Thyroid®

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. Interferon-γ (IFN-γ) is an important mediator of inflammatory and immune responses. The aim of the present study was to investigate whether the polymorphism of IFN-γ gene is associated with the development of GD or with clinical course during the antithyroid drug therapy. We have studied the CA repeat polymorphisms in the first intron of IFN γ gene in Japanese patients with GD (n = 162) and healthy control subjects without antithyroid autoantibodies or family history of autoimmune disorders (n= 133). There was no difference in allele frequency of IFN-γ gene polymorphism between patients with GD and control subjects. However, the allele 4 (15 CA repeats) frequency was significantly greater in patients whose antithyrotropin receptor antibody (TRAb) became negative within 3 years by antithyroid drug treatment than those with consistently positive TRAb for more than 3 years (34.1% vs. 15.7%,χ² = 8.545, p = 0.0035, pc = 0.049). The in vitro production of IFN-γ by concanavalin A-stimulated peripheral blood mononuclear cells was significantly smaller in control subjects with the allele 4 compared to those with the other alleles. In conclusions, the CA repeat polymorphism of the IFN-γ gene might be associated with the outcome of anti-thyroid drug treatment.

Cold thyroid nodules (CTNs) are characterized by a reduced iodide uptake in comparison to normal thyroid tissue. The sodium iodide symporter (NIS) is the first step in thyroid hormone synthesis and mediates the active iodide transport in the thyroid cells suggesting that decreased iodide uptake could be a result of changes in NIS expression or molecular defects in the NIS gene. In contrast to previous studies, an intraindividual comparison of NIS mRNA expression in CTNs and their corresponding surrounding tissue was performed using direct detection of NIS mRNA. A significant reduction in NIS mRNA expression was detected in 86% of the 14 investigated CTNs. We hypothesized that human sodium iodide symporter (hNIS) transcriptional failure could be caused by primary molecular NIS gene defects and/or methylation of DNA in the NIS promoter. However, no mutation in the NIS cDNA nor in the NIS promoter region upstream up to-443 bp from the ATG start codon was detected. Therefore, primary molecular NIS gene defects were excluded. However, in 50% of CTNs with reduced NIS mRNA expression, the promoter region was hypermethylated. NIS mRNA expression in these hypermethylated CTNs only reached a maximum of 30% of the corresponding surrounding tissue. Hence, methylation of CpG islands in the NIS promotor could be a regulatory mechanism of NIS transcription in CTNs. Immunoblot revealed absent hNIS protein expression in the total cell membrane fraction in 45% of investigated nodules. In the majority of the remaining CTNs NIS protein expression was decreased in the nodule tissue compared to the corresponding surrounding tissue. For investigating protein expression immunhistochemistry has two advantages. First, the whole nodule area can be investigated, and second, NIS expression can be detected in areas where an immunoblot of a cell membrane fraction is negative. Interestingly, immunhistochemistry revealed higher NIS expression in 50% of CTNs compared to their corresponding surrounding tissues and NIS staining was predominantly intracellular. These data demonstrate that NIS protein expression does not reflect NIS mRNA expression. Therefore, factors that affect targeting of NIS to the plasma membrane are likely to be affected.

The aim of this study was to estimate accuracy, intraobserver variability, and repeatability of thyroid volume measurement by ultrasound using conventional two-dimensional ellipsoid model (2D US) and manual planimetry of three-dimensional images (3D US). The sonographic images of 47 children with thyroid nodular pathology who were referred for thyroid surgery in Belarus were evaluated prospectively. Two-dimensional images were acquired using the ultrasound scanner with 7.5-MHz linear probe. Three-dimensional data sets were created using three-dimensional system, FreeScan. For each patient thyroid volume was measured three times using both two- and three-dimensional methods. Results of volume estimation were then compared to the volume of thyroid gland determined after surgery. Standardized difference between thyroid volume estimated by ultrasound and surgery (mean ± standard deviation (SD), %) for 3D and 2D US methods was 1.8 ± 5.2% and 3.2 ± 15.3%, respectively. The 3D US has lower intraobserver variability (3.4%) and higher repeatability (96.5%) than 2D US with 14.4% variability and 84.8% repeatability (p < 0.001). In conclusion, three-dimensional sonography allows accurate measurement of thyroid volume with low intraobserver variability and high repeatability.

The occurrence of carcinoma of the thyroglossal duct remnant (TDRCa) is reported to be less than 1%. We retrospectively analyzed 18 cases (14 females, 4 males; mean age, 38.17 years) of TDRCa who underwent surgery in our department, to evaluate the correct workup for diagnosis and treatment. Nine patients underwent a total thyroidectomy and a Sistrunk procedure (SP) whereas 8 underwent a completion total thyroidectomy after a postoperative diagnosis of TDRCa. One patient was diagnosed with TDRCa several years after total thyroidectomy for goiter. Postoperatively all patients were given radioiodide and levothyroxine therapy. Mean follow-up was 85 months. No patient died of tumor-related disease. Thyroglossal duct neoplasms were represented by papillary carcinoma in 16 cases; thyroid histology demonstrated papillary carcinoma in 6 cases (33.3%). Three patients demonstrated single regional node metastasis and only one of them demonstrated the presence of malignant thyroid disease. When clinical diagnosis of thyroglossal duct cyst is made, the workup should be completed by ultrasound (US) scan and fine-needle aspiration cytology (FNAC) in order to plan the correct surgery for a possible TDRCa. Total thyroidectomy should always be considered with SP to permit the correct treatment and follow-up in those patients. Long-term survival of patients with cTDRCa is excellent.

Goal: To establish the role of percutaneous ethanol injection (PEI) treatment in benign thyroid lesions by evaluating: (1) the long-term efficacy and side effects of the treatment, (2) the factors predictive of efficacy of PEI, and (3) the cost effectiveness of the procedure. Materials and Methods: Fifty-eight recurrent cystic nodules, 95 autonomously functioning nodules (AFTN), and 17 hyperfunctioning nodules causing thyrotoxicosis (toxic nodules) were treated by PEI from 1990 to 1996 in our center. Ultrasound (US) and color flow doppler (CFD) examinations were carried out before and after each treatment. In patients with AFTN, serum thyrotropin (TSH), free triiodothyronine (FT₃), free thyroxine (FT₄), thyroid peroxidase antibody (TPOAb) levels were tested before and after PEI. All patients were independently reexamined by two external reviewers after a minimum follow-up of 5 years (median, 6.9 years). Results: The median number of treatments was 2.0 (range, 1.0-4.0) for cystic nodules, 4 (range, 2.0-6.0) for AFTN, and 5 (range, 3.0-7.0) for toxic nodules. At the 5-year evaluation cystic nodules showed a volume reduction greater than 75% versus baseline in 86.2% of cases and an improvement of local symptoms in 91.4% of cases. AFTN presented serum TSH within normal limits in 60.0% of patients. Toxic nodules showed a detectable serum TSH and normal FT₃ and FT₄ values in 35.3% of cases. Two cases of transient dysphonia were observed. In cystic lesions no significant correlation was found between the baseline and the final volume (r ² = 0.17) and no significant predictor of treatment efficacy was found. However, unilocularity was associated with a lower number of treatments than multilocularity (median, 2.0 vs. 3.0). Independent predictors of clinical efficacy in both AFTN and toxic nodules were a baseline volume less than 5.0 mL and a fluid component greater than 30% (odds ratio [OR] = 6.1 and 3.3, respectively). Conclusions: Most recurrent cystic lesions of the thyroid can be cured by PEI, which should become the first line of treatment. The majority of AFTN and toxic nodules with volume less than 5.0 mL presented a marked volume decrease and normal serum TSH levels when treated by PEI, which seems a valid alternative to clinical follow-up alone in patients refusing 131I. PEI is not indicated in large or toxic nodules, for which 131I is the treatment of choice.

Introduction: Patients with well-differentiated thyroid cancer have a good prognosis but a significant chance for local recurrence. In the past, limited surgery with postoperative ¹³¹I only for extremely high-risk cases or recurrence was not uncommon. As more aggressive surgical and postoperative treatments appear to gain wider acceptance, toxicity and long-term morbidity become more important issues. Our goal is to present the experience of a single institution with emphasis on oral side effects related to ¹³¹I as well as acute and chronic symptoms related to this diagnosis and their impact on quality of life. Methods: Fifty-seven patients were followed for a median time of 19.3 months. All patients received therapeutic ¹³¹I (mean dose, 154.7 mCi) between January 1, 1996 and August 30, 2002. Results: Fifty-four patients (94.7%) were alive at the time of analysis. Sixteen (28.1%) required a second treatment: any sign of persistence resulted in retreatment. Complaints with ¹³¹I treatment included altered taste, 26.3%; acute xerostomia, 21.1%; and acute sialoadenitis, 15.8%. Chronic xerostomia occurred in 6 (35.3%) of all patients who received multiple treatments. The incidence of chronic xerostomia was reduced to 1 of 11 (9.1%) with amifostine pretreatment. Other chronic side effects associated with this disease included fatigue 54.4%, weight gain of more than 6 months duration 24.6%, with 12 (27.9%) of those under 60 experiencing an average gain of 2.3 kg from initial diagnosis. Conclusion : Review of treatment-related symptoms prompted policies to reduce toxicity including amifostine pretreatment for ¹³¹I therapy and thyrotropin (synthetic TSH) use in place of iatrogenic hypothyroidism for thyroglobulin testing and scanning.

Background: A population-based registry (PBR) in Lower Frankonia in southern Germany was conducted to evaluate the changes of incidence and prognosis of thyroid carcinoma (TC) in this area. Methods: The study comprised 476 patients with differentiated thyroid carcinoma (DTC) from Lower Franconia (1.3×10⁶ inhabitants) registered between 1981 and 1995 at the Regional Tumor Center. The incidence was assessed with respect to gender, age, histology, tumor stage, lymph node involvement and distant metastases in 5-year intervals (1981-1985, 1986-1990, and 1991-1995). Results: An increasing rate of papillary thyroid carcinoma PTC and a decreasing rate of follicular thyroid carcinoma (FTC) were observed over the three time periods (1981-1985, 1986-1990, and 1991-1995). The overall incidence revealed no significant change with time for both females from 3.22 to 3.25 and 3.73 and males (1.07 to 1.54 and 1.69) between the three time periods. There was a significant improvement in outcome of patients with DTC with respect to life expectancy. Conclusions: Iodine prophylaxis does influence the distribution of the histologic types of thyroid cancer and leads to an increase in the ratio of papillary versus follicular carcinoma. Our study supports the hypothesis that the benefits of correcting iodine deficency outweigh the risks of iodine supplementation.

Thyrotoxicosis is a well-documented and studied complication of treatment with amiodarone, but little has been written about the risks and treatment of recurrent thyrotoxicosis upon re-exposure to amiodarone. One such case is outlined here and discussed by a panel of experts.

Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T₄). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T₄ levels but normal TSH. While the majority of T₄was bound to albumin, T₄ binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T₄ but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT₄) levels were increased when measured with some commercial kits including equilibrium dialysis followed by radioimmunoassay (RIA) but not when determined by RIA after ultrafiltration of sera. These results indicate an increased T₄ binding to TBG during pregnancy in the patients with FDH. Furthermore, our results suggest that normal serum FT₄ determined by equilibrium dialysis is not an ultimate standard for the diagnosis of FDH in the patients with the mutant albumin R218P.