Journal of Thyroid Research The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. The End-Diastolic Velocity of Thyroid Arteries Is Strongly Correlated with the Peak Systolic Velocity and Gland Volume in Patients with Autoimmune Thyroiditis Thu, 14 Sep 2017 07:47:32 +0000 Background. The end-diastolic velocity (EDV) of thyroid arteries reflects peripheral blood flow resistance. Objective. The aim was to evaluate EDV correlations with other Doppler sonography parameters and with clinical and biochemical variables in a sample of patients with hypothyroidism caused by chronic autoimmune thyroiditis (CAT). Methods. A sample of 48 CAT hypothyroid patients receiving treatment with stable doses of levothyroxine was selected. The participants underwent clinical evaluation and measurement of serum thyrotropin (TSH), total triiodothyronine (T3), total thyroxine (T4), free T4, thyroid peroxidase antibodies (anti-TPO), and antithyroglobulin antibodies (anti-Tg) and Doppler sonography. Results. The EDV of the inferior thyroid arteries (ITA-EDV) was strongly and positively correlated with the peak systolic velocity of the inferior thyroid arteries (ITA-PSV, ), thyroid volume (), and thyroid visual vascularization pattern (TVP, ). There was no correlation between ITA-EDV and the clinical variables, hormones, anti-TPO, or anti-Tg. Conclusion. The strong correlation of ITA-EDV with ITA-PSV, TVP, and volume suggests that increased vascularization in CAT may be associated with a reduction in thyroid blood flow resistance, possibly due to an angiogenesis-induced increase in the total vascular cross-sectional area of the parenchyma. Danilo Bianchini Höfling, Suemi Marui, Carlos Alberto Buchpiguel, Giovanni Guido Cerri, and Maria Cristina Chammas Copyright © 2017 Danilo Bianchini Höfling et al. All rights reserved. Corrigendum to “The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology” Sun, 20 Aug 2017 10:36:15 +0000 Stephen Paul Fitzgerald and Nigel Geoffrey Bean Copyright © 2017 Stephen Paul Fitzgerald and Nigel Geoffrey Bean. All rights reserved. Hypermetabolic Thyroid Incidentaloma on Positron Emission Tomography: Review of Laboratory, Radiologic, and Pathologic Characteristics Sun, 20 Aug 2017 07:18:04 +0000 Introduction. Incidental hypermetabolic thyroid lesions on Positron Emission Tomography have significant clinical value and may harbor malignancy. In this study we evaluated laboratory, radiologic, and pathologic characteristics of incidental hypermetabolic thyroid lesions. Materials and Methods. We evaluated 18 patients prospectively with various malignancies and hypermetabolic thyroid incidentaloma. The thyroid function tests, ultrasound assessment, and guided FNA biopsy were performed on all cases. Results. We included 9 male and 9 female patients with mean age of 51 years. Most common malignancy was colon cancer. Metabolic activity quantification using maximum standard uptake value demonstrated range between 1.4 and 65.4 with mean value of 9.4. We found highest metabolic activity in patients with lung adenocarcinoma, B-cell lymphoma, and colon adenocarcinoma. On ultrasound exam most thyroid lesions were of solid, hypoechoic, noncalcified nature with either normal or peripheral increased vascularity. FNA biopsy report was benign in 15 cases and malignant or highly suggestive for malignancy in 3 other cases. Two of the three malignant cases demonstrated metabolic activity higher than average SUV max. Conclusion. Most thyroid hypermetabolic incidentalomas are benign lesions, while higher values of SUV max are in favor of malignancy. This mandates further evaluation of incidentally found thyroid hypermetabolic lesions on routine PET/CT scans. Mehrdad Bakhshayesh Karam, Abtin Doroudinia, Farzaneh Joukar, Kobra Nadi, Atosa Dorudinia, Payam Mehrian, and Abbas Yousefikoma Copyright © 2017 Mehrdad Bakhshayesh Karam et al. All rights reserved. Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins Tue, 15 Aug 2017 08:56:34 +0000 Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. Datis Kharrazian, Martha Herbert, and Aristo Vojdani Copyright © 2017 Datis Kharrazian et al. All rights reserved. Outcome, Pain Perception, and Health-Related Quality of Life in Patients Submitted to Percutaneous Ethanol Injection for Simple Thyroid Cysts Sun, 09 Jul 2017 06:44:38 +0000 Thyroid cysts are usually benign lesions that when voluminous may induce cosmetic concerns or local discomfort. Percutaneous ethanol injection (PEI) has been demonstrated to be effective for shrinkage of such cysts. In this retrospective study, we evaluated the efficacy, pain perception, and health-related quality of life (HRQL) in patients submitted to PEI for pure cystic lesions. We reviewed the data of 101 patients who underwent ≤3 PEI. In the whole group of patients, the volume reduction was 66% after the first, 74.4% after the second, and 79.4% after the third PEI treatment. 55.4% had a cystic volume ≤ 10 ml; 85.7% of cysts ≤ 10 ml were cured by just one PEI. The number of PEI was significantly higher in the >30.0 ml group; this latter group obtained the smallest percent reduction versus baseline after the first PEI when compared with smaller cysts. The sensation of pain reported during PEI was absent in 78.3% of cases, and HRQL significantly improved from pre- to the posttreatment. PEI is a safe and effective technique for pure cystic lesions. In addition, HRQL significantly improves, providing a further support for this procedure. Roberto Negro, Ermenegildo Colosimo, and Gabriele Greco Copyright © 2017 Roberto Negro et al. All rights reserved. Thyroid Disorders in Central Ghana: The Influence of 20 Years of Iodization Tue, 04 Jul 2017 00:00:00 +0000 Background. Ghana began mandatory iodization of salt in 1996. This study compares the prevalence of thyroid disorders before and after the introduction of iodization. Methods. This is a retrospective study of thyroid cases from the middle belt of Ghana between 1982 and 2014. To demonstrate a link between iodization and hyperthyroidism and autoimmunity, we compared the prevalence of hyperthyroidism and autoimmune thyroid disorders before and after the iodization programme. Results. A total of 10,484 (7548 females, 2936 males) cases were recorded. The rate of thyroid cases seen was 343/100,000. Nontoxic nodular goiters (25.7%) and toxic nodular goiters (22.5%) represented the second commonest thyroid disorders recorded. The prevalence of hyperthyroid disorders seen after 1996 was significantly higher than the prevalence seen before the iodization (40.0 versus 21.1%, ). The prevalence of autoimmune disorders recorded after iodization was significantly higher than that before the iodization programme started (22.3% versus 9.6%, ). Conclusions. This study has revealed a significant increase in thyroid admissions in Central Ghana over the decades. A connection between iodine fortification and iodine-induced hyperthyroidism and between iodine fortification and autoimmune thyroiditis has been shown in this study. Osei Sarfo-Kantanka, Ishmael Kyei, Fred Stephen Sarfo, and Eunice Oparebea Ansah Copyright © 2017 Osei Sarfo-Kantanka et al. All rights reserved. Ultrasound Risk Categories for Thyroid Nodules and Cytology Results: A Single Institution’s Experience after the Adoption of the 2016 Update of Medical Guidelines by the American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi Wed, 28 Jun 2017 09:12:47 +0000 Objectives. In 2016, the American Association of Clinical Endocrinologists (AACE) and Associazione Medici Endocrinologi (AME) released updated guidelines for the diagnosis and management of thyroid nodules. The aim of this study was to evaluate the AACE/AME recommendations for FNA in clinical practice, by comparing the (US) stratification risk and indications for FNA with cytologic results. Methods. From May to December 2016, we collected the cytologic results from FNAs of nodules that were classified using a three-tier US category system (low, intermediate, and high risk). Results. We obtained 859 FNAs from 598 patients: 341 (39.7%) from low, 489 (56.9%) from intermediate, and 29 (3.4%) from high risk nodules. Of these, 88.5% and 74.9% of low and intermediate risk nodules, respectively, were cytologically benign, whereas 84.6% of high risk nodules had a moderate-to-elevated risk of malignancy or were malignant. If FNAs had been limited to intermediate risk nodules >20 mm, we would have missed 13/17 (76.5%) nodules that had moderate-to-elevated risk of malignancy or were malignant (11/13 were malignant based on histology). Conclusions. A nonnegligible number of cytologically malignant nodules or nodules that were suspected to be malignant would be missed if intermediate US risk nodules <20 mm were not biopsied. Roberto Negro, Gabriele Greco, and Ermenegildo Colosimo Copyright © 2017 Roberto Negro et al. All rights reserved. Impact of Obesity on Serum Levels of Thyroid Hormones among Euthyroid Saudi Adults Tue, 23 May 2017 00:00:00 +0000 Aim of Study. To assess serum thyroid hormones levels among Saudi adults and to correlate participants’ serum levels with their grades of body mass index (BMI). Methodology. A total of 278 adult subjects were recruited. Participants were categorized according to their BMI grades into normal weight (BMI < 25 kg/m2), overweight (BMI 25–29.9 kg/m2), or obese (BMI 30 kg/m2). Serum thyroid hormones levels were assessed at the central laboratory of Aseer Central Hospital, Abha City, by chemiluminescence immunoassay. Results. More than three-fourths of participants were either overweight (31.3%) or obese (44.6%). Mean TSH serum levels showed a significantly increasing trend with increasing BMI (). A negative trend was observed regarding participants’ mean serum levels of fT4 with their BMI, but there were no significant differences in mean serum fT4 levels according to BMI. Moreover, no significant differences were observed in serum fT3 levels according to BMI. Conclusions. Mean TSH serum levels increase with BMI increase. Further largescale multicentric and longitudinal studies are necessary to prove the association between serum levels of thyroid hormones and BMI of euthyroid adults. Hassan M. Al-Musa Copyright © 2017 Hassan M. Al-Musa. All rights reserved. Beneficial Effects on Pregnancy Outcomes of Thyroid Hormone Replacement for Subclinical Hypothyroidism Tue, 14 Feb 2017 00:00:00 +0000 Background. Hypothyroidism and raised thyroid antibody levels have been associated with adverse obstetrical outcomes. Several studies have investigated causal associations, but results have been inconsistent and few studies have reported the effects of thyroxine replacement therapy on pregnancy outcomes in hypothyroid patients. Objective. The primary study objective was to determine the outcome of pregnancies in women diagnosed with overt and subclinical hypothyroidism (SCH) (serum TSH > 2.5 mIU/L) and those with elevated circulating thyroid autoantibody levels in the first trimester of pregnancy and after the institution of appropriate thyroxine replacement therapy to maintain the serum TSH ≤ 2.5 mIU/L. Study Design. This prospective observational study was undertaken between 2013 and 2016. Blood samples were taken from 1025 women at presentation for thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies (TGAb), and thyroid peroxidase antibodies (TPOAb). Those with a TSH > 2.5 mIU/L were treated with thyroxine and managed appropriately to ensure that the TSH was maintained ≤2.5 mIU/L. Outcomes in these patients were compared to those in euthyroid patients. Maternal antenatal complications and perinatal outcomes were recorded. Results. There were a total of 1025 patients of whom 382 (37.5%) were nulliparous. 10.1% had a TSH level > 2.5 mIU/L and 18.2% had at least one raised thyroid antibody level. No differences in adverse outcomes of pregnancy were evident in women treated for SCH or overt hypothyroidism compared to the euthyroid group. There was also no association between raised thyroid antibodies and adverse pregnancy outcomes in either group. Conclusion. There were no adverse outcomes of pregnancy found in pregnant women who had been diagnosed and treated with thyroxine for SCH at the time of presentation when compared to euthyroid patients. There was also no relationship with thyroid antibodies and adverse pregnancy outcomes in the two groups. It is not possible to unequivocally advocate for thyroxine replacement in pregnant women with subclinical and overt hypothyroidism until large scale randomized controlled trials are performed. Norman J. Blumenthal and Creswell J. Eastman Copyright © 2017 Norman J. Blumenthal and Creswell J. Eastman. All rights reserved. Regional Variation across Canadian Centers in Radioiodine Administration for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer Diagnosed in 2000–2010 Tue, 29 Nov 2016 12:45:52 +0000 Background. Use of radioactive iodine (RAI) ablation has been reported to vary significantly between studies. We explored variation in RAI ablation care patterns between seven thyroid cancer treatment centers in Canada. Methods. The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe and analyze patterns of care for thyroid cancer. We analyzed data from seven participating centers on RAI ablation in patients diagnosed with well-differentiated (papillary and follicular) thyroid cancer between 2000 and 2010. We compared RAI ablation protocols including indications (based on TNM staging), preparation protocols, and administered dose. We excluded patients with known distant metastases at time of RAI ablation. Results. We included 3072 patients. There were no significant differences in TNM stage over time. RAI use increased in earlier years and then declined. The fraction of patients receiving RAI varied significantly between centers, ranging between 20–85% for T1, 44–100% for T2, 58–100% for T3, and 59–100% for T4. There were significant differences in the RAI doses between centers. Finally, there was major variation in the use of thyroid hormone withdrawal or rhTSH for preparation of RAI ablation. Conclusion. Our study identified significant variation in use of RAI for ablation in patients with well-differentiated thyroid cancer both between Canadian centers and over time. I. Rachinsky, M. Rajaraman, W. D. Leslie, A. Zahedi, C. Jefford, A. McGibbon, J. E. M. Young, K. A. Pathak, M. Badreddine, S. De Brabandere, H. Fong, and S. Van Uum Copyright © 2016 I. Rachinsky et al. All rights reserved. Morphological Diversity of Pretibial Myxedema and Its Mechanism of Evolving Process and Outcome: A Retrospective Study of 216 Cases Thu, 25 Aug 2016 10:03:47 +0000 Background. Pretibial myxedema (PTM) is a rare dermopathy. The morphologic features and mechanism of its evolving process are not reported in large case series. Methods. 216 cases with PTM were retrospectively reviewed to analyze demographics, history, lesional morphology and its evolving process, histopathology and immunohistochemistry, serum TRAb levels, treatment, and outcome. Results. First appearing lesions evolved into 6 variants that were correlated with serum TRAb levels. Subvariants were caused by different kinds and frequencies of local trauma. The evolving process could be classified into 4 stages that were correlated with serum TRAb levels and perivascular infiltration of CD8+ and CD4+ lymphocytes. Serum TRAb levels at remission and in nonrecurred cases became lower than those before therapy and in recurred cases, respectively, but increased when PTM relapsed. TRAb level in nodule variant went down invariably with the extension of course and its autoimmune activity had a trend to stop but in other 5 variants TRAb levels fluctuated. Their autoimmune activities had no trends to stop and clinically worsen through intermittent repeats of active and stable stages. Conclusions. In the chronic course of PTM, nodule variant is self-limited and other 5 variants are not self-limited. PTM needed early treatment to avoid severe variants. Changgui Lan, Yi Wang, Xia Zeng, Jing Zhao, and Xiaoxi Zou Copyright © 2016 Changgui Lan et al. All rights reserved. Corrigendum to “How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer” Tue, 28 Jun 2016 06:16:40 +0000 Hugo Prazeres, Joana Torres, Fernando Rodrigues, Joana P. Couto, João Vinagre, Manuel Sobrinho-Simões, and Paula Soares Copyright © 2016 Hugo Prazeres et al. All rights reserved. Predictors of Regional Lymph Node Recurrence after Initial Thyroidectomy in Patients with Thyroid Cancer Tue, 14 Jun 2016 09:09:32 +0000 Background. Regional lymph node recurrence (RLNR) is common in patients with thyroid cancer but clinicopathological predictors are unclear. We aimed to clarify these predictors and identify patients who would benefit from prophylactic lymph node dissection the most. Method. 343 patients with different types of thyroid cancer were analyzed retrospectively. All patients underwent total thyroidectomy between 2007 and 2013. Results. The median ± interquartile range of patients’ age was 40 ± 25 years. 245 (71.4%) patients were female. Regarding the risk of regional lymph node recurrence, we found that male gender, age ≥45 years, non-PTC (i.e., medullary, follicular, and anaplastic types) histopathology, T3 (i.e., tumor size >4 cm in the greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension), stage IVa, and isolated cervical lymphadenopathy as initial manifestation (ICL) are significant risk factors. T3 (p < 0.001; odds ratio = 156.41, 95% CI [55.72–439.1]) and ICL (p < 0.001; odds ratio = 77.79, 95% CI [31.55–191.81]) were the strongest predictors of regional lymph node recurrence. Conclusion. We found easily achievable risk factors for RLNR in thyroid cancers patients. We suggested that patients with specific clinicopathological features like male gender, age ≥45 years, larger tumor size, and extrathyroidal extension be considered as prophylactic lymphadenectomy candidates. Amirsina Sharifi, Abolfazl Shojaeifard, Ahmadreza Soroush, Mehdi Jafari, Ali Ghorbani Abdehgah, and Hossein Mahmoudzade Copyright © 2016 Amirsina Sharifi et al. All rights reserved. FRTL-5 Rat Thyroid Cells Release Thyroglobulin Sequestered in Exosomes: A Possible Novel Mechanism for Thyroglobulin Processing in the Thyroid Thu, 09 Jun 2016 12:10:57 +0000 Exosomes are 30–100 nm, membrane-bound vesicles containing specific cellular proteins, mRNAs, and microRNAs that take part in intercellular communication between cells. A possible role for exosomes in thyroid function has not been fully explored. In the present study, FRTL-5 rat thyroid cells were grown to confluence and received medium containing either thyroid stimulating hormone (TSH), exogenous bovine thyroglobulin (bTg), or neither additive for 24 or 48 hours followed by collection of spent medium and ultracentrifugation to isolate small vesicles. Transmission electron microscopy and Western blotting for CD9 indicated the presence of exosomes. Western blotting of exosome extract using a monoclonal anti-Tg antibody revealed a Tg-positive band at ~330 kDa (the expected size of monomeric Tg) with a higher density in TSH-treated cells compared to that in untreated cells. These results are the first to show that normal thyroid cells in culture produce exosomes containing undegraded Tg. Pavel Vlasov, Sonia Q. Doi, and Donald F. Sellitti Copyright © 2016 Pavel Vlasov et al. All rights reserved. Change in Practice over Four Decades in the Management of Graves’ Disease in Scotland Mon, 30 May 2016 09:40:31 +0000 There is continuing debate on the optimal treatment for Grave’s thyrotoxicosis with a resultant variation in clinical practice. The present study aimed to ascertain changes in practice in the treatment of Grave’s thyrotoxicosis in Tayside, Scotland, over the past four decades. Methods. The “Scottish automated follow-up register” (SAFUR) was queried to identify all patients treated for Grave’s thyrotoxicosis from 1968 to 2007 inclusive. Patients were divided into 4 groups (Groups A to D) according to the decades. Demographic profile, treatment modalities, radioactive iodine (RAI) dose, and recurrence rates were studied and outcomes were compared by test and ANOVA using SPSS v15.0. A value of < 0.05 was considered significant. Results. Altogether, 3737 patients were diagnosed with Grave’s thyrotoxicosis over the 4 decades. Use of RAI has increased from 43.1% in Group A to 68% in Group D (). The dose of RAI has increased () and there has been a reduction in recurrence rate with higher dose of RAI. Surgical intervention rates decreased from 55.3% to 12.3% () over time. Conclusions. Analysis of a large dataset of patients with Grave’s thyrotoxicosis suggests increasing use of RAI as the preferred first line of treatment. Furthermore, using a single higher dose of RAI and adoption of total thyroidectomy have decreased recurrence rates. D. M. Smith, S. Dutta, F. Ahmed, and M. A. Thaha Copyright © 2016 D. M. Smith et al. All rights reserved. Association between Tumor Size and Bilateral Involvement in Papillary Thyroid Carcinoma Sun, 24 Apr 2016 14:17:42 +0000 Background. Tumor multifocality and bilaterality of papillary thyroid carcinoma (PTC) are important factors when selecting the most appropriate surgical procedure. The aim of this study was to assess the bilaterality rate in PTC and the relationship between the tumor size and bilaterality. Materials and Methods. Thyroidectomy specimens with a diagnosis of PTC were retrospectively reviewed in the Pathology Department of a tertiary care medical center. Specimens were divided into three groups according to the size of the primary and contralateral tumor foci. Tumors less than or equal to 1 cm in each lobe were included in group 1. Group 2 consisted of tumors greater than 1 cm in one lobe and less than 1 cm in the other lobe. Tumors greater than 1 cm in each lobe were included in group 3. Results. We identified 868 total thyroidectomy specimens with a diagnosis of PTC between 2001 and 2011. Of these cases, both thyroid lobes were involved in 262 cases (32%). There were 109 (42%), 121 (46%), and 32 cases (12%) in group 1, group 2, and group 3, respectively. Conclusion. Bilaterality is frequent in PTC and is not related to tumor size. Accordingly, the high frequency of bilateral disease in PTC should be kept in mind when determining the extent of the surgical procedure. Suna Erkilic, Fatih Celenk, and Zehra Bozdag Copyright © 2016 Suna Erkilic et al. All rights reserved. Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion—Preliminary Observations Thu, 31 Mar 2016 13:05:46 +0000 According to the epidemiological studies, about 4.4% of American general elderly population has a pronounced hypothyroidism and relies on thyroid hormone supplements daily. The prevalence of hypothyroidism in our patients with pancreatic cancer was much higher, 14.1%. A retrospective analysis was performed on patients who underwent pancreaticoduodenectomy (Whipple procedure) or distal pancreatectomy and splenectomy (DPS) at Thomas Jefferson University Hospital, Philadelphia, from 2005 to 2012. The diagnosis of hypothyroidism was correlated with clinicopathologic parameters including tumor stage, grade, and survival. To further understand how thyroid hormone affects pancreatic cancer behavior, functional studies including wound-induced cell migration, proliferation, and invasion were performed on pancreatic cancer cell lines, MiaPaCa-2 and AsPC-1. We found that hypothyroid patients taking exogenous thyroid hormone were more than three times likely to have perineural invasion, and about twice as likely to have higher T stage, nodal spread, and overall poorer prognostic stage (). Pancreatic cancer cell line studies demonstrated that exogenous thyroid hormone treatment increased cell proliferation, migration, and invasion (). We conclude that exogenous thyroid hormone may contribute to the progression of pancreatic cancer. Konrad Sarosiek, Ankit V. Gandhi, Shivam Saxena, Christopher Y. Kang, Galina I. Chipitsyna, Charles J. Yeo, and Hwyda A. Arafat Copyright © 2016 Konrad Sarosiek et al. All rights reserved. The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology Thu, 31 Mar 2016 09:14:05 +0000 Context. Population studies of the distribution of T4/TSH set points suggest a more complex inverse relationship between T4 and TSH than that suggested by physiological studies. The reasons for the similarities and differences between the curves describing these relationships are unresolved. Methods. We subjected the curve, derived from empiric data, describing the TSH suppression response to T4, and the more mathematically derived curve describing the T4 response to TSH, to the different possible models of population variation. The implied consequences of these in terms of generating a population distribution of T4/TSH equilibrium points (a “population curve”) were generated and compared to the empiric population curve. The physiological responses to primary hypothyroidism and hyperthyroidism were incorporated into the analysis. Conclusions. Though the population curve shows a similarly inverse relationship, it is describing a different relationship than the curve describing the suppression of TSH by T4. The population curve is consistent with the physiological studies of the TSH response to T4 and implies a greater interindividual variation in the positive thyroid T4 response to TSH than in the central inhibitory TSH response to T4. The population curve in the dysthyroid states is consistent with known physiological responses to these states. Stephen Paul Fitzgerald and Nigel Geoffrey Bean Copyright © 2016 Stephen Paul Fitzgerald and Nigel Geoffrey Bean. All rights reserved. Significance of Interleukin-6 in Papillary Thyroid Carcinoma Sun, 13 Mar 2016 07:27:11 +0000 This study sought to reveal the significance of IL-6 in papillary thyroid carcinoma by determining its circulating levels, tumoral protein, and mRNA expressions. As compared to the healthy individuals, serum IL-6 was significantly higher in patients with benign thyroid diseases and PTC. Further, its level was significantly higher in PTC patients as compared to patients with benign thyroid diseases. ROC curves also confirmed a good discriminatory efficacy of serum IL-6 between healthy individuals and patients with benign thyroid diseases and PTC. The circulating IL-6 was significantly associated with poor overall survival in PTC patients. IL-6 immunoreactivity was significantly high in PTC patients as compared to the benign thyroid disease patients. Significantly higher IL-6 mRNA expression was also observed in the primary tumour tissues of PTC patients than the adjacent normal tissues. The protein expression of IL-6 at both the circulating and tissue level correlated with disease aggressiveness in PTC patients. Moreover, a significant positive correlation was observed between the IL-6 protein and mRNA expression in the primary tumours of PTC patients. Finally in conclusion, IL-6 has an important role in thyroid cancer progression. Thus targeting IL-6 signalling can help in clinical management of thyroid carcinoma patients. 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. Effect of Preoperative Nerve Block on Postthyroidectomy Headache and Cervical Pain: A Randomized Prospective Study Sun, 13 Mar 2016 06:25:47 +0000 The aim of the current study was to investigate the efficacy of greater occipital nerve (GON) block and bilateral superficial cervical plexuses (BSCP) blocks in alleviating postoperative occipital headache and posterior neck pain after thyroidectomy. This randomized prospective study consisted of 75 women undergoing total thyroidectomy. Patients were randomized into three groups: Group I (): patients receiving GON, Group II (): patients receiving bilateral (BSCP) blocks, and Group III (): patients receiving no block. Assessment of occipital headache, posterior neck, and incision site pains was made at 12 hours and 24 hours after extubation by Visual Analogue Scale (VAS). In comparison to Group III significantly fewer patients in Groups I and II experienced occipital headache at 12 () and 24 hours () and also posterior neck pain at 24 hours (). Mean VAS scores at 12 and 24 hours for occipital headache ( and ) and posterior neck pain ( and ) were significantly lower in Group I. The differences between Groups II and III were not significant except for the occipital headache at 12 hours. The efficacy of GON block is superior to BSCP blocks in alleviating postthyroidectomy occipital headache and posterior cervical pain. Sunil Malla Bujar Barua, Anjali Mishra, Kamal Kishore, Saroj Kanta Mishra, Gyan Chand, Gaurav Agarwal, Amit Agarwal, and Ashok Kumar Verma Copyright © 2016 Sunil Malla Bujar Barua et al. All rights reserved. Safety and Effectiveness of Total Thyroidectomy and Its Comparison with Subtotal Thyroidectomy and Other Thyroid Surgeries: A Systematic Review Wed, 24 Feb 2016 15:29:00 +0000 Diseases associated with the thyroid gland are one of the most frequently seen endocrine disorders across the globe. Total thyroidectomy is currently the preferred treatment for many thyroid diseases. Controversies exist among surgeons regarding safety of total thyroidectomy due to the risk associated with it like postoperative hypoparathyroidism or recurrent laryngeal nerve damage. Since, in the recent years, the incidence of thyroidectomy is in increasing trend in south Indian population, this review aims to study the available data regarding the appropriateness and safety of total thyroidectomy and compares it with subtotal thyroidectomy and other thyroid surgeries. This is a retrospective comprehensive review of various articles and publications regarding total and partial thyroidectomy performed across the world. Many retrospective studies and few prospective studies suggest that the incidence of transient hypocalcemia is higher after total thyroidectomy than after subtotal thyroidectomy, but the incidence of other complications including recurrent laryngeal nerve palsy and postoperative hematoma is not significantly different between the two procedures. Hence in our review we found that total thyroidectomy is safe and cost effective with low complication rates and provides little significant advantage of being safer procedure compared to subtotal thyroidectomy. Ashwini Aithal Padur, Naveen Kumar, Anitha Guru, Satheesha Nayak Badagabettu, Swamy Ravindra Shanthakumar, Murlimanju Bukkambudhi Virupakshamurthy, and Jyothsna Patil Copyright © 2016 Ashwini Aithal Padur et al. All rights reserved. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism Wed, 17 Feb 2016 13:27:51 +0000 Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. Deborah Molehin, Marloes Dekker Nitert, and Kerry Richard Copyright © 2016 Deborah Molehin et al. 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.