Postoperative Radioiodine Treatment within 9 Months from Diagnosis Significantly Reduces the Risk of Relapse in Low-Risk Differentiated Thyroid Carcinoma / 대한핵의학회잡지

PURPOSE: Although postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC.MATERIAL: The analyzed group involved 701 DTC patients staged pT(1b)-T₄N₀-N₁M₀, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months (N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228). Median follow-up was 12.1 years (1.5−15.2).RESULTS: Based on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant.CONCLUSION: If postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes.

The role of prophylactic central compartment lymph node dissection in differentiated thyroid carcinoma

Background: Differentiated thyroid carcinoma, arising from thyroid follicular epithelial cells, accounts for the vast majority of thyroid carcinomas. Of the differentiated cancers, papillary cancer comprises about 85% of cases compared to about 12% that have follicular histology, including conventional and oncocytic (Hurthle cell) carcinomas, and <3% that are poorly differentiated tumors. In general, stage for stage, the prognoses of PTC and follicular cancer are similar. The aim of this study is to evaluate the benefit of central compartment lymph node dissection in accurate staging of the disease and plan radioiodine treatment and dosing. And also to assess the morbidity associated with central neck dissection. Materials and methods: This was a prospective clinical study conducted at MNJIO and RCC, Hyderabad. 20 patients with carcinoma thyroid who underwent total thyroidectomy and prophylactic central compartment lymph node dissection from December 2015 to December 2017 were included. The protocol was submitted to the ethics committee at Osmania Medical College and was approved. Results: We analyzed the number of patients of that age in whom the disease stage changed due to the presence of central nodal dissection. Prophylactic CND resulted in upstaging of tumour in 2/20 (10%) patients from stage I to stage II. Also in 4/20 (20%) patients, the evidence of node metastases influenced also the therapeutic strategy because these patients would not have been treated with 131-I if the prophylactic central neck dissection had not been performed. Thus a prophylactic CLND may play an even larger role in determining RAI use. A prophylactic CLND that demonstrates a lack of lymph node metastasis would strengthen the case not to use RAI treatment in a low-risk patient. Nived Rao, M. Muralidhar, M. Srinivasulu. The role of prophylactic central compartment lymph node dissection in differentiated thyroid carcinoma. IAIM, 2018; 5(9): 91-98. Page 92 Conclusion: With the available evidence, we advocate a selective approach to performing prophylactic CND and to be done in high volume centres. Routine prophylactic central lymph node dissection should be avoided in the absence of involved lymph nodes, reserving the procedure to “high-risk” patients as defined by ATA and European Society of Endocrine Surgeons, which include extremes of ages, large primary tumor size, and male gender, which were similar to high risk cases seen in our study.

Recombinant human thyrotropin-aided radioiodine treatment of differentiated thyroid carcinoma / 中华内分泌代谢杂志

Objective To observe the influence of recombinant human thyrotropin(rhTSH)on serum concentration of endogenous thyrotropin(TSH), free triiodothyronine(FT3), free thyroxine(FT4), thyroglobulin antibody(TGAb), and thyroglobulin(Tg). To evaluate the efficacy of rhTSH-aided radioiodine treatment in patients with differentiated thyroid carcinoma(DTC). Methods The study recruitment took place between November 2007 and March 2009. 62 patients(including 45 females)with biopsy confirmed DTC had undergone total or nearly total thyroidectomy, and received 131I treatment. 31 patients(including 22 females), median age of 45 years(23-72), received radioiodine treatment 4 weeks after L-thyroxine(T4)withdrawal. The other 31 patients(including 23 females), median age of 44 years(14-70), underwent rhTSH-aided radioiodine treatment. Before and after rhTSH injection, serum TSH, FT3, FT4, TGAb, and thyroglobulin were tested. Post-radiotherapy whole body scan was performed 5 to 7 days after radioiodine treatment and qualitatively and blindly evaluated by two nuclear medicine physicians. Follow-up took place 6 to 12 months after radioiodine treatment. The efficacy of rhTSH-aided radioiodine treatment was evaluated by whole body scan with diagnostic dose radioiodine. SPSS 13.0 statistical software was applied. Results (1)Before and after rhTSH-aided radioiodine treatment, the serum TSH was(1.08±4.01)vs(140.26±27.20)mIU/L(P＜0.05), thyroglobulin(23.75±132.92)vs(169.58±178.49)μg/L(P＜0.05), FT3(4.52±1.16)vs(4.42±1.11)pmol/L(P＞0.05), and FT4(15.09±5.83)vs(13.66±5.85)pmol/L(P＞0.05),respectively.(2)rhTSH-aided radioiodine ablation treatment had the same effect as L-T4withdrawal aided. The complete response ratio was 77.4% vs 71.0%(P＞0.05)by radioiodine whole body scan of diagnostic dose. Conclusion rhTSH-aided radioiodine treatment of DTC was effective and safe, and did at least at equivalent degree as did L-T4withdrawal. Furthermore, Serum thyroglobulin level could be effectively stimulated by rhTSH with tumor relapse or metastasis.

New Trends in Radioiodine Treatment for the Advanced Differentiated Thyroid Cancer / 대한내분비외과학회지

Iodine-131 (I-131) has been used in the therapy of well-differentiated thyroid cancer for over 60 years and has been an important component in the management of well-differentiated thyroid cancer. Differentiated thyroid carcinoma (DTC) is one of the most curable cancers, associated with a 10-year survival rate of 80~95%. Total (or near-total) thyroidectomy followed by radioiodine ablation is considered to be the ideal treatment for the high risk tumors. The selective use of radioactive iodine on the basis of clinicopathologic features that define the risk of recurrence and disease specific mortality is generally recommended in many kinds of international or institutional guidelines. However, recurrence in the thyroid bed or cervical lymph nodes develops in 5~20% of patients with DTC and some patients develop distant metastatic disease decreasing the 10-year survival of patients by 50%. Unfortunately, many of these patients ultimately die from advanced disease and other therapeutic approaches are needed. The goals of therapy for those patients should be to improve survival, relieve symptoms, and decrease the morbidity of disease progression and limit the morbidity associated with therapy. Safe practice of radioiodine treatment should be balanced with the benefit and the risk. This review will address the results of the radioiodine treatments in patients with the advanced thyroid cancer with the recent clinical trials.

Acceleration of the Increase of Endogenous Thyrotropin Hormone for Follow up Studies or Radioiodine Treatment in Patients with Differentiated Thyroid Carcinoma / Incremento rápido de tirotrofina endógena en pacientes con carcinoma diferenciado de tiroides para seguimiento o tratamiento con radioyodo

In follow up (F-U), ablation (A), or treatment (T) with radioiodine of patients with differentiated thyroid carcinoma (DTC), it is necessary to obtain elevated figures of serum TSH to assess hTg serum values or carry out 131I scanning. During the past few decades, the method employed was the withdrawal of hormonal treatment (WTH) for several weeks and its variants with the inconvenient symptoms of hypothyroidism, often restraining the use of this method. We aimed to obtain a rapid rice of serum TSH after a very short withdrawal of thyroid hormonal treatment (eight to nine days ) with the use of three or four intravenous application of TRH (200 mcg) during the first 6 days of withdrawal (TRH-St). One hundred determinations were carried out in 66 patients with DTC (ages19-80 y.o ), 20 males and 46 females. Sixty seven TRH-St were carried out for F-U, 20 for FU/T and 13 for A. In all cases the TSH values after the 3rd or 4th TRH application (samples 1 and 2) were over the value of 25 mIU/L and in the case of the second sample 99/100 determination were over the value of 30 mU/L. The values obtained were for the first sample 70.9 mIU/L ± 54.5 (range 25-310) and for the second sample 85.2 ± 61.3 (range 26-360), p<0.001. Patients considered that the symptoms and discomfort observed were mild when compared to those observed in patients submitted previously to the WTH method for 4/5 weeks. The results observed with TRH-St, allow us to consider the method as an alternative to the classic withdrawal method or the use of rhTSH with an adequate relation cost benefit.

Para efectuar ablación (A) , tratamiento con radioyodo (T) o seguimiento (S) en pacientes portadores de carcinoma diferenciado de tiroides (CDT) se hace necesario incrementar los valores de tirotrofina sérica (TSH) para elevar la sensibilidad del centellograma y la especificidad de la determinación de tiroglobulina sérica (hTg). Por años el método clásico fue la suspensión del tratamiento opoterápico (WTH) o sus variantes y ocasionalmente el uso de TSH de origen animal o , raramente, humana. Hace una década, la introducción de la TRH recombinante (rhTSH) significó evitar la desagradable sintomatología del hipotiroidismo que conllevaba el uso del método (WTH) y que en ocasiones impedía su utilización. Nuestro objetivo: el rápido ascenso de la TSH sérica después de muy breve WTH (ocho a nueve días) utilizando tres o cuatro aplicaciones intravenosas de la hormona liberadora de tirotrofina (TRH) durante los primeros seis días de WTH, método que denominamos TRH-St. Se efectuaron cien TRH-St en 66 pacientes: 20 masculinos, 46 femeninos, edades 19-80 años; 61 carcinomas papilares de diversas variantes anatomopatológicas, 4 foliculares y una variantes Hürthle. En todos los estudios después de la 3ra y cuarta aplicación de TRH (muestras 1 y 2 respectivamente) los valores de TSH fueron superiores a 25 mUI/L y con respecto a la cuarta TRH, 99/100 estudios ofrecieron valores de TSH superiores a 30 mUI/L. Los promedios obtenidos fueron: muestra 1 : 70.9 ± 54,5 mUI/L de TSH (rango 25-310); muestra 2: 85.2 ± 61.3 (rango 26-360): p < 0,001. Los pacientes consideraron que la sintomatología adversa del hipotiroidismo y el "disconformismo" fueron leves y sin comparación con los observados por aquellos pacientes sometidos anteriormente al método de supresión hormonal por 4/5 semanas.. Estas observaciones nos llevan a considerar que el método TRH-St , es una alternativa válida del método clásico de suspensión hormonal o del uso de rhTSH con una relación adecuada costo / beneficio.

A systematic review of the effect of radioiodine.131 in treatment of pulmonary metastases from differentiated thyroid carcinoma and the main prognostic factors / 中华内分泌代谢杂志

Objective To assess the effect of radioiodine-131 (131Ⅰ) on treatment of pulmonary metastases from differentiated thyroid carcinoma and the main prognostic factors. Methods Five databases were retrieved and all published studies which analyzed the effect of 131Ⅰ on pulmonary metastases from differentiated thyroid carcinoma and the main prognostic factors were systematically reviewed. The data about the impact of 131Ⅰ treatment and the main prognostic factors on the 5-yr and 10-yr survival rates of the patients were abstracted. RevMan 4.2 software was used to statistically analyze. Results Eleven retrospective cohort studies were included. The pooled results suggested that the 5-yr survival rates of the patients who received 131Ⅰ therapy and who did not received 131Ⅰl therapy were 74.9% and 27.1% , respectively ;The lO-yr survival rates(P<0.01)of the two groups were 60.8% % 12.2% , respectively;The difference between them had statistical significance (P<0.01). The 5-yr and 10-yr survival rates of the patients only with pulmonary metastases were higher than those of the patients with multiple metastases (P<0.01). The 5-yr (P = 0.01) and 10-yr (P = 0. 002)surviv10al rates of the patients only with papillary thyroid carcinoma were higher than those of the patients with follicular thyroid carcinoma. The 5-yr and 10-yr survival rates of male and female patients were similar(P>0.05). Conclusions 131Ⅰ treatment increases the 5-yr and 10-yr survival rates of patients with pulmonary metastases from differentiated thyroid carcinoma. The extent of metastases and the histologie type of differentiated thyroid carcinoma are two main predicting factors of prognosis. The 5-yr and 10-yr survival rates of patients are not influenced by gender.

Optimization of Inpatient Management of Radioiodine Treatment in Korea / 핵의학분자영상

We established a model to calculate radioactive waste from sewage disposal tank of hospitals to optimize the number of patients receiving inpatient radioiodine therapy within the safety guideline in our country. According to this model and calculation of radioactivity concentration using the number of patients per week, the treatment dose of radioiodine, the capacity and the number of sewage tanks and the daily amount of water waste per patient, estimated concentration of radioactivity in sewage waste upon disposal from disposal tanks after longterm retention were within the safety guideline (30 Bq/L) in all the hospitals examined. In addition to the fact that we could increase the number of patients in two thirds of hospitals, we found that the daily amount of waste water was the most important variable to allow the increase of the number of patients within the safety margin of disposed radioactivity. We propose that saving the water amount be led to increase the number of patients and they allow two patients in an already furnished hospital inpatient room to meet the increasing need of inpatient radioiodine treatment for thyroid cancer.

A Retrospective Review of the Effectiveness of Recombinant Human TSH-Aided Radioiodine Treatment of Differentiated Thyroid Carcinoma / 대한내분비학회지

BACKGROUND: The aim of the study was to evaluate the biochemical effects of recombinant human thyroid stimulating hormone (rhTSH) as an adjunct to radioiodine (RI) treatment of a differentiated thyroid carcinoma (DTC). We retrospectively reviewed the clinical response rates of DTC patients treated with RI after thyroid hormone withdrawal and compared with those after rhTSH stimulation. METHOD: We included the patients treated with RI for locally recurrent DTC from February 1, 2002 to August 31, 2005 and followed with diagnostic studies at our hospital. Forty totally (or near totally) thyroidectomized adults were included in this study. Nine patients underwent RI treatment after rhTSH stimulation while euthyoid on L-thyroxine (LT4), and 31 patients were treated with RI after thyroid hormone withdrawal. The clinical response was defined as >25% decrease in serum thyroglobulin (Tg) level on LT4 3 months after the RI treatment. RESULTS: In each group, serum Tg levels were significantly decreased 3 months after the RI treatment. And we found that 77.8 and 71.0% of those prepared by rhTSH and LT4 withdrawal, respectively, had clinical responses 3 months after the RI treatment by our criteria and there was no significant difference in response rates between two groups (P=0.238). CONCLUSIONS: Given the biases that exist in retrospective studies, at the current time we cannot recommend the routine use of rhTSH to prepare RI treatment of DTC. However, our study provided preliminary evidence that rhTSH effectively aided RI treatment of DTC at least to an equivalent degree as LT4 withdrawal.

A Retrospective Review of the Effectiveness of Recombinant Human TSH-Aided Radioiodine Treatment of Differentiated Thyroid Carcinoma / 대한내분비학회지

BACKGROUND: The aim of the study was to evaluate the biochemical effects of recombinant human thyroid stimulating hormone (rhTSH) as an adjunct to radioiodine (RI) treatment of a differentiated thyroid carcinoma (DTC). We retrospectively reviewed the clinical response rates of DTC patients treated with RI after thyroid hormone withdrawal and compared with those after rhTSH stimulation. METHOD: We included the patients treated with RI for locally recurrent DTC from February 1, 2002 to August 31, 2005 and followed with diagnostic studies at our hospital. Forty totally (or near totally) thyroidectomized adults were included in this study. Nine patients underwent RI treatment after rhTSH stimulation while euthyoid on L-thyroxine (LT4), and 31 patients were treated with RI after thyroid hormone withdrawal. The clinical response was defined as >25% decrease in serum thyroglobulin (Tg) level on LT4 3 months after the RI treatment. RESULTS: In each group, serum Tg levels were significantly decreased 3 months after the RI treatment. And we found that 77.8 and 71.0% of those prepared by rhTSH and LT4 withdrawal, respectively, had clinical responses 3 months after the RI treatment by our criteria and there was no significant difference in response rates between two groups (P=0.238). CONCLUSIONS: Given the biases that exist in retrospective studies, at the current time we cannot recommend the routine use of rhTSH to prepare RI treatment of DTC. However, our study provided preliminary evidence that rhTSH effectively aided RI treatment of DTC at least to an equivalent degree as LT4 withdrawal.

Current Opinions on the Radioiodine Treatment of Graves' Hyperthyroidism / 대한핵의학회잡지

Radioactive iodine therapy using I-131 for hyperthyroidism has been used for more than 50 years, and generally considered safe and devoid of major side effects. Appropriate patient selection criteria and clinical judgement concerning patient preparation should be employed for its optimal use. It has not been possible to resolve the trade-off between efficient definite cure of hyperthyroidism and the high incidence of post-therapy hypothyroidism. The dose of the I-131 needed to maintain euthyroid state remains an area of uncertainity and debate. Early side effects are uncommon and readily managable. Other than the need for long-term monitoring and, in most cases, lifelong thyroid hormone treatment for late adverse consequences of this treatment remains only conjectural. We have reviewed general principles and recent advances in radioiodine treatment for Graves' hyperthyroidism, specially regarding to several controversies.

Changes in Properties of Thyrotropin Receptor Antibodies Following Radioiodine Treatment in Patients with Graves' Disease / 대한내분비학회지

BACKGROUND: It has been suggested that thyroid stimulation blocking antibody (TSBAb) is involved in the development of early hypothyroidism after radioiodine treatment in patient with Graves disease. However, previous studies have reported the effect of radioiodine treatment on overall changes of TSH receptor antibodies without detailed observation of changes in properties of TSH receptor antibodies. The aim of this study is to evaluate the effect of radioiodine treatment on thyroid stimulation antibody (TSAb) or on thyroid stimulation blocking antibody (TSBAb) activities and to see whether the appearance of TSBAb after radioiodine treatment is involved in the development of early hypothyroidism in patients with Graves disease. METHODS: The activities of TSAb, TSBAb were measured serially with human TSH receptor transfected Chinese hamster ovary (CHO) cells in 36 patients with Graves disease who received 131I treatment. In addition to the wild type TSH receptor-expressing cells, we used a chimeric receptor that 90-165 amino acid residues were substituted by those of rat LH/CG receptor (Mc2) for measurement of TSBAb without interference by the presence of TSAb and for evaluation of TSAb epitope spreading. We evaluated the association of early hypothyroidism after 131I treatment with changes of various immunologic parameters. RESULTS: In 14 (39%) of 36 patients, TSBAb activities were present in their sera before or after 131I treatment. Four of them had TSBAb activities before 131 treatment, and 12 newly acquired TSBAb activities after 131I treatment. The existence of TSBAb was not associated with the development of early hypothyroidism after 131I treatment but with low TSAb activities before 131 treatment, high thyroidal uptake of 131I given and with old age. The phenomena of epitope spreading measured by TSAb with Mc2 mutant clone before and after 131I treatment was not infrequent, but it had no clinical relevance. CONCLUSION: These results suggest that the existence of TSBAb may be not a major factor in the development of early hypothyroidism after radioiodine treatment in Graves disease. Other factors such as TSAb activities before radioiodine treatment, the efficiency of thyroidal uptake of 131I or old age are associated with the development of early hypothyroidism.