Journal of Thyroid Research The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Incidental Papillary Thyroid Microcarcinoma in an Endemic Goiter Area Tue, 02 Feb 2016 13:38:11 +0000 Clinical and pathological characteristics of incidental papillary thyroid microcancer cases, surgical, medical, and nuclear treatment methods, and patients’ outcome were studied during follow-up period of 102 months. We studied 37 patients with incidental papillary thyroid microcancer (I-PTM). The surgical procedure was total thyroidectomy in 29 and hemithyroidectomy in 8 patients. Size, multifocality, and bilateralism of PTM foci, thyroid capsule invasion, and presence of lymphovascular invasion were histopathological parameters. We analysed adjuvant medical and nuclear treatment and patients’ outcome during follow-up period of 102 (61–144) months. The prevalence rates of I-PTM were 9.4% in 395 thyroidectomy cases. Histopathological examination reported unifocal disease in 30 and multifocal disease in 7 (18%) patients. Multifocal disease was bilateral in 6 (20.1%) patients. The mean size of the PTM foci was 4.88 mm. The rate of thyroid capsule invasion was 5.4%. All patients received a suppressive dose of LT4 to achieve a low serum TSH level. Adjuvant surgical and nuclear treatment was not performed in our cases. We did not find any negative changes in blood chemistry and ultrasound imaging, and any unfavourable events as locoregional and systemic recurrence. In conclusion, diagnosis of I-PTM is common that multifocality and bilateralism appear as pathologic features. The prognosis is excellent after surgical treatment and TSH suppression. Routine adjuvant nuclear treatment is unnecessary in majority of patients. Emin Gürleyik, Gunay Gurleyik, Banu Karapolat, and Ufuk Onsal Copyright © 2016 Emin Gürleyik et al. All rights reserved. Quercetin-Induced Cell Death in Human Papillary Thyroid Cancer (B-CPAP) Cells Wed, 20 Jan 2016 13:13:21 +0000 In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells. Ergül Mutlu Altundağ, Tolga Kasacı, Ayşe Mine Yılmaz, Betül Karademir, Semra Koçtürk, Yavuz Taga, and A. Süha Yalçın Copyright © 2016 Ergül Mutlu Altundağ et al. All rights reserved. Significance of TNF-α and the Adhesion Molecules: L-Selectin and VCAM-1 in Papillary Thyroid Carcinoma Mon, 11 Jan 2016 12:30:53 +0000 Circulating levels of TNF-α and the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC) have been determined in this study. The serum levels of TNF-α, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-α and L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF-α and L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-α levels significantly positively correlated with the levels of L-Selectin, while TNF-α immunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-α was found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-α and the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer. Toral P. Kobawala, Trupti I. Trivedi, Kinjal K. Gajjar, Darshita H. Patel, Girish H. Patel, and Nandita R. Ghosh Copyright © 2016 Toral P. Kobawala et al. All rights reserved. Prevalence and Predictors of Thyroid Dysfunction in Patients with HIV Infection and Acquired Immunodeficiency Syndrome: An Indian Perspective Tue, 22 Dec 2015 13:59:17 +0000 Background. Predictors of thyroid dysfunction in HIV are not well determined. This study aimed to determine the prevalence and predictors of thyroid dysfunction in HIV infected Indians. Methods. Consecutive HIV patients, 18–70 years of age, without any severe comorbid state, having at least 1-year follow-up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results. From initially screened 527 patients, 359 patients ( months’ disease duration), having good immune function [CD4 count >200 cell/mm3: 90.25%; highly active antiretroviral therapy (HAART): 88.58%], were analyzed. Subclinical hypothyroidism (ScH) was the commonest thyroid dysfunction (14.76%) followed by sick euthyroid syndrome (SES) (5.29%) and isolated low TSH (3.1%). Anti-TPO antibody (TPOAb) was positive in 3.90%. Baseline CD4 count had inverse correlation with TPOAb after adjusting for age and body mass index. Stepwise linear regression revealed baseline CD4 count, TPOAb, and tuberculosis to be best predictors of ScH after adjusting for age, weight, duration of HIV, and history of opportunistic fungal and viral infections. Conclusion. Burden of thyroid dysfunction in chronic HIV infection with stable immune function is lower compared to pre-HAART era. Thyroid dysfunction is primarily of nonautoimmune origin, predominantly ScH. Severe immunodeficiency at disease onset, TPOAb positivity, and tuberculosis were best predictors of ScH. Neera Sharma, Lokesh Kumar Sharma, Deep Dutta, Adesh Kisanji Gadpayle, Atul Anand, Kumar Gaurav, Sabyasachi Mukherjee, and Rahul Bansal Copyright © 2015 Neera Sharma et al. All rights reserved. Thyroid Autoantibodies in the Cerebrospinal Fluid of Subjects with and without Thyroid Disease: Implications for Hashimoto’s Encephalopathy Mon, 21 Dec 2015 11:55:27 +0000 Introduction. Plasma antithyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies (anti-Tg) are widely used in the diagnosis of autoimmune thyroiditis. No research has compared anti-TPO and anti-Tg both in plasma and cerebrospinal fluid (CSF) of healthy individuals vis-à-vis patients with thyroid disease. Methods. We measured anti-TPO and anti-Tg antibodies in plasma and CSF in nine subjects (mean age ± SD: 73 ± 6 years) with hypothyroidism and nine subjects (mean age ± SD: 73 ± 8 years) without thyroid disease. Results. The concentration of anti-TPO autoantibodies in CSF was very low compared to plasma in both subjects with thyroid and without thyroid disease (). CSF anti-Tg autoantibodies titers were very low compared to the plasma in subjects with thyroid disease (), whereas, in subjects without thyroid disease, this difference did not reach statistical significance (). Conclusions. Thyroid autoantibodies levels were low in plasma and CSF; we did not observe any transfer of thyroid autoantibodies from the peripheral blood to the CSF. Therefore, regarding Hashimoto’s encephalopathy, where elevated antithyroid autoantibodies are often measured in blood, it is more likely that thyroiditis and encephalopathy represent nonspecific, but distinct, events of an aggressive immune system. Ioannis Ilias, Vasiliki Karagiorga, George Paraskevas, Anastasia Bougea, Mara Bourbouli, Athina Pappa, Stamatina Nikopoulou, and Elisabeth Kapaki Copyright © 2015 Ioannis Ilias et al. All rights reserved. Relationship between Clinical and Immunological Features of Thyroid Autoimmunity and Ophthalmopathy during Pregnancy Mon, 21 Dec 2015 06:33:34 +0000 Problem. Clinical features of Graves’ hyperthyroidism (GH) generally improve during pregnancy and rebound in the postpartum period. It is unclear whether the ophthalmopathy that is associated with GH and, less often, Hashimoto’s thyroiditis (HT) changes in parallel with the thyroid associated antibody reactions and clinical features or runs a different course. Method of Study. We retrospectively studied 19 patients with autoimmune thyroid disease over 22 pregnancies: 9 pregnancies with GH and 13 with HT. Ophthalmopathy was defined by NOSPECS class. Results. Thyroid peroxidase (TPO) and thyroglobulin (Tg) antibody titres decreased during pregnancy and rose in the postpartum period. During pregnancy, 5 patients with GH and 4 patients with HT developed mild ophthalmopathy and two patients with GH and HT developed new upper eyelid retraction (UER). In the postpartum period, eye scores improved in 3 patients with GH and 3 with HT, remained stable in two and 5 patients, respectively, and worsened in 2 patients with GH and one with HT. Conclusions. In patients with mild to moderate eye signs associated with GH and HT, the orbital and thyroid reactions ran different courses during pregnancy. Since no patient had severe ophthalmopathy, we cannot draw definitive conclusions from this preliminary study. Jack R. Wall, Hooshang Lahooti, Emily J. Hibbert, and Bernard Champion Copyright © 2015 Jack R. Wall et al. All rights reserved. Patient Benefit-Risk Tradeoffs for Radioactive Iodine-Refractory Differentiated Thyroid Cancer Treatments Mon, 30 Nov 2015 16:56:43 +0000 Background. The aims of this study were to assess patients’ preferences to wait or start systemic treatment and understand how patients would make tradeoffs between certain severe adverse events (AEs) and additional months of progression-free survival (PFS). Materials and Methods. Adults in France, Germany, and Spain with a diagnosis of DTC and who have had at least one RAI treatment completed a direct-elicitation question and a discrete-choice experiment (DCE) online. The direct-elicitation question asked respondents whether they would opt out of treatment when their tumor is RAI-R. In the DCE, respondents chose between 12 pairs of hypothetical RAI-R DTC treatment profiles. Profiles were defined by magnitudes of efficacy (PFS) and safety (severe hand-foot skin reaction [HFSR], severe proteinuria, and severe hypertension). A main-effects random-parameters logit model was estimated. Results. 134 patients completed the survey. Most patients (86.6%) opted for treatment rather than “wait and see” decision. Patients placed a greater weight on the risk of severe hypertension than the risk of proteinuria and HFSR. Conclusions. DTC patients showed preference toward treatment for RAI-R DTC over watchful waiting. Patients’ concerns about the risk of severe hypertension appeared to have had a greater effect on patients’ choice than severe proteinuria or HFSR. Ateesha F. Mohamed, Juan Marcos González, and Angelyn Fairchild Copyright © 2015 Ateesha F. Mohamed et al. All rights reserved. Cardiovascular Risk Factors in Subclinical Hypothyroidism: A Case Control Study in Nepalese Population Wed, 07 Oct 2015 12:03:46 +0000 Objectives. To assess cardiovascular risk factors in Nepalese population with subclinical hypothyroidism as compared to age and sex matched controls. Materials and Methods. A case control study was conducted among 200 subjects (100 subclinical hypothyroid and 100 euthyroid) at B.P. Koirala Institute of Health Sciences, Dharan, Nepal. Demographic and anthropometric variables including systolic and diastolic blood pressure (BP) were taken. Blood samples were assayed for serum free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and high sensitivity C reactive protein (hs-CRP). Results. Subclinical hypothyroid patients had significantly higher diastolic BP, total cholesterol, LDL cholesterol, and hs-CRP than controls. The odds ratio of having hypercholesterolemia (>200 mg/dL), low HDL cholesterol (<40 mg/dL), undesirable LDL-cholesterol (>100 mg/dL), high hs-CRP (>1 mg/L), and high diastolic BP (>80 mmHg) and being overweight (BMI ≥ 23 Kg/m2) in subclinical hypothyroidism was 2.29 (95% CI; 1.2–4.38, ), 1.73 (95% CI; 0.82–3.62, ), 3.04 (95% CI; 1.66–5.56, ), 2.02 (95% CI; 1.12–3.64, ), 3.35 (95% CI; 1.72–6.55, ), and 0.9 (95% CI; 0.48–1.67, ), respectively, as compared to controls. Conclusion. Subclinical hypothyroid patients are associated with higher risk for cardiovascular disease than euthyroid subjects. Rajendra KC, Saroj Khatiwada, Kishun Deo Mehta, Pratikshya Pandey, Madhab Lamsal, and Shankhar Majhi Copyright © 2015 Rajendra KC et al. All rights reserved. Tumor Growth Mitigating Effects of Valproic Acid in Systemic Malignancies Tue, 28 Jul 2015 12:06:59 +0000 Shailendra Kapoor Copyright © 2015 Shailendra Kapoor. All rights reserved. Utility of Shear Wave Elastography for Diagnosing Chronic Autoimmune Thyroiditis Thu, 16 Jul 2015 07:03:30 +0000 The aims of this study were to evaluate the utility of shear wave elastography (SWE) using acoustic radiation force impulse (ARFI) for diagnosing chronic autoimmune thyroiditis (CAT) and to verify the effect of fibrotic thyroid tissue on shear wave velocity (SWV). The subjects were 229 patients with 253 normal thyroid lobes (controls) and 150 CAT lobes. The SWV for CAT (2.47 ± 0.57 m/s) was significantly higher than that for controls (1.59 ± 0.41 m/s) (). The area under the receiver operating characteristics (ROC) curve for CAT was 0.899, and the SWV cut-off value was 1.96 m/s. The sensitivity, specificity, and diagnostic accuracy were 87.4%, 78.7%, and 85.1%, respectively. Levels of anti-thyroperoxidase antibodies and thyroid isthmus thickness were correlated with tissue stiffness in CAT. However, there was no correlation between levels of anti-thyroglobulin antibodies and tissue stiffness. Quantitative SWE is useful for diagnosing CAT, and it is possible that SWE can be used to evaluate the degree of fibrosis in patients with CAT. Takahiro Fukuhara, Eriko Matsuda, Shoichiro Izawa, Kazunori Fujiwara, and Hiroya Kitano Copyright © 2015 Takahiro Fukuhara et al. All rights reserved. Bone Indices in Thyroidectomized Patients on Long-Term Substitution Therapy with Levothyroxine Assessed by DXA and HR-pQCT Mon, 13 Jul 2015 11:24:29 +0000 Background. Studies on bone effects of long-term substitution therapy with levothyroxine (LT4) have shown discrepant results. Previous studies have, however, not evaluated volumetric bone mineral densities (vBMD), bone structure, and strength using high resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). Using a cross-sectional design, we aimed to determine whether BMD, structure, and strength are affected in hypothyroid patients on LT4 substitution therapy. Methods. We compared 49 patients with well-substituted hypothyroidism with 49 age- and gender-matched population based controls. Areal BMD was assessed by DXA, vBMD and bone geometry by HR-pQCT, and bone strength by FEA. Results. Patients had been thyroidectomized due to thyroid cancer (10%) and nontoxic (33%) or toxic goiter (57%). 82% were women. TSH levels did not differ between groups, but patients had significantly higher levels of T4 () and lower levels of T3 (). Compared to controls, patients had higher levels of magnesium (), whereas ionized calcium and PTH were lower (). Bone scans did not reveal any differences in BMD, bone geometry, or strength. Conclusion. If patients with hypothyroidism are well-substituted with LT4, the disease does not affect bone indices to any major degree. Emil Moser, Tanja Sikjaer, Leif Mosekilde, and Lars Rejnmark Copyright © 2015 Emil Moser et al. All rights reserved. Anti-Thyroid Peroxidase Antibody in Vitiligo: A Prevalence Study Sun, 11 Jan 2015 11:34:30 +0000 Aim. The aim of the study was to study the relation of vitiligo with demographic data like age, sex, and duration and determine the prevalence of thyroid autoimmunity in vitiligo patients. Materials and Methods. This study was a cross sectional study consisting of 100 patients clinically diagnosed (old and new) as having vitiligo irrespective of age or sex. Patients with known thyroid disease on supplementation therapy, or who had undergone thyroid surgery, those on antithyroid medication, patients with other causes of leukoderma, and cases who do not provide informed consent were excluded from the study. Serum TSH and anti-TPO antibodies were measured in all the patients. Results. The prevalence of anti-TPO antibody positivity was found to be 28%. Conclusion. According to our study, none of our vitiligo patients had symptoms or signs of thyroid disease at the time of presentation but, on biochemical evaluation, anti-TPO antibodies were found in a considerable number of patients. Hence, we recommend screening of these patients with thyroid antibodies. R. Dash, A. Mohapatra, and B. S. Manjunathswamy Copyright © 2015 R. Dash et al. All rights reserved. Elevated Serum Thyroglobulin and Low Iodine Intake Are Associated with Nontoxic Nodular Goiter among Adults Living near the Eastern Mediterranean Coast Sun, 14 Dec 2014 09:53:53 +0000 Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequate iodine intake can lead to thyroid diseases, including nontoxic nodular goiter (NNG). Objective. To estimate iodine intake and explore its correlation with thyroid diseases among Israeli adults living near the Mediterranean coast, where iodine-depleted desalinated water has become a major source of drinking water. Methods. Cross-sectional study of patients attending Barzilai Medical Center Ashkelon. Participants, who were classified as either NNG (), hypothyroidism (), or control (), provided serum thyroglobulin (Tg) and completed a semiquantitative iodine food frequency questionnaire. Results. Elevated serum Tg values (Tg > 60 ng/mL) were significantly more prevalent in the NNG group than in the other groups (29% versus 7% and 0% for hypothyroidism and controls, resp., ). Mean estimated iodine intake was significantly lower in the NNG group ( μg/d) than in controls ( μg/d) () with intermediate intake in the hypothyroid group ( μg/d). Conclusions. Elevated serum Tg values and low dietary iodine intake are associated with NNG among adult patients in Ashkelon District, Israel. Larger studies are needed in order to expand on these important initial findings. Yaniv S. Ovadia, Dov Gefel, Svetlana Turkot, Dorit Aharoni, Shlomo Fytlovich, and Aron M. Troen Copyright © 2014 Yaniv S. Ovadia et al. All rights reserved. Urinary Iodine Clearance following Iodinated Contrast Administration: A Comparison of Euthyroid and Postthyroidectomy Subjects Wed, 12 Nov 2014 11:41:26 +0000 Purpose. To compare iodine clearance following iodinated contrast administration in thyroidectomised thyroid cancer patients and euthyroid individuals. Methods. A convenience population (6 thyroidectomised thyroid cancer patients and 7 euthyroid controls) was drawn from patients referred for iodinated contrast-enhanced computed tomography (CT) studies. Subjects had sequential urine samples collected up to 6 months (50 samples from the thyroidectomised and 63 samples from the euthyroid groups). -tests and generalised estimating equations (GEE) were used to test for group differences in urinary iodine creatinine ratios. Results. Groups had similar urinary iodine creatinine ratios at baseline, with a large increase 2 weeks following iodinated contrast (). Both groups had a return of urinary iodine creatinine ratios to baseline by 4 weeks, with no significant group differences overall or at any time point. Conclusions. Thyroidectomised patients did not have a significantly different urinary iodine clearance than euthyroid individuals following administration of iodinated contrast. Both had a return of urinary iodine creatinine ratios to baseline within 4 weeks. Janice D. Ho, James F. Tsang, Kylie A. Scoggan, and William D. Leslie Copyright © 2014 Janice D. Ho et al. All rights reserved. Parathyroid Gland Involvement by Thyroid Cancer: Results from a Large Series of Thyroidectomies Performed in Two Italian University Hospitals and Review of the Literature Tue, 11 Nov 2014 06:45:44 +0000 Objectives.Parathyroid involvement by thyroid cancer (TC) has not been frequently investigated in thyroidectomy-based studies. We aimed to detect cases of parathyroid invasion by TC in a large series of thyroidectomies and to review the literature on this topic. Study Design. A 10-yr period database research was made from the files of the Section of Pathology of two Italian University Hospitals. Out of 22,310 thyroidectomies, 10 patients with parathyroid involvement by TC were found. Results. The 10 patients, 7 females and 3 males, aged years (range 34–76, median 56) had papillary thyroid carcinoma and accounted for 0.4% of subjects affected by all TCs and submitted to thyroidectomy. The tumor invaded perithyroid soft tissues in 6 patients and central neck (level VI) lymph nodes in 3. Parathyroid involvement by TC occurred by infiltration in 6 cases, extension through an intervening pseudocapsule in 1, and both patterns in 3. All patients are alive and disease free at -yr follow-up. Conclusion. Limited to thyroidectomy series, our results and literature data suggest that parathyroid involvement by TC has a 0.4–3.9% incidence rate; mainly affects women in their sixth-seventh decade of life; is associated to a good prognosis, unless massive extrathyroid extension of TC occurs. Giampaolo Papi, Stefania Corrado, Guido Fadda, Antonino Maiorana, Livia Maccio, Salvatore Maria Corsello, and Alfredo Pontecorvi Copyright © 2014 Giampaolo Papi et al. All rights reserved. What Happens in a 5-Year Follow-Up of Benign Thyroid Nodules Tue, 04 Nov 2014 12:40:05 +0000 To determine an optimal time for follow-up of benign thyroid nodules, we retrospectively evaluated 249 euthyroid patients with uni-multinodular goiter, who underwent annual visit, and significant events that occurred in 5 years’ time were registered. A significant event (appearance of new nodule, increase of nodule diameter >50%, appearance of compressive symptoms, thyroidectomy, repetition of FNA on the same nodule, and execution of FNA on new nodule) occurred in 26.1% of patients, with more than one event occurring in the same patient in 27.7% of cases. The majority of events (71.9%) were observed at 24- and 36-month follow-up visit. These results suggest that a patient diagnosed with benign nodular goiter may be safely followed-up at a 2-3-year interval time. Roberto Negro Copyright © 2014 Roberto Negro. All rights reserved. Symptoms and Signs Associated with Postpartum Thyroiditis Mon, 27 Oct 2014 12:53:26 +0000 Background. Postpartum thyroiditis (PPT) is a common triphasic autoimmune disease in women with thyroid peroxidase (TPO) autoantibodies. This study evaluated women's thyroid disease symptoms, physical findings, stress levels, and thyroid stimulating hormone (TSH) levels across six postpartum months in three groups, TPO negative, TPO positive, and PPT positive women. Methods. Women were recruited in midpregnancy and TPO status was determined which then was used to form the three postpartum groups. The three groups were compared on TSH levels, thyroid symptoms, weight, blood pressure, heart rate, a thyroid exam, and stress scores. Results. Fifty-six percent of the TPO positive women developed PPT. Hypothyroid group (F (2, 742) = 5.8, ) and hyperthyroid group (F (2, 747) = 6.6, ) subscale scores differed by group. Several symptoms and stress scores were highest in the PPT group. Conclusions. The normal postpartum is associated with many symptoms that mimic thyroid disease symptoms, but severity is greater in women with either TPO or PPT positivity. While the most severe symptoms were generally seen in PPT positive women, even TPO positive women seem to have higher risk for these signs and symptoms. Maureen Groer and Cecilia Jevitt Copyright © 2014 Maureen Groer and Cecilia Jevitt. All rights reserved. Short Course High Dose Radiotherapy in the Treatment of Anaplastic Thyroid Carcinoma Tue, 14 Oct 2014 08:05:55 +0000 Purpose. Anaplastic thyroid carcinoma (ATC) is a rare but aggressive tumor with limited survival. To date, the ideal radiation treatment schedule, one that balances limited survival with treatment efficacy, remains undefined. In this retrospective series we investigate the effectiveness and tolerability of hypofractionated radiation therapy in the treatment of ATC. Methods. 17 patients with biopsy proven ATC treated between 2004 and 2012 were reviewed for outcomes and toxicity. All patients received short course radiation. Results. The most commonly prescribed dose was 54 Gy in 18 fractions. Median survival was 9.3 months. 47% of patients were metastatic at diagnosis and the majority of patients (88%) went on to develop metastasis. Death from local progression was seen in 3 patients (18%), 41% experienced grade 3 toxicity, and there were no grade 4 toxicities. Conclusions. Here we demonstrated the safety and feasibility of hypofractionated radiotherapy in the treatment of ATC. This approach offers shorter treatment courses (3-4 weeks) compared to traditional fractionation schedules (6-7 weeks), comparable toxicity, local control, and the ability to transition to palliative care sooner. Local control was dependent on the degree of surgical debulking, even in the metastatic setting. Mark J. Stavas, Eric T. Shinohara, Albert Attia, Matthew S. Ning, Jeffrey M. Friedman, and Anthony J. Cmelak Copyright © 2014 Mark J. Stavas et al. All rights reserved. Antitumor Activity of Lenvatinib (E7080): An Angiogenesis Inhibitor That Targets Multiple Receptor Tyrosine Kinases in Preclinical Human Thyroid Cancer Models Wed, 10 Sep 2014 06:14:31 +0000 Inhibition of tumor angiogenesis by blockading the vascular endothelial growth factor (VEGF) signaling pathway is a promising therapeutic strategy for thyroid cancer. Lenvatinib mesilate (lenvatinib) is a potent inhibitor of VEGF receptors (VEGFR1–3) and other prooncogenic and prooncogenic receptor tyrosine kinases, including fibroblast growth factor receptors (FGFR1–4), platelet derived growth factor receptor α (PDGFRα), KIT, and RET. We examined the antitumor activity of lenvatinib against human thyroid cancer xenograft models in nude mice. Orally administered lenvatinib showed significant antitumor activity in 5 differentiated thyroid cancer (DTC), 5 anaplastic thyroid cancer (ATC), and 1 medullary thyroid cancer (MTC) xenograft models. Lenvatinib also showed antiangiogenesis activity against 5 DTC and 5 ATC xenografts, while lenvatinib showed in vitro antiproliferative activity against only 2 of 11 thyroid cancer cell lines: that is, RO82-W-1 and TT cells. Western blot analysis showed that cultured RO82-W-1 cells overexpressed FGFR1 and that lenvatinib inhibited the phosphorylation of FGFR1 and its downstream effector FRS2. Lenvatinib also inhibited the phosphorylation of RET with the activated mutation C634W in TT cells. These data demonstrate that lenvatinib provides antitumor activity mainly via angiogenesis inhibition but also inhibits FGFR and RET signaling pathway in preclinical human thyroid cancer models. Osamu Tohyama, Junji Matsui, Kotaro Kodama, Naoko Hata-Sugi, Takayuki Kimura, Kiyoshi Okamoto, Yukinori Minoshima, Masao Iwata, and Yasuhiro Funahashi Copyright © 2014 Osamu Tohyama et al. All rights reserved. Papillary Thyroid Cancer, Macrofollicular Variant: The Follow-Up and Analysis of Prognosis of 5 Patients Wed, 10 Sep 2014 00:00:00 +0000 Objective. The main aim of this study was to comparatively analyze the recurrence and prognosis of this rare variant with the literature by analyzing the follow-up data of 5 patients diagnosed with papillary cancer macrofollicular variant. Methods. The demographic data, radiological and pathological data, and prognostic data of 5 patients who underwent surgery for thyroid cancer and were diagnosed with papillary cancer macrofollicular variant pathologically were retrospectively analyzed. Results. The mean age of patients whose mean follow-up period was determined as 7.2 years was 41, and the male/female ratio was 4/1. All patients underwent total thyroidectomy. The pathology report of 2 patients (40%) revealed macrofollicular variant of papillary microcancer, and 3 patients papillary cancer macrofollicular variant. Central dissection was performed in one patient (20%) due to macroscopic pathologic lymph node and 4 metastatic lymph nodes were reported. Also, locoregional recurrence was present in 3 out of 5 patients (60%). Conclusions. Although an impression of earlier and increased risk of recurrence in papillary carcinoma with macrofollicular variant has been documented, more studies with extensive follow-up times and large populations are required. Varlık Erol, Özer Makay, Yeşim Ertan, Gökhan İçöz, Mahir Akyıldız, and Mustafa Yılmaz Copyright © 2014 Varlık Erol et al. All rights reserved. Differential Profile of Ultrasound Findings Associated with Malignancy in Mixed and Solid Thyroid Nodules in an Elderly Female Population Mon, 23 Jun 2014 08:20:42 +0000 Objective. Ultrasonographic characteristics are associated with thyroid malignancy. Our aim was to compare the diagnostic value of ultrasound features in the detection of thyroid malignancy in both solid and mixed nodules. Methods. We prospectively studied female patients (≥50 years) referred to ultrasound-guided fine needle aspiration biopsy. Ultrasound features considered suspicious were hypoechogenicity, microcalcifications, irregular margins, high anteroposterior (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed and solid nodules. Results. In a group of 504 elderly female patients (age =  years), the frequency of malignant cytology was 6%. Thirty-one percent of nodules were mixed and 60% were solid. The rate of malignant cytology was similar for mixed and solid nodules (7.4 versus 5.8%, : 0.56). While in mixed nodules none of the ultrasound characteristics were associated with malignant cytology, in solid nodules irregular margins and microcalcifications were significant (all ). The combination of irregular margins and/or microcalcifications significantly increased the association with malignant cytology only in solid nodules (OR: 2.76 (95% CI: 1.25–6.10), : 0.012). Conclusions. Ultrasound features were of poor diagnostic value in mixed nodules, which harbored malignant lesions as often as solid nodules. Our findings challenge the recommended minimal size for ultrasound-guided fine needle aspiration biopsy in mixed nodules. María Inés Vera, Tomás Meroño, María Agustina Urrutia, Carina Parisi, Yanina Morosan, Melanie Rosmarin, Marta Schnitman, Fernando Brites, Silvio Grisendi, María Sol Serrano, Wilfredo Luciani, Leonardo Serrano, Carlos Zuk, Guillermo De Barrio, Claudia Cejas, María Cristina Faingold, and Gabriela Brenta Copyright © 2014 María Inés Vera et al. All rights reserved. The Hypothalamic-Pituitary-Thyroid Axis in Infants and Children: Protection from Radioiodines Sun, 25 May 2014 12:05:25 +0000 Potassium iodide (KI) is recommended as an emergency treatment for exposure to radioiodines, most commonly associated with nuclear detonation or mishaps at nuclear power plants. Protecting the thyroid gland of infants and children remains a priority because of increased incidence of thyroid cancer in the young exposed to radioiodines (such as 131I and 133I). There is a lack of clinical studies for KI and radioiodines in children or infants to draw definitive conclusions about the effectiveness and safety of KI administration in the young. In this paper, we compare functional aspects of the hypothalamic-pituitary-thyroid (HPT) axis in the young and adults and review the limited studies of KI in children. The HPT axis in the infant and child is hyperactive and therefore will respond less effectively to KI treatment compared to adults. Research on the safety and efficacy of KI in infants and children is needed. Jeffrey Fisher, Xiaoxia Yang, Curtis Harris, Igor Koturbash, and Annie Lumen Copyright © 2014 Jeffrey Fisher et al. All rights reserved. The Beneficial Effects of Valproic Acid in Thyroid Cancer Are Mediated through Promoting Redifferentiation and Reducing Stemness Level: An In Vitro Study Thu, 15 May 2014 09:52:44 +0000 Valproic acid (VPA) has been identified as a histone deacetylase inhibitor, inducing differentiation in transformed cells. However, no study has shown the effect of VPA in the redifferentiation induction and stemness of anaplastic thyroid. The main objective of this study was to evaluate the efficacy of VPA as a differentiation therapy agent in human thyroid cancer based on its effect on stemness and differentiation process. Indications for differentiation of 8305C and B-CPAP cell lines following VPA treatment were obtained by analyzing cell proliferation rate, morphological changes, adherent-dependent colony formation, and Hoechst 33342 staining. The expressions of stemness, differentiation, and aggressiveness specific marker genes were measured by quantitative RT-PCR. VPA treatment effectively showed growth inhibition in both cell lines. The high nuclear-cytoplasmic (N : C) ratio of 8305C cells markedly decreased and treated cells became more epithelial-like. Treated cells showed stronger Hoechst 33342 fluorescence compared with control cells. The hTERT and OCT-4 reduction was paralleled with adherent-dependent colony formation decrement in both cell lines. VPA effectively induced NIS and TTF-1 in anaplastic cells, it whereas showed no clear pattern in papillary cell line. VPA treatment also resulted in the reduction of MMP-2 and MMP-9. These finding suggest that VPA could redifferentiate the anaplastic thyroid cancer cells. Vahid Haghpanah, Mohsen Malehmir, Bagher Larijani, Shahin Ahmadian, Kamran Alimoghaddam, Ramin Heshmat, Ardeshir Ghavamzadeh, Khadijeh Adabi, and Seyed H. Ghaffari Copyright © 2014 Vahid Haghpanah et al. All rights reserved. Weight Gain and Serum TSH Increase within the Reference Range after Hemithyroidectomy Indicate Lowered Thyroid Function Wed, 14 May 2014 06:18:11 +0000 Background. Weight gain is frequently reported after hemithyroidectomy but the significance is recently discussed. Therefore, the aim of the study was to examine changes in body weight of hemithyroidectomized patients and to evaluate if TSH increase within the reference range could be related to weight gain. Methods. In a controlled follow-up study, two years after hemithyroidectomy for benign euthyroid goiter, postoperative TSH and body weight of 28 patients were compared to preoperative values and further compared to the results in 47 matched control persons, after a comparable follow-up period. Results. Two years after hemithyroidectomy, median serum TSH was increased over preoperative levels (1.23 versus 2.08 mIU/L, ) and patients had gained weight (75.0 versus 77.3 kg, ). Matched healthy controls had unchanged median serum TSH (1.70 versus 1.60 mIU/L, ) and weight (69.3 versus 69.3 kg, ). Patients on thyroxin treatment did not gain weight. TSH increase was significantly correlated with weight gain (, ). Conclusion. Two years after hemithyroidectomy for benign euthyroid goiter, thyroid function is lowered within the laboratory reference range. Weight gain of patients who are biochemically euthyroid after hemithyroidectomy may be a clinical manifestation of a permanently decreased metabolic rate. Tina Toft Kristensen, Jacob Larsen, Palle Lyngsie Pedersen, Anne-Dorthe Feldthusen, Christina Ellervik, Søren Jelstrup, and Jan Kvetny Copyright © 2014 Tina Toft Kristensen et al. All rights reserved. There Is No Elevation of Immunoglobulin E Levels in Albanian Patients with Autoimmune Thyroid Diseases Wed, 14 May 2014 00:00:00 +0000 Background. Studies in several ethnic groups reported high incidence of elevated levels of immunoglobulin E (IgE) in patients with autoimmune thyroid diseases (ATD), especially in patients with Graves’ disease. Objective. To study association between serum levels of IgE and thyroid stimulating hormone receptor antibodies (TRAb) in Albanian patients with ATD. Material and Methods. Study was performed in 40 patients with Graves’ disease, 15 patients with Hashimoto’s thyroiditis, and 14 subjects in the control group. The IgE levels were measured by immunoradiometric assay, whereas the TRAb levels were measured by radioreceptor assay. Results. In all groups of subjects the IgE levels were within reference values (<200 kIU/L). Significant difference in mean concentration of IgE was found between two groups of Graves’ disease patients, and those with normal and elevated TRAb levels (22.57 versus 45.03, ). Positive correlation was found between TRAb and IgE only in Graves’ disease patients (, ). Conclusion. In Albanian patients with ATD there is no elevation of IgE levels. This could be the result of low prevalence of allergic diseases in Albanian population determined by genetic and environmental factors. Hatixhe Latifi-Pupovci, Besa Gacaferri-Lumezi, and Violeta Lokaj-Berisha Copyright © 2014 Hatixhe Latifi-Pupovci et al. All rights reserved. Preablation Stimulated Thyroglobulin/TSH Ratio as a Predictor of Successful I131Remnant Ablation in Patients with Differentiated Thyroid Cancer following Total Thyroidectomy Wed, 09 Apr 2014 09:01:02 +0000 Background. About 90% of thyroid cancers are differentiated thyroid cancers. Standard treatment is total thyroidectomy followed by radioactive I131remnant ablation and TSH suppression with thyroxine. Unsuccessful ablation drastically affects the prognosis of patients with DTC particularly high risk individuals; therefore, identifying the factors that affect the success of ablation is important in the management of patients with DTC. sTg is a good predictor of successful ablation in DTC. Its levels can be influenced by tumor staging and TSH values, as well as other factors. Therefore, we did this study using TSH to correct the predictive value of sTg in success of RRA. Methods. We retrospectively reviewed the records of 75 patients with DTC, who underwent total thyroidectomy followed by RRA and TSH suppression. Results. Preablation sTg and sTg/TSH ratio are significantly associated with ablation outcome. Cutoff value for sTg to predict successful and unsuccessful ablation was 18 ng/mL with 76.7% sensitivity and 79.1% specificity, while for sTg/TSH cutoff was 0.35 with 81.4% sensitivity and 81.5% specificity (). Association was stronger for sTg/TSH ratio with adjusted odds ratio (AOR) 11.64 (2.43–55.61) than for sTg with AOR 5.42 (1.18–24.88). Conclusions. Preablation sTg/TSH ratio can be considered as better predictor of ablation outcome than sTg, tumor size, and capsular invasion. Syed Zubair Hussain, Maseeh uz Zaman, Sarwar Malik, Nanik Ram, Ali Asghar, Unaib Rabbani, Nida Aftab, and Najmul Islam Copyright © 2014 Syed Zubair Hussain et al. All rights reserved. Correlation of Fine Needle Aspiration Cytology Findings with Thyroid Function Test in Cases of Lymphocytic Thyroiditis Sun, 06 Apr 2014 16:13:11 +0000 Background. Chronic lymphocytic thyroiditis is the second most common thyroid lesion diagnosed on FNAC after goiter. FNAC is reliable tool in the diagnosis of thyroid lesion. Objective. To correlate FNAC cytologic findings with TFT in the lymphocytic thyroiditis. Methods. 175 patients with thyroid swellings were referred for FNAC as well as TFT during 2011–2013. Fine needle aspiration cytology was performed using non-aspiration or aspiration techniques and TFT performed on Beckman culter access 2. Results. Lymphoid infiltrate was seen in 55 cases. The commonest age group of lymphocytic thyroiditis was 21–30 years with male : female ratio being 1 : 10. Anti-TPO and TSH were elevated in 96.16% (25/26) of cases with grade 3 lymphoid infiltrate, 94.12% (16/17) of cases with grade 2, and 91.67% (11/12) of cases with 1 grade. Increased anti-TPO with raised TSH without any lymphoid infiltrate was seen in 5 cases and 5 cases showed only raised TSH without raised anti-TPO and without any lymphoid infiltrate. We observed that grade 3 lymphocytic infiltration has correlation with anti-TPO and TSH together or TSH alone but not with anti-TPO alone. We also observed that anti-TPO and TSH together are significant even if no lymphocytic infiltration is present. Conclusion. Grade 3 lymphocytic infiltration has statistical correlation with anti-TPO and TSH together or TSH alone but not with anti-TPO alone. Anti TPO was adjunct to TSH in grade 3. The presence of Hurthle cell change, giant cells, and granulomas has no statistical correlation with lymphocytic thyroiditis. Neelam Sood and Jitendra Singh Nigam Copyright © 2014 Neelam Sood and Jitendra Singh Nigam. All rights reserved. Maternal Hypothyroidism in Early Pregnancy and Infant Structural Congenital Malformations Wed, 12 Mar 2014 13:01:04 +0000 Background. The question is debated on whether maternal hypothyroidism or use of thyroxin in early pregnancy affects the risk for infant congenital malformations. Objectives. To expand the previously published study on maternal thyroxin use in early pregnancy and the risk for congenital malformations. Methods. Data from the Swedish Medical Birth Register were used for the years 1996–2011 and infant malformations were identified from national health registers. Women with preexisting diabetes or reporting the use of thyreostatics, anticonvulsants, or antihypertensives were excluded from analysis. Risk estimates were made as odds ratios (ORs) or risk ratios (RRs) after adjustment for year of delivery, maternal age, parity, smoking, and body mass index. Results. Among 23 259 infants whose mothers in early pregnancy used thyroxin, 730 had a major malformation; among all 1 567 736 infants, 48012 had such malformations. The adjusted OR was 1.06 (95% CI 0.98–1.14). For anal atresia the RR was 1.85 (95% CI 1.00–1.85) and for choanal atresia 3.14 (95% CI 1.26–6.47). The risk of some other malformations was also increased but statistical significance was not reached. Conclusions. Treated maternal hypothyroidism may be a weak risk factor for infant congenital malformations but an association with a few rare conditions is possible. Bengt Källén and Birgitta Norstedt Wikner Copyright © 2014 Bengt Källén and Birgitta Norstedt Wikner. All rights reserved. Thyrotoxic Periodic Paralysis: Clinical Challenges Thu, 20 Feb 2014 08:31:44 +0000 Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and is secondary to thyrotoxicosis. The underlying hyperthyroidism is often subtle causing difficulty in early diagnosis. Factors like high-carbohydrate meal exercise, steroid, and stress can precipitate an attack of TPP. Evidence is building up showing role of genetic mutations in Kir2.6 channel in the pathogenesis of TPP. Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle of hypokalemia. Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes are characteristic of TPP. Treatment with low-dose potassium supplements and nonselective beta-blockers should be initiated upon diagnosis, and the serum potassium level should be frequently monitored to prevent rebound hyperkalemia. Abhishek Vijayakumar, Giridhar Ashwath, and Durganna Thimmappa Copyright © 2014 Abhishek Vijayakumar et al. All rights reserved. Association between TSH-Receptor Autoimmunity, Hyperthyroidism, Goitre, and Orbitopathy in 208 Patients Included in the Remission Induction and Sustenance in Graves’ Disease Study Tue, 18 Feb 2014 07:51:16 +0000 Background. Graves’ disease may have a number of clinical manifestations with varying degrees of activity that may not always run in parallel. Objectives. To study associations between serum levels of TSH-receptor autoantibodies and the three main manifestations of Graves’ disease (hyperthyroidism, goiter, and presence of orbitopathy) at the time of diagnosis of hyperthyroidism. Methods. We describe a cohort of 208 patients with newly diagnosed Graves’ hyperthyroidism. Patients were enrolled in a multiphase study of antithyroid drug therapy of Graves’ hyperthyroidism, entitled “Remission Induction and Sustenance in Graves’ Disease (RISG).” Patients were systematically tested for degree of biochemical hyperthyroidism, enlarged thyroid volume by ultrasonography, and the presence of orbitopathy. Results. Positive correlations were found between the levels of TSH-receptor autoantibodies in serum and the three manifestations of Graves’ disease: severeness of hyperthyroidism, presence of enlarged thyroid, and presence of orbitopathy, as well as between the different types of manifestations. Only around half of patients had enlarged thyroid gland at the time of diagnosis of hyperthyroidism, whereas 25–30% had orbitopathy. Conclusions. A positive but rather weak correlation was found between TSH-receptor antibodies in serum and the major clinical manifestation of Graves’ disease. Only half of the patients had an enlarged thyroid gland at the time of diagnosis. Peter Laurberg, Birte Nygaard, Stig Andersen, Allan Carlé, Jesper Karmisholt, Anne Krejbjerg, Inge Bülow Pedersen, and Stine Linding Andersen Copyright © 2014 Peter Laurberg et al. All rights reserved.