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.

Comparison of I-131 Biokinetics after Recombinant Human TSH Stimulation and Thyroid Hormone Withdrawal Measured by External Detector in Patients with Differentiated Thyroid Cancer / 전남의대학술지

The aim of this study was to compare radioactive iodine (I-131) biokinetics after recombinant human TSH stimulation (rhTSH) and thyroid hormone withdrawal (THW) in patients with differentiated thyroid cancer (DTC). External effective dose rates were measured using external detectors and imaged quantitatively at the time of discharge from the isolation wards. We retrospectively analyzed 32 patients who had been diagnosed with DTC, papillary or follicular, and underwent remnant ablation after either rhTSH stimulation (n=22) or THW (n=10). The uptake of I-131 by remnant thyroid tissue was measured from 20.0 cm, 100.0 cm and 200.0 cm distances using a handheld external detector. The remnant thyroid tissue measured by the whole body images two to five days from administration was 10.7+26.0% (range 0.5 to 60.0%). The values measured at 20 cm were best correlated to the thyroid residual uptake measured by SPECT/CT. The half-lives of I-131washout (T1/2) in rhTSH group measured by external detector were shorter than those of THW group. T1/2 becomes longer when it was measured over longer distances. They were 10.9, 12.3 and 13.1 hours at distances of 20, 100, and 200 cm in rhTSH group, respectively. The TWH group showed 12.8, 14.9 and 17.7 hours, respectively. We conclude that I-131 biokinetics can be measured by external detector after high dose I-131 therapy for DTC. It showed that washout of I-131 was faster after rhTSH stimulation than THW, and slower in patients with distant metastasis than those without metastasis.

Tratamiento con radioyodo endovenoso y estimulación con TSH recombinante humana en paciente con cáncer de tiroides extenso: caso clínico / Intravenous radioiodine and recombinant human TSH in a patient with extensive thyroid cáncer: report of one case

Abstract: We report a 72-years-old male patient with extensive differentiated thyroid cancer (DTC), who required a tracheostomy and gastrostomy. Considering his clinical condition, risk of aspiration and management of the ostomies, radioiodine (131I) was administered intravenously, using recombinant human thyrotropin (rhTSH) and levothyroxine. The procedure was successful, both clinically and in terms of radioprotection.

Recombinant human TSH versus thyroid hormone withdrawal in adjuvant therapy with radioactive iodine of patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central compartment (cN1b)

ABSTRACT Objective To compare the short- and long-term outcomes of adjuvant therapy with radioactive iodine (RAI) preceded by the administration of recombinant human TSH (rhTSH) versus thyroid hormone withdrawal (THW) in patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central neck compartment (cN1b). Subjects and methods The sample consisted of 178 cN1b patients at intermediate risk who underwent total thyroidectomy with apparently complete tumor resection [including postoperative ultrasonography (US) without anomalies] and who received adjuvant therapy with RAI (30-100 mCi) preceded by the administration of rhTSH (n = 91) or THW (n = 87). Results One year after RAI, the rates of excellent response to therapy, i.e., nonstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL with negative antithyroglobulin antibodies and negative neck US, and of structural disease were similar for the two preparations (84% and 4.5%, respectively, in both groups). During follow-up (median 66 months), the rate of structural or biochemical (nonstimulated Tg > 1 ng/mL, with increment) recurrence was also similar in the two groups (4.5%). In the last assessment, the percentage of patients without evidence of disease, i.e., nonstimulated Tg < 1 ng/mL and no evidence of structural disease, was similar for the two preparations [92.3% in the rhTSH group and 97.7% in the THW group (p = 0.17)]. Conclusion Preparation with rhTSH was equally effective (short- and long-term) as THW for adjuvant RAI therapy of cN1b patients at intermediate risk and with apparently complete tumor resection.

Is 131I ablation necessary for patients with low-risk papillary thyroid carcinoma and slightly elevated stimulated thyroglobulin after thyroidectomy?

ABSTRACT Objective This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with131I. Subjects and methods The study included 53 low-risk patients (nonaggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). Results The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. Conclusions Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with 131I.

Comparison of Thyroglobulin Measurements Using Three Different Immunoassay Kits: A BRAMHS Tg-Plus RIA Kit, a BRAMHS hTg Sensitive Kryptor Kit, and a Beckman Coulter ACCESS Immunoassay Kit

BACKGROUND: Second-generation thyroglobulin immunometric assays (Tg-IMAs) have been developed with improved sensitivity. Our aim was to compare the diagnostic value of Tg-IMA measurements using a Kryptor (BRAHMS AG) kit (Tg-K) and an ACCESS (Beckman Coulter) kit (Tg-A) with that of the first-generation Tg measurement using a Tg-plus (BRAHMS AG) kit (Tg+). METHODS: We enrolled 82 differentiated thyroid cancer patients who underwent total thyroidectomy with radioactive iodine remnant ablation and who underwent diagnostic whole body scan using recombinant human thyroid stimulating hormone (rhTSH). The Tg+, Tg-K, and Tg-A were measured before rhTSH administration during levothyroxine treatment (suppressed Tg) from the same sample. Serum Tg+ was measured after rhTSH stimulation (stimulated Tg). RESULTS: Suppressed Tg+ was more significantly correlated with suppressed Tg-K (R²=0.919, P<0.001) than with suppressed Tg-A (R²=0.536, P<0.001). The optimal cut-off values of suppressed Tg+, Tg-K, and Tg-A for predicting stimulated Tg+ of 1 ng/mL were 0.3, 0.2, and 0.2 ng/mL, respectively. The sensitivity, specificity, and accuracy of suppressed Tg+ were 67%, 100%, and 90%, respectively; those of suppressed Tg-K were 83%, 90%, and 88%; those of suppressed Tg-A were 96%, 82%, and 87%, respectively. The positive predictive and negative predictive values of Tg+ were 100% and 87%, respectively; those of Tg-K were 79% and 92%; and those of Tg-A were 73% and 98%. CONCLUSION: We could not clearly demonstrate which kit had better diagnostic performance after comparison of first-generation Tg measurements with Tg-IMA measurements. Also, there were kit-to-kit variations between Tg-IMA kits. Suppressed Tg measured by Tg-IMA was insufficient to completely substitute for a stimulated Tg measurement.

Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

BACKGROUND: There are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH). METHODS: We retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up. RESULTS: Significant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods. CONCLUSION: Female DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT.

Economic Evaluation of Recombinant Human Thyroid Stimulating Hormone Stimulation vs. Thyroid Hormone Withdrawal Prior to Radioiodine Ablation for Thyroid Cancer: The Korean Perspective

BACKGROUND: Previous studies have suggested that recombinant human thyroid stimulating hormone (rhTSH) stimulation is an acceptable alternative to thyroid hormone withdrawal (THW) when radioiodine remnant ablation is planned for thyroid cancer treatment, based on superior short-term quality of life with non-inferior remnant ablation efficacy. This study evaluated the cost-effectiveness of radioiodine remnant ablation using rhTSH, compared with the traditional preparation method which renders patients hypothyroid by THW, in Korean perspective. METHODS: This economic evaluation considered the costs and benefits to the Korean public healthcare system. Clinical experts were surveyed regarding the current practice of radioiodine ablation in Korea and their responses helped inform assumptions used in a cost effectiveness model. Markov modelling with 17 weekly cycles was used to assess the incremental costs per quality-adjusted life year (QALY) associated with rhTSH. Clinical inputs were based on a multi-center, randomized controlled trial comparing remnant ablation success after rhTSH preparation with THW. The additional costs associated with rhTSH were considered relative to the clinical benefits and cost offsets. RESULTS: The additional benefits of rhTSH (0.036 QALY) are achieved with an additional cost of Korean won 961,105, equating to cost per QALY of 26,697,361. Sensitivity analyses had only a modest impact upon cost-effectiveness, with one-way sensitivity results of approximately 33,000,000/QALY. CONCLUSION: The use of rhTSH is a cost-effective alternative to endogenous hypothyroid stimulation prior to radioiodine ablation for patients who have undergone thyroidectomy in Korea.

Factors That Influence TSH Levels after Thyrogen Injection before RAI Therapy / 대한내분비외과학회지

PURPOSE: Radioactive iodine therapy was used for detection and destruction of remnant normal of malignant thyroid tissue after thyroidectomy for differentiated thyroid gland cancer. To achieve a high level of TSH, discontinuation of levothyroxine is required. Discontinuation of L-T4 causes hypothyroidism, serious adverse impacts on patients, therefore, rhTSH is used. The aim of this study was to evaluate the factors influencing serum peak TSH levels after administration of rhTSH in patients with thyroid papillary carcinoma. METHODS: Retrospective review was conducted of 249 patients who underwent total thyroidectomy and subsequent RAI therapy at Kangbuk Samsung Hospital between October 2008 and February 2014. We divided patients into two groups according to the stimulated serum TSH level after administration of rhTSH (Group 1: TSH or =30). Clinicopathological characteristics were compared between the two groups. RESULTS: Serum peak TSH was negatively related to height, weight, BSA, and BMI, and positively related to LBM. A non-significant negative correlation was found between serum peak TSH and body composition. CONCLUSION: Patients' weight, height, BMI, BSA, and LBM were not associated with serum peak TSH after rhTSH administration. More pharmakokinetic study of rhTSH is needed in order to find correlation between pharmacokinetic factors and TSH level.

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.

Clinical application of recombinant human thyroid-stimulating hormone in management of differentiated thyroid carcinoma / 生物医学工程学杂志

Traditionally, during the follow-up and in order to receive 131 I therapy, patients with differentiated thyroid carcinoma (DTC) have to withdraw from using thyroid hormone. The hypothyroidism induced by hormone withdrawal can negatively affect the quality-of-life (QOL) of DTC patients. Without the hormone withdrawal, recombinant human thyroid-stimulating hormone-aided management of DTC patients can effectively obviate the consequences of hypothyroidism. This review will focus on the clinical application of recombinant human thyroid-stimulating hormone (rhTSH) in the management of DTC patients.

Value of the Serum Thyroglobulin Level Alteration at the First High Dose Radioiodine Treatment in Patients with Differentiated Thyroid Carcinoma / 핵의학분자영상

PURPOSE: The purpose of this study was to evaluate if short-term serum thyroglobulin (Tg) elevation after radioiodine administration can predict successful radioiodine remnant ablation (RRA) and whether comparable RRA effectiveness is exhibited between a group administered with recombinant human thyrotropin (rhTSH) and a group experiencing thyroid hormone withdrawal (THW), in preparation for RRA. MATERIALS AND METHODS: A retrospective chart review was performed on 39 patients in the rhTSH group and 46 patients in the THW group. They were treated for differentiated thyroid carcinoma by total or near total thyroidectomy, and referred for RRA between 2003 and 2006 (the rhTSH group) and between January and June of 2006 (the THW group). They were assessed for serum Tg levels just before I-131 administration (TgD0), reassessed 9 days later (TgD9), and again 6-12 months later. RESULTS: RRA was successful in 64 (37 from the THW group and 27 from the rhTSH group) of the total 85 patients. The success rates of RRA had no statistically significant differences between the two groups. In both groups, TgD9/TgD0 values were significantly higher in the RRA success group (the rhTSH group; P=0.03, the THW group; P=0.04). By combining cutoff values of TgD0 and TgD9/TgD0, the successful RRA value was determined to be 96.7% (29/30) with TgD04.37 in both groups (the rhTSH group; 100% (16/16), the THW group; 92.9% (13/14)). Using logistic multivariate analysis, only TgD0 was independently associated with successful RRA. CONCLUSION: We may predict successful ablation by evaluating short-term serum Tg elevation after I-131 administration for RRA, in both rhTSH and THW patients.

Recent Advances in Radioiodine Therapy for Thyroid Cancer / 핵의학분자영상

Well-differentiated thyroid cancer is the most common endocrine malignancy with an increasing incidence. Most patients with well-differentiated thyroid caner have a favorable prognosis with high survival rate. While surgery and radioiodine therapy is sufficient treatment for the majority of patients with differentiated thyroid cancer, a minority of these patients experiences progressive, life-threatening growth and metastatic spread of the disease. Because there is no prospective controlled study to evaluate the differences of management of thyroid cancer, it is hard to choose the best treatment option. And there are still lots of controversies about the management of this disease, such as surgical extent, proper use of radioiodine for remnant ablation and therapy, use of rhTSH instead of withdrawal of thyroid hormone, long-term follow-up strategy, thyroglobulin as a tumor marker, etc. In this review, recent data related to these conflicting issues and recent advances in diagnosis, radioiodine therapy and long-term monitoring of well-differentiated thyroid cancer are summarized.

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.

Analysis of the Pharmacokinetics of Recombinant Human TSH in Patients with Thyroid Papillary Carcinoma / 대한내분비학회지

BACKGROUND: Individual variations of the pharmacokinetics of recombinant human TSH (rhTSH) might influence the efficacy of the radioactive iodine (RAI) uptake. We studied to investigate the individual pharmacokinetics of rhTSH and the effect of the anthropometric parameters on the serum TSH levels in patients with thyroid papillary carcinoma. METHODS: We selected 16 patients with conventional rhTSH administration for the preparation of RAI administration between June 2004 and May 2005. We measured serum TSH levels at 24-hour (prior to second rhTSH injection), 48-hour (peak level, prior to RAI administration) and 96-hour (prior to scanning) after the first rhTSH injection. We analyzed the correlation of each TSH levels with age, height, weight, creatinine clearance, body mass index (BMI), and body surface area (BSA). RESULTS: Peak TSH levels were negatively correlated with weight, BMI, and BSA. Among them, weight was an independent parameter by multivariate analysis. Decrement of serum TSH levels from the peak to the level at 96-hour was negatively correlated with weight, BMI, and BSA. It was positively correlated with increment of serum TSH levels from the level at 24-hour to the peak level. Serum TSH level at 96-hour was lower than 25 mU/L in nine of 16 patients. CONCLUSION: Body weight was inversely correlated with peak TSH level after rhTSH administration. rhTSH-stimulated TSH levels might be exaggerated to unwanted levels, and very rapidly degraded in lower-weighted patients. We should make up for the rhTSH regimen considering the individual variations of its pharmacokinetics.

Postoperative Adjuvant Therapy and Follow-Up of Thyroid Carcinoma

Differentiated thyroid cancer is usually a curable disease, for which treatment modalities such as surgery, radioiodine, and thyroid hormone have been used for the last 50 years, yet little consensus has been established due to the lack of prospective randomized controlled therapeutic trials. After an initial surgery, the patients' outcome can be predicted by staging classification on the basis of several parameters such as the age of the patient, tumor size, tumor grade or differentiation, presence of local invasion, and regional or distant metastases. However, regardless of the pathologic stage, most patients(except those with micopapillary or minimally invasive follicular carcinomas who underwent only a lobectomies) are supposed to receive radioiodine therapy for ablation of any remnant thyroid tissue, which increases the sensitivity of serum Tg and 131I whole body scan used to detect recurrence or metastasis during a long-term follow-up. Until recently, a high dose of 131I has been preferred, however, low dose therapy(30mCi) is a new trend nowadays, which decreases the incidence of both acute and late complications of radioiodine with the same ablation rate. All patients take thyroid hormone after surgery and radioremnant ablation to suppress the level of serum TSH, which is thought to stimulate tumor cell growth.The T4 dose should be adjusted according to the age of the patient, other medical conditions and the risk of recurrence. During the follow-up, the serum Tg level with anti-Tg antibody and the TSH level and 131I whole body scan should be checked regularly. Recently the serum Tg level stimulated by T4 withdrawal or rhTSH injection is suggested to be the most sensitive marker for the detection of recurrence or metastasis. When the stimulated Tg is undetectable (< 2ng/mL), residual or metastatic cancer can be nearly excluded; when it is higher than 10ng/mL, a high dose 131I therapy and posttherapy 131I whole body scan are needed. In cases where the localization fails(Tg-positive/131I scan-negative cases), other imaging studies such as high-resolution ultrasonography of the neck, spiral CT of chest, bone X-ray or 99mTc-MDP bone scan and 18F-FDG PET scan can be useful. 18F-FDG PET is especially sensitive to detect poorly differentiated thyroid cancers that have lost the ability to uptake radioiodine.

Serum Thyroglobulin Levels Predicting Recurrence and Distant Metastasis after Surgery in Patients with Differentiated Thyroid Cancer / 대한내분비학회지

BACKGROUND: Reports on serum thyroglobulin(Tg) levels being used to predict recurrence or distant metastasis during the follow-up of patients with differentiated thyroid cancer(DTC) has been inconsistent. In addition, there have been few reports that attempt to define the cut-off value of Tg for recurrence or distant metastasis obtained by a receiver operating characteristic(ROC) curve. As well, there are differences in opinions on what the value should be on the first serum Tg level measured just before radioactive iodine(RAI) ablation(Tg-RAI), during thyroxine administration (Tg-on), and after thyroxine withdrawal(Tg-off) during the follow-up. Reports on the positive predictive values(PPVs) and negative predictive values(NPVs) of these Tg values are rare. METHODS: A total of 205 patients(42 males, 163 females) with DTC were studied. All patients had undergone total or near-total thyroidectomy. After surgery and RAI ablation, annual thyroxine withdrawal 131I-whole body scan(WBS) with Tg measurements was performed. The mean duration of follow-up was 5.0 (1.4~7.4) years. The most sensitive and specific Tg values(cut-off values) for tumor recurrence and/or distant metastasis were selected by using ROC curves. We also calculated the PPVs and NPVs for recurrence and/or distant metastasis using two-by-two tables. RESULTS: Cut-off values of Tg-RAI, Tg-on, and Tg-off for recurrence were 11.8, 1.4, and 3.3ng/mL, respectively. For these values, the sensitivities were 85.4, 82.2, and 93.3%, with the specificitiesat 89.2, 92.4, and 88.0%. PPVs were 71.9, 77.1, and 77.0% while NPVs were 95.0, 94,4, and 97.8%. The cut-off values for distant metastasis were 27.4, 2.5, and 7.9ng/mL, respectively. For these cut-off values, the sensitivities were 86.7, 87.5, and 92.3%, with the specificities being 86.2, 90.8, and 80.2%. PPVs were 34.2, 46.7, and 25.0% and NPVs were 98.7, 98.8, and 99.3%. CONCLUSION: All three serum Tg levels were sensitive and specific markers for recurrence and distant metastasis. Their PPVs were low in contrast to the high NPVs. In comparison with Tg-on, Tg-off showed higher sensitivity and NPV as well as lower specificity and PPV. Therefore, in the case of higher Tg-on during the follow-up period, efforts to find recurrence and distant metastasis,such as 131I-WBS, should be done. In addition, regular measurement of Tg-off or Tg after stimulation with recombinant human TSH is recommended as a screening test.

rhTSH in Thyroid Cancer / 대한내분비학회지

No abstract available.