Head Neck. 2012 Feb 2;
Gilbert KC, Dhiwakar M, Stevens WS, Robbins KT

BACKGROUND: We report a rare case of a mediastinal goiter confined to the thoracic inlet and cavity presenting with ventricular tachycardia as the sole clinical manifestation. METHODS AND RESULTS: The patient did not have any of the typical features of a mediastinal goiter such as neck swelling, dysphagia, or respiratory difficulty, but instead had spontaneous onset of wide-complex tachycardia requiring emergency treatment. This atypical presentation led to initial misinterpretation of imaging studies and delayed diagnosis of the mediastinal mass. The large, completely intrathoracic thyroid goiter abutted the cardiac muscle and required a combined transcervical and median sternotomy approach for removal. The arrhythmia resolved postoperatively. CONCLUSION: To our knowledge, this case represents the first documented presentation of ventricular tachycardia as a unique and sole feature of mediastinal goiter. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.

Toxicol Sci. 2012 Feb 2;
Cassone CG, Vongphachan V, Chiu S, Williams KL, Letcher RJ, Pelletier E, Crump D, Kennedy SW

Perfluoroalkyl acids (PFAAs), specifically perfluorinated sulfonates (PFSAs) and carboxylates (PFCAs), are synthetic substances known for their chemical stability, resistance to degradation and potential to biomagnify in food chains. The toxicological and biological effects of PFAAs in avian species are not well characterized, although there is some evidence to suggest that they can impact neurodevelopment and hatching success. Our laboratory recently reported significant effects of perfluorohexane sulfonate (PFHxS) and perfluorohexanoate (PFHxA) on mRNA levels of thyroid hormone (TH)-responsive genes in chicken embryonic neuronal cells. In this study, we determined in ovo effects of PFHxS and PFHxA exposure (maximum dose = 38,000 and 9,700 ng/g egg, respectively) on embryonic death, developmental endpoints, tissue accumulation, mRNA expression in liver and cerebral cortex and plasma TH levels. Pipping success was reduced to 63% at the highest dose of PFHxS; no effects were observed for PFHxA. PFHxS exposure (38,000 ng/g) decreased tarsus length and embryo mass. PFHxS and PFHxA accumulated in the three tissue compartments analyzed as follows: yolk sac > liver > cerebral cortex. Type II and type III 5'-deiodinases (D2 and D3) and cytochrome P450 3A37 (CYP3A37) mRNA levels were induced in liver tissue of chicken embryos exposed to PFHxS, while D2, neurogranin (RC3) and octamer motif binding factor 1 (OCT1) mRNA levels were up-regulated in cerebral cortex. Plasma TH levels were reduced in a concentration-dependent manner following PFHxS exposure; PFHxA had no effect. This in ovo study successfully validated previous in vitro results concerning the modulation of TH-responsive genes and identified adverse effects associated with TH homeostasis in response to PFHxS treatment.

World J Surg. 2012 Feb 1;
Lombardi CP, Raffaelli M, De Crea C, Sessa L, Rampulla V, Bellantone R

BACKGROUND: Although video-assisted (VA) thyroidectomy emerged as effective treatment for selected patients with papillary thyroid carcinoma (PTC), some concerns remain about obtaining adequate central neck node clearance. We compared patients who underwent VA and conventional total thyroidectomy (TT) and central compartment dissection (CCD) for PTC. METHODS: A total of 52 consecutive patients successfully underwent VA-TT and VA-CCD for PTC (VA group) were compared to 52 controls who underwent conventional TT and CCD (C group) for PTC. RESULTS: The two groups were matched for age (p = 0.75), sex (p = 0.07), and tumor size (p = 1.0). Operating time (p = 0.23), overall postoperative complications (p = 0.41), pT (p = 0.44), and pN (p = 0.84) were similar in the two groups. The mean number of removed nodes was similar (10.6 ± 4.6 in VA group vs. 12.2 ± 5.6 in C group) (p = 0.11). Mean postoperative serum thyroglobulin (sTg) off levothyroxine (LT4) suppressive treatment was 3.2 ± 5.0 ng/ml in the VA group and 2.6 ± 7.4 ng/ml in the C-group (P = 0.67). Mean postoperative radioiodine uptake (RAIU) was similar in the two groups (1.5 ± 1.3 vs. 1.7 ± 1.3%) (p = 0.49). When pN1a patients alone were considered, no difference was found between the VA group (21 patients) and the controls (24 patients) concerning the mean number of removed nodes (10.3 ± 4.1 vs. 12.4 ± 5.6) (p = 0.16), the mean sTg off LT4 (4.4 ± 6.0 vs. 1.9 ± 2.7 ng/ml) (p = 0.07) and the mean RAIU (1.9 ± 1.5 vs. 1.7% ± 1.3%) (p = 0.63). CONCLUSIONS: The results of VA-TT and CCD in selected cases of PTC appear to be comparable to those of conventional surgery. A longer follow-up and larger series are necessary to draw definitive conclusions concerning long-term outcomes.

Endocr Relat Cancer. 2012 Feb 1;
Huijbers A, Plantinga TS, Joosten LA, Aben KK, Gudmundsson J, den Heijer M, Kiemeney LA, Netea MG, Hermus AR, Netea-Maier RT

Autophagy has important roles in both carcinogenesis and modulation of inflammation. Autophagy defects result in increased interleukin-1β (IL-1β) production, a cytokine known to have antineoplastic effects in thyroid malignancies. We investigated whether the Thr300Ala missense polymorphism in the autophagy gene ATG16L1 influences susceptibility to and prognosis of epithelial cell derived thyroid carcinoma (TC) in a Dutch population (139 patients; 1,964 healthy controls). The ATG16L1 300Ala allele was associated with decreased risk of TC (dominant model OR 0.63, 95% CI 0.43-0.94). In addition, we observed an association of the ATG16L1 300Ala allele with a lower dose of radioactive iodine (RAI) required to reach remission, and a lower probability of persistent disease after thyroidectomy and radioiodine ablation. In conclusion, the 300Ala allele may be associated with lower susceptibility for TC. More importantly, bearing the ATG16L1 300Ala was associated with a more favorable response of TC to treatment with RAI.

Mol Endocrinol. 2012 Feb 2;
Chocarro-Calvo A, Zaballos MA, Santisteban P, García-Jiménez C

Modulation of MAPK signaling duration by cAMP defines its physiological output by driving cells toward proliferation or differentiation. Understanding how the kinetics of MAPK signaling are integrated with other cellular signals is a key issue in development and cancer. Here we show that dopamine and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32), a protein required for thyroid cell differentiation, determines whether MAPK/ERK activation is sustained or transient. Serum, a stimulus that activates MAPK signaling and does not independently increase DARPP-32 levels results in transient activation of the MAPK pathway. By contrast, TSH + (IGF-I) activate MAPK signaling but also independently increase DARPP-32 levels. Our results are consistent with a model in which maintenance of DARPP-32 expression by TSH + IGF-I leads to sustained MAPK signaling. Moreover, the sensitivity of MAPK/ERK signaling in thyroid cells is lost when de novo DARPP-32 expression is blocked by small interfering RNA. Because both DARPP-32 levels and function as inhibitor of protein phosphatase 1, a key inhibitor of MAPK kinase activity, are governed by cAMP/protein kinase A, the results may explain why in thyroid cells cAMP signaling downstream from TSH controls the duration of MAPK pathway activity. Thus, fine-tuning of DARPP-32 levels leads to changes in the kinetics or sensitivity of MAPK/ERK signaling. Given the implications of MAPK signaling in thyroid cancer and the loss of DARPP-32 in tumor and transformed thyroid cells, DARPP-32 may represent a key therapeutic target.

Mol Endocrinol. 2012 Feb 2;
Grasberger H, De Deken X, Barca Mayo O, Raad H, Weiss M, Liao XH, Refetoff S

Dual oxidases (DUOX1 and DUOX2) are evolutionary conserved reduced nicotinamide adenine dinucleotide phosphate oxidases responsible for regulated hydrogen peroxide (H(2)O(2)) release of epithelial cells. Specific maturation factors (DUOXA1 and DUOXA2) are required for targeting of functional DUOX enzymes to the cell surface. Mutations in the single-copy Duox and Duoxa genes of invertebrates cause developmental defects with reduced survival, whereas knockdown in later life impairs intestinal epithelial immune homeostasis. In humans, mutations in both DUOX2 and DUOXA2 can cause congenital hypothyroidism with partial iodide organification defects compatible with a role of DUOX2-generated H(2)O(2) in driving thyroid peroxidase activity. The DUOX1/DUOXA1 system may account for residual iodide organification in patients with loss of DUOX2, but its physiological function is less clear. To provide a murine model recapitulating complete DUOX deficiency, we simultaneously targeted both Duoxa genes by homologous recombination. Knockout of Duoxa genes (Duoxa(-/-) mice) led to a maturation defect of DUOX proteins lacking Golgi processing of N-glycans and to loss of H(2)O(2) release from thyroid tissue. Postnatally, Duoxa(-/-) mice developed severe goitreous congenital hypothyroidism with undetectable serum T4 and maximally disinhibited TSH levels. Heterozygous mice had normal thyroid function parameters. (125)I uptake and discharge studies and probing of iodinated TG epitopes corroborated the iodide organification defect in Duoxa(-/-) mice. Duoxa(-/-) mice on continuous T4 replacement from P6 showed normal growth without an overt phenotype. Our results confirm in vivo the requirement of DUOXA for functional expression of DUOX-based reduced nicotinamide adenine dinucleotide phosphate oxidases and the role of DUOX isoenzymes as sole source of hormonogenic H(2)O(2).

Mol Endocrinol. 2012 Feb 2;
Akama T, Sue M, Kawashima A, Wu H, Tanigawa K, Suzuki S, Hayashi M, Yoshihara A, Ishido Y, Ishii N, Suzuki K

TSH is a major regulator of thyroid cell growth and endocrine function. It is known that cAMP and phosphatidylinositol 3-kinase (PI3K) are responsible for mediating the action of TSH. Activation of these signals results in the induction of a series of transcription factors and cell cycle regulating proteins, which induce cell proliferation. In addition to such canonical transcriptional regulation, it was recently shown that microRNA (miRNA or miR) constitutes another key mechanism for the regulation of gene expression. However, whether TSH action is mediated by miRNA in the thyroid is unknown. In this study, we have performed miRNA microarray analysis and demonstrated that TSH significantly decreases expression of 47 miRNA in thyroid cells. Among these, we have shown, using their specific agonists, that overexpression of miR-16 and miR-195 suppressed cell cycle progression and DNA synthesis that was induced by TSH. In silico analysis predicted that Mapk8, Ccne1, and Cdc6, the expression of which was up-regulated by TSH, are potential target genes for these miRNA, and overexpression of miR-16 and miR-195 suppressed expression of these target genes. The decrease of miR-16 and miR-195 expression by TSH was reproduced by forskolin and N(6),2'-O-dibutyryladenosine cAMP and reversed by the protein kinase A inhibitor H89 and the PI3K inhibitor LY294002. These results suggest that TSH activates cAMP/protein kinase A and PI3K cascades to decrease miR-16 and miR-195, which induce Mapk8, Ccne1, and Cdc6 to activate cell proliferation.

Dentomaxillofac Radiol. 2012 Feb; 41(2): 159-64
Shahab S, Kavosi A, Nazarinia H, Mehralizadeh S, Mohammadpour M, Emami M

Dentists use radiographs in their daily practice. Their knowledge and behaviour towards radiographic examination can affect patients' exposure to radiation. The aim of this study was to survey the knowledge and behaviour of Iranian dentists regarding oral radiology safety standards.1000 questionnaires were given to the participants of the 48th Annual Congress of the Iranian Dental Association, of which 700 were returned. The participants were asked about demographic data, primary knowledge of radiation protection, selection criteria, radiographic equipment and technique, methods of patient and personnel protection and management of radiographic waste. Descriptive analysis of data was performed.44% of respondents said the initial radiograph they took was of the periapical view of a limited area. 12% preferred the periapical paralleling technique. F-speed film was used by 9% and E-speed film by 62%. Only 2% had digital receptors. Proper exposure time was selected by 26.5%. The use of long and rectangular collimators was 15% and 6%, respectively. 34% occasionally covered their patients with both thyroid shields and lead aprons. 36% used the position and distance rule correctly for their own protection. Proper disposal of the used processing solutions and the lead foils were done by only 1% and 3%, respectively.It can be concluded that the majority of dentists in the study group did not select the proper method, material and equipment in order to minimize the exposure of their patient to unnecessary radiation in dental radiography.

Am J Surg Pathol. 2012 Jan 31;
Tanaka M, Kato K, Gomi K, Yoshida M, Niwa T, Aida N, Kigasawa H, Ohama Y, Tanaka Y

In this study, we report 2 pediatric cases of nuclear protein of the testis (NUT) midline carcinoma (NMC) suggestive of pulmonary origin: case 1 was a 14-year-old Japanese boy and case 2 was a 7-year-old Japanese girl. Initial symptoms of both cases were prolonged cough and chest pain, and the case 2 patient also complained of lumbago and lumbar mass due to bone metastases. Imaging studies revealed that pulmonary tumors from both patients were located at the hilar region of the lower lobe. Biopsies of the tumors showed undifferentiated carcinoma in case 1 and combined undifferentiated and squamous cell carcinoma in case 2. Despite intensive treatment with chemotherapy and radiation, progression of neither tumor was controlled, and both patients died of the tumors at 1 year (case 1) and 4 months (case 2) after onset of disease. Both tumors were diffusely positive for p63 and NUT expression and were partially positive for various cytokeratins. Reverse transcription polymerase chain reaction analysis and subsequent direct sequencing revealed that the bromodomain-containing protein 4-NUT chimeric gene was present in tumor tissue of both patients, leading to a diagnosis of NMC. The tumor cells of case 1 were also positive for thyroid transcription factor-1 expression, but those of case 2 were negative. Histologic examination of the surgically removed lung tumor of case 1 indicated that the origin of the tumor was basal cells of the bronchiolar epithelia.

Pediatr Rev. 2012 Feb; 33(2): 75-82
Osipoff JN, Wilson TA

AJNR Am J Neuroradiol. 2012 Feb 2;
Lee TC, Selvarajan SK, Curtin H, Mukundan S

BACKGROUND AND PURPOSE:The posterior thyroid tubercle, also known as ZT, is an important surgical landmark due to its close proximity to the recurrent laryngeal nerve. A recent case of ZT with a nodular configuration caused clinical concern but was shown on biopsy to be normal thyroid tissue. The purpose of this study was to review a series of CT neck studies to identify how often ZT-specifically, a nodular subtype-was present.MATERIALS AND METHODS:A total of 96 neck CTs from sequential patients were retrospectively identified from January 2010 to July 2010. ZT was defined on imaging as a thyroid lobe extending posterior to the tracheoesophageal groove. A nodular subtype was defined as having a narrowed neck at the level of the tracheoesophageal groove.RESULTS:There were 31 women and 45 men (mean age of 56.1 years, range 22-100 years) who met inclusion criteria. Sixty-seven patients had thyroid glands that extended posterior to the tracheoesophageal groove at CT imaging; this finding was bilateral in 43 patients, more commonly on the right (60 versus 49). Thirty-two of these patients (42.1%; 16 male, 16 female) had a nodular subtype.CONCLUSIONS:ZT is an important surgical landmark of the thyroid that has important radiologic variations. It has a nodular shape in over a third of CT neck studies in our series. Recognition of this feature of the thyroid gland at CT imaging can obviate the need for biopsy and avoid potential recurrent laryngeal nerve injury.

AJNR Am J Neuroradiol. 2012 Feb 2;
Kim DW, Park JS, In HS, Choo HJ, Ryu JH, Jung SJ

BACKGROUND AND PURPOSE:The ability of US to differentiate benign thyroid nodules from malignant ones is still a matter of debate. The aim of this study was to assess the diagnostic efficacy of a US-based classification system for solid and PCTNs through a prospectively designed study.MATERIALS AND METHODS:We studied 1289 thyroid nodules in 1036 patients who underwent thyroid US, US-FNA, and thyroid surgery. Each thyroid nodule was prospectively classified into 1 of 5 diagnostic categories following real-time US examination: benign, probably benign, borderline, possibly malignant, and malignant. Solid nodules were classified by using all 5 categories, and PCTNs were classified by all except the borderline category. We calculated the diagnostic efficacy of thyroid US by comparing US diagnoses with histopathologic results of surgically resected thyroid nodules.RESULTS:One thousand fifty-five solid nodules and 234 PCTNs were prospectively classified as benign (n = 435 and 179), probably benign (n = 213 and 25), borderline (n = 94 and 0), possibly malignant (n = 115 and 15), and malignant (n = 198 and 15), respectively. Of these 1289 nodules, 505 were surgically resected and confirmed by pathology (191 benign and 314 malignant nodules); there were 44 resected solid nodules with a borderline category. For solid nodules and PCTNs, the sensitivity, specificity, positive and negative predictive values, and accuracy of US diagnosis were 86.1 and 66.7, 90.0 and 88.9, 94.3 and 75.0, 77.3 and 84.2, and 87.5% and 81.5%, respectively, based on 505 surgical specimens and excluding the 42 solid borderline nodules.CONCLUSIONS:Our US-based classification system can provide helpful guidance for the management of thyroid nodules.