months. LN growth was defined as an increase of ≥3 mm in any of its diameters. Results: A total of 50 patients had a median age of 41 years (range, 18-75). Most patients were women (80%) and had classical papillary thyroid cancer (86%). The mean size of the LNs was 10.1 ± 4.4 mm. After a median follow-up of 29 months (range, 12-144), 12 patients (24%) had an increase in size of the metastatic LN, 7 (58%) of whom were surgically removed. None of these seven patients had a structural incomplete response at the end of follow-up. The only variable that predicted an increase in LN size was a rise in Tg levels ≥0.5 ng/mL (p = 0.016). Based on a multivariate analysis, patients with increase in Tg levels ≥0.5 ng/mL had a significantly higher chance of developing LN growth (odds ratio [OR] 16.2 [confidence interval, CI 1.5-120.2], p = 0.020). The median progression-free survival rate was 6.6 years [CI 5.6-9.5]. Conclusion: AS of small LNs could be a feasible alternative to immediate surgery in properly selected patients.

Análisis de tiroglobulina preablativa y cáncer diferenciado de tiroides preoperatorio / Analysis of pre-ablative and preoperative thyroglobulin in differentiated thyroid cancer

BACKGROUND: The measurement of plasma thyroglobulin (Tg) is widely used in the monitoring of differentiated thyroid cancer (CDT). In recent years, its value as a prognostic marker prior to ablation with radioiodine has increased, demonstrating its high negative predictive value. Recent studies indicate that a wide variety of factors could potentially influence pre-ablative Tg values, including residual tumor burden and stimulation modality. Aim: To relate the value of pre-ablative Tg with the amount of preoperative disease burden, lymph node metastases, treatment, and presence of residual disease. MATERIAL AND METHODS: Retrospective observational study of 70 patients with CDT treated between 2012 and 2018. The amount of disease burden was defined as the sum of largest diameter of individual tumors in each patient, and as the individually largest tumor per patient and number of metastatic lymph nodes. RESULTS: A smaller tumor size and absence of remnant tissue was associated with lower Tg values, although the association was not always significant. Furthermore, no significant difference was found between Tg levels measured within or more than 14 days after the surgical procedure. Thus, an early measurement of pTg after surgery would allow an initial therapeutic decision making. Conclusions: A statistical association between pre-ablative Tg levels and the amount of preoperative tumor tissue burden was found in some subgroups of patients.

[Analysis of pre-ablative and preoperative thyroglobulin in differentiated thyroid cancer]. / Análisis de tiroglobulina preablativa y cáncer diferenciado de tiroides preoperatorio.

BACKGROUND: The measurement of plasma thyroglobulin (Tg) is widely used in the monitoring of differentiated thyroid cancer (CDT). In recent years, its value as a prognostic marker prior to ablation with radioiodine has increased, demonstrating its high negative predictive value. Recent studies indicate that a wide variety of factors could potentially influence pre-ablative Tg values, including residual tumor burden and stimulation modality. AIM: To relate the value of pre-ablative Tg with the amount of preoperative disease burden, lymph node metastases, treatment, and presence of residual disease. MATERIAL AND METHODS: Retrospective observational study of 70 patients with CDT treated between 2012 and 2018. The amount of disease burden was defined as the sum of largest diameter of individual tumors in each patient, and as the individually largest tumor per patient and number of metastatic lymph nodes. RESULTS: A smaller tumor size and absence of remnant tissue was associated with lower Tg values, although the association was not always significant. Furthermore, no significant difference was found between Tg levels measured within or more than 14 days after the surgical procedure. Thus, an early measurement of pTg after surgery would allow an initial therapeutic decision making. CONCLUSIONS: A statistical association between pre-ablative Tg levels and the amount of preoperative tumor tissue burden was found in some subgroups of patients.

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.

Effects of sample storage and diluents in the reliability of thyroglobulin measurement in the washout of fine needle aspirates.

OBJECTIVE: To evaluate two variables affecting Thyroglobulin stability in the washout of fine needle aspiration biopsies of thyroid nodules and metastatic lymph nodes. MATERIALS AND METHODS: Thyroglobulin stability after storage at -20 °C up to 14 days was studied in washout performed with normal saline solution and further dilutions with normal saline solution from five metastatic thyroid nodes and six benign thyroid nodules. We also studied thyroglobulin stability in diluents compared with normal saline solution: 4% bovine serum albumin in normal saline solution and diluents free from thyroglobulin or Calcitonin or parathyroid hormone in paired and simultaneous thyroglobulin measurements of washout dilutions from 5/6 benign thyroid nodules and 2/5 metastatic lymph nodes. Thyroglobulin and Thyroglobulin antibodies were measured by a chemiluminescent assay. Positive samples with thyroglobulin antibodies in serum and/or washout were excluded. RESULTS: Thyroglobulin decreased with storage in washout or dilutions of washout performed in normal saline solution (p < 0.05). Lower thyroglobulin concentrations, close to the commonly used cut-off (1.1 ng/mL), showed the highest decrease as soon as after 1 day of storage. Diluents other than normal saline solution stabilized thyroglobulin in dilutions of all washout. CONCLUSIONS: The results suggest that the reliability of thyroglobulin measurements in washout of fine needle aspirates could be preserved by immediate measure of thyroglobulin or the use of stabilizing diluents to perform washout.

Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases.

OBJECTIVE: The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS: Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS: The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100%. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION: The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.

Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases / Determinação da tireoglobulina no lavado da agulha da punção aspirativa de linfonodos cervicais para detecção de metástases do câncer papilar de tireoide

OBJECTIVE: The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS: Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS: The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100 percent. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION: The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.

OBJETIVO: O objetivo deste estudo foi avaliar a acurácia da dosagem de tireoglobulina no lavado da agulha da punção aspirativa (PAAF-Tg) de linfonodos (LN) cervicais para detecção de metástases do câncer papilar de tireoide (CPT). SUJEITOS E MÉTODOS: Foram incluídos 43 pacientes (51,4 ± 14,6 anos) com diagnóstico de CPT e evidência de LN cervicais aumentados. Os LN suspeitos foram submetidos à punção aspiração com agulha fina guiada por ecografia para análise citológica e dosagem de tireoglobulina (PAAF-Tg). RESULTADOS: A mediana dos valores de PAAF-Tg nos LN metastáticos (n = 5) foi 3.419,0 ng/mL (11,1-25.538), enquanto nos LN não metastáticos (n= 38) a mediana foi de 3,7 ng/mL (0,8-7,4). Utilizando-se o nível de 10 ng/mL como ponto de corte, observaram-se sensibilidade e especificidade de 100 por cento. Os níveis de TSH sérico não interferiram na dosagem de PAAF-Tg (3,3 e 3,8 ng/mL nos grupos com TSH supresso (TSH 0,07 mUI/mL) e hipotireoidismo (TSH 97,4 mUI/mL), respectivamente, P = 0,2). CONCLUSÃO: Os resultados demonstram que a dosagem de PAAF-Tg é uma ferramenta importante no diagnóstico de metástases do CPT, podendo ser utilizada independente do "status" tireoidiano.

Etiology of congenital hypothyroidism using thyroglobulin and ultrasound combination.

Methods currently employed to establish the etiology of congenital hypothyroidism include thyroid ultrasound and scintigraphic exams. Thyroglobulin is a protein almost exclusively secreted by thyroid tissue and indirectly reflects the amount of follicular cells. Even though thyroglobulin is easy to measure, it has been not frequently used because of discordant results to distinguish mainly athyreosis and ectopy (dysgenesis). Knowing the differences in inheritance and prognosis of thyroid dysgenesis and dyshormonogenesis, it is important to define the etiology of CH, combining tools that are easy, fast and available in most medical centers. Our objective was to evaluate and compare color Doppler ultrasound and serum thyroglobulin with radionuclide scan to define the etiology of congenital hypothyroidism. We evaluated 38 children above 3 years-old off-treatment that performed serum thyroglobulin by immunofluorometric assay, color Doppler ultrasound and radionuclide study. On color Doppler ultrasound, 11 patients had athyreosis, 5 ectopic glands, being 1 associated to hemiagenesis. Twenty one had topic thyroid (3 goiters, 10 normal, 8 hypoplastic). Hemiagenesis and cystic lesion were not revealed by radionuclide scan. We observed substantial agreement between color Doppler ultrasound and radionuclide scan (kappa=0.745, p<0.0001). Serum thyroglobulin in athyreosis ranged from <1.0 to 18.7 micro g/L. Patients with ectopic glands showed wider thyroglobulin range (4.5 to 123 micro g/L, median 28.4 micro g/L). Only one patient showed thyroglobulin deficiency. By using color Doppler ultrasound and serum thyroglobulin levels as valuable combined tools, we established the etiology of congenital hypothyroidism limiting excessive and harmful exams in children, like radionuclide scan.

The p.A2215D thyroglobulin gene mutation leads to deficient synthesis and secretion of the mutated protein and congenital hypothyroidism with wide phenotype variation.

CONTEXT: Thyroglobulin (TG) is a large glycoprotein and functions as a matrix for thyroid hormone synthesis. TG gene mutations give rise to goitrous congenital hypothyroidism (CH) with considerable phenotype variation. OBJECTIVES: The aim of the study was to report the genetic screening of 15 patients with CH due to TG gene mutations and to perform functional analysis of the p.A2215D mutation. DESIGN: Clinical evaluation and DNA sequencing of the TG gene were performed in all patients. TG expression was analyzed in the goitrous tissue of one patient. Human cells were transfected with expression vectors containing mutated and wild-type human TG cDNA. RESULTS: All patients had an absent rise of serum TG after stimulation with recombinant human TSH. Sequence analysis revealed three previously described mutations (p.A2215D, p.R277X, and g.IVS30+1G>T), and two novel mutations (p.Q2142X and g.IVS46-1G>A). Two known (g.IVS30+1G/p.A2215D and p.A2215D/p.R277X) and one novel (p.R277X/g.IVS46-1G>A) compound heterozygous constellations were also identified. Functional analysis indicated deficiency in TG synthesis, reduction of TG secretion, and retention of the mutant TG within the cell, leading to an endoplasmic reticulum storage disease, whereas small amounts of mutant TG were still secreted within the cell system. CONCLUSION: All studied patients were either homozygous or heterozygous for TG gene mutations. Two novel mutations have been detected, and we show that TG mutation p.A2215D promotes the retention of TG within the endoplasmic reticulum and reduces TG synthesis and secretion, causing mild hypothyroidism. In the presence of sufficient iodine supply, some patients with TG mutations are able to compensate the impaired hormonogenesis and generate thyroid hormone.

[Thyroglobulin levels in needle lymph node cytology for the detection of papillary thyroid cancer recurrence]. / Utilidad de la detección de tiroglobulina en el aspirado de punción ganglionar cervical en el seguimiento de pacientes con cancer papilar de tiroides.

BACKGROUND: During the detection of neck recurrence in patients with Papillary Thyroid Carcinoma (PTC), sometimes it is difficult to distinguish metastatic from inflammatory neck lymph nodes. The measurement of serum thyroglobulin (sTg) under thyroid hormone suppression therapy the presence of serum thyroglobulin antibodies (sAbTg), the diagnostic whole body scan and cytology can give false negative results. Measurement of thyroglobulin in the washout fluid from fine-needle aspiration biopsy (FNAB) of suspicious neck lymph nodes could improve the diagnostic accuracy. AIM: To evaluate the usefulness of detecting Tg in lymph nodes (LTg) suspicious by ultrasonography (US) and compare it to cytology. PATIENTS AND METHODS: Between the years 2004 and 2007 we prospectively studied 30 patients with PTC and cervical US findings of suspicious recurrence. LTg was assayed in US guided FNAB used for cytology. RESULTS: Sixteen out of 30 patients underwent surgery using as selective criteria an LTg higher than sTg or a positive cytology. Surgery confirmed the presence of metastasis in all 15 patients with positive LTg (8 with positive cytology) and in 1 patient with negative LTg and positive cytology (a case with undifferentiated thyroid cancer). The sensitivity was 93.7% for LTg and 56.2% for cytology. We identified by LTg 3 of 6 patients with undetectable sTg and positive sAbTg. CONCLUSIONS: The presence of LTg showed a higher sensitivity than cytology for the detection of cervical lymph node metastasis. This method is useful even in the presence of sAbTg.

Utilidad de la detección de tiroglobulina en el aspirado de punción ganglionar cervical en el seguimiento de pacientes con cancer papilar de tiroides / Thyroglobulin levels in needle lymph node cytology for the detection of papillary thyroid cancer recurrence

Background: During the detection ofneck recurrence in patients with Papillary Thyroid Carcinoma (PTC), sometimes it is difficult to distinguish metastatic from inflammatory neck lymph nodes. The measurement of serum thyroglobulin (sTg) under thyroid hormone suppression therapy the presence of serum thyroglobulin antibodies (sAbTg), the diagnostic whole body sean and cytology can give false negative results. Measurement of thyroglobulin in the washout fluid from fine-needle aspiration biopsy (FNAB) of suspicious neck lymph nodes could improve the diagnostic aecuracy Aim: To evaluate the usefulness of detecting Tg in lymph nodes (LTg) suspicious by ultrasonography (US) and compare it to cytology. Patients and Methods: Between the years 2004 and 2007 we prospectively studied 30 patients with PTC and cervical US findings of suspicious recurrence. LTg was assayed in US guided FNAB used for cytology. Results: Sixteen out of 30 patients underwent surgery using as selective criteria an LTg higher than sTg or a positive cytology. Surgery confirmed the presence of metástasis in all 15 patients with positive LTg (8 with positive cytology) and in 1 patient with negative LTg and positive cytology (a case with undifferentiated thyroid cancer). The sensitivity was 93.7 percent for LTg and 56.2 percent for cytology. We identified byLTg 3 of 6 patients with undetectable sTg and positive sAbTg. Conclusions: The presence of LTg showed a higher sensitivity than cytology for the detection of cervical lymph node metástasis. This method is useful even in the presence ofsAbTg.

Q12 cáncer diferenciado de tiroides (CDT): estimulación de la TSH endógena con múltiples dosis de TRH y su tratamiento con 131I: experiencia de 3 años / Differentiated thyroid carcinoma: endogenous TSH stimulation by multiple dosage of TRH and treatment with 131I

La búsqueda un método alternativo a la rh-TSH para estimular el aumento de la TSH sérica previo al tratamiento con 131I en pacientes con CDT operados con reducción del tiempo del hipotiroidismo pre ablativo fue el propósito del trabajo que iniciamos en el año 2001 en el Paraguay utilizando múltiples dosis de TRH para estimular la TSH endógena de los pacientes para luego lograr la ablación del remanente tiroideo con 131I. Se conoce que la inyección de una dosis única de 200µU de TRH por vía EV logra el aumento de la TSH endógena en los pacientes con carcinoma diferenciado de tiroides logrando elevar la TSH entre 30 - 35 mUI/L al final de la primera hora , sin embargo, no se cuentan con datos estadísticos de los efectos de múltiples inyecciones de TRH aplicadas por vía EV o por vía IM en los pacientes operados de tiroides por CDT previamente a la ablación con 131I. Material y Método: Desde el 2001al 2007 doscientos pacientes operados por CDT fueron estudiados por este método en el Centro de Diagnostico y Tratamiento Nuclear (CEDIN), 120 correspondieron a cáncer papilar y 80 a cáncer folicular. Ciento ochenta no presentaron metástasis a distancia y 20 presentaron metástasis en cuello, tórax, pelvis y columna dorsal. Tiroidectomía total se realizó en 120 y lobectomía total e itsmectomía más hemilobectomía del lado contra lateral en 80. Todos fueron tratados con dosis ablativas (100 mCi (3.700 mBq) de 131I excepto aquellos con metástasis que recibieron 150 mCi (5.500 mBq) previa estimulación con TRH por vía EV en dos dosis diarias por dos días con previa suspensión de L-tiroxina por 25 días antes del tratamiento reemplazándola por triyodotironina 25 mcg/día por 15 días tras lo cual también fue suspendida 10 días antes de la estimulación con TRH y el tratamiento con 131I. Dos pacientes con metástasis recibieron otra dosis extra de 150 mCi (5.550 MBq) 6 meses después...

The search of an alternative method to the rh-TSH to stimulate endogenous rising of TSH previous to thyroid ablation with 131I in patients with CDT operated. The purpose of the work began in 2001 in Paraguay using multiple dose of TRH IV (200µU of TRH Threlea® Argentina) to stimulate the own TSH of patients previous to 131I ablation. It is known that the injection of an unique dose of 200µU of TRH IV achieves the increasing of the endogenous TSH in patients with differentiated thyroid carcinoma up to 30 - 35 mUI/L at the end of the first hour, however, there is not statistical data of the effects of multiple injections of TRH applied IV or IM in operated patients of DTC previous to the ablation with 131I. Since 2001-2007, two hundred patients operated for DTC were studied by this method, 120 were papillary cancer and 80 follicular cancer. One hundred eighty did not have distance metastasis and 20 presented metastasis in thorax, pelvis and dorsal spine. Total thyroidectomy was carried out in 120 and total lobectomy with itsmectomy plus hemilobectomy of the other lobe in 80. All were treated with ablative dose of 100 mCi (3.700 mBq) of 131I, except those with metastasis which receive 150 mCi (5.500 mBq) with the previous stimulation with TRH IV with two daily dose for three days with previous suspension of L-tiroxine for 25 days and replaced by triyodotiroxine 25 mcg/d for 15 days with suspension 10 days before the stimulation with TRH and treatment with 131I. Two patients with metastasis received another extra dose of 150 mCi (5.550 MBq) 6 months later. One presented uptake in thyroid bed one year after the ablation received a new ablative dose of 100 mCi (3.700 mBq) of 131I. All the patients were interned and isolated by 48 hours. Twenty feminine patients had later pregnancies in 1-3 years after their ablative dose with healthy products. TSH was measured during the stimulation with TRH in all patients...

[Diagnosis of metastases in patients with papillary thyroid cancer by the measurement of thyroglobulin in fine needle aspirate]. / Diagnóstico de metástases de carcinoma papilífero de tiróide através da dosagem de tiroglobulina no líquido obtido da lavagem da agulha utilizada na punção aspirativa.

The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA-Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those 25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2 indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine needle aspiration biopsy and FNA-Tg combined with neck US are essential for detecting positive cervical lymph nodes due to its high sensitivity and specificity and it should be considered the standard for investigating locally recurrent disease in patients with PTC.

Management of low-risk patients with thyroid carcinoma and detectable thyroglobulin on T4 after thyroidectomy and ablation with iodine-131.

OBJECTIVE: To evaluate the positive predictive value of detectable Tg during T4 therapy (Tg on T4) in patients with thyroid cancer after total thyroidectomy and remnant ablation, discussing the work-up in this situation and the empirical indication of 131I. PATIENTS AND METHODS: Initially, 234 low-risk patients [tumor < 5cm, completely resected, no extensive extrathyroid invasion (pT4)] submitted to total thyroidectomy and ablation with 131I (3.7-5.5 GBq) who presented no ectopic uptake on RxWBS were studied. Of these, 23 patients with detectable Tg on T4 (> 1ng/ml) during the first year after initial therapy were selected. RESULTS: Metastases were detected by neck US in 7 patients, by chest CT in 2 and by US and CT in 3. Four of five patients with lung metastases upon CT had a positive RxWBS. Eleven patients with negative US and CT received a new 131I dose (without DxWBS), and RxWBS showed ectopic uptake in 3 patients. Among the patients with negative RxWBS, 7 remained free of apparent disease and Tg was declining (5 with undetectable Tg on T4 at the end of the study). One patient presented an increase in Tg and FDG-PET was positive for lymph node and bone metastases. CONCLUSIONS: All patients with Tg on T4 > 5ng/ml presented apparent disease. In these cases, even when US and CT are negative, the administration of a therapeutic dose of 131I (without DxWBS) and FDG-PET are recommended. Among patients with detectable Tg on T4

Diagnóstico de metástases de carcinoma papilífero de tiróide através da dosagem de tiroglobulina no líquido obtido da lavagem da agulha utilizada na punção aspirativa / Diagnosis of metastases in patients with papillary thyroid cancer by the measurement of thyroglobulin in fine needle aspirate

Com a introdução da ultra-sonografia cervical (USC) no seguimento dos pacientes com carcinoma papilífero de tiróide (CPT), tornou-se freqüente o encontro de pequenos linfonodos (LNs) cervicais. Porém, apesar de a USC apresentar alta sensibilidade, o estudo citológico obtido por punção aspirativa (PAAF) e, nos últimos anos, a dosagem da tiroglobulina (Tg) no lavado da agulha da PAAF (Tg-PAAF) vêm assumindo papel importante no diagnóstico de LNs cervicais. O objetivo deste estudo é verificar a acurácia da combinação da USC, citologia e Tg-PAAF em LNs suspeitos. Estudamos 32 pacientes que apresentavam 44 LNs à USC, classificados como "inflamatórios" (19) ou "suspeitos" (25). Dos 25 LNs suspeitos, 15 apresentavam Tg-PAAF elevada (13 com citologia compatível com metástases e 2 com citologia não-diagnóstica). Esses 15 LNs (11 pacientes) foram confirmados como metástase de CP pelo exame histopatológico. Os 19 LNs "inflamatórios" e os 10/25 LNs "suspeitos" apresentaram citologia negativa e Tg-PAAF indetectável. Concluímos que a USC apresenta alta sensibilidade na detecção de linfonodos cervicais, porém citologia e dosagem de Tg-PAAF são fundamentais para o diagnóstico. A associação USC, citologia e Tg-PAAF pode ser considerada a abordagem mais sensível e específica na detecção de LNs metastáticos em pacientes com CPT.

The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA-Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those 25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2 indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine needle aspiration biopsy and FNA-Tg combined with neck US are essential for detecting positive cervical lymph nodes due to its high sensitivity and specificity and it should be considered the standard for investigating locally recurrent disease in patients with PTC.

Management of low-risk patients with thyroid carcinoma and detectable thyroglobulin on T4 after thyroidectomy and ablation with iodine-131

OBJECTIVE: To evaluate the positive predictive value of detectable Tg during T4 therapy (Tg on T4) in patients with thyroid cancer after total thyroidectomy and remnant ablation, discussing the work-up in this situation and the empirical indication of 131I. PATIENTS AND METHODS: Initially, 234 low-risk patients [tumor < 5cm, completely resected, no extensive extrathyroid invasion (pT4)] submitted to total thyroidectomy and ablation with 131I (3.7­5.5 GBq) who presented no ectopic uptake on RxWBS were studied. Of these, 23 patients with detectable Tg on T4 (> 1ng/ml) during the first year after initial therapy were selected. RESULTS: Metastases were detected by neck US in 7 patients, by chest CT in 2 and by US and CT in 3. Four of five patients with lung metastases upon CT had a positive RxWBS. Eleven patients with negative US and CT received a new 131I dose (without DxWBS), and RxWBS showed ectopic uptake in 3 patients. Among the patients with negative RxWBS, 7 remained free of apparent disease and Tg was declining (5 with undetectable Tg on T4 at the end of the study). One patient presented an increase in Tg and FDG-PET was positive for lymph node and bone metastases. CONCLUSIONS: All patients with Tg on T4 > 5ng/ml presented apparent disease. In these cases, even when US and CT are negative, the administration of a therapeutic dose of 131I (without DxWBS) and FDG-PET are recommended. Among patients with detectable Tg on T4 < 5ng/ml and negative US and CT, only 12 percent presented ectopic uptake on RxWBS. These cases could be followed up by monitoring Tg on T4, and RxWBS and FDG-PET should only be performed if this marker does not decrease after 1­2 years.

OBJETIVO: Avaliar o valor preditivo positivo da Tg detectável durante terapia com T4 (Tg sob T4) em pacientes com câncer de tireóide após tireoidectomia total e ablação dos remanescentes, discutindo o manuseio dessa situação e a indicação empírica de 131I. PACIENTES E MÉTODOS: Inicialmente, foram estudados 234 pacientes de baixo risco [tumor < 5cm, completamente ressecado, sem invasão extratireoideana extensa (pT4)] submetidos à tireoidectomia total e ablação com 131I (3,7­5,5 GBq) que não apresentaram captação ectópica com RxWBS. Desses, foram selecionados 23 pacientes com Tg detectável com T4 (> 1ng/ml) durante o primeiro ano após a terapia inicial. RESULTADOS: Metástases foram detectadas em 7 pacientes pelo US cervical, em 2 pela TC de tórax e em 3 pela US e TC. Quatro de 5 pacientes com metástases pulmonares à TC tiveram um RxWBS positivo; 11 pacientes com US e TC negativos receberam uma nova dose de 131I (sem DxWBS), e a RxWBS mostrou captação ectópica em 3 pacientes. Entre os pacientes com RxWBS negativo, 7 permaneceram livres de doença aparente e a Tg estava em declínio (5 com Tg indetectável sob T4 ao final do estudo). Um paciente apresentou aumento da Tg e o FDG-PET foi positivo para linfonodos e metástases ósseas. CONCLUSÕES: Todos os patients com Tg sob T4 > 5ng/ml apresentaram doença aparente. Nesses casos, mesmo quando a US e a TC são negativos, é recomendada a administração de dose terapêutica de 131I (sem DxWBS) e FDG-PET. Em pacientes com Tg detectável sob T4 < 5ng/ml, mas US e TC negativos, apenas 12 por cento apresentaram captação ectópica com a RxWBS. Estes casos podem ser seguidos pelo monitoramento da Tg sob T4, e RxWBS e FDG-PET devem ser feitos apenas se esse marcador não diminuir.

Papillary cystadenocarcinoma: report of a case of high-grade histopathologic malignancy.

Papillary cystadenocarcinoma is an extremely rare malignant tumor of the salivary gland which is cytologically considered to be of low-grade malignancy, showing an indolent biological behavior. Histologically, the tumor is characterized by cysts and papillary endocystic projections. This tumor most commonly arises in the major salivary glands, mainly the parotid gland. We report here a case of papillary cystadenocarcinoma originating from the minor salivary gland, which showed marked growth over a short period of time. Histologically, the tumor was characterized by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy.

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma.

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have led to an increased interest in its use for preparation for radioiodine (RI) dose administration in patients with recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RI therapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients. Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin (Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease. Median follow-up after the first rhTSH-aided radioiodine treatment was 32 +/- 13 months (range 8 to 54 months). Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease. In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, in four in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels were undetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free, four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. In conclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients (GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSH is a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing the quality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patients only with stimulated Tg levels.

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels.

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes.

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels. (AU)

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes. (AU)