Patients with high-risk differentiated thyroid cancer have a lower I-131 ablation success rate than low-risk ones in spite of a high ablation activity.

OBJECTIVE: To examine success rates in strictly defined high-risk differentiated thyroid cancer (DTC) patients who received a high-activity (≥5550 MBq) adjuvant postoperative I-131 therapy and compare these to the rates found in highest risk and low-risk patients. DESIGN: Retrospective database study. PATIENTS: We examined 377 patients with DTC who received I-131 ablation. Patients with distant metastases were classified as very high risk. Patients with primary tumours >4 cm, extensive extrathyroidal invasion (pT4a or pT4b in accordance with the 7th edition of the TNM system), and patients with ≥5 lymph node metastases or any lateral compartment lymph node metastases were considered high risk. All other patients were considered low risk. MEASUREMENTS: Ablation success rate at first TSH-stimulated follow-up. RESULTS: The ablation success rate was 72·6% in low-risk patients, 51·7% in high-risk patients and 13·8% in highest risk patients (all differences P < 0·001). In none of the groups, a significant difference in the initial I-131 activity was found between patients with successful and unsuccessful ablation (low risk: P = 0·16, high risk: P = 0·91 and highest risk: P = 0·48). Furthermore, there was no difference in ablation success between patients who received <5550 MBq and those who received ≥5550 Mbq (low risk: P = 0·31, high risk: P = 0·69 and highest risk: P = 0·22). CONCLUSIONS: Patients with high-risk DTC have a significantly reduced I-131 ablation success rate compared to low-risk ones in spite of high initial I-131 activities. As successful ablation is prognostically important, efforts should be made to improve outcome in these patients.

Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

PURPOSE: To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. METHODS: Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. RESULTS: In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. CONCLUSION: In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

The thyroid axis 'setpoints' are significantly altered after long-term suppressive LT4 therapy.

The aim of the study was to investigate the changes in the thyroid axis setpoint after long-term suppressive levothyroxine therapy for differentiated thyroid carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine differentiated thyroid cancer patients were reviewed. All patients had at least one known TSH-level≥0.01 mU/l (lower detection limit) and <1.0 mU/l within 2 years of initial treatment (time 1) and had at least one TSH-value≥0.01 mU/l and <1.0 mU/l after continuous LT4 therapy for a minimum of 5 years (time 2).At time 2 the mean LT4 dosage/kg body weight, TSH, FT3, and FT4 levels were significantly lower than at time 1, while body weight was higher. At time 2, the FT3/FT4 ratio rate had dropped significantly (p<0.001). At time 1, patients would require 2.96 µg/kg body weight to reach total TSH suppression. The dose of levothyroxine/kg required for suppression can be lowered by about 0.05 µg/kg body weight for each year of suppressive therapy. After a median of 12.7 years of continuous suppressive levothyroxine therapy, patients would require 2.25 µg/kg body weight (-23.5%) to reach total TSH-suppression. At least part of this reduction was independent of aging. As a result of changes in thyroid hormone metabolism and thyroid axis setpoint, long-term TSH-suppressive therapy contributes to a reduction in the dosage of levothyroxine per kilogram body weight required for full TSH suppression over time.

Hybrid FDG-PET/MRI for Diagnosis and Clinical Management of Patients with Suspected Perihilar Cholangiocarcinoma: A Feasibility Pilot Study.

Purpose: Recently introduced hybrid 2-[18 F]-fluoro-2-deoxy-D-glucose (18 F-FDG) Positron Emission Tomography (PET) combined with Magnetic Resonance Imaging (MRI) may aid in proper diagnosis and staging of perihilar cholangiocarcinoma (pCCA). The aim of this study is to assess the effect of 18 F-FDG PET/MRI on diagnosis and clinical decision making in the pre-operative work up of pCCA. Methods: In this single-centre pilot study patients with presumed resectable pCCA underwent state-of-the-art 18 F-FDG hybrid PET/MRI using digital silicone photomultiplier detectors integrated within a 3-Tesla bore. Data were collected on several baseline and imaging characteristics. The primary outcome measure was the added diagnostic information and the effect on clinical decision making. Secondary aim was to correlate quantitative PET signal intensity to patient- and tumour characteristics. High and low SUVmax subgroups related to the mean value were made. Significance of lesion- and patient characteristics with the high and low SUVmax subgroups, as well as TLR and TBR, was evaluated with Fisher's exact test or Mann-Whitney-U test. Results: In total 14 patients were included (mean age 62.4 years, 64% male). Final diagnosis was pCCA in 10 patients (71.4%), follicular lymphoma in one patient (7.1%) and benign disease in the remaining three patients. FDG-PET/MRI added valuable diagnostic information in six (43%) patients and affected clinical decision making in two of these patients (14%) by increasing confidence for malignancy which lead to the decision for surgery on short term. High SUVmax values were seen in half of cases with pCCA and half of cases with non-cancerous lesions. In addition, high SUVmax values were directly associated with primary sclerosing cholangitis when present (p = 0.03). Conclusion: Simultaneous 18 F-FDG-PET/MRI added diagnostic information in six of fourteen patients and influenced clinical decision making in two patients (14%) with presumed resectable pCCA.

Relationship between antithyroglobulin autoantibodies and thyroglobulin recovery rates using different thyroglobulin concentrations in the recovery buffer.

The aim of the work was to examine the relationship between thyroglobulin autoantibody (TgAb) levels and the Tg recovery rate (TgRR) using different concentrations of Tg (50, 10, 5, and 1 µg/l) in the recovery buffer. A total number of 225 serum samples from individual patients were analyzed. Samples were selected for their TgAb in 6 groups: TgAb1 000 IU/ml (n=28). TgAb were measured with 2 different assays (VARELISA and BRAHMS Anti-Tgn RIA). TgAb levels and the TgRR determined using the 50, 10, 5, and 1 µg/l buffers showed strong significant correlations with a Spearmans' rho of - 0.720, - 0.688, - 0.686, and - 0.356, respectively, for the VARELISA assay and - 0.670, -0.617, - 0.570, and - 0.274, respectively, for the Anti-Tgn assay (all p<0.001). TgRRs were a median of 94.8% (30.5-113.0%), 90.8% (40.6-127.6%), 90.0% (8.2-119.3%), and 89.4% (range - 43.6-121.6%) for the TgRR determined using recovery buffers with concentrations of 50, 10, 5, and 1 µg/l respectively. With decreasing Tg concentration in the recovery buffer the percentage of abnormal results increased, although the extreme increase we found in the 1 µg/l group is largely caused by a lack of analytical precision in the 73 sera with Tg levels exceeding 5 µg/l. Our results give cause for further investigation into reviving the concept of Tg-recovery measurement using 5 µg/l Tg in the recovery buffer instead of the traditional 50 µg/l.

Short-term severe thyroid hormone deficiency does not influence sleep parameters.

PURPOSE: The influence of short-term severe thyroid hormone deficiency on sleep is currently still unknown. Several studies have demonstrated an effect of long-term hypothyroidism on sleep disorders due to anatomical changes of the pharynx or body mass. The aim of this preliminary study, however, is to evaluate the changes in sleep patterns of patients with short-term hypothyroidism to elucidate the isolated effect of thyroid hormone withdrawal before anatomical changes can potentially occur. METHODS: Ten patients with differentiated thyroid carcinoma were enrolled in this study. Two patients discontinued the study and one patient was finally excluded due to obesity, so that the datasets of seven patients were available for study analysis. During the course of carcinoma treatment, each patient had previously undergone total thyroidectomy and I-131 remnant ablation. Polysomnographic measurements were performed twice: (1) over the course of two consecutive nights during severe thyroid hormone deficiency after levothyroxine withdrawal and prior to further diagnostics and therapy and (2) during euthyroidism after substitution with levothyroxine. RESULTS: Comparison of the Epworth Sleepiness Scale during hypo- and euthyroidism for each patient revealed no statistically significant difference. Furthermore, the comparison of polysomnographic parameters like (1) apnea-hypopnea index, (2) the duration of various sleep stages, (3) duration of rapid eye movement sleep, (4) latency until rapid eye movement sleep, (5) total sleep time, (6) periodic leg movements, and (7) arousal index showed no statistically significant differences between the hypothyroid or euthyroid state. CONCLUSIONS: We conclude that, in this preliminary experimental setting, short-term severe thyroid hormone deficiency per se does not cause sleep disturbances and a feeling of fatigue as described in other studies may be due to changes in perception or brain metabolism during hypothyroidism.

Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol.

Background: Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis: The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination: Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.

Evaluation of the BRAHMS KRYPTOR thyroglobulin "mini-recovery" test in thyroid healthy subjects.

The aim of the work was to compare the automated thyroglobulin (Tg) assay on the automated BRAHMS KRYPTOR platform (hTG KRYPTOR) to the established BRAHMS Tg Plus immunoradiometric assay for the measurement of Tg levels and regular Tg recovery rates and to assess a recovery test using a low Tg concentration of 10 µg/l ("mini-recovery") in samples with a native Tg level of <10 µg/l. Tg levels and recovery rates, as well as the mini-recovery, were determined in 208 serum samples from thyroid-healthy patients using both assays. The reference ranges for the Tg-Plus assay are 2.0-51.0 µg/l for Tg levels and 81.5-108% for recovery rates at 100 µg/l. The reference ranges for hTG KRYPTOR are 2.4-47.8 µg/l for Tg, 83.3-110.4% for a conventional recovery with 80 µg/l in Tg levels ≥ 10.0 µg/l (n=121) and 94.4-122.9% for the mini-recovery with Tg <10.0 µg/l (n=87). The correlation between the Tg-Plus and hTG KRYPTOR is excellent for Tg (r2=0.95; p<0.001), but not significant for recovery rates. Tg levels determined using the KRYPTOR Tg assay are clinically comparable to the conventional Tg-Plus assay. New features of the KRYPTOR assay such as the ability to perform a "mini-recovery" still require further study before clinical use.

Radioiodine therapy of metastatic lesions of differentiated thyroid cancer.

Seventy years after the first successful radioiodine treatment of metastatic differentiated thyroid cancer (DTC), radioiodine (131I) therapy for this type of tumor is still without alternative. During the last decade, some key issues such as individual dosimetry, and preparation of 131I therapy by recombinant human TSH have been addressed, but this has not yet lead to conclusive results; furthermore a number of questions related to indication, preparation, and treatment protocol of 131I therapy still remain unanswered. In this review, we will address the literature pertaining to the latest developments in the field of 131I therapy of advanced DTC and we will give an overview of the state of the art regarding patient preparation, dosimetry, and therapy.

Thyroglobulin and thyroglobulin autoantibodies measurement using the automated KRYPTOR® platform in patients with differentiated thyroid carcinoma.

The aim of the present study is 1) to compare our established manual thyroglobulin (Tg) and Tg autoantibody (TgAb) immunoassays to the automated KRYPTOR® platform from the same manufacturer, in a large group of DTC patients and 2) to evaluate whether a change in assay methods could be made without disrupting the serial monitoring pattern. Sera from 160 patients with histologically proven DTC were obtained and Tg and TgAb measured by manual immunoassays and a fully automated platform. We found an excellent agreement between the 2 methods for Tg measurement (R=0.9888, p<0.00001) with a 90% overall concordance rate. At the same time, a weak relationship was found between the two methods for TgAb measurement (R=0.4438, p<0.03). However, 151 patients had concordant results with a 94% overall concordance rate. In conclusion, the excellent correlation we found between the Tg assays make the fully automated KRYPTOR® Tg assay interchangeable with the established Dyno-test® Tg-plus in patients with DTC. A very high qualitative concordance rate was found between Dyno-test® TgAbn and KRYPTOR® TgAb assays, making these methods interchangeable to screen sera for the presence of TgAb. However, since quantitative discordances still occurred in some patients a re-baseline of TgAb positive patients is strongly supported before changing the TgAb assay method.

Reference ranges for analytes of thyroid function in children.

Promptly detecting pediatric thyroid dysfunction requires age-appropriate reference ranges for serum thyroid-stimulating hormone (TSH), serum free thyroxine (FT4), and serum free triiodothyronine (FT3). We sought to establish such ranges, employing the widely-used Immulite® 2000 automated immunoluminometric assays in a large population. We assayed the analytes according to manufacturer's instructions in serum samples from 359 male and 297 female university hospital patients, aged between newborn to 18 years, without evidence of thyroid or pituitary dysfunction. As data were not normally distributed, the reference ranges were assumed to lie between the 2.5th and 97.5th percentiles. Curves for age-related changes in the reference ranges were calculated using the linearity, median and skewness method. TSH, FT4, and FT3 reference ranges showed a wide spread immediately after birth, rapidly decreasing within the first 2 years of life. Reference range width was fairly stable after about age 4 years. However, from that time, the ranges' lower and upper limits steadily declined, essentially reaching (FT3) or approximating (TSH, FT4) healthy adult values by age 18 years. Age-specific reference ranges should be used when measuring TSH, FT4, and FT3 in children. During very early life, values of these analytes range widely, making it challenging to interpret measurements in infants, and, especially, newborns.

(131)I therapy in patients with benign thyroid disease does not conclusively lead to a higher risk of subsequent malignancies.

UNLABELLED: Due to its excellent tolerability and low incidence of side effects, 131I therapy has been the treatment of choice for benign thyroid diseases for over 60 years. A potentially increased risk of malignancies due to this therapy is however still subject of debate. AIM: To review the literature pertaining to 131I therapy of benign thyroid diseases in order to establish whether there is an increased incidence of, or increased mortality due to malignancies of the thyroid or other organs. METHODS: In order to allow for sufficient long-term follow-up time after 131I therapy, only literature after 1990 was reviewed. Two criteria were applied to consider an increased incidence of malignancies linked to 131I therapy: a) there should be a latency period of at least 5 years between 131I therapy and the observation of an increased risk b) an elevated risk should increase with increasing radiation exposure. RESULTS: A total of 7 studies reporting cancer incidence and / or mortality in 4 different patient collectives spanning a total of 54510 patients over an observation period varying from 2-49 years were found. Although some studies detected a slightly increased risk for malignancies of the thyroid or the digestive system, others did not find these effects - while other studies even reported a slightly lower risk of malignant (thyroid) disease after 131I therapy for benign thyroid diseases. CONCLUSION: As over 60 years of experience has thus far failed to produce conclusive evidence to the contrary, it can be concluded that there is no increased risk of malignancies after 131I therapy for benign thyroid disease.

Controversies in Radioiodine Treatment of Low- and Intermediate-risk Thyroid Cancer.

In differentiated thyroid cancer, radioiodine therapy (RIT) is usually carried out after thyroidectomy. Although the potent beneficial effects of radioiodine are undisputed in high-risk patients, much controversy remains surrounding many aspects of RIT in low- and intermediate-risk patients. Other than the indication for postoperative RIT, controversies also include, among others, the intent of RIT and the choice of activity for RIT or the mode of thyroid stimulating hormone stimulation. Furthermore, there is even controversy on the definition of what constitutes low- or intermediate-risk patients. Here the various issues will be discussed and an overview of the different points of view in a number of more prominent national and international guidelines and current literature is presented.

Heterophile antibodies rarely influence the measurement of thyroglobulin and thyroglobulin antibodies in differentiated thyroid cancer patients.

The aim of the study was to determine the impact of heterophile antibodies on the measurement of serum thyroglobulin (Tg), thyroglobulin recovery, and thyroglobulin antibody levels in differentiated thyroid carcinoma patients. We studied serum samples of 201 individual patients that were followed in our hospital for differentiated thyroid carcinoma and 52 control samples. Samples were split; half were treated by incubating the sample for 1 h in HAB-blocking tubes, the remainder was left untreated. Subsequently thyroglobulin and thyroglobulin antibody levels were measured in both the blocked and untreated samples. A difference between the two samples was considered significant if the blocked sample deviated from the untreated one by more than 2.77 times the standard deviation for the method. In the measurement of Tg, 2 patients showed a moderate, but significant lowering of Tg levels after blocking treatment, but not so great as to affect clinical management. None of the 52 controls showed heterophile antibody interference in thyroglobulin measurement. Neither in DTC patients, nor in controls was any possible heterophile antibody interference encountered. And in all thyroid carcinoma patients, and in all but one controls, no interference was found in the thyroglobulin antibody measurement. All in all a possible heterophile antibody interference was found in 3/759 tests (0.4%). We can assume that heterophile antibody interference is not a factor to be reckoned with in the daily practice of Tg measurement in the treatment and follow-up of differentiated thyroid carcinoma patients.

The association between multinodular goiter and thyroid cancer.

In many parts of the world, especially those of current or former iodine deficiency, multinodular goiter is still an endemic disease. In this brief review several clinically relevant issues in the complex association between nodular goiter and differentiated thyroid cancer will be highlighted. There are some intriguing links between the etiologies of multinodular goiter and that of thyroid cancer. This could also influence the incidence of thyroid cancer in multinodular goiter. However, multinodular goiter causes extra difficulties in the diagnosis of differentiated thyroid cancer; these same difficulties also cause additional issues in thyroid cancer treatment in multinodular goiter patients. Last but not least it will be discussed whether there is a possibility to impede the development of thyroid cancer in multinodular goiter.

Diagnostic imaging work up in multi-nodular goiter.

Ultrasound, scintigraphy and sonographically guided fine-needle biopsy are the cornerstones in the diagnostic work-up multinodular goitre. Subsequent decisions for adequate treatments should be based on accurate tests to avoid unnecessary intervention. Especially in areas with endemic goitre a preselection of patients for the most effective procedure e.g. surgical or medical treatment is mandatory. Autoimmune hyperthyroidism (Graves' disease), solitary hyperfunctioning thyroid nodules and toxic multinodular goitre (Plummer's disease) constitute a clear indication for radioiodine treatment in many cases. Recently, there is an emerging role for I-131 in the treatment for so called subclinical hyperthyroidism caused by either of three first entities and for patients with non-toxic goitre, in whom surgery is not an option. These patients with large non toxic goitre encompass a group of patients who are euthyroid but may benefit from diminishment of thyroid volume. We review the spectrum of diagnostic tests and provide some recommendations regarding (nuclear medicine) therapy.

Low-risk differentiated thyroid carcinoma patients still deserve I-131 remnant ablation after total thyroidectomy.

After total thyroidectomy for differentiated thyroid carcinoma (DTC), I-131 ablation is usually recommended in all patients but those classified as "very low risk", and mandatory for all patients classified as "high risk". For those classified as "low risk" there is some discussion as to whether I-131 ablation should still be performed. In this review various staging systems for classifying patients as "very low risk" "low risk" or "high risk" are discussed, followed by an overview of why I-131 ablation remains an eminently sensible idea in "low risk" patients.

The success of 131I ablation in thyroid cancer patients is significantly reduced after a diagnostic activity of 40 MBq 131I.

OBJECTIVE: Dosimetry studies have shown that activities of 131I as small as 10-20 MBq may cause a stunning effect. A result of this stunning effect may be a lower success rate of the ablative 131I therapy for differentiated thyroid carcinoma (DTC). The aim of this study was to determine whether pre-therapeutic uptake measurement with 40 MBq 131I causes a lower success rate of ablation. DESIGN: retrospective chart review study. PATIENTS, METHODS: In two hospitals the ablation protocols differed in one respect only: in the one hospital no diagnostic 131I was applied before ablation (group 1, n = 48), whereas in the other hospital a 24-h uptake-measurement with 40 MBq 131I was performed (group 2, n = 51). Included were all DTC patients without distant metastases who had undergone 131I ablation between July 2002 and December 2005, and who had returned for 131I follow-up. Successful ablation was defined as absence of pathological 131I uptake on diagnostic whole-body scintigraphy and undetectable thyroglobulin-levels under TSH stimulation. RESULTS: Overall, ablation was successful in 31/48 patients (65%) in group 1 and in 17/51 patients (33%) in group 2 (p=0.002). Multivariate analysis showed that pre-therapeutic uptake measurement using 40 MBq 131I was an independent determinant for success of ablation (p = 0.002). CONCLUSIONS: After applying a diagnostic activity of 40 MBq 131I before ablation, the success rate of ablation is severely reduced. Consequently, the routine application of 131I for diagnostic scintigraphy or uptake measurement prior to 131I ablation is best avoided.

Value of diagnostic radioiodine scintigraphy and thyroglobulin measurements after rhTSH injection.

UNLABELLED: Measurements of thyroglobulin (Tg) levels 72 h after administration of recombinant human thyrotropin (rhTSH) are recommended by the manufacturer in the follow-up of patients with differentiated thyroid carcinoma (DTC). In our department, Tg measurements are performed both 24 h and 72 h after administration of rhTSH, together with 72 h post rhTSH 131I whole body scintigraphy (WBS). The OBJECTIVE of this study is to compare the diagnostic usefulness of Tg measurements 24 and 72 h after rhTSH administration, and 131I WBS. PATIENTS AND METHODS: 181 patients were included who had been referred to our Nuclear Medicine Department for follow-up after 131I ablation of DTC. Tg measurements 24 h (Tg24) and 72 h (Tg72) after rhTSH, and 131I WBS, were done in all patients. The lower detection limit of Tg was 0,2 microg/l. RESULTS: 47 patients (26%) had detectable Tg levels: in 4/47 cases (8%) only Tg24 was detectable (always <1 microg/l), and in 6/47 cases (11%), only Tg72 was detectable. In 10/47 patients with detectable Tg-levels, Tg24 and Tg72 tested equally. In 27/47 cases, Tg24 was lower, and in 10/47 higher, than Tg72. Two patients with one or two positive Tg-test results also had a positive 131I WBS. In 8 patients (14%) only the 131I WBS was positive; an anatomical substrate for such a Tg-negative positive WBS was confirmed in only 2 patients. CONCLUSION: Tg-measurement 72 hours after rhTSH injection reveals all clinically relevant detectable Tg-levels. Diagnostic 131I scintigraphy may be omitted, even in high-risk patients.