False-Positive Iodine-131 Uptake Due to Wasp Sting.

Thyroid hyperplasia/multinodular goiter, characterized by cellular and follicular overgrowth, is a very common endocrine condition, resulting in various functional and structural consequences and certain malignant potential. Its genetic background is completely unknown. Given previous genetic and epigenetic data suggesting that RASAL1 might be a thyroid tumor suppressor gene, particularly in follicular thyroid neoplasm, we hypothesized that the RASAL1 gene could play a fundamental role in the development of thyroid hyperplasia/multinodular goiter. To explore the role of the RASAL1 gene in the development of thyroid hyperplasia/multinodular goiter, we developed a novel Rasal1 knockout mouse model using the CRISPR/Cas9 approach and the C57BL/6J zygotes, followed by observing the pathological changes in the thyroid gland of the knockout mice in comparison with the wildtype mice. We successfully created a novel Rasal1 knockout mouse model with establishment of several generations of mice carrying the heterozygous and homozygous knockout of the Ra-sal1 gene at exon 2, which was confirmed by genetic testing and by Western blotting of the Rasal1 protein. All the mice with Rasal1 knockout, whether heterozygous or homozygous, developed grossly visible multinodular goiter with microscopic confirmation of follicular cell hyperplasia, with occasional case showing thyroid cancer. In contrast, only occasional case of aged wild-type mice developed thyroid hyperplasia and no wild-type mice developed thyroid malignancy. These data demonstrate that defect of Rasal1 can cause full and complete development of thyroid hyperplasia/multinodular goiter in mice. Given the striking similarity of thyroid hyperplasia/multinodular goiter in these Rasal1 knockout mice with that in humans, it is plausible to suggest that RASAL1 is a master gene involved in the development and pathogenesis of human thyroid hyperplasia/ multinodular goiter. This project also provides a new genetic knockout mouse model for future study of thyroid neoplasm.

Many differentiated thyroid cancers (DTC) dedifferentiate and become radioactive iodine (RAI)-refractory (RAIR) with worse outcomes. Targeted therapy (TTx) may downregulate MAPK signaling and sensitize tumors to RAI. We describe patients with RAIR DTC receiving TTx with demonstrated RAI uptake allowing for iodine-131 (I131) administration. Charts of patients with metastatic, progressive, RAIR DTC in whom TTx increased RAI uptake on a diagnostic whole-body scan (WBS), were reviewed. Results of WBS, I131 administration, thyroglobulin (TG) panels, and cross-sectional studies were recorded. Thirteen patients [median age (range), 56 (45 to 75) years; seven men] were included; 11 (85%) had DTC, two (15%) had poorly DTC. Nine (69%) had BRAF mutations, three (23%) had RAS mutations, and one (8%) was wild type. Selective BRAF or an MEK inhibitor TTx was continued for a median (range) of 14.3 (1 to 76.4) months before diagnostic WBS. Nine (69%) patients were treated with I131 [median (range) activity, 204.4 (150 to 253) mCi], after which TTx was discontinued. Median (range) follow-up was 8.3 (0 to 17.4) months after I131 therapy. All nine patients had durable disease control (three had partial response, six had stable disease). TG and TG antibody levels increased in patients who demonstrated uptake before TTx, and declined in eight of the nine patients after I131 treatment. Adverse events included pneumonitis and sialadenitis. TTx in BRAF-/RAS-mutated RAIR DTC resensitizes tumors to iodine. Subsequent I131 administration results in meaningful responses. Patient selection, adverse events, response duration, and survival impact require additional study.

Response assessment in advanced differentiated thyroid cancer.

Aim. The aim of this study is to present the personal experience of the authors regarding the use of positron emission tomography-computer tomography fusion image (PET/CT), with 18 Ffluoro-2-deoxy-D-glucose (FDG), in the follow-up of differentiated thyroid carcinoma (DTC). Patients and Methods. Twenty seven cases of DTC admitted and treated in the “Prof. Ion Chiricuþa” Institute of Oncology Cluj-Napoca (IOCN), performed PET/CT investigation between 2007 and 2009, in DOTE Centre Debrecen (Hungary) and Pozitron Center Oradea (Romania). The patients underwent the surgical intervention and had histology of differentiated carcinoma; they received radioiodine therapy with I-131, had suppression therapy with thyroid hormones and had in the follow-up whole body scans (WBS) with I-131, neck ultrasound and serological determination of thyroglobulin (Tg) and anti-thyroglobulin antibodies (anti-Tg). All patients were referred to PET/CT after radical treatment, after a negative WBS I-131 and a dynamic increase of the serological level of Tg or anti-Tg, without any clinical signs of recurrence and no neck ultrasound pathological findings. Results. All patients included in this study presented abnormal levels of Tg: between 2.76 ng/ml and 4173 ng/ml, with a median value of 43.15 ng/ml. In 23 cases (85.1%) the PET/CT results revealed the neoplasm recurrence, in 3 cases we obtained true negative results and in 1 case a false negative image; in 2 cases (7.4%) we found a second malignancy. All patients needed to change the treatment strategies. Conclusion. The significant increase of the number of DTC and the more aggressive behaviour of the disease in some situations, determines the existence of a clear strategy of treatment and monitoring, where the role of PET/CT is well defined.

Objective Our objective was to study the radiation exposure rate as function of time in the administration of radioiodine iodine-131 (I-131) for the treatment of thyrotoxicosis or Graves' disease and remnant ablation on an outpatient basis at the Department of Nuclear Medicine, and also, to study the impact of revised discharge criteria for radioiodine therapy enforced by the Atomic Energy Regulatory Board (AERB) of India. Materials and Methods This study included patients who underwent low-dose radioiodine therapy using I-131. Patients were classified into two different groups, that is, group A and group B. Group A included patients receiving low dose I-131 for the treatment of thyrotoxicosis, whereas group B included patients receiving I-131 therapy for the ablation of residual thyroid tissue after total thyroidectomy. The radiation exposure rate was measured using a radiation detector in milli roentgen per hour (mR/h) at 5 cm distance of stomach and neck levels and with the patient standing at the distance of 1 m after oral administration of I-131 at 0, 1, and 2 hours. Results A total of 134 (17 males and 117 females) patients were included in the study. Group A comprised 102 (14 male and 88 females) patients and group B of 32 (3 males and 29 females) patients. At the neck level, the average exposure rate in group A versus group B after 0, 1, and 2 hours was observed to be 6.9 versus 22.27 mR/h, 33.67 versus 43.39 mR/h, and 41.75 versus 48.90 mR/h, respectively. At the stomach level, the exposure rate was 23.65 versus 71.32 mR/h, 13.27 versus 48.45 mR/h, and 9.91 versus 39.43 mR/h after 0, 1, and 2 hours, respectively. At a distance of 1 m, the exposure rate was 1.31 versus 2.99 mR/h, 1.05 versus 2.58 mR/h, and 0.92 versus 2.21 mR/h, respectively. Conclusion Exposure rate measured for patients treated with up to 1,110 MBq (30 mCi) of I-131 was under permissible limits as per revised discharged limits, that is, 50 µSv/h (5 mR/h) prescribed by AERB, India. The patients undergoing radioiodine therapy I-131 (up to 1,110 MBq/30 mCi) can be discharged safely 2 hours postadministration following good work practice along with providing proper radiation safety instructions to patients.

Sjögren's Syndrome Accompanied by Prolactinoma: a case report and literature review.

Mutual interference between serum thyroglobulin and antithyroglobulin antibody in an automated chemiluminescent immunoassay

Anti thyroglobulin antibodies are present in 25% of patients treated for a differentiated thyroid cancer, invalidating thyroglobulin determination. Those patients subjected to total thyroidectomy and free of disease, should reduce the production of these antibodies, due to the lack of antigenic stimulus. Therefore, anti thyroglobulin antibodies could be useful to detect early relapses. To assess the relationship between anti thyroglobulin antibodies and the evolution of the disease in patients treated for thyroid cancer. Retrospective analysis of 26 patients treated for thyroid cancer with positive anti thyroglobulin antibodies, followed for three years. These were divided in those with or without lymphocytic thyroiditis (19 and 7 respectively). At the first year of follow up, anti thyroglobulin antibody concentration was 401 +/- 94.9 UI/ml (x +/- sem) in patients with thyroiditis and 38.9 +/- 8.9 UI/ml in those without thyroiditis (p < 0.005). During the three years of follow up, no differences in anti thyroglobulin antibodies were observed between patients with or without tumor relapse. Concentration of anti thyroglobulin antibodies was higher in patients with thyroiditis and did not differentiate patients with tumor relapse.

Objective: The association between thyroid hormones, thyroid autoantibodies, and thyroid nodules are still not clear. The cross-sectional study, conducted in Hangzhou, China in 2010, aimed to identify the relationship of thyroid hormones and autoantibodies with thyroid nodules. Methods: Information regarding social demography was collected by a questionnaire. Thyroid hormones (triiodothyronine, thyroxin, free triiodothyronine, free thyroxin, thyrotropin), thyroid autoantibodies (thyroid peroxidase antibody, antithyroglobulin antibody), and thyroid nodules (diagnosed by ultrasonography) was measured in 1271 adults. The association of thyroid hormones and thyroid autoantibodies with thyroid nodules was evaluated using multiple logistic regression models. Results: The prevalence of thyroid nodules among males and females was 29.49% and 33.15%, respectively. The thyroid hormone level in the thyroid nodules group was significantly higher than the non-nodules group (all p values < 0.05), except reversely in TSH (thyroid stimulating hormone) (p = 0.0532) and TGAb (thyroglobulin antibody) (p = 0.0004). High levels of TPOAb (thyroid peroxidase antibody) (OR (Odds Ratio) = 1.51, 95% CI (confidence interval): 0.99–2.30) and TGAb (OR = 2.86, 95% CI: 1.49–5.51) were associated with increased risk of thyroid nodules, compared with corresponding low levels. However, following sub-analyses in two genders, the similar associations were only observed in females (TPOAb: OR = 1.63, 95% CI: 0.99–2.68; TGAb: OR = 3.13, 95% CI: 1.53–6.40). Conclusions: The present study indicated that thyroid autoantibodies were positively associated with the risk of thyroid nodules in Chinese coastal adults.

To understand stunning effects of a diagnostic dose of iodine-131 (I-131). Four hundred and sixty-eight patients (101 males, 367 females, ages: 6-75 years with well differentiated thyroid cancer, following total or nearly total thyroidectomy, were studied. One hundred and eleven MBq (3 mCi) diagnostic (Dx) doses of I-131 whole body scan (WBS) were obtained after withholding thyroxine after 6 weeks and triiodothyronine for 2 weeks. One week to one month later, 3.7-7.4 GBq (100-200 mCi) I-131 was given to them, then a therapeutic (Tx) dose of I-131 WBS was performed. The serum thyroid simulating hormone level was usually above muIU/ml. Of the 468 patients, 344 (73.5%) had scintigraphic patterns of apparently decrease uptake in 240 thyroid remnants and 104 metastatic lesions on the Tx dose of I-131 WBS compared to Dx dose of I-131 WBS. Stunning phenomenon occurred in 50 cases, including 42 thyroid remnants and 18 metastatic lesions. Dx dose of I-131 may influence the uptake of a subsequently administered Tx dose of I-131.

Anti-thyroglobulin antibodies in differentiated thyroid carcinoma patients: Study of the clinical and biological parameters

Objective The aim was to compare the ablative efficacy of low vs high doses of radioactive iodine-131 (131I) in patients with differentiated thyroid carcinoma (DTC) after total or near total thyroidectomy. Materials and methods A randomized, double-armed clinical study compared the ablation outcomes of patients with low and intermediate risk DTC after administration of low (30 mCi) vs high doses (80–120 mCi) of 131I for 20 and 25 patients, respectively. All the included patients were re-examined under thyroid-stimulating hormone stimulation 6–8 months after 131I administration. Successful ablation is defined as follows: Absence of any significant 131I uptake at the thyroid bed or abnormal uptake elsewhere in the body in the diagnostic whole-body scan, stimulated serum thyroglobulin less than 2 ng/ml with negative antithyroglobulin antibodies, and free neck ultrasonography (no thyroid residue or pathological cervical lymph nodes). Results Overall successful ablation after a single dose of 131I was reported in 34/45 patients representing 75.6% of the whole patient population, while unsuccessful ablation was reported in the remaining 11 (24.4%) patients. Successful ablation was reported in 15 out of 20 patients (75%) in the low-dose group and in 19 out of 25 cases in the high-dose group (76%) (P=1.000). Conclusion Ablation with low-dose radioactive iodine (30 mCi) in patients with DTC who did not have gross residual disease or cervical lymphadenopathy after surgical treatment is as effective as the high one (80–120 mCi).

Recombinant human TSH (rhTSH) is used to increase radioiodine uptake during imaging of thyroid cancer, obviating the need to render the patient hypothyroid. We assessed the reproducibility of radioiodine uptake, serum thyrotropin (TSH), and stimulated serum thyroglobulin (Tg) levels after rhTSH administration. A retrospective review was performed of patients at Stanford who underwent whole-body (131)I scanning for surveillance of thyroid cancer twice after thyroidectomy and (131)I ablation, with rhTSH prior to each scan. Forty-eight hour radioiodine uptake, peak serum TSH, and stimulated serum Tg levels for each study were recorded. Paired t tests and correlation analysis were used to assess interexamination repeatability. Twenty-three patients underwent two scintiscans with rhTSH, for a total of 46 exams. There was no significant difference between percent uptake at 48 h in the paired exams (p=0.40). Serum TSH level was measured in 45 of 46 exams; TSH exceeded 50 mIU/l in all cases, and there was no significant difference between paired TSH levels (p=0.93). All patients had stimulated serum Tg levels measured, with no significant difference between paired Tg levels (p=0.40); after excluding one patient whose Tg changed from 15.8 ng/ml to undetectable between scans without interval treatment, the p value rose to 0.95. There was a strong correlation among paired uptake values (r=0.85, p<0.0001), peak serum TSH (r=0.69, p=0.0003), and stimulated Tg levels (r=0.81, p<0.0001). No discordant scan interpretations were reported. Forty-eight hour radioiodine uptake, peak serum TSH, and stimulated serum Tg levels after administration of rhTSH are repeatable between studies, demonstrating reproducibility of diagnostic results without rendering patients hypothyroid.

SUMMARYAlthough thyroid nodule is a common presentation, malignancy is rare. The present study investigated biochemical predictors of malignancy in enlarged thyroid. This is a prospective study of all willing patients 18 to 70 years presenting with a complaint of thyroid swelling and who underwent definitive surgery over a period of 19 months. All subjects were initially evaluated with detailed history, physical examination, ultrasonography of neck and fine needle aspiration cytology (FNAC). Preoperative estimation of serum thyroid stimulating hormone (TSH), thyroglobulin (Tg) and anti-thyroglobulin (anti Tg) antibody was obtained. The treatment plan was based on FNAC results and included hemi- or total thyroidectomy. During the study period, 110 patients underwent thyroidectomy, and met the selection criteria, of which 47 patients had malignancy on final histopathology. The majority were females, 30 to 60 years old. Median serum Tg, TSH and anti Tg levels in the benign group were, respectively 29 ng/ml, 1,6 mIU/L and 1,1 IU/ml, whereas in malignant nodules they were 162 ng/ml. 1,7 mIU/L and 0,9 IU/ml. On receiver operating characteristic curve analysis, a Tg cut off value of 53 ng/ml predicted malignancy risk with a sensitivity and specificity of 72% and 73%, respectively (p < 0.001). Our study showed the utility of preoperative Tg in predicting risk of malignancy. Its role should be further explored especially in the backdrop of indeterminate cytology through a larger study.

Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma.