30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study.

OBJECTIVE: To determine the efficacy of low-dose radioactive iodine (RAI) therapy (30 mCi, 1110 MBq) in Chinese patients with intermediate- to high-risk papillary thyroid cancer (PTC) without distant metastasis. DESIGN AND METHODS: This large retrospective study included Chinese patients with PTC that tested negative for thyroglobulin antibodies. Patients were categorized into low-dose (30 mCi, 1110 MBq) and high-dose (>100 mCi, 3700 MBq) RAI groups. Ablation rate and long-term response were compared between groups using propensity score matching (PSM) to minimize bias and confounding. RESULTS: In total, we included 446 patients. No significant difference in ablation success rate was found between groups (P = 0.305) before or after PSM (N = 162; P = 0.200). Excellent response (ER) rate was not significant between groups before (P = 0.917) or after PSM (P = 0.798). Efficacy of low-dose RAI was similar to that of high-dose RAI in N0- (P = 1.000), N1a- (P = 0.981), and N1b-stage (P = 0.903) patients. Low- and high-dose RAI groups achieved similar ER rates in pre-ablative stimulated thyroglobulin level (≤1 ng/mL, P = 1.000; 1 < ps-Tg ≤ 5 ng/mL, P = 0.444; 5 < ps-Tg ≤ 10 ng/mL, P = 0.665; >10 ng/mL, P = 1.000) and BRAFV600E-positive (P = 0.324) subgroups. CONCLUSIONS: Efficacy of low-dose RAI therapy was similar to that of high-dose for ablation and achieving ER in Chinese nonmetastatic intermediate- to high-risk PTC patients. High-dose RAI could not rectify ablation failure or non-ER rates in PTC patients with BRAFV600E, lymph node metastases, or unfavorable thyroglobulin levels.

A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma.

BACKGROUND: Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis, as well as cell status like metabolism changes in distant metastatic tumours have not been clearly elucidated. OBJECTIVE: To identify serum metabolic signature of distant metastatic PTC. DESIGN, PATIENTS AND MEASUREMENTS: In this study, gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) was used to analyse the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and 40 in ablation group). Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) scores plots were used to analyse the data. RESULTS: Principal component analysis and OPLS-DA analyses demonstrated an evident trend of separation between 40 serum samples from the ablation group and 37 samples from distant metastasis group. A total of 31 metabolites were identified, which are related to amino acid, lipid, glucose, vitamin metabolism and diet/gut microbiota interaction. Pathway analysis showed "alanine, aspartate and glutamate metabolism" and "inositol phosphate metabolism" were the most relevant pathways. CONCLUSION: Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biological behaviours of tumour cells including proliferation, invasion/migration and immune escape. Diet/gut microbiota-produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding the distant metastasis of PTC as well as potential adjuvant therapy targets.

The need of prophylactic central lymph node dissection is controversial in terms of postoperative thyroglobulin follow-up of patients with cN0 papillary thyroid cancer.

PURPOSE: The objective of this study was to investigate whether prophylactic central lymph node dissection (pCLND) facilitates postoperative thyroglobulin (Tg) follow-up in the patients with papillary thyroid carcinoma (PTC). We also questioned whether radioactive iodine (RAI) remnant ablation provides any further advantage in this regard. METHODS: The records of patients with low-intermediate risk PTC who underwent either only total thyroidectomy (TT) or TT in conjunction with pCLND were reviewed. Adjuvant RAI ablation was performed depending on tumor diameter, multifocality, the presence of positive lymph nodes and adverse histopathologic features. Pre-ablative and post-ablative Tg levels, post-operative complications and clinico-pathological characteristics were compared between the two groups (TT alone and TT with pCLND). RESULTS: Among the 302 patients, TT was performed in 140 (46.4%) and TT with pCLND in 162 (53.6%). More than half of all patients in both groups had papillary microcarcinoma (58.0% and 53,1%, respectively). Postoperatively, the median preablative Tg level was higher in the TT only group than that of the TT with pCLND group (0.96 vs 0.27 ng/ml, respectively). The post-ablative Tg levels were undetectable in both groups at the last follow-up visit. Also, a subgroup of patients (19.5%) who did not receive RAI ablation all became athyroglobulinemic at one year after surgery. CONCLUSIONS: Although performing pCLND with TT seems to have an advantage over TT alone as to achieve lower Tg levels in the early post-operative period, Tg levels become comparable following RAI ablation. On the other hand, the patients who have not been treated with adjuvant RAI ablation, also became athyroglobulinemic regardless of the surgical method.

Impact of co-existent thyroiditis on clinical outcome in papillary thyroid carcinoma with high preoperative serum antithyroglobulin antibody: a retrospective cohort study.

OBJECTIVES: The aim of this study was to investigate the impact of co-existent chronic lymphocytic thyroiditis (CLT) on changes in serum antithyroglobulin antibody (TgAb) and clinical outcome in papillary thyroid carcinoma (PTC) patients with high preoperative serum TgAb. DESIGN: A retrospective cohort study. SETTING: University teaching hospital. PARTICIPANTS: Thirty-seven PTC patients with high preoperative serum TgAb level (≥100 U/mL) were evaluated. All patients underwent total thyroidectomy followed by high-dose I-131 ablation. MAIN OUTCOME MEASURES: Per cent changes of TgAb between pre-treatment and post-treatment, and disease-free survival were calculated. RESULTS: Twenty-two patients (59.5%) had co-existent CLT, and seven had residual/recurrent tumours. There was a higher proportion of females among the patients with CLT compared to those without CLT (95.5% versus 66.7%; P = 0.0306). There were trends towards more aggressive pathologies, such as tumour size, extrathyroidal extension, surgical margin and lymph node stage, in PTC without CLT than in that with co-existent CLT. Pre-treatment and post-treatment TgAb were all higher in PTC with co-existent CLT. But, per cent changes of TgAb between pre-treatment and post-treatment were no significant difference between PTC with and without CLT (P < 0.05). Patients with co-existent CLT showed a significantly lower residual/recurrent tumour rate than those without CLT (4.5% versus 40%; P = 0.0113). CONCLUSION: Residual/recurrent tumour rate was lower in PTC patients with co-existent CLT than in those without CLT.

[Postoperative radioiodine ablation in patients with low risk differentiated thyroid carcinoma]. / Ablación posquirúrgica con radioyodo en pacientes con carcinoma diferenciado de tiroides de bajo riesgo.

Most patients with newly diagnosed differentiated thyroid carcinoma have tumors with low risk of mortality and recurrence. Standard therapy has been total or near total thyroidectomy followed by postoperative radioiodine remnant ablation (RRA). Although RRA provides benefits, current clinical guidelines do not recommend it universally, since an increase in disease-free survival or a decrease in mortality in low risk patients has not been demonstrated so far. Advancements in our understanding of the biological behavior of thyroid cancer have been translated into the clinic in a personalized approach to the patients based on their individual risk of recurrence and mortality. Current evidence suggests that RRA is not indicated in most low-risk patients, especially those with papillary carcinomas smaller than 1cm, without extrathyroidal extension, unfavorable histology, lymph node involvement or distant metastases. Follow-up of these patients with serial measurements of serum thyroglobulin and neck ultrasound is adequate. Careful evaluation of all risk factors of clinical relevance will allow a more realistic assessment of each individual patient.

Baseline stimulated thyroglobulin level as a good predictor of successful ablation after adjuvant radioiodine treatment for differentiated thyroid cancers.

BACKGROUND: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: This retrospective study accrued 64 patients (23 male and 41 female; mean age of 40±14 years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg<2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. RESULTS: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of ≤14.5 ng/ml was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg≤14.5 ng/ml and 12/36 (33%) patients with baseline STg>14.5 ng/ml ((p value<0.05). Age>40 years, female gender, PTS>2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. CONCLUSIONS: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg <2 ng/ ml, a negative DWBIS and a negative US neck).

Importance of postoperative stimulated thyroglobulin level at the time of 131I ablation therapy for differentiated thyroid cancer.

BACKGROUND: Serum thyroglobulin detection plays an essential role during the follow-up of thyroid cancer patients treated with total/near total thyroidectomy and radioiodine ablation. The aim of this retrospective study was to evaluate the relationship between stimulated serum thyroglobulin (Tg) level at the time of high dose 131I ablation and risk of recurrence, using a three-level classification in patients with differentiated thyroid cancer (DTC) according to the ATA guidelines. Also we investigated the relationship between postoperative stimulated Tg at the time of ablation and DxWBS results at 8-10 months thereafter. MATERIALS AND METHODS: Patients with radioiodine accumulation were regarded as scan positive (scan +). If there was no relevant pathological radioiodine accumulation or minimal local accumulation in the thyroid bed region, this were regarded as scan negative (scan-) at the time of DxWBS. We classified patients in 3 groups as low, intermediate and high risk group for assessment of risk of recurrence according to the revised ATA guidelines. Also, we divided patients into 3 groups based on the stimulated serum Tg levels at the time of 131I ablation therapy. Groups 1-3 consisted of patients who had Tg levels of ≤ 2 ng/ml, 2-10 ng/ml, and ≥ 10 ng/ml, respectively. RESULTS: A total of 221 consecutive patients were included. In the high risk group according to the ATA guideline, while 45.5% of demonstrated Scan(+) Tg(+), 27.3% of patients demonstrated Scan(-) Tg(-); in the intermediate group, the figures were 2.3% and 90.0% while in the low risk group, they were 0.6% and 96.4%. In 9 of 11 patients with metastases (81.8%), stimulated serum Tg level at the time of radioiodine ablation therapy was over 10, however in 1 patient (9.1%) it was < 2 ng/mL and in one patient it was 2-10 ng/mL (p = 0.005). Aggressive subtypes of DTC were found in 8 of 221 patients and serum Tg levels were ≤ 2 ng/ml in 4 of these 8. CONCLUSIONS: We conclude that TSH-stimulated serum thyroglobulin level at the time of ablation may not determine risk of recurrence. Therefore, DxWBS should be performed at 8-12 months after ablation therapy.

Adjuvant radioactive therapy after reoperation for locoregionally recurrent papillary thyroid cancer in patients who initially underwent total thyroidectomy and high-dose remnant ablation.

CONTEXT: Some patients have elevated stimulated thyroglobulin (sTg) concentrations after reoperation for locoregionally recurrent/persistent papillary thyroid cancer (PTC). Little is known, however, about the efficacy of adjuvant radioactive iodine (RAI) therapy in these patients. OBJECTIVE: The objective of the study was to evaluate the efficacy of adjuvant RAI therapy in patients with elevated sTg after reoperation for locally recurrent/persistent PTC. DESIGN AND SETTINGS: This was a retrospective observational cohort study in a tertiary referral hospital. PATIENTS: We evaluated 45 consecutive patients with sTg greater than 2 ng/ml after reoperation for locoregionally recurrent PTC, all of whom had previously undergone initial total thyroidectomy followed by high-dose RAI remnant ablation. Of these 45 patients, 23 received adjuvant RAI therapy (adjuvant group) and 22 did not (control group). MAIN OUTCOME MEASURES: Main outcome measures included changes in sTg concentration after reoperation and disease-free survival. RESULTS: Over time, there were no significant differences in mean sTg concentration in the adjuvant (P = 0.35) and control (P = 0.74) groups. Only 15% of patients in the adjuvant group and 33% in the control group showed a greater than 50% decrease in sTg level from baseline. There were no between-group differences in changes (P = 0.83) or percent decrease (P = 0.97) in sTg concentration and no difference in clinical recurrence-free survival (P = 0.20). CONCLUSION: In patients who still have elevated sTg after reoperation for locally recurrent/persistent PTC, adjuvant RAI therapy compared with no additional RAI therapy resulted in no significant differences in the subsequent sTg changes or the recurrence-free survival.

The value of postoperative parathyroid hormone levels in predicting the need for long-term vitamin D supplementation after total thyroidectomy.

BACKGROUND: Few studies have examined the need for vitamin D supplementation after total thyroidectomy. This study examines the role of postoperative day (POD) 1 serum calcium and parathyroid hormone (PTH) levels in predicting the need for long-term vitamin D supplementation after total thyroidectomy. METHODS: A retrospective, single institutional study of patients who underwent total thyroidectomy between January 2007 and December 2008 was performed. Data collected included extent of surgery, final pathology, postoperative calcium (mg/dl) and PTH (pg/ml) values, and duration of vitamin D supplementation. Patients were divided into 4 groups based on POD1 PTH values: group 1 (<5.0); group 2 (5.0-10); group 3 (10.1-20); and group 4 (>20). RESULTS: Of the 104 patients, 26 were in group 1, 12 in group 2, 18 in group 3, and 48 in group 4, with median PTH values of <2.5, 8.2, 14.1, and 30 pg/ml, respectively. All 7 (7%) patients who required vitamin D supplementation >1 month were in group 1. The positive predictive value of POD1 PTH <5.0 in predicting supplementation >1 month was 27% (sensitivity 100%, specificity 80%). Seventy-eight patients had a POD1 PTH level ≥5, and none required vitamin D supplementation >1 month (100% negative predictive value). The positive predictive value of various POD1 calcium thresholds (<7.5, <8.0, and <8.5 mg/dl) was 17, 14, and 15%, respectively. CONCLUSIONS: Postoperative PTH levels better predict long-term hypocalcemia requiring vitamin D supplementation than serum calcium levels. A PTH level ≥5.0 may identify patients who can be safely discharged without routine vitamin D supplementation.

Empiric high-dose 131-iodine therapy lacks efficacy for treated papillary thyroid cancer patients with detectable serum thyroglobulin, but negative cervical sonography and 18F-fluorodeoxyglucose positron emission tomography scan.

CONTEXT: Some patients with elevated serum thyroglobulin (Tg) but a negative diagnostic whole body scan (WBS) after initial therapy for differentiated thyroid carcinoma may benefit from empirical radioactive iodine (RAI) therapy. However, previous studies enrolled patients with negative diagnostic WBS, regardless of neck ultrasonography (USG) and/or (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), which have become the preferred diagnostic procedures in such patients. OBJECTIVE: The aim of this study was to evaluate the usefulness of empirical RAI therapy in patients with elevated stimulated Tg level and negative USG/FDG-PET findings after initial therapy for papillary thyroid carcinoma (PTC). DESIGN: This comparative study enrolled 39 patients with elevated stimulated Tg, negative diagnostic WBS, and negative USG/FDG-PET 1 yr after initial treatment. Empirical RAI therapy was performed in 14 patients (treatment group), whereas 25 patients were followed up without therapy (control group). RESULTS: There was no significant between-group difference in basal clinicopathological parameters. None of the 14 patients in the treatment group showed iodine uptake on posttreatment WBS. Five of 14 patients (36%) in the treatment group and eight of 25 (32%) in the control group had recurrence during the median 37 months of follow-up (P = 0.99). Changes in serum stimulated Tg concentrations did not differ between the two groups. CONCLUSION: Empirical RAI therapy and posttreatment WBS were not useful diagnostically or therapeutically in patients with positive serum stimulated Tg if such patients had negative USG and negative FDG-PET findings after initial treatment of PTC.

Normocalcemic, subclinical, asymptomatic primary hyperparathyroidism in patients with goiter or papillary thyroid cancer--preliminary report. Normocalcemic primary hyperparathyroidism and thyroid pathology.

UNLABELLED: The aim of the prospective study was the evaluation of primary, subclinical, normocalcemic hyperparathyroidism (PHPT) incidence in patients, operated on because of non-toxic (NTG), toxic (TG) goiter and papillary thyroid cancer (PTC). MATERIAL AND METHODS: The study was performed in the group of 196 patients operated on NTG (115 patients), TG (43 patients) and PTC (38 patients). All patients had never been operated because of goiter. No patient had clinical symptoms of PHPT. Calcium concentration (Ca), phosphorus concentration (P) and alkaline phosphatase activity (ALP) in blood serum were measured in all patients a day before operation. When those parameters were out of range, parathormone concentration (PTH) in blood serum was measured. In the case of elevated PTH concentration PHPT was diagnosed. Furthermore, in order to exclude renal failure and insufficiency tests for creatinine and urea concentrations in blood serum and urinalysis were performed. RESULTS: There was no case of increased Ca concentration among 158 patients with benign goiter. The values of at least one measured parameters (P or ALP) were abnormal in 47 out of 158 patients with benign goiter (29.7%). Increased PTH concentration (mean 101.5 pg/ml) was in 16 of 47 patients (10.1% of 158 patients). Normocalcemic PHPT was diagnosed in 12 (10.4%) NTG patients and 4 (9.3%) TG patients. In patients with PTC hypercalcemia was not affirmed. In 7 (18.42%) cases of 38 PTC patients P concentration and ALP activity were abnormal. Increased PTH concentration (84.85 pg/ml) was found in one female with PTC with normal values of P and ALP. Incidence of PHPT was observed in 2.63% of PTC patients. CONCLUSIONS: 1. There was no significant difference of PHPT incidence between various type of goiter. 2. In our study coexistence of PTC and normocalcemic, asymptomatic PHPT is rare.

Should 'low-risk' thyroid cancer patients with residual thyroglobulin be re-treated with iodine 131?

OBJECTIVE: The American consensus statement on patients with low-risk thyroid cancer, published in 2003, suggests repeat (131)I therapy if the thyroglobulin value is elevated at first follow-up. We evaluated this strategy in our practice. METHODS: Among 407 patients with thyroid cancer who had total thyroidectomy and (131)I ablation between January 2000 and December 2003, 12 patients with stage I thyroid cancer (any tumour (T), any node (N), metastasis (M)0 if < 45 years or T1, N0, M0 if > 45 years), were re-treated on the basis of their thyroglobulin level at first follow-up. Mean patient age was 32.8 years. None of them had a T4 tumour. Thyroglobulin levels after thyroid hormone withdrawal 'off-T4' ranged between 4.5 and 251 ng/ml (median 8). One to four courses of 3.7 GBq (131)I were given. RESULTS: Three patients had a negative (131)I therapy scan and an uneventful course. Two patients had slight residual uptake only in the thyroid bed and negative ultrasound examination. Four patients had isolated (131)I uptake in the mediastinal region. No abnormalities were found on complementary mediastinal imaging. This finding was interpreted as benign (131)I thymic uptake. The last three patients also had mediastinal thymic uptake associated with a slight thyroid bed uptake. One patient had a gradual increase in the thyroglobulin level, and underwent resection of nonfunctioning neck lymph nodes. Thyroglobulin levels declined in all other patients. CONCLUSIONS: No distant lesions were found in a group of young 'low-risk' thyroid cancer patients given empirical (131)I therapy for residual thyroglobulin. When blind (131)I therapy shows no uptake, or uptake limited to the thymus, (131)I therapy should not be repeated. The authors also briefly discuss the hypothesis that enhanced thymus might be a source of benign thyroglobulin secretion.

A randomized clinical trial comparing 50mCi and 100mCi of iodine-131 for ablation of differentiated thyroid cancers.

OBJECTIVE: To compare the efficacy of low (50 mCi) and high dose (100 mCi) Iodine-131 in ablation of differentiated thyroid cancer remnants. METHODS: Baseline serum thyroglobulin (sTg), thyroglobulin antibody (Tg Ab) and diagnostic whole body iodine scan with 2 mCi of I-131 were performed in each individual. After 6 months serum Tg, Tg Ab (of-thyroxin) and WB iodine scan with 10 mCi of I-131 were done to assess the efficacy of the low and high dose of I-131. Iodine ablative therapy (IAT) was considered successful (complete ablation) if the I-131 whole body scan was negative and sTg level was undetectable. In case of positive scan and/or sTg level detectable the patient was considered as unsuccessfully/partially ablated. RESULTS: In group A, (high dose) successful IAT was seen in 12/20 (60%) patients. Of these 5/7 (71%) had follicular Carcinoma on histopathology and 7/13 (54%) had papillary Ca. In group B, (low dose) successful IAT was seen in 8/20 (40%) patients, out of which 3/10 (30%) had follicular Carcinoma on histopathology and had successful IAT. 5/10 (50%) patients with papillary Carcinoma had successful IAT. As far as histopathology is concerned, in group A, response to high dose I-131 was better in follicular type than papillary type. Whereas in group B, response to low dose I-131 was better in patients with papillary type than follicular. CONCLUSION: 100 mCi of radioactive Iodine-131 (I-131) is a more effective therapeutic dose than 50 mCi (I-131) in the treatment of differentiated thyroid cancer remnants. Furthermore, follicular Carcinoma respond better to 100 mCi I-131 than 50 mCi while papillary Carcinoma showed an almost equal response to both.

The role of positron emission tomography/computed tomography in the management of recurrent papillary thyroid carcinoma.

OBJECTIVES/HYPOTHESIS: The aim of the study was to evaluate the role of combined positron emission tomography/computed tomography (PET/CT) fusion imaging in the detection and management of recurrent papillary thyroid cancer. STUDY DESIGN: A retrospective analysis of 33 patients with suspected recurrent papillary thyroid carcinoma who had undergone PET/CT was performed. PET/CT was compared with standard imaging techniques in each patient to determine whether PET/CT contributed to the therapeutic management plan. Histopathological findings were correlated to PET/CT in patients who underwent surgery. METHODS: The senior author reviewed the charts of 33 patients with recurrent papillary thyroid carcinoma to determine the impact PET/CT had on management. PET/CT was compared with conventional imaging results. In surgical patients, PET/CT was compared with histopathological findings to determine its sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. RESULTS: In 67% of the cases (22 of 33), PET/CT supplied additional information that altered or confirmed the management plan. Twenty of 33 patients underwent surgery with 36 sites assessed by histopathological analysis. PET/CT correlated with histopathological findings in 25 of 36 distinct anatomical sites, with an accuracy of 70%. The sensitivity of PET/CT in identifying recurrence was found to be 66%, with a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 27%. CONCLUSION: Combined PET/CT fusion scanning was most useful in the detection and management of recurrent papillary thyroid cancer in patients who had average thyroglobulin levels greater than 10 ng/mL and when the tumor no longer concentrated radioactive iodine. In 100% of the cases in which PET/CT localized a region suspicious for malignancy, histopathological analysis confirmed the results. When PET/CT is positive, it is a powerful tool for predicting exact locations of recurrent papillary thyroid cancer, thus making it a reliable guide for surgical planning. PET/CT is a supplement to conventional imaging and fine-needle aspiration in the workup of recurrent papillary thyroid cancer. A negative finding on PET/CT is not sufficiently reliable to preclude further investigation and treatment.

Plasmapheresis rapidly eliminates thyroid hormones from the circulation, but does not affect the speed of TSH recovery following prolonged suppression.

OBJECTIVE: To report an attempt to shorten the preparation interval before radioactive iodine administration using plasmapheresis in a 77-year-old woman with a history of papillary thyroid carcinoma with local recurrence and lung metastases, in whom the administration of a high dose of radioactive iodine was intended as a desperate rescue procedure. METHODS: The patient was initially started on cholestyramine. Two days later, plasmapheresis was performed. RESULTS: Plasmapheresis rapidly decreased free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)). Serum FT(4) subsequently remained low, while FT(3) recovered the next day. Thyroid-stimulating hormone (TSH) reached 25 mIU/l in 14 days, which is within the time frame required to reach the target TSH level by withdrawing levothyroxine alone. CONCLUSION: Plasmapheresis is very effective in eliminating thyroid hormones from the circulation. However, it does not seem to accelerate thyrotroph recovery to a considerable extent after prolonged suppression.

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.

Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin.

BACKGROUND: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative (131)I diagnostic whole-body scan (WBS) is advocated. However, the therapeutic benefit of this "blind" treatment is not clear. OBJECTIVE: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic (131)I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose (131)I. DESIGN: Retrospective single-center study. METHODS: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi (131)I. Median follow-up from this treatment until the end of observation was 4.2 Years (range 0.5-13.5 Years). RESULTS: The post-treatment WBS revealed (131)I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive post-treatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P=0.001). CONCLUSIONS: High-dose iodine treatment in diagnostically negative patients who have a negative post-treatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.

Lack of impact of radioiodine therapy in tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer.

Several reports have suggested a benefit from radioactive iodine (RAI) therapy in Tg-positive, whole-body scan-negative patients with follicular cell-derived thyroid cancer, who were said to have high rates of visualization of uptake in metastases after therapeutic doses of RAI. We sought to evaluate the rate of visualization of RAI uptake in these patients and determine the effect of such therapy on tumor progression and Tg levels. We studied 24 consecutive patients who had been treated with high-dose RAI, four of whom had no evidence of metastasis or persistent cancer. Our results showed that four patients had some uptake in posttherapy scans: in the neck, lung, and mediastinal metastases in one patient, in the thyroid remnant in two, and in a possible neck microrecurrence in one. In 13 patients with macrometastases-tumors 1 cm or greater-tumors progressed and serum Tg increased; five have died of thyroid cancer. The disease remained stable in the seven patients with micrometastases. We concluded that in high-risk patients with follicular cell-derived thyroid cancer with high Tg levels and negative diagnostic whole-body scans, only a small number showed meaningful uptake after high doses of RAI. Therefore, widespread use of empiric RAI therapy for such patients who have a large tumor burden should not be encouraged.

Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET.

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

Follow-up regimen of differentiated thyroid carcinoma in thyroidectomized patients after thyroid hormone withdrawal.

UNLABELLED: For differentiated, nonmedullary thyroid carcinoma, postsurgical ablation of thyroid remnants and treatment of residual tumor and metastases with 131I is a potentially curative therapy. The aim of this study was to optimize the diagnostic protocol for the follow-up of thyroidectomized patients. METHODS: Two hundred fifty-four patients (187 females, 67 males; mean age, 45 y; range, 8-83 y) were studied retrospectively for a mean follow-up period of 2.7 y (range, 1-12.5 y). An evaluation study consisted of a low-dose 131I diagnostic procedure under hyperthyroid conditions (thyroid-stimulating hormone > 30 MicroU/mL), 201TI scintigraphy, and measurement of thyroglobulin (Tg) under hypothyroid conditions. A total of 254 preablation studies (1 study per patient) and 586 follow-up studies (average number of studies, 2.3 per patient) were evaluated. RESULTS: Before ablation, low-dose 131I screening was useful to estimate the size of the thyroid remnant. Low Tg levels (<10 pmol/L) indicated the absence of metastases. After ablation, undetectable Tg levels indicated the absence of tumor recurrence. When Tg levels were high (>10 pmol/L), local recurrence or metastases were always observed, providing the basis for additional high-dose 131I therapy. In these patients, 201TI imaging did not provide a significant contribution to patient management. In the case of autoantibodies against Tg, both low-dose 131I screening and 201TI scintigraphy may be advocated to allow an aggressive diagnostic work-up. CONCLUSION: Tg plays a key role in follow-up and in making decisions to treat patients with differentiated thyroid carcinoma. The role of 201TI imaging is very limited. In patients with negative low-dose 131I screening, 201TI scintigraphy can be considered when Tg is elevated or cannot be evaluated because of autoantibodies against Tg. Under such circumstances, administration of a therapeutic 131I dose without 201TI imaging can be considered.