Resultados a corto plazo del tratamiento con 131I en el bocio multinodular: valor adicional de la estimulación previa con rhTSH / Short-term results of treatment with 131I in multinodular goiter: additional value of previus stimulation with Recombinant human thyrotropin

OBJETIVO: El yodo radiactivo (131I) es una opción terapeútica segura y eficaz cuando se utiliza solo o con la estimulación previa de TSH recombinante humana (rhTSH) en el tratamiento del bocio multinodular (BMN). En espera de ensayos clínicos que determinen la dosis óptima, demuestren seguridad y confirmen la eficacia, diferentes protocolos se utilizan para aplicar la dosis de 131I. Analizamos la respuesta al tratamiento con una dosis calculada por protocolo mixto (dosis fijas y cálculo por porcentaje de captación) en pacientes con BMN toxico y no toxico en nuestro hospital, en el periodo 2010-2013. MATERIALES Y MÉTODOS: Estudio prospectivo en pacientes con BMN no quirúrgico (BMNNQ) que requerían reducción del volumen glandular y/o tratamiento del hipertiroidismo. Se evaluaron 134 pacientes, 14 cumplieron con los criterios de inclusión (13mujeres) de edad media 71.08 años. Un grupo con BMN toxico, otro grupo con BMN no toxico, un tercer grupo con BMN no toxico estimulado con 0,1 mg de rhTSH previo a la dosis. Se evaluó, función tiroidea, captación tiroidea de 99ᵐTc, volumen tiroideo y síntomas compresivos. Se siguió a los pacientes durante 12 meses. RESULTADOS: Se aplicaron dosis entre 15 y 30 mCi de 131I. Remitió el hipertiroidismo en 6 de 7 pacientes. Hubo una reducción del volumen glandular (p<0.01).Los pacientes con estímulo de 0,1 mg rhTSH, aumentaron el porcentaje de captación de 99ᵐTc a las 24 h en un 32.43±10.61 permitiendo aplicar menor dosis de 131I. La tasa de aparición de hipotiroidismo fue de 7.41 por cada 100 pacientes.mes, mayor en pacientes con BMN toxico tratados con dosis bajas (p-=0.03). Hubo una mejoría subjetiva de la clínica compresiva en todos los pacientes. No hubo eventos adversos. CONCLUSIONES: Una dosis de 131I calculada por protocolo mixto es efectiva y segura para la reducción del volumen glandular y control del hipertiroidismo asociado. La estimulación con rhTSH logra el mismo efecto con una menor dosis administrada.

OBJECTIVE: Radioactive iodine (131I) is a safe and effective therapeutic option when used alone or with prior stimulation of recombinant human Thyrotropin (rhTSH) in the treatment of multinodular goiter (MNG). In absence of clinical trials that determine the optimal dose, demonstrate safety and confirm efficacy, different protocols are used to apply the dose of 131I. We analyze the response to treatment with a dose calculated by mixed protocol (fixed doses and calculation by percentage of uptake) in patients with toxic and non-toxic MNG in our hospital, in the period 2010-2013. MATERIALS AND METHODS: Prospective study in patients with non-surgical MNG that required glandular volume reduction and / or treatment of hyperthyroidism. 134 patients were evaluated, 14 met the inclusion criteria (13 women) of average age 71.08 years. One group with toxic MNG, another group with non-toxic MNG and a third with non-toxic multinodular goiter stimulated with 0.1 mg of rhTSH prior to the dose. Patients were followed for 12 months. Upon following, we assessed Thyroid function, 99ᵐTc thyroid uptake, thyroid volume and compressive symptoms. RESULTS: Doses between 15 and 30 mCi of 131I were applied. We observed hyperthyroidism remission in 6 of 7 patients. There was a reduction in glandular volume (p <0.01) considering all patients. Patients with a stimulus of 0.1 mg rhTSH, increased the percentage of uptake of 99ᵐTc at 24 h by 32.43 ± 10.61, allowing a lower dose of 131I to be applied. The rate of onset of hypothyroidism was 7.41 per 100 patients-month, and was higher in patients with toxic MNG treated with low doses (p = 0.03). There was a subjective improvement of the compression clinic in all patients. No adverse events were observed. CONCLUSIONS: A dose of 131I calculated by a mixed protocol is effective and safe for achieving glandular volume reduction and associated hyperthyroidism control. Stimulation with rhTSH produces the same effect with a lower administered dose.

Study on rhTSH-aided radioiodine treatment with 131 I therapy in children and adolescents with differen-tiated thyroid cancer / 实用肿瘤学杂志

Objective The study is mainly on the effect and outcome of 131 I treatment for children and adolescents with differentiated thyroid cancer .Methods We compared the difference between rhTSH -aided ra-dioiodine treatment and L -thyroxin withdrawal .Our study collected 87 patients in a retrospective study .In order to analysis the effect,we divided into two groups.The experimental group has 46 patients,and control check has 41 patients.We compared the basic characteristics and mortality in different groups by χ2 -test,t-test and F-test based on data type .Results The thyroid stimulating hormone concentrations of experimental group patients have significant differences in the first ,the third and the sixth day after the injected of rhTSH ,the third day is the highest.The TSH concentration has significant difference between the two groups before 131I treatment(t=2.362, P=0.023).For the Tg(thyrobolulin)negative patients,Tg concentration in control check is higher than the third day after injected of rhTSH in the experiment group (1.5 ±1.2 vs.0.7 ±1.4,P=0.034).Whole body image has been done by scintigraphic after 3~8 months of 131I treatment.Thirty four(84%)patients have no radioiodine up-take in experiment group,and 40(87%)patients have no radioiodine uptake in control check ,there is no differ-ence between the two groups (χ2 =0.277,P=0.599).There is no difference between the two groups on the rea-son for retreatment(P=0.875).Conclusion The outcome of rhTSH -aided radioiodine treatment is similar to L-thyroxin withdrawal in short -term recurrences ,and rhTSH-aided radioiodine treatment with 131 I therapy for children and adolescents with DTC is a better method .

Asociación de carcinoma papilar de tiroides y enfermedad de Graves: Inesperada evolución y eficacia de la dosis ablativa con tirotrofina recombinante humana (rhTSH) / Association of Papillary Thyroid Carcinoma and Graves' Disease: Unexpected Development and Efficiency of Ablative Dose with Recombinant Human Thyrotropin (rhTSH)

El carcinoma diferenciado de tiroides (CDT) asociado a enfermedad de Graves (EG) es una asociación relativamente rara, ocurriendo en el 0,3 % al 9,8 % de los pacientes operados por EG. Se presenta el caso de un paciente con EG y CDT de tiroides con características evolutivas y terapéuticas peculiares. Varón de 22 años que consultó por obesidad. Peso: 116,4 kg, Talla: 1,73 m, BMI: 38,9, clínicamente eutiroideo, con palpación tiroidea dificultosa por grosor de cuello. Análisis iniciales: T3, T4 y TSH dentro de rango normal y ecografía tiroidea con nódulo hipoecoico en lóbulo derecho (LD) de 11 x 10 mm. Se le solicitó punción aspirativa con aguja fina (PAAF) bajo guía ecográfica. Vuelve a los 4 meses con cuadro clínico de hipertiroidismo. Análisis: T3: 557 ng/dL, T4: 18,8 mcg/dL, T4 L: 3,73 ng/dL, TSH: < 0,01 μUI/mL, ATPO: 186 UI/mL, ATG: 965 UI/mL. La citología mostró: "Hallazgos citológicos vinculables con carcinoma papilar (CP) tiroideo". Centellograma tiroideo: "Nódulo integrado en LD". Es tratado con metimazol y se opera a los 2 meses: "Tiroidectomía total"; cuya anatomía patológica (AP) reveló un "CP variante folicular en lóbulo derecho y zona de CP variante clásica en lóbulo izquierdo". A los 35 y 60 días de operado (sin instaurar levotiroxina): presenta TSH <0,1 μUI/ml con T3 y T4 normales. Clínicamente eutiroideo, con palpación de cuello normal. Tomografía axial computada (TAC) de tórax: "Normal". Ecografía de cuello: "Lodge tiroidea bilateral libre". TRab 29 % (V.N. hasta 15 %). Centellograma tiroideo con Tc99m: "Captación patológica en región cervical media e inferior derecha y cervical inferior izquierda". Se reopera a los 4 meses de la primera cirugía (Cx). Se resecó proliferación epitelial en región de mediastino superior". AP: "Ganglio con infiltración de CP variante folicular". Análisis a los 40 días de la 2° Cx: TSH: 2,3 μUL/ml, T4 L: 0,82 ng/dL, tiroglobulina (Tg): 4,7 ng/mL. TAC de cuello y de tórax normales. Captación de I131: 1 h: 8 %, 24 h: 12 % y centellograma con 7,4 MBq de I131 "Múltiples áreas de fijación del trazador en cuello". Resonancia magnética nuclear (RMN) de cuello sin contraste: "Imagen redondeada de 10 mm a nivel paratraqueal derecha". Se logra hacer dosis ablativa con 0,9 mg de rhTSH con 200 mCi de I131, alcanzando una TSH >100 μUI/ml. A los 6 meses de la DT (sin levotiroxina): TSH >100 μUI/ml, Tg: 13,81 ng/mL, ATG: 431 UI/mL. Rastreo con 2 mCi: "Aumento patológico del radioyodo solo a nivel de la articulación esternoclavicular derecha". RMN de cuello: "Imagen en región pretraqueal derecha de menor tamaño que la anterior". Se le indicó DT de 150 mCi de I131. Posteriormente requirió 2 DT de I131 más. En la actualidad, a 4 años de la primera operación, el paciente se halla en buen estado general, con Tg negativa, con ATG en disminución franca y rastreo corporal de I131 negativo y sin signos de persistencia o recidiva de la enfermedad. Conclusiones: Varón obeso de 22 años portador de un CP de tiroides concomitante con la instalación de un hipertiroidismo por EG, con ATG positiva. Se resalta: 1) La importancia de la evaluación ecográfica inicial de un paciente con EG, 2) Tejido neoplásico residual ganglionar después de 2 Cx, efectuada por cirujano experimentado, suficientemente funcionante como para impedir elevación significativa de TSH y permitir dosis ablativa de I131; 3) Agresividad local del tumor demostrado por infiltración ganglionar y tejidos adyacentes; 4) TAC y ecografía de cuello que no pudieron identificar restos en cuello y efectividad, en cambio, de la RMNde cuello sin contraste y del centellograma tiroideo con Tc99m; 5) Eficaz utilización de la dosis ablativa con rhTSH.

Introduction: Differentiated thyroid cancer (DTC) associated with Graves' disease (GD) is a relatively rare disease, occurring in 0.3 % to 9.8 % of GD patients. Some studies suggest an increased aggressiveness of DTC in GD patients, apparently related to thyroid stimulating antibodies. We report the case of a patient with DTC and GD, describing his peculiar evolution. Case report: 22-year-old male who presented with obesity. History of a cousin with DTC and grandmother and mother with goiter. Physical examination: Weight: 116.4 kg, height: 1.73 m, BMI: 38.9. Clinically euthyroid. Thyroid palpation was difficult due to his thick neck. Initial analysis: T3, T4 and TSH within normal range. Thyroid ultrasound (US) showing 11 x 10 mm hypoechoic nodule in right lobe (RL). US-guided fine-needle aspiration (FNA) was requested. Four months later, the patient returned with clinical symptoms of hyperthyroidism (diarrhea, palpitations, insomnia, tremors, cramps and difficulty walking). Laboratory: T3: 557 ng/dl, T4: 18.8 mcg/dl, FT4: 3.73 ng/dl, TSH <0.01 μIU/mL, TPOA: 186 IU/mL, TGA: 965 IU/mL. US-guided FNA: "Cytological findings are related to papillary thyroid cancer". Thyroid Scan: "Diffuse enlargement of the gland, "warm" nodule in RL". 131I uptake was: 1st hour: 12 %, 24 hours: 58 %. He received methimazole 20 mg daily. He was operated on 2 months later ("total thyroidectomy"). Pathology: "Follicular variant of papillary thyroid carcinoma in right lobe and classical variant of papillary carcinoma in area of the left lobe". Thirty-five days after surgery (S) (without levothyroxine): TSH <0.01 μIU/mL, Tyroglobulin (Tg) 32.1 ng/mL. Sixty days after S: TSH <0.1 μIU/mL, FT4 1.2 ng/dL, T3 1.3 ng/dL. Clinically euthyroid with normal neck palpation. Chest Computed axial tomography (CT): "Normal". US of the neck: "Bilateral thyroid lodge is free". Ninety days later: TSH 0.32 μIU/mL, TRAb 29 % (normal: until 15 %). Thyroid Scan with 99mTc pertechnetate: "Pathological uptake in middle and lower cervical region right and left lower neck." He was reoperated on 4 months after his initial S: "Resection of epithelial proliferation with thyroid aspect in superior mediastinum region". Pathology: "Node with extensive infiltration of neoplastic proliferation of follicular variant of papillary carcinoma with areas of connective tissue infiltrated periganglionar of papillary thyroid cancer". Lab 40 days after the second surgery: TSH 2.3 μIU/mL, FT4 0.82 ng/dL, Tg 4.7 ng/mL. Neck and chest CT showed neither pathological lesions nor lymphadenopathy. 131I uptake with 7.4 MBq was: 1st hour: 8 % and 24 hours: 12 %. Neck Scan: "Multiple areas of tracer fixation in the neck". No pathological signs on neck palpation. Ablative dose of 7.4 GBq of 131I was performed to the patient, previously using rhTSH (two doses of 0.9 mg), reaching TSH >100 μIU/mL. Scan post ablative dose: "Important focus on right paratracheal region." Neck MRI showed: "Absence of thyroid gland. Rounded image of about 10 mm at right paratracheal level". The patient initiates suppressive therapy with levothyroxine (LT4). Six months after ablation therapy (without LT4): TSH >100 μIU/mL, Tg: 13.8 ng/mL, TGA: 431 IU/mL. Body Scan with 2 mCi: "Pathological focus of radioiodine behind the right sternoclavicular joint". New neck MRI: "Image in right pretracheal region smaller than the previous study". The patient received 5.55 GBq of 131I. The same radioiodine treatment was repeated 8 months later. At present, 4 years after the patient's initial surgery, he is in good general health, performing his normal activities, with TGA in sharp decline, negative 131I body scan and without signs of persistent or recurrent disease. Conclusions: We report a case of follicular variant papillary TC associated with GD with concomitant development of hyperthyroidism, with positive TGA, in a 22-year-old obese man. Highlights: 1) The importance of initial US exploration in a patient with GD, 2) Residual neoplastic lymph node tissue after 2 S, performed by an experienced surgeon, with enough functioning tissue to prevent a significant elevation of TSH and allow 131I ablative therapy, 3) Tumor local aggressiveness shown by adjacent tissues and lymph node infiltration, 4) Failure to identify residues in the neck by CT and US; instead, effectiveness of the neck MRI without contrast and 99mTc thyroid scan, 5) Effective use of ablative radioiodine therapy with rhTSH.

Cáncer de tiroides: En búsqueda del tratamiento individualizado / Thyroid cancer: In search of individualized treatment

La incidencia de cáncer de tiroides, principalmente carcinoma papilar, aumentó exponencialmente en todo el mundo. Este incremento podría reflejar los efectos combinados de las prácticas de detección , sumados a cambios en los factores de riesgo. A pesar de este aumento, la mortalidad específica se mantuvo estable en las últimas tres décadas. Dado que los pacientes con carcinoma papilar de tiroides a menudo tienen un muy buen pronóstico, con elevada supervivencia en el seguimiento a largo plazo en comparación con otro tipo de carcinomas, no ha habido una necesidad de cambiar el tratamiento convencional por mucho tiempo. Los pilares del tratamiento, cirugía (tiroidectomía total o casi total) y la terapia con radioyodo (131I), se encuentran en este momento en el centro de discusión en los foros mundiales. La tendencia actual es garantizar el tratamiento más eficaz y menos deletéreo para el paciente. En este momento lo más importante es individualizar el enfoque terapéutico considerando cuál es el estadio tumoral y el riesgo de recurrencia, para determinar qué pacientes se beneficiarán de una terapia más agresiva y cuáles podrán ser tratados con un enfoque más conservador.

The incidence of thyroid cancer has increased exponentially around the world (mostly papillary thyroid carcinoma). This growth may reflect the combined effects of increased screening practices, together with changes in risk factors for thyroid cancer. In spite of this, disease specific mortality remained stable in the last three decades. Due to the fact that patients with papillary thyroid carcinoma often have a very good prognosis, with high survival in the long term follow-up compared with other types of carcinomas, there has been no need to change the standard treatment. The mainstays of thyroid cancer treatment are surgery (total or near-total thyroidectomy) with or without the additional administration of radioiodine (131I). These approaches are now in the center of discussion in all global forums. The current trend is to ensure the most effective and less harmful treatment and the most important issue at this point is to individualize patients according to tumor stage and risk of recurrence, to define which patients will benefit of more aggressive therapy and who could be handled with a more conservative approach.