Radioiodine ablation and therapy in differentiated thyroid cancer under stimulation with recombinant human thyroid-stimulating hormone

We investigated whether recombinant human TSH (rhTSH) safely and effectively induces uptake of high-dose 131-iodine (131I) to ablate thyroid remnant or treat disease, in patients with well-differentiated thyroid carcinoma. Eleven consecutive patients unable to tolerate thyroid hormone withdrawal received one im injection of 0.9 mg rhTSH on 2 consecutive days before receiving 4000 MBq (approximately 108 mCi) radioiodine orally. Eight patients received one, and 3 patients 2 courses. Our series comprised 7 women and 4 men (mean age, 78 yr, range: 56-87 yr). Ten patients had undergone total or near-total thyroidectomy up to 19 yr earlier. rhTSH-stimulated single course radioiodine with the intention to ablate thyroid remnant was performed in 3 patients, with following estimation of radioiodine uptake and TG measurements. Of another 8 patients given this treatment palliatively, 5 had radiological, clinical and/or laboratory response, including: 80% decreased pathological uptake between treatment courses; pronounced decrease in bone pain; diminished symptoms; improved physical condition and quality of life; lower serum TG concentration; and/or normalization of TG recovery test. Two patients with small lung metastases on computed tomography had no detectable radioiodine uptake or other response; they also lacked uptake after withdrawal-stimulated radioiodine treatment. Despite being elderly and frail, patients generally tolerated treatment well; rhTSH caused nausea in one patient and transiently increased pain in bone and soft tissue lesions in another. We conclude that rhTSH-stimulated high-dose radioiodine for remnant ablation or tumor treatment is safe, feasible and seemingly effective, enhancing quality of life and offering reasonable palliation in patients with advanced disease.     

Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid.

We performed a retrospective record review of patients who received large lobar remnant ablation after surgery for well-differentiated thyroid carcinoma including 30 with papillary carcinoma, 14 with follicular carcinoma, and 6 with Hürthle cell carcinoma. We compared these 50 patients to a group of patients who underwent total or near-total thyroidectomy for well-differentiated thyroid carcinoma. The ablation group was treated with single outpatient doses of 29.9 mCi (131)I to prepare for whole-body radioiodine scanning. Subsequent serum thyrotropin (TSH) concentration during thyroid hormone withdrawal was greater than 25 microU/mL in 94% of patients. The mean TSH in this population (76 microU/mL) was not statistically different from a group of 50 patients who underwent total or near-total thyroidectomy (mean, TSH 71 microU/ml p = 0.84). Twenty-four hour radioiodine uptake post-29.9 mCi (131)I ablation was less than 1% in 80% of patients. The mean radioiodine uptake (0.8%) in the lobe ablation population was significantly lower than in patients treated with total thyroidectomy (mean, 2.4%, p < 0.001). There was minimal morbidity after 29.9 mCi (131)I ablation of large lobar remnants. Outpatient 29.9 mCi (131)I ablation is a safe, effective, and less costly alternative to completion thyroidectomy in selected patients. Although we included patients with both papillary and follicular carcinoma in our review, we recommend this method for patients with minimally invasive follicular carcinoma requiring whole body scanning, even with large postsurgical remnants in place.     

Ablation of the thyroid remnant and 131I dose in differentiated thyroid cancer

AIMS: To compare the efficacy of remnant ablation following a single low dose (specific activity of 131I administered, 1074-1110 MBq) vs. a single high dose (mostly 2775-3700 MBq) of 131I in patients with differentiated thyroid cancer and to determine whether or not the extent of surgery influences outcome. METHODS: Nineteen studies have reported the results of low dose 131I ablation. Of these, 11 met our criteria for a comparative analysis. Two additional cohorts of ours were added and these were analysed in two groups based on the extent of surgery (near-total [NT; Woodhouse1] vs. sub-total [ST; Woodhouse2]). There were 518 low dose and 449 high dose patients in all. RESULTS: The average failure of a single low dose was 46 +/- 28% (SD). Meta-analysis revealed a statistically significant advantage for a single high over a single low dose and a pooled reduction in relative risk of failure of the high dose of about 27% (P < 0.01). From this we estimate that for every seven patients treated one more would be ablated given a high rather than a low dose (assuming a low dose failure risk of 50%). Also, a significantly greater proportion of patients are ablated after a single high or low dose, if they underwent near-total as opposed to sub-total thyroidectomy (summary relative risk (RR) 1.4; P < 0.05). CONCLUSION: High dose 131I is more efficient than low dose for remnant ablation particularly after less than total thyroidectomy. Results suggest that patients with differentiated thyroid cancer should routinely have a total thyroidectomy followed by high dose 131I (2775-3700MBq) for ablation of the remnant.     

Enhanced scintigraphic visualization of thyroglossal duct remnant during hypothyroidism after total thyroidectomy: prevalence and clinical implication in patients with differentiated thyroid cancer.

OBJECTIVE: The exact prevalence and clinical significance of ectopic thyroid or thyroglossal duct remnant (TGDR) in the general population have not yet been fully determined despite numerous case reports. This study was prepared to assess the prevalence of TGDR in asymptomatic subjects during hypothyroidism after a total thyroidectomy for differentiated thyroid cancer (DTC) and to clarify the clinical implication. DESIGN: Tc-99m pertechnetate scintigraphy (Tc-scan) of the head and neck before radioiodine ablation therapy and whole-body and pinhole I-131 scintigraphy (I-scan) after ablation therapy were reviewed for 131 consecutive DTC patients with hypothyroidism after a total thyroidectomy. MAIN OUTCOME: Forty-four among the 131 patients (33.6%) revealed an unexpected linear or focal radioactivity at the anterior midline of the neck, suggesting the presence of TGDR. The Tc-scan and pinhole I-scan were concordant in all cases of abnormal midline neck uptake, although the planar I-scan failed to delineate TGDR due to prominent photon scattering in most cases. Preoperative enhanced neck computed tomography scan was performed in 49 patients and showed no evidence of thyroid glandular tissue separated from thyroid gland in midline of the anterior neck except 1 case. The success rate after radioiodine ablation did not differ significantly between the positive and negative TGDR patients. CONCLUSIONS: TGDR can be frequently observed in scintigraphy of hypothyroid subjects after a thyroidectomy, even when clinically unexpected. Therefore, care should be taken not to confuse the tracer uptake by TGDR with metastatic foci in I- and Tc-scans of patients with hypothyroidism after a thyroidectomy for DTC.     

Local reactions to radioiodine in the treatment of thyroid cancer

PURPOSE: To compare the rate of local complications resulting from radioiodine ablation of thyroid cancer in patients with a residual intact thyroid lobe to that in patients who had more extensive surgical treatment prior to radioiodine administration. PATIENTS AND METHODS: We retrospectively studied 59 patients who had received 131I between 1979 and 1989. The patients were divided into two groups, depending on the extent of their previous surgical thyroid excision. Group 1 comprised 10 patients with a lobectomy or hemithyroidectomy before the ablative radioiodine dose, and Group 2 comprised 49 patients with more extensive thyroid excision (near-total or subtotal thyroidectomy) before the radioiodine treatment. RESULTS: Sixty percent of the 10 patients in Group 1 experienced some degree of neck pain or tenderness following radioiodine ablation of their residual thyroid. In one case, the local reaction was very severe and accompanied by the development of transient hyperthyroidism. There was only a 6% local complication rate in the patients who had undergone more extensive thyroid excision before ablative therapy (p less than 0.001), and none had a severe reaction. CONCLUSIONS: Patients with only unilateral surgical excision before radioiodine therapy have a higher rate of local complications than do patients treated with more extensive surgery prior to radioiodine ablation. If radioiodine is to be employed in such patients, they should be informed of this possible complication. Since evidence supports a dose effect in the pathogenesis of the complications, we recommend using a dose of less than 30 mCi for the initial ablation in these patients even though it may be necessary to repeat this dose to complete thyroid ablation.     

Follow-up of differentiated thyroid carcinoma

Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.     

Radioiodine dose for remnant ablation in differentiated thyroid carcinoma: a randomized clinical trial in 509 patients

Remnant ablation can be achieved by either administering an empiric fixed dose or using dosimetry-guided techniques. Because of the technical and logistic difficulties, most centers have adapted the fixed-dose or standard-dose technique for remnant ablation using (131)I. In the late 1970s, low-dose (131)I remnant ablation was introduced, and subsequently many centers confirmed the effectiveness of such therapy. However, the optimal dose (administered activity) of (131)I for remnant ablation is not yet settled. In a randomized clinical trial to find out the smallest possible effective dose for remnant ablation in cases of differentiated thyroid carcinoma, between July 1995 and January 2002, 565 patients were randomized into eight groups according to (131)I administered activity, starting at 15 mCi and increasing activity in increments of 5 mCi until 50 mCi. In the postrandomization phase, 56 patients were excluded from the study for various reasons, and final analysis was done with 509 patients. The mean age of the patients was 37.5 +/- 12.7 yr with a female to male ratio of 2.6. The surgical procedure was total/near-total thyroidectomy in 72% and subtotal or hemithyroidectomy in the rest. Histology was papillary thyroid carcinoma in 80.6% of patients and follicular thyroid carcinoma in the rest. With one dose of (131)I, remnant ablation was achieved in 59.6, 63.6, 81.4, 83.6, 79.4, 78.3, 84.4, and 81.8% of patients in the 15- to 50-mCi groups, respectively (overall ablation rate, 77.6%). The successful ablation rate was statistically different in patients receiving less than 25 mCi of (131)I compared with those receiving at least 25 mCi [63 of 102 (61.8%) vs. 332 of 407 (81.6%); P = 0.006]. However, there was no significant intergroup difference in outcome among patients receiving 25-50 mCi of (131)I. Patients with small tumor size (相似文献   

Thyroglobulin measurement before rhTSH-aided 131I ablation in detecting metastases from differentiated thyroid carcinoma

Aim Thyroidectomy followed by administration of large activities of 131‐iodine (¹³¹I) is the treatment of choice for differentiated thyroid carcinoma (DTC). The serum thyroglobulin (Tg) measurement during hypothyroidism (offT4‐Tg), just before radioiodine thyroid ablation, has proved to be effective for predicting persistent/recurrent disease. However, the Tg measurement cannot be used as a corresponding value for pre‐ablative offT4‐Tg when recombinant human TSH (rhTSH) is used as stimulus before treatment. The present study was undertaken to evaluate if post‐thyroidectomy Tg values, measured before rhTSH‐stimulated radioiodine ablation is of prognostic value in patients affected by DTC. Methods We enrolled 126 patients with DTC submitted to total thyroidectomy. T4 treatment was started just after surgery to suppress TSH levels and Tg levels (onT4‐Tg) were measured just before rhTSH‐aided thyroid ablation by ¹³¹I (3700 MBq). Neck radioiodine uptake (RAIU) was measured just before ablation and a post‐treatment whole body scan (PT‐WBS) was performed. Results A significant relationship was found between thyroid remnants’ RAIU and onT4‐Tg levels (P < 0·001). The 1·10 ng/ml onT4‐Tg threshold selected by ROC curve analysis identifies patients with positive PT‐WBS with 83·3% sensitivity, 65·7% specificity, 44·5% positive predictive value (PPV) and 93·6% negative predictive value (NPV). The 0·65 ng/ml cut‐off level recognizes metastatic patients with 82·9% sensitivity, 55·2% specificity, 43·3% PPV and 97·8% NPV when compared with 12 months restaging results. Among 63 patients with initially undetectable onT4‐Tg (i.e. ≤ 0·2 ng/ml) none had positive PT‐WBS nor DTC relapse at 12‐month restaging (NPV 100%). Conclusions Based on our data we conclude that pre‐ablative onT4‐Tg is a prognostic marker and should be used instead of pre‐ablative TSH‐stimulated Tg measurement when rhTSH‐aided radioiodine ablation is done.     

Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review

Well under 15% of differentiated thyroid carcinoma (DTC) is diagnosed at < or =18 years of age. The population is heterogenous and the differences between prepubertal children and pubertals and adolescents are to be considered. Although very little has been reported on children with sporadic DTC under the age of 10 years, juvenile DTC has at least some undeniable differences with adult DTC: (1) larger primary tumor at diagnosis; (2) metastatic pattern and features, namely: (a) greater prevalence of neck lymph node and distant metastases at diagnosis, (b) lungs almost the sole distant metastatic site, (c) pulmonary metastases nearly always functional; (3) closer-to-normal and more frequent sodium-iodide symporter (NIS) expression; and (4) higher recurrence rate but longer overall survival. These differences are especially distinct in prepubertal children. The goals of primary treatment of juvenile DTC are to eradicate disease and extend not only overall, but recurrence-free survival (RFS). Extending RFS is itself a desirable goal in children because it improves quality-of-life, alleviates anxiety during psychologically formative years, reduces medical resource consumption, and may increase overall survival. Primary treatment of DTC generally comprises a combination of surgery, radioiodine ((131)I) ablation, and thyroid hormone therapy applied at varying levels of intensity. Therapeutic decision-making must rely on retrospective adult and/or pediatric outcome studies and on treatment guidelines formulated mostly for adults. Differences between juvenile and adult DTC and physiology dictate distinct treatment strategies for children. We, and many others, advocate a routine intensive approach because of the more advanced disease at diagnosis, propensity for recurrence, and greater radioiodine responsiveness in children, as well as published evidence of significant survival benefits, especially regarding RFS. This intensive approach consists of total thyroidectomy and central lymphadenectomy in all cases, completed by modified lateral lymphadenectomy when necessary and followed by radioiodine administration. However, absence of prospective studies and of universal proof of overall cause-specific survival benefits of this approach have led some to propose more conservative strategies. Most European centers give radioiodine ablation to the vast majority of juvenile DTC patients. Ablation seeks to destroy any residual cancer, including microfoci, as well as healthy thyroid remnant. Large studies have documented the procedure to decrease cause-specific death rates and, in children, to significantly lessen locoregional recurrence rates (by factors of 2-11) independent of the extent of surgery. There is universal agreement on treating inoperable functional metastases with large radioiodine activities. Treatment is especially effective in small tumor foci up to 1 cm in diameter, and should be administered every 6-12 months until complete response, loss of functionality, or attainment of cumulative activities between 18.5-37 GBq (500-1000 mCi). Radioiodine therapy is generally safe. Short-term side effects include nausea and vomiting (more frequent in children than in adults), transient neck pain and edema, sialadenitis (<5% incidence), mild myelosuppression (approximately 25%), transient impairment of gonadal function both in females and males (sperm quality in boys), or nasolacrimal obstruction (approximately 3%), with most cases generally being asymptomatic-moderate, self-limiting, or easily prevented or treated. If pregnancy is ruled out before each (131)I administration, and conception avoided in the year afterward, radioiodine therapy appears not to impair fertility. However, therapeutic (131)I carries a small but definite increase in cancer risk, particularly in the salivary glands, colon, rectum, soft tissue and bone. To better guide primary treatment, different therapeutic combinations should be prospectively compared using RFS as the primary endpoint. Efforts also should be made to identify molecular signatures predicting recurrence, metastasis and mortality.     

The management of well-differentiated thyroid cancer with end-stage renal disease

The occurrence of thyroid cancer in patients with endstage renal disease is rare. We have had the experience of treating two such patients. The problems, encountered in these patients, were the enlarged parathyroid glands at the time of total thyroidectomy and the treatment of these patients with 131I when the biologic halflife of radioiodine increases after hemodialysis. Both patients were treated by total thyroidectomy and postoperative administration of 131I, either empirically or dosimetrically, and are living and well, 9 yr and 7 yr after operations, respectively.     

Natural history, treatment, and course of papillary thyroid carcinoma

We have analyzed the course of papillary thyroid carcinoma in 269 patients managed at the University of Chicago, with an average follow-up period of 12 yr from the time of diagnosis. Patients were categorized by clinical class; I, with intrathyroidal disease; II, with cervical nodal metastases; III, with extrathyroidal invasion; and IV, with distant metastases. Half of the patients had a history of thyroid enlargement known, on the average, for over 3 yr. In 15% of patients given thyroid hormone, the mass decreased in size. The peak incidence of cancer was when subjects were between 20-40 yr of age. Tumors averaged 2.4 cm in size; 21.6% had tumor capsule invasion, and 46% of patients had multifocal tumors. Sixty-six percent of the patients had near-total or total thyroidectomy. The overall incidence of postoperative hypoparathyroidism was 8.4%, but the incidence was zero in 83 near-total or total thyroidectomies carried out by 1 surgeon. Twenty-five percent of the patients had continuing or recurrent disease, and 8.2% died from cancer. Deaths occurred largely in patients with class III or IV disease. Cervical lymph nodes were associated with increased recurrences, but not increased deaths. Extrathyroidal invasion carried an increased risk of 5.8-fold for death, and distant metastases increased this risk 47-fold. Age over 45 yr at diagnosis increased the risk of death 32-fold. Tumor size over 3 cm increased the risk of death 5.8-fold. Surgical treatment combining lobectomy plus at least contralateral subtotal thyroidectomy was associated, by Cox proportional hazard analysis, with decreased risk of death in patients with tumors larger than 1 cm and decreased risk of recurrence among all patients, including patients in classes I and II, compared to patients who underwent unilateral thyroid surgery or bilateral subtotal resections. By chi 2 analysis, 131I ablation of residual thyroid tissue after operation was associated with decreased risk of recurrence in tumors larger than 1 cm and decreased risk of death in patients in classes I and II with tumors more than 1 cm in size. The data strongly support the use of more extensive initial surgery in class I and II patients with tumors more than 1 cm in size as well as postoperative radioactive 131I ablation of thyroid remnant tissue.     

Is chest x-ray or high-resolution computed tomography scan of the chest sufficient investigation to detect pulmonary metastasis in pediatric differentiated thyroid cancer?

We reviewed the clinical characteristics, pattern of disease at presentation, histopathologic subtype, treatment, course, and outcome of differentiated thyroid cancer (DTT) in children and adolescents presenting with pulmonary metastasis and tried to assess the effectiveness of routine chest x-ray and high-resolution computed tomography (CT) scan of the chest vis-à-vis 131I whole-body scan (WBS) in revealing pulmonary metastasis. In our series of 1754 patients, 122 (7%) were 20 years of age or younger, of whom 28 (23%) had pulmonary metastasis. Mean age was 13.9 +/- 4.4 years (F:M ratio = 12:16). All but 2 patients had undergone near-total thyroidectomy with some form of neck dissection. Histopathologic examination was papillary in 89% and follicular in 11% cases, with confirmed nodal metastasis in all. Twenty-one (75%) patients had normal chest x-ray. However, WBS revealed pulmonary metastasis in all cases. In 15 (54%) children pulmonary metastasis was detected by first postsurgery 2-3 mCi 131I WBS and in 4 (14%) patients by postablation 131I WBS. Seven cases (25%) and 2 cases were detected by first and second posttherapy 131I WBS, respectively. No statistically significant difference was observed in any of the demographic or clinical parameters in patients in whom pulmonary metastasis was detected by first postsurgical low-dose WBS versus those in whom metastasis was discovered at a later stage. When chest x-ray-positive children were compared to x-ray-negative children, a statistically significant difference was observed only for mean first dose, cumulative dose, and total number of doses of 131I, which were significantly higher in x-ray-positive children. Eighteen of 21 children who had normal chest x-ray also underwent CT scan of the chest. CT could detect micronodular pulmonary shadows in 5 (28%) children only. Complete radioiodine treatment and outcome information was available in 20 patients. Mean first dose and cumulative doses of administered 131I were 75.4 +/- 39.5 mCi and 352 +/- 263 mCi, respectively. After an average number of 3.3 doses of (131)I and mean duration of 33.2 +/- 28.5 months, pulmonary lesions disappeared in 14 (70%) patients and thyroglobulin (Tg) becoming undetectable. In 4 children, however, there was no radiologic or scintigraphical evidence of pulmonary metastasis, Tg was high and in 2 patients, disease was persisting clinically. To conclude, a large majority of pediatric patients with DTC have x-ray- and even high-resolution-negative pulmonary metastasis. However, these metastases are 131I avid, and thus are amenable to detection and treatment with radioiodine. Therefore, postsurgical evaluation with 131I is recommended in all children and adolescents.     

Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review.

Current treatment strategies for pediatric patients with nonmedullary, well-differentiated thyroid carcinoma (WDTC) are derived from single-institution clinical cohorts, reports of extensive personal experience, and extrapolation of several common therapeutic practices for this tumor in adults. Because pediatric WDTC is an uncommon malignancy, the issues of its optimal initial and subsequent long-term treatment and follow-up remain controversial. Pediatric patients with WDTC can be divided into two groups: children younger than 10 years of age and teenagers/adolescents between 10 and 18 years of age because these groups have different recurrence and mortality rates. We hereby present our views and interpret them in the light of the pertinent literature. Our recommendations on treatment strategies are more relevant for younger children. After midpuberty, optimal treatment is adequately addressed in the relevant literature on adults. For the majority of patients, total/near-total thyroidectomy is currently recommended as the standard initial therapy for WDTC. This is commonly followed by administration of radioiodine (RAI; (131)I) therapy to destroy residual normal thyroid tissue (remnant). Routine (131)I remnant ablation has been shown to: (1). decrease the risk of local recurrences, (2) increase the sensitivity of subsequent diagnostic RAI whole-body scanning (WBS), and (3) render serum thyroglobulin (Tg) a highly sensitive marker for recurrent/residual disease during long-term follow-up. We recognize that the above practices are not universally adhered to in children and adolescents, because the risk stratification and intensity of applied therapeutic measures are influenced by institutional traditions and personal experience. In our view, aggressive initial management, followed by evaluations at regular intervals after thyroidectomy and (131)I remnant ablation, in conjunction with long-term thyroid hormone suppressive therapy (THST), result in decreased recurrence rates in pediatric patients with WDTC. Follow-up examinations should include a diagnostic RAI ((131)I or (123)I) WBS and measurement of serum Tg, both performed under conditions of TSH stimulation, as well as neck ultrasonography (US). Our strategy is corroborated by data from retrospective clinical cohort studies. In this malignancy, no evidence of disease (NED) status can be defined as the combination of a negative diagnostic WBS and the presence of undetectable or low serum Tg levels, both tested under TSH stimulation. These findings should be accompanied by the absence of anatomically definable disease by standard imaging modalities, e.g., neck US or chest computed tomography (CT). Although the long-term survival rates are good overall in this disease, selected patients may require further surgery or (131)I therapy for the eradication or clinical control of metastases. Finally, and importantly, because the duration of follow-up is lifelong, the care of children with prior diagnosis of WDTC should be transferred to an adult endocrinologist after they reach adulthood, even if they have achieved NED status by that time.     

Incidentally Visualization of the Thymus on Whole-Body Iodine Scintigraphy: Report of 2 Cases and Review of the Latest Insights

Radioiodine uptake is not commonly seen by the thymus gland. On the contrary, the gland is slowly replaced by fat after puberty. Herein, we present 2 patients with papillary thyroid carcinoma, follicular variant, and cervical lymph node involvement. After total/near-total thyroidectomy, the patients received ¹³¹I for ablation therapy. On posttreatment radioiodine scintigraphy, mediastinal ¹³¹I uptake was noted that finally was histologically/anatomically diagnosed as thymus gland uptake. It should be borne in mind as a potential cause of false-positive whole-body ¹³¹I scintigraphy.     

Management of papillary and follicular (differentiated) thyroid cancer: new paradigms using recombinant human thyrotropin

The incidence of differentiated thyroid cancer (DTC) has increased in many places around the world over the past three decades, yet this has been associated with a significant decrease in DTC mortality rates in some countries. While the best 10-year DTC survival rates are about 90%, long-term relapse rates remain high, in the order of 20-40%, depending upon the patient's age and tumor stage at the time of initial treatment. About 80% of patients appear to be rendered disease-free by initial treatment, but the others have persistent tumor, sometimes found decades later. Optimal treatment for tumors that are likely to relapse or cause death is total thyroidectomy and ablation by iodine-131 ((131)I), followed by long-term levothyroxine suppression of thyrotropin (TSH). On the basis of regression modeling of 1510 patients without distant metastases at the time of initial treatment and including surgical and (131)I treatment, the likelihood of death from DTC is increased by several factors, including age >45 years, tumor size >1.0 cm, local tumor invasion or regional lymph-node metastases, follicular histology, and delay of treatment >12 months. Cancer mortality is favorably and independently affected by female sex, total or near-total thyroidectomy, (131)I treatment and levothyroxine suppression of TSH. Treatments with (131)I to ablate thyroid remnants and residual disease are independent prognostic variables favorably influencing distant tumor relapse and cancer death rates. Delay in treatment of persistent disease has a profound impact on outcome. Optimal long-term follow-up using serum thyroglobulin (Tg) measurements and diagnostic whole-body scans (DxWBS) require high concentrations of TSH, which until recently were possible to achieve only by withdrawing levothyroxine treatment, producing symptomatic hypothyroidism. New paradigms, however, provide alternative pathways to prepare patients for (131)I treatment and to optimize follow-up. Patients with undetectable or low Tg concentrations and persistent occult disease can now be identified within the first year after initial treatment by recombinant human (rh)TSH-stimulated serum Tg concentrations greater than 2 microg/l, without performing DxWBS. These new follow-up paradigms promptly identify patients with lung metastases that are not evident on routine imaging, but which respond to (131)I treatment. In addition, rhTSH can be given to prepare patients for (131)I remnant ablation or (131)I treatment for metastases, especially those who are unable to withstand hypothyroidism because of concurrent illness or advanced age, or whose hypothyroid TSH fails to increase.     

Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas

Data for patients with bone metastases (BMs) of differentiated thyroid carcinoma (DTC) were retrospectively studied to identify factors associated with survival. We especially studied the impact of therapies. Among the 1977 patients followed for DTC in our department from 1958 to 1999, 109 (77 females and 32 males; age range, 20--87 yr) presented BMS: All patients except 1 underwent total thyroidectomy, followed by radioiodine therapy (> or =3.7 gigabecquerels) in 95 cases. Survival rates at 5 and 10 yr were 41% and 15%, respectively. Univariate analyses indicated that a young age at BM discovery (P < 0.005) and the discovery of BM as a revealing symptom of DTC (P < 0.05) were features significantly associated with improved survival as well as radioiodine therapy (P < 10(-4)) and BM complete surgery (P < 0.02). Using multivariate analysis, the detection of BMs as a revealing symptom of thyroid carcinoma (P < 0.0005), the absence of metastasis appearance in other organs than bones during the follow-up (P < 0.03), the cumulative dose of radioiodine therapy (P < 0.0001), and complete BM surgery in young patients (P < 0.04) appeared as independent prognostic features associated with an improved survival.     

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with 131I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after 131I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.     

Clinical value of different responses of serum thyroglobulin to recombinant human thyrotropin in the follow-up of patients with differentiated thyroid carcinoma.

In the present study we examined the clinical value of a differential response of thyroglobulin (Tg) concentration after recombinant human thyrotropin (rhTSH) stimulation (rhTSH Tg testing) and its correlation with (131)I uptake and whole-body scanning (rhTSH-WBS) in 104 patients who had previously undergone near-total thyroidectomy and (131)I ablation for differentiated thyroid carcinoma (DTC). rhTSH Tg testing was considered negative for rhTSH-Tg less than 0.9 ng/mL, low positive for rhTSH-Tg of 1-5 ng/mL and high positive for rhTSHTg greater than 5 ng/mL. rhTSH Tg testing was negative in 70 patients, 1 of whom had a lymph-node metastasis, but no (131)I uptake. Seven patients had low positive rhTSH Tg testing and no (131)I uptake, but 2 of these patients had cervical lymph node metastases. Twenty-seven patients had high positive rhTSH Tg testing and (131)I uptake was detected in lung, bone, or mediastinum in 11. Imaging techniques (computed tomography [CT], magnetic resonance imaging [MRI], fluorine-18 2-fluoro-2-deoxy-D-glucose-positron emission tomography [FDGPET]) documented metastatic disease in 22. In conclusion, our results suggest that any rise in rhTSH-Tg, even at low level, should raise the suspicion of persistent or recurrent DTC. Patients with rhTSH-Tg at high level should be carefully evaluated, because DTC persistence is highly probable. TSH-WBS provides little adjunctive information.     

An overview of the management of papillary and follicular thyroid carcinoma.

Long-term survival rate for papillary and follicular carcinoma is more than 90%, but this varies considerably among subsets of patients. About 30% of patients, however, develop tumor recurrence, depending on the initial therapy. Two-thirds of the recurrences occur within the first decade after therapy, but the others may appear years later. We found that among patients with recurrent cancer, 30% could not be fully eradicated and another 15% died of disease. Tumor recurred outside the neck in 21% of our patients, most commonly in the lungs (63%), which resulted in death in about half the patients. Mortality rates are lower when recurrences are detected early by radioiodine scans rather than by clinical signs. We believe that the best treatment for most patients with differentiated thyroid carcinoma is near-total thyroidectomy followed by 131I ablation of the thyroid remnant, which in our experience reduces the recurrence rate, improves survival and facilitates follow-up. A long delay in initiating this therapy has an adverse and independent effect on prognosis, more than doubling the 30-year cancer mortality rate. If only partial lobectomy has been performed, it is best to consider completion thyroidectomy for lesions 1 cm or larger because of the high rate of residual carcinoma in the contralateral lobe. Completion thyroidectomy and 131I whole-body scanning allows for the diagnosis and treatment of unrecognized carcinoma and when performed early, results in significantly fewer lymph node and hematogenous recurrences and enhances survival. A large and growing number of studies demonstrates decreased recurrence of papillary carcinoma and decreased disease-specific mortality attributable to 131I therapy. On the basis of our observations and other studies, we believe that an aggressive approach to initial management and follow-up may render nearly 90% of the patients permanently free of disease. Periodic follow-up should be done with whole-body scanning and serum thyroglobulin (Tg) measurements, performed either during thyroid hormone withdrawal or by recombinant human thyrotropin (TSH)-stimulated scanning and Tg measurement. A scheme for follow-up management is presented.     

重组人促甲状腺素介导分化型甲状腺癌的131I治疗

目的 研究重组人促甲状腺素(rhTSH)介导分化型甲状腺癌131I治疗对内源性TSH、甲状腺球蛋白、FT3、FT4的影响及其清甲成功率.方法 31例(年龄14～70岁,其中女性23例)接受rhTSH介导的131I治疗(甲状腺功能正常组),31例(年龄23～72岁,其中女性22例)停用甲状腺素后的行131I治疗[甲状腺功能减退组(甲减组)]观察注射rhTSH前后血清TSH、FT3、FT4以及甲状腺球蛋白抗体(TGAb)、甲状腺球蛋白浓度变化,以及131I治疗后6～12个月131I全身诊断显像评价其疗效.结果 使用rhTSH前后,血清TSH、甲状腺球蛋白、FT3、FT4的平均浓度分别是(1.08±4.01)和(140.26±27.20)mIU/L(P＜0.05)、(23.75±132.92)和(169.58±178.49)μg/L(P＜0.05)、(4.52±1.16)和(4.42±1.11)pmol/L(P＞0.05)、(15.09±5.83)和(13.66±5.85)pmol/L(P＞0.05).诊断剂量131I-全身显像显示甲状腺功能正常组24/31(77.4%)及甲减组22/31(71.0%)被考虑成功清甲(P＞0.05).以甲状腺球蛋白评价两组131I治疗疗效统计学无显著差异(P＞0.05),甲状腺功能正常组20/31(64.50%)及甲减组18/31(58.06%)被考虑成功清甲.结论 使用rhTSH能有效刺激内源性TSH增高,提高生活质量,获得较高的清甲成功率.使用rhTSH能有效刺激血清甲状腺球蛋白,有利于监测肿瘤残存、复发与转移.

Abstract：

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.