Journal of Thyroid Research The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. Impact of Maternal Thyroperoxidase Status on Fetal Body and Brain Size Wed, 29 Jan 2014 11:22:29 +0000 The obstetric consequences of abnormal thyroid function during pregnancy have been established. Less understood is the influence of maternal thyroid autoantibodies on infant outcomes. The objective of this study was to examine the influence of maternal thyroperoxidase (TPO) status on fetal/infant brain and body growth. Six-hundred thirty-one (631) euthyroid pregnant women were recruited from prenatal clinics in Tampa Bay, Florida, and the surrounding area between November 2007 and December 2010. TPO status was determined during pregnancy and fetal/infant brain and body growth variables were assessed at delivery. Regression analysis revealed maternal that TPO positivity was significantly associated with smaller head circumference, reduced brain weight, and lower brain-to-body ratio among infants born to TPO+ white, non-Hispanic mothers only, distinguishing race/ethnicity as an effect modifier in the relationship. No significant differences were noted in body growth measurements among infants born to TPO positive mothers of any racial/ethnic group. Currently, TPO antibody status is not assessed as part of the standard prenatal care laboratory work-up, but findings from this study suggest that fetal brain growth may be impaired by TPO positivity among certain populations; therefore autoantibody screening among high-risk subgroups may be useful for clinicians to determine whether prenatal thyroid treatment is warranted. Roneé E. Wilson, Hamisu M. Salihu, Maureen W. Groer, Getachew Dagne, Kathleen O’Rourke, and Alfred K. Mbah Copyright © 2014 Roneé E. Wilson et al. All rights reserved. Histopathological Changes of the Thyroid and Parathyroid Glands in HIV-Infected Patients Wed, 22 Jan 2014 08:16:13 +0000 Objective. To study histopathology of the thyroid and parathyroid glands in HIV-infected African Americans in the United States. Methods. A retrospective review of 102 autopsy cases done by the Department of Pathology at Howard University Hospital from 1980 through 2007 was conducted. The histopathological findings of the thyroid and parathyroid glands were reviewed, both macroscopically and microscopically. A control group of autopsy patients with chronic non-HIV diseases was examined. Results. There were 71 males (70%) and 31 females (30%) with an average age of 38 years (range: 20–71 y). Thirteen patients with abnormal thyroid findings were identified. Interstitial fibrosis was the most common histological finding (4.9%), followed by thyroid hyperplasia (1.9%). Infectious disease affecting the thyroid gland was limited to 2.9% and consisted of mycobacterium tuberculosis, Cryptococcus neoformans, and cytomegalovirus. Kaposi sarcoma of the thyroid gland was present in only one case (0.9%). Parathyroid hyperplasia was the most common histological change noted in the parathyroid glands. Comparing the histological findings of cases and controls, we found a similar involvement of the thyroid, with a greater prevalence of parathyroid hyperplasia in HIV patients. Conclusion. Thyroid and parathyroid abnormalities are uncommon findings in the HIV-infected African American population. Rabia Cherqaoui, K. M. Mohamed Shakir, Babak Shokrani, Sujay Madduri, Faria Farhat, and Vinod Mody Copyright © 2014 Rabia Cherqaoui et al. All rights reserved. The Morbidity of Reoperative Surgery for Recurrent Benign Nodular Goitre: Impact of Previous Unilateral Thyroid Lobectomy versus Subtotal Thyroidectomy Sun, 19 Jan 2014 08:38:05 +0000 Background. Subtotal thyroidectomy (STT) was previously considered the gold standard in the surgical management of multinodular goitre despite its propensity for recurrence. Our aim was to assess whether prior STT or unilateral lobectomy was associated with increased reoperative morbidity. Methods. A retrospective analysis was conducted extracting data from our endocrine surgical database for the period from January 1991 to June 2006. Two patient groups were defined: Group 1 consisted of patients with previous unilateral thyroid lobectomy; Group 2 had undergone previous STT. Specific outcomes investigated were transient and permanent recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. Results. 494 reoperative cases were performed which consisted of 259 patients with previous unilateral lobectomy (Group 1) and 235 patients with previous subtotal thyroidectomy (Group 2). A statistically significant increase relating to previous STT was demonstrated in both permanent RLN injury (0.77% versus 3.4%, RR 4.38, ) and permanent hypoparathyroidism (1.5% versus 5.1%, RR 3.14, ). Transient nerve injury and hypocalcaemia incidence was comparable. Conclusions. Reoperative surgery following subtotal thyroidectomy is associated with a significantly increased risk of permanent recurrent laryngeal nerve injury and hypoparathyroidism when compared with previous unilateral thyroidectomy. Subtotal thyroidectomy should therefore no longer be recommended in the management of multinodular goitre. Navin Rudolph, Claudia Dominguez, Anthony Beaulieu, Pierre De Wailly, and Jean-Louis Kraimps Copyright © 2014 Navin Rudolph et al. All rights reserved. Frequency of Adverse Events of Antithyroid Drugs Administered during Pregnancy Thu, 09 Jan 2014 16:21:09 +0000 The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves’ disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low. Ai Yoshihara, Jaeduk Yoshimura Noh, Natsuko Watanabe, Kenji Iwaku, Sakiko Kobayashi, Miho Suzuki, Hidemi Ohye, Masako Matsumoto, Yo Kunii, Koji Mukasa, Kiminori Sugino, and Koichi Ito Copyright © 2014 Ai Yoshihara et al. All rights reserved. Influence of a Medium-Impact Exercise Program on Health-Related Quality of Life and Cardiorespiratory Fitness in Females with Subclinical Hypothyroidism: An Open-Label Pilot Study Tue, 31 Dec 2013 10:29:01 +0000 Objective. To examine the influence of a medium-impact exercise program (MIEP) on health-related quality of life (HRQoL) and cardiorespiratory fitness () in females with subclinical hypothyroidism (sHT). Materials and Methods. We selected 17 sedentary women with sHT (mean age: 43.1 (standard deviation: 9.7) years). Participants carried out an MIEP consisting of 3 weekly sessions of 60 minutes during 12 weeks. Before and after the exercise program HRQoL was assessed by the SF-12v2 questionnaire, and was evaluated by Rockport walk test. Results. After the 12-week intervention, the participants that performed an MIEP showed improvements in HRQoL in most domains, particularly the vitality domain by 7 points, the social functioning domain by 10 points, the mental health domain by 7 points, and the mental component summary by 7 points. One of the four domains within the physical component summary (general health domain) showed significant effect of the exercise intervention: 6 points. Moreover, the participants that performed exercise showed a higher (28%; ). Conclusion. After 12 weeks of medium-impact exercise program, there were remarkable improvements in HRQoL in most domains. Moreover, this exercise program proved to have a positive influence on cardiorespiratory fitness. Andrea Garces-Arteaga, Nataly Nieto-Garcia, Freddy Suarez-Sanchez, Héctor Reynaldo Triana-Reina, and Robinson Ramírez-Vélez Copyright © 2013 Andrea Garces-Arteaga et al. All rights reserved. Thyroid Lobectomy Is Associated with Excellent Clinical Outcomes in Properly Selected Differentiated Thyroid Cancer Patients with Primary Tumors Greater Than 1 cm Mon, 23 Dec 2013 08:33:02 +0000 Background and Objective. An individualized risk-based approach to the treatment of thyroid cancer is being extensively discussed in the recent literature. However, controversies about the ideal surgical approach remain an important issue with regard to the impact on prognosis and follow-up strategies. This study was designed to describe clinical outcomes in a cohort of low and intermediate risk thyroid cancer patients treated with thyroid lobectomy. Methods. Retrospective review of 70 patients who underwent lobectomy. Results. After a median follow-up of 11 years, 5 patients (5/70, 7.1%) recurred and 5 had a completion for benign lesions, while 60 patients (86%) continued to be observed without evidence for disease recurrence. Suspicious ultrasound findings were significantly more common in patients that had structural disease recurrence (100% versus 4.3%, ). Furthermore, a rising suppressed Tg value over time was also associated with structural disease recurrence (80% versus 21.5%, ). After additional therapy, 99% of the patients had no evidence of disease. Conclusions. Properly selected thyroid cancer patients can be treated with lobectomy with excellent clinical outcomes. Fernanda Vaisman, Denise Momesso, Daniel A. Bulzico, Cencita H. C. N. Pessoa, Manuel Domingos Gonçalves da Cruz, Fernando Dias, Rossana Corbo, Mario Vaisman, and R. Michael Tuttle Copyright © 2013 Fernanda Vaisman et al. All rights reserved. Mechanisms of L-Triiodothyronine-Induced Inhibition of Synaptosomal Na+-K+-ATPase Activity in Young Adult Rat Brain Cerebral Cortex Thu, 07 Nov 2013 13:54:39 +0000 The role of thyroid hormones (TH) in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na+-K+-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na+-K+-ATPase activity (but not Mg2+-ATPase activity) in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3 and the β-adrenergic agonist isoproterenol inhibited Na+-K+-ATPase activity in cerebrocortical synaptosomes in similar ways, the β-adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na+-K+-ATPase activity in a dose-dependent manner, suggesting that the effect of T3 on synaptosomal Na+-K+-ATPase activity was independent of β-adrenergic receptor activation. The effect of T3 on synaptosomal Na+-K+-ATPase activity was inhibited by the -adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activate -proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition. Pradip K. Sarkar, Avijit Biswas, Arun K. Ray, and Joseph V. Martin Copyright © 2013 Pradip K. Sarkar et al. All rights reserved. Combined Treatment with Myo-Inositol and Selenium Ensures Euthyroidism in Subclinical Hypothyroidism Patients with Autoimmune Thyroiditis Wed, 02 Oct 2013 13:55:00 +0000 Background. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis, is the most common form of thyroiditis affecting more than 10% of females and 2% of males. The present study aims to evaluate the beneficial effect of a combined treatment, Myo-Inositol plus selenomethionine, on subclinical hypothyroidism. Methods. The study was designed as a double-blind randomized controlled trial. Eligible patients were women diagnosed with subclinical hypothyroidism having Tg antibodies (TgAb) titer higher than 350 IU/mL. Outcome measures were Thyroid Stimulating Hormone (TSH) levels, thyroid peroxidase antibodies (TPOAb) and TgAb titer, selenium, and Myo-Inositol plasma concentration. Results. In the present paper, we demonstrated that the beneficial effects obtained by selenomethionine treatment on patients affected by subclinical hypothyroidism, likely due to the presence of autoantibody (TPOAb and TgAb), are further improved by cotreatment with Myo-Inositol. Conclusions. Indeed, due to its action as TSH second messenger, Myo-Inositol treatment reduces TSH levels closer to physiological concentrations. Maurizio Nordio and Raffaella Pajalich Copyright © 2013 Maurizio Nordio and Raffaella Pajalich. All rights reserved. Survival and Failure Outcomes in Primary Thyroid Lymphomas: A Single Centre Experience of Combined Modality Approach Thu, 12 Sep 2013 16:01:14 +0000 Primary thyroid lymphoma (PTL) is a rare malignancy and represents 2%–5% of all thyroid malignancies and 1%–2.5% of all malignant lymphomas. We present our institute’s experience in combined modality management of 16 successive patients of PTL treated from 2005 to 2010. The median age of the patients was 56.0 years. Five patients were males, and 11 patients were females. An enlarging thyroid mass was the most common presenting symptom. 14 patients had diffuse large B-cell lymphoma, and 2 patients had follicular lymphoma. The most common stage of presentation was stage II comprising 6 (37.5%) patients. All patients received CCT, and only 12 patients received involved field RT with a median dose of 36.0 Gy. 10 patients (62.5%) had CR, and 6 patients (27.5%) had PR. Eight patients had disease progression in subsequent followup and this included the initial 6 patients with PR. The 5-year DFS was 40.0%, and median DFS was 47 months. The 5-year OS was 41.0%, and median OS was 51 months. Most common presentation in our series was locally advanced tumors. Most of these patients require combined modality management. Risk-adapted and multimodality approach is the need of the hour to achieve good control rates while minimizing treatment related toxicity. Ritesh Kumar, Divya Khosla, Narendra Kumar, Sushmita Ghoshal, Anjan Bera, Ashim Das, and Suresh Chander Sharma Copyright © 2013 Ritesh Kumar et al. All rights reserved. Malignancy Risk Assessment in Patients with Thyroid Nodules Using Classification and Regression Trees Wed, 11 Sep 2013 10:07:34 +0000 Purpose. We sought to investigate the utility of classification and regression trees (CART) classifier to differentiate benign from malignant nodules in patients referred for thyroid surgery. Methods. Clinical and demographic data of 271 patients referred to the Sadoughi Hospital during 2006–2011 were collected. In a two-step approach, a CART classifier was employed to differentiate patients with a high versus low risk of thyroid malignancy. The first step served as the screening procedure and was tailored to produce as few false negatives as possible. The second step identified those with the lowest risk of malignancy, chosen from a high risk population. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the optimal tree were calculated. Results. In the first step, age, sex, and nodule size contributed to the optimal tree. Ultrasonographic features were employed in the second step with hypoechogenicity and/or microcalcifications yielding the highest discriminatory ability. The combined tree produced a sensitivity and specificity of 80.0% (95% CI: 29.9–98.9) and 94.1% (95% CI: 78.9–99.0), respectively. NPV and PPV were 66.7% (41.1–85.6) and 97.0% (82.5–99.8), respectively. Conclusion. CART classifier reliably identifies patients with a low risk of malignancy who can avoid unnecessary surgery. Shokouh Taghipour Zahir, Fariba Binesh, Mehrdad Mirouliaei, Elias Khajeh, and Sina Noshad Copyright © 2013 Shokouh Taghipour Zahir et al. All rights reserved. Thyroid and Aging or the Aging Thyroid? An Evidence-Based Analysis of the Literature Mon, 09 Sep 2013 11:41:30 +0000 Thyroid hormone production, metabolism, and action change with aging. The reference ranges for serum thyrotropin and thyroid hormones are derived mainly from younger populations. Thus, the prevalence of subclinical thyroid dysfunction is increased greatly in the elderly. However, it is unclear whether mild thyroid dysfunction in the elderly is associated with adverse outcomes. In this review, we discuss current evidence-based literature on thyroid function in the elderly and whether subclinical thyroid dysfunction in the elderly should be treated. Naveen Aggarwal and Salman Razvi Copyright © 2013 Naveen Aggarwal and Salman Razvi. All rights reserved. Increasing the Radioiodine Dose Does Not Improve Cure Rates in Severe Graves' Hyperthyroidism: A Clinical Trial with Historical Control Wed, 31 Jul 2013 08:52:56 +0000 Objective. It is generally accepted that higher doses of radioiodine (131I) improve cure rates in Graves’ disease (GD). In this trial we sought to evaluate whether very high 131I doses increase the efficacy of treatment in severe GD. Design. Clinical trial with historical control. Patients with GD and a goiter ≥48 mL were eligible for the study. The patients in the contemporaneous intervention cohort were treated with 250 μCi of 131I/mL thyroid tissue, corrected by 24-RAIU values (Group 1; ). A subgroup of patients with GD and a goiter ≥48 mL who were treated with 200 μCi of 131I/mL/24-RAIU in a previously published randomized controlled trial served as a historical control group (Group 2; ). The primary outcome evaluated was the one-year cure rate. Results. There were no significant baseline differences regarding age, gender, body mass index, smoking status, pretreatment with methimazole, thyroid volume, or thyroid hormone levels of the two treatment groups. The cumulative 12-month cure rate for the patients in Group 1 was 66.6%, a figure similar to the 12-month cure rate observed in Group 2 (60.0%; ). Conclusions. Our results suggest that increasing the 131I dose does not improve cure rates in severe GD. This trial is registered with NCT01039818. Jose Miguel Dora, Walter Escouto Machado, Vânia A. Andrade, Rafael Selbach Scheffel, and Ana Luiza Maia Copyright © 2013 Jose Miguel Dora et al. All rights reserved. New Approaches to Thyroid Hormones and Purinergic Signaling Wed, 17 Jul 2013 09:33:32 +0000 It is known that thyroid hormones influence a wide variety of events at the molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal roles in growth, cell proliferation, differentiation, apoptosis, development, and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. Most of these effects result in pathological and physiological events and are already well described in the literature. Even so, many recent studies have been devoted to bringing new information on problems in controlling the synthesis and release of these hormones and to elucidating mechanisms of the action of these hormones unconventionally. The purinergic system was recently linked to thyroid diseases, including enzymes, receptors, and enzyme products related to neurotransmitter release, nociception, behavior, and other vascular systems. Thus, throughout this text we intend to relate the relationship between the TH in physiological and pathological situations with the purinergic signaling. Gabriel Fernandes Silveira, Andréia Buffon, and Alessandra Nejar Bruno Copyright © 2013 Gabriel Fernandes Silveira et al. All rights reserved. Trimester-Specific Reference Ranges for Thyroid Hormones in Iranian Pregnant Women Sun, 09 Jun 2013 13:27:18 +0000 Background. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester-specific reference intervals for a specific population. There is no normative data documented for thyroid hormones on healthy pregnant women in Iran. The present survey was conducted to determine trimester-specific reference ranges for serum TSH, thyroxine (TT4), and triiodothyronine (TT3). Methods. The serum of 215 cases was analyzed for measurement of thyroid function tests by immunoassay method of which 152 iodine-sufficient pregnant women without thyroid autoantibodies and history of thyroid disorder or goiter were selected for final analysis. Reference intervals were defined as 5th and 95th percentiles. Results. Reference intervals in the first, second, and third trimesters were as follows: TSH (0.2–3.9, 0.5–4.1, and 0.6–4.1 mIU/l), TT4 (8.2–18.5, 10.1–20.6, and 9–19.4 g/dl), and TT3 (137.8–278.3, 154.8–327.6, and 137–323.6 ng/dl), respectively. No correlation was found between TSH and TT4 or TT3. Significant correlation was found between TT4 and TT3 in all trimesters (, ). Conclusion. The reference intervals of thyroid function tests in pregnant women differ among trimesters. Applying trimester-specific reference ranges of thyroid hormones is warranted in order to avoid misclassification of thyroid dysfunction during pregnancy. Ladan Mehran, Atieh Amouzegar, Hossein Delshad, Sahar Askari, Mehdi Hedayati, Golshan Amirshekari, and Fereidoun Azizi Copyright © 2013 Ladan Mehran et al. All rights reserved. Extralaryngeal Terminal Division of the Inferior Laryngeal Nerve: Anatomical Classification by a Surgical Point of View Thu, 30 May 2013 14:23:37 +0000 Background. Complete anatomic knowledge including all variations of the inferior laryngeal nerve (ILN) is mandatory for thyroid surgeon. Extralaryngeal terminal division (ETD) of the ILN has significant importance for the safety of thyroidectomy. Material and Methods. Surgical dissection of 200 ILNs was performed on 100 cases. The presence of ETD of the nerve was determined intraoperatively. We propose by a surgical point of view a regional (segmental) classification of ETD of the ILN along its cervical course. Results. ETD has been observed in 54/200 nerves (27%). Great majority are bifurcated nerves (trifurcation 2%). Four types of ETD are classified. In type 1 (arterial; 46.3%), ETD has occurred near inferior thyroid artery (ITA). In type 2 (postarterial; 31.5%), division has been found on postarterial segment. In type 3 (prelaryngeal; 11%), division has been located very close to laryngeal entry point. In type 4 (prearterial; 11%), ETD has occurred before the nerve crossing the ITA. Conclusions. ETD of the ILN is a common anatomical variation. The bifurcation occurs in the ILN at various distances from laryngeal entry point. The classification increasing surgeons’ awareness may help to simplify identification and exposure of terminal branches. Preservation of both extralaryngeal terminal branches of the ILN has paramount importance for the safety of thyroid operations. Emin Gurleyik Copyright © 2013 Emin Gurleyik. All rights reserved. Is the Use of a Drain for Thyroid Surgery Realistic? A Prospective Randomized Interventional Study Thu, 30 May 2013 11:00:43 +0000 Background. The use of a suction drain in thyroid surgery is common practice in order to avoid hematomas or seromas. The aim of this study was to determine the efficacy of routine drainage after thyroid surgery. Methods. In this prospective randomized trial, 400 patients who underwent either a total thyroidectomy or lobectomy for thyroid disorders were randomly allocated to either the nondrainage (group 1) or the drainage (group 2) group. The volume of fluid collection in the operative bed, postoperative pain, complications, and length of hospital stay were then recorded. Results. Both groups were homogeneous according to age, gender, thyroid volume, type of procedure performed, and histopathological diagnosis. After assessment by USG, no significant difference was found between the groups in the fluid collection of the thyroid bed (), but the length of hospital stay was significantly reduced in group 1 (). Conclusions. In our experience, the use of drain for thyroid surgery is not a routine procedure. However, it should be used in the presence of extensive dead space, particularly when there is retrosternal or intrathoracic extension, or when the patient is on anticoagulant treatment. This trial was registered with clinical NCT01771523. Ugur Deveci, Fatih Altintoprak, Mahmut Sertan Kapakli, Manuk Norayk Manukyan, Rahmi Cubuk, Nese Yener, and Abut Kebudi Copyright © 2013 Ugur Deveci et al. All rights reserved.