Subcutaneous implantation of nodular goiter after transoral endoscopic thyroidectomy vestibular approach: A case study and review of literature.

BACKGROUND: Extrathyroid implantation or dissemination of thyroid tissue secondary to a thyroid procedure is rare. Most of these belonged to thyroid carcinoma with metastatic potential and uncommon for benign pathologies. METHODS: We report the case of a 31-year-old female who was identified to have multiple subcutaneous implantation of thyroid tissue 5 years after transoral endoscopic thyroidectomy vestibular approach. A comprehensive literature search on implantation of thyroid tissue secondary to thyroid procedures was performed. RESULTS: Accidental tearing of the capsule during previous surgery may lead to the subcutaneous implantation. Through literature review, a total 29 articles with 47 patients were identified. 33.3% were benign lesions, and implantation was mostly secondary to fine needle aspiration biopsy (46.5%). CONCLUSIONS: Subcutaneous or port site implantation after endoscopic thyroid surgery may occur in benign thyroid pathologies and therefore, oncologic principles must be strictly followed during surgery regardless of its histopathological nature.

Uncommon diagnosis of multinodular goiter - isolated extrapulmonary manifestation of sarcoidosis in thyroid gland (scientific case reports).

AIM: By means of the scientific description of two uncommon cases who underwent. surgical resection of multinodous goiter and following histopathological investigation revealing isolated extrapulmonary manifestation of sarcoidosis, this uncommon diagnosis including symptomatology, clinical findings, diagnostic and therapeutic management is to be illustrated. CASE DESCRIPTIONS: Diagnostics: Scintigraphy of the thyroid gland with a left-thyroid cold node; ultrasound-guided puncture (cytological investigation, non-suspicious). THERAPY: Elective thyroidectomy with no macroscopic anomalies und no abnormal aspects with regard to surgical tactic and technique. Histopathological investigation: Complete resection specimen of the thyroid gland with granulomatous inflammation consistent with sarcoidosis. CLINICAL COURSE: Uneventful with no further manifestations of sarcoidosis in the following diagnostics. DIAGNOSTICS: Ultrasound, inhomogeneous node (37×30×35 mm) of the right thyroideal gland with echo-poor parts and peripheral vascularization; scintigraphy showing marginally compensated unifocal autonomy of the thyroid gland (laboratory parameters, increased serum level of thyroglobulin [632 ng/mL]). THERAPY: Planned right hemithyroidectomy with confirmed nodous structure of thyroid parenchyma, without suspicious lymph nodes. Histopathological investigation: 33-mm follicular, nodular, encapsulated structure of thyroid parenchyma (diagnosed as follicular adenoma); 2nd opinion: low-grade differentiated carcinoma of thyroid gland with angioinfiltrating growth and granulomatous inflammation of sarcoidosis type. Procedural intent: After tumor-board consultation, completing thyroidectomy was performed within a 5-weeks interval (pT2 pN0[0/1] V1 L0 G3 R0) with subsequent ablating radio'active iodine therapy; 18 F-FDG-PET-CT (several atypical infiltrates within the right upper lobe of the lung) and bronchoscopy with no detection of further manifestation of sarcoidosis. CONCLUSION: Sarcoidosis is considered a rare granulomatous multi-locular, systemic disease of not completely known etiopathogenesis with substantial heterogeneity. In most cases, it is associated with the lung, but which can become manifest in various organs. Frequently, extrapulmonary manifestations are usually detected as histological findings by coincidence, which require further investigation to find out additional manifestations as well as to exclude florid infection or other granulomatous processes (clarifying competently differential diagnosis). Therapy is only indicated in symptomatic organ manifestations, taking into account the high rate of spontaneous healing and possible side effects.

Risk of papillary thyroid carcinoma and nodular goiter associated with exposure to semi-volatile organic compounds: A multi-pollutant assessment based on machine learning algorithms.

BACKGROUND: Exposure to semi-volatile organic compounds (SVOCs) may link to thyroid nodule risk, but studies of mixed-SVOCs exposure effects are lacking. Traditional analytical methods are inadequate for dealing with mixed exposures, while machine learning (ML) seems to be a good way to fill the gaps in the field of environmental epidemiology research. OBJECTIVES: Different ML algorithms were used to explore the relationship between mixed-SVOCs exposure and thyroid nodule. METHODS: A 1:1:1 age- and gender-matched case-control study was conducted in which 96 serum SVOCs were measured in 50 papillary thyroid carcinoma (PTC), 50 nodular goiters (NG), and 50 controls. Different ML techniques such as Random Forest, AdaBoost were selected based on their predictive power, and variables were selected based on their weights in the models. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to assess the mixed effects of the SVOCs exposure on thyroid nodule. RESULTS: Forty-three of 96 SVOCs with detection rate >80 % were included in the analysis. ML algorithms showed a consistent selection of SVOCs associated with thyroid nodule. Fluazifop-butyl and fenpropathrin are positively associated with PTC and NG in single compound models (all P < 0.05). WQS model shows that exposure to mixed-SVOCs was associated with an increased risk of PTC and NG, with the mixture dominated by fenpropathrin, followed by fluazifop-butyl and propham. In the BKMR model, mixtures showed a significant positive association with thyroid nodule risk at high exposure levels, and fluazifop-butyl showed positive effects associated with PTC and NG. CONCLUSION: This study confirms the feasibility of ML methods for variable selection in high-dimensional complex data and showed that mixed exposure to SVOCs was associated with increased risk of PTC and NG. The observed association was primarily driven by fluazifop-butyl and fenpropathrin. The findings warranted further investigation.

Analysis of clinical characteristics of thyroid phenotype in Pendred syndrome based on multiple databases.

OBJECTIVE: This study aimed to provide statistical data support for the development of thyroid phenotype-related follow-up and reference for follow-up duration and project selection by analyzing the clinical characteristics of thyroid phenotype in Pendred syndrome (PDS) based on multiple databases. MATERIALS AND METHODS: PDS-related pathogenic or possibly/pathogenic mutations were searched by Deafness Variation Database (DVD), ClinVar, and PubMed databases, the mutation sites were counted and the characteristics and thyroid phenotypes were analyzed. RESULTS: The median age of hearing phenotype onset in PDS cases reported in multiple databases was 1.0 (1.0, 2.0) years, the median age of thyroid phenotype onset was 14.5 (5.8, 21.0) years, and the median age that thyroid phenotype was more delayed than hearing phenotype was 10.0 (4.0, 17.0) years. There were significant differences in the distribution of onset time between the two phenotypes (Z=-4.560, p<0.01). In these patients, the positive rates of goiter, thyroid nodules, abnormal thyroid function, and perchlorate discharge test (PDT) were 78%, 78%, 69%, and 78%, respectively. Moreover, the number of thyroid phenotype-positive items in the genotype group with frameshift mutation was not significantly higher than that in the group without frameshift mutation (Z=-1.452, p=0.147). CONCLUSIONS: The early missed diagnosis of PDS may be due to the late onset of thyroid phenotype and the non-100% positive rate of examination items. Therefore, multi-item follow-up of the thyroid gland into adulthood will benefit patients. At present, the relationship between genotype and phenotype is still unclear, and prognosis cannot be determined according to genotype.

Ectopic intrapulmonary thyroid masquerading as metastatic carcinoma of the lung: a rare case scenario.

BACKGROUND: The intrapulmonary ectopic thyroid gland is exceedingly rare since the ectopic thyroid was discovered. Only eight cases have been reported in the worldwide literature. We present a case of multiple intrapulmonary ectopic thyroid glands with nodular goiter in a 10-year-old girl. CASE PRESENTATION: The girl was found with multiple intrapulmonary nodules in bilateral lungs during the treatment of nodular goiter. The intrapulmonary lesions were initially thought to be a high possibility of metastatic cancer. A computed tomography-guided percutaneous lung biopsy was performed, and the pathological examination confirmed that the diagnosis was ectopic intrapulmonary thyroid. CONCLUSION: The ectopic intrapulmonary thyroid should be considered when children with nodular goiter presenting with suspected metastases in the lung.

Histopathological Features of Pendred Syndrome Thyroids Align with Differences in the Expression of Thyroid-Specific Markers, Apical Iodide Transporters, and Ciliogenesis Process.

Pendred syndrome (PDS) is an autosomal recessive disorder caused by mutations in the gene that encodes pendrin. Pendred thyroid tissue is supposedly altered by the absence of functional pendrin, but it is still unknown whether other iodide exchangers could compensate for the loss of the protein. Moreover, we have recently described that primary cilium, a conserved structure present at the apical surface of normal follicular cells, suffers different alterations in functional thyroid diseases. We aimed (1) to better understand the histopathological changes experienced by PDS thyroids, (2) to analyze the expression of different thyroid-specific genes and alternative iodide transporters and, finally, (3) to determine whether those changes may alter the morphological pattern of primary cilia in follicular cells. Thyroid samples from a series of four PDS patients were analyzed by immunohistochemistry, double immunofluorescence, and morphometry to evaluate changes in primary cilia frequency and length. We found thyroid follicular nodular disease in all PDS thyroids, frequently in association with follicular adenomas. There were only slight changes in the expression of thyroid-specific markers. Although no positivity for pendrin was found, cytoplasmic immunostaining for ANO-1, CLC-5, and CFTR was stronger in diffuse hyperplastic areas when compared to areas with highly cellular follicular nodules (HCFNs). HCFNs and follicular adenomas always showed diminished ciliary frequency and length. Our results suggest a direct relationship between the absence of functional pendrin and the loss of the normal thyroid architecture in PDS patients, which was also accompanied by differences in the expression of specific immunohistochemical markers and altered ciliogenesis. The present data may help the pathologist in screening for PDS.

Comparison of Modified Rose Method of Thyroid Palpation Versus Other Methods for the Detection of Retrosternal and Nodular Goitre.

Objectives: This is a diagnostic test research study to evaluate the various existing methods of thyroid examination and their comparison with the novel modified Rose method. It also aims to measure inter-examiner variation in clinical findings based on the level of education and training, as compared to ultrasonography. Methodology: This cross-sectional study was conducted at a tertiary care hospital with 83 patients presenting to surgery OPD with neck swelling. Each patient was examined by one trained Junior Resident and a Surgery Consultant with all the four methods and with ultrasonography. Data was analysed by Stata-14, agreement between the two categorical variables was assessed by Kappa. In case of continuous variable agreement was assessed by Intra class correlation and Bland-Altman plot. Results: Modified Rose method by the consultant has the highest sensitivity (98%) and diagnostic odds (210) as compared to others but its specificity ranges from 46.7-91.1% to diagnose retro-sternal extension of a goiter. It has 93.98% agreement for identification of nodules. It has a high specificity (Consultant - 100%, Resident - 95.5%) with relatively lower sensitivity (Consultant - 94%, Resident - 86.8%) to diagnose solitary thyroid nodule (STN) but the sensitivity and specificity for diagnosing a multinodular goitre (MNG) was high. However, the highest sensitivity to diagnose STN was highest with Crile's method, but specificity was low. Lahey's method was a better clinical method to palpate lymph nodes compared to the other three. Conclusion: Examination in modified Rose's position is a better method of clinical examination of thyroid especially in patients with occult substernal extension. Lahey's method is a better method to examine cervical lymph nodes.

Preoperative platelet distribution width-to-platelet ratio combined with serum thyroglobulin may be objective and popularizable indicators in predicting papillary thyroid carcinoma.

OBJECTIVES: The incidence of papillary thyroid carcinoma (PTC) has increased more rapidly than that of any other cancer type in China. Early indicators with high sensitivity and specificity during diagnosis are required. To date, there has been a paucity of studies investigating the relationship between preoperative platelet distribution width-to-platelet count ratio (PPR) and PTC. This study thus aimed to assess the diagnostic value of PPR combined with serum thyroglobulin (Tg) in patients with PTC. METHODS: A total of 1001 participants were included in our study. 876 patients who underwent surgery for nodular goiter were divided into the PTC group or benign thyroid nodule (BTN) group according to pathology reports, and 125 healthy controls (HCs) were included. Preoperative hemogram parameters and serum Tg levels were compared among three groups. Receiver operating characteristic (ROC) curve was used to evaluate the value of PPR combined with serum Tg for diagnosing PTC. RESULTS: Platelet distribution width (PDW) and PPR levels were higher in the PTC group than in the BTN and HC groups (both p < 0.05) but did not significantly differ between the BTN and HC groups. PDW and PPR levels significantly differed in the presence/absence of lymph node metastasis, the presence/absence of capsule invasion (p = 0.005), and TNM stages (p < 0.001). Multivariable analyses indicated that high serum Tg levels [adjusted odds ratio (OR), 1.007; 95% confidence interval (CI), 1.004-1.009; p < 0.001], high neutrophil-to-lymphocyte ratio (NLR,adjusted OR, 1.928; 95% CI, 1.619-2.295; p < 0.001), and high PPR (adjusted OR, 1.378; 95% CI, 1.268-1.497; p < 0.001) were independent risk factors for PTC. In ROC analysis, the areas under the curves (AUCs) of serum Tg, PDW, PPR, and NLR for predicting PTC were 0.603, 0.610, 0.706, and 0.685, respectively. PPR combined with serum Tg (PPR + Tg) had a higher diagnostic value (AUC, 0.738; sensitivity, 60%; specificity, 74.7%) compared with PDW + Tg (AUC, 0.656; sensitivity, 64.4%; specificity, 59.9%) and NLR + Tg (AUC, 0.714; sensitivity, 61.6%; specificity, 71.1%). CONCLUSIONS: Preoperative PPR combined with serum Tg may be objective and popularizable indicators for effective predicting PTC.

Presentation and Management Outcomes of Goitres at a District Hospital in Abuja, North Central Nigeria: A 15-Year-Review.

BACKGROUND: The clinical and pathologic spectrums of goitres are wide. Even though Nigeria's Federal Capital Territory is within the geographic goitre bed, there is a paucity of thyroidrelated data from this region. The objective of this study was to determine the clinical presentation, management and outcomes of patients with goitre operated-on at the Department of Surgery, Asokoro District Hospital, in Abuja, Nigeria. METHODOLOGY: This is a retrospective study involving patients managed between January 2001 and December 2015. Data were extracted from patients' medical records, operation registers, and histopathology records. Variables were; age, sex, diagnosis, types of operation performed, post-operative complications and histological findings. All patients had general anaesthesia via cuffed endotracheal intubation and the surgical technique used was skin crease transverse collar stud incision. RESULTS: One hundred and thirty four (134) patients were involved in the study: 124(92.5%) were females and 10(7.5%) males. Mean age was 38years±11.0SD. Seventy-seven (57.5%) patients had simple multi-nodular goitre, followed by simple left nodular goitre 20(14.9%) and simple right nodular goitre 17(12.7%). One hundred and twenty-one (90.5%) patients did not have any complications. On histologic examination, most of the lesions were multinodular goitres 60(44.8%), followed by simple nodular goitres, 23(17.2%). Follicular adenoma was the commonest neoplastic variant accounting for 12(9.1%) cases. CONCLUSION: The pattern of goitres in Abuja simulates that from other parts of Nigeria and many other African countries though with fewer malignancies in the present study. The management and outcome of goitres in Asokoro District Hospital Abuja is comparable to those obtained from other centres in Nigeria. Pre-and postoperative complications were also minimal.

CONTEXTE: Le spectre clinique et pathologique des goitres sont larges. Bien que le territoire de la capitale fédérale du Nigeria se trouve dans le lit géographique du goitre, il y a peu de données sur la thyroïde dans cette région. L'objectif de cette étude était de déterminer la présentation clinique, la gestion et les résultats des patients atteints de goitre opérés au département de chirurgie de l'hôpital du district d'Asokoro, à Abuja, au Nigeria. MÉTHODOLOGIE: Il s'agit d'une étude rétrospective portant sur des patients pris en charge entre janvier 2001 et décembre 2015. Les données ont été extraites des dossiers médicaux des patients, des registres d'opérations et des dossiers d'histopathologie. Les variables étaient : l'âge, le sexe, le diagnostic, les types d'opérations pratiquées, les complications postopératoires et les résultats histologiques. Tous les patients ont bénéficié d'une anesthésie générale par une intubation endotrachéale à ballonnet, et la technique chirurgicale utilisée était l'incision transversale du pli cutané incision du collet. RÉSULTATS: Cent trente-quatre (134) patients ont participé à l'étude: 124 (92,5%) étaient des femmes et 10 (7,5%) des hommes. L'âge moyen était de 38 ans±11,0SD. Soixante-dix-sept (57,5 %) patients présentaient un goitre simple et multi-nodulaire, suivi d'un goitre nodulaire simple gauche 20(14,9%, et le goitre nodulaire simple droit 17 (12,7 %). Cent vingt et un (90,5 %) patients n'ont présenté aucune complication. A l'examen histologique, la plupart des lésions étaient des goitres multinodulaires 60(44,8%), suivis par des goitres nodulaires simples, 23(17,2%). L'adénome folliculaire était la variante néoplasique la plus courante avec 12 cas (9,1 %). CONCLUSION: Le modèle de goitres à Abuja simule celui d'autres régions du Nigeria et de nombreux autres pays africains, bien qu'avec moins de tumeurs malignes dans la présente étude. La gestion et le résultatmde goitres à l'hôpital du district d'Asokoro à Abuja sont comparables à celles obtenus dans d'autres centres au Nigeria. Les complications pré et postopératoires étaient également minimes. Mots-clés: Goitres, modèle, résultat de la gestion, Abuja.

Total thyroidectomy for giant nodular goiter guided by pre-operative 3D computed tomography reconstruction and 3D printing: A case report.

BACKGROUND: Nodular goiter is a common clinical problem, and thyroidectomy is preferred in patients with obstructive symptoms. Thyroidectomy is a complex procedure with some common complications. Three-dimensional (3D) computed tomography (CT) reconstruction and 3D printing provide visualized 3D anatomical structure, posing an enormously valuable potential in precise surgery with optimal efficacy and minimum complications. Here, we aimed to perform a precise thyroidectomy guided by this technology. METHODS: The patient was an 80-year-old woman with 10 years of goiter, 1 year of labored dyspnea, and a history of thyroid surgery 62 years ago. In addition to ultrasonography examination, CT images were obtained to construct the 3D model to identify the 3D relationship between the lesion and adjacent structures, and a 3D model of the trachea was created and printed using a 3D printer. RESULTS: The 3D model clearly presented the diffuse enlargement of the two lobes and isthmus and the compression of the goiter. Under the 3D guidance, the operative resection specimen of the right lobe and isthmus was 12 ´ 7 ´ 5 cm, whereas the left lobe specimen was 12 ´ 9 ´ 6 cm. Nodular goiter and lymphocytic thyroiditis were confirmed by postoperative histopathology. There were no complications after total thyroidectomy except for non-permanent hypocalcemia and hypoparathyroidism. CONCLUSION: Our results proved that total thyroidectomy for giant goiter is challenging, and 3D image-guided thyroidectomy facilitates precise and safe resection with fewer complications. 3D CT reconstruction and 3D printing can provide anatomical details and may be considered in thyroidectomy planning for patients with giant goiter.

Pendred Syndrome, or Not Pendred Syndrome? That Is the Question.

Pendred syndrome (PDS) is the most common form of syndromic Hearing Loss (HL), characterized by sensorineural HL, inner ear malformations, and goiter, with or without hypothyroidism. SLC26A4 is the major gene involved, even though ~50% of the patients carry only one pathogenic mutation. This study aims to define the molecular diagnosis for a cohort of 24 suspected-PDS patients characterized by a deep radiological and audiological evaluation. Whole-Exome Sequencing (WES), the analysis of twelve variants upstream of SLC26A4, constituting the "CEVA haplotype" and Multiplex Ligation Probe Amplification (MLPA) searching for deletions/duplications in SLC26A4 gene have been carried out. In five patients (20.8%) homozygous/compound heterozygous SLC26A4 mutations, or pathogenic mutation in trans with the CEVA haplotype have been identified, while five subjects (20.8%) resulted heterozygous for a single variant. In silico protein modeling supported the pathogenicity of the detected variants, suggesting an effect on the protein stabilization/function. Interestingly, we identified a genotype-phenotype correlation among those patients carrying SLC26A4 mutations, whose audiograms presented a characteristic slope at the medium and high frequencies, providing new insights into PDS. Finally, an interesting homozygous variant in MYO5C has been identified in one patient negative to SLC26A4 gene, suggesting the identification of a new HL candidate gene.

Diagnostic performance of Midkine ratios in fine-needle aspirates for evaluation of Cytologically indeterminate thyroid nodules.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a basic diagnostic tool for thyroid nodules. However, 15-30% of nodules are cytologically indeterminate. Midkine (MK), a pleiotropic growth factor, is often upregulated in patients with cancers. This study aimed to evaluate the role of MK and its ratios in fine-needle aspirates (FNA) for predicting thyroid malignancy. METHODS: This retrospective study included patients with thyroid nodules who underwent preoperative FNA and/or thyroidectomy between April 2017 and September 2017. MK levels in FNA washout were measured by enzyme-linked immunosorbent assay, and thyroglobulin (TG) and free thyroxine (FT4) levels in FNA washout were measured by chemiluminescent immunometric assays. RESULTS: A total of 217 patients with 242 nodules were included in this study. The concentrations of TG, FT4, MK/TG, MK/FT4, and FT4/MK were significantly different between papillary thyroid carcinomas and benign thyroid nodules. Both MK/TG and MK/FT4 ratios were positively correlated with maximum tumor diameter, extrathyroidal extension, and T and N stages. The area under the curve for MK/TG was 0.719 with a cutoff value of 55.57 ng/mg, while the area under the curve for MK/FT4 was 0.677 with a cutoff value of 0.11 µg/pmol. FNAC in combination with MK/FT4 had a higher sensitivity (95% vs. 91%) and accuracy (96% vs. 92%) than FNAC alone for cytologically indeterminate specimens, those of unknown significance, or those suspected of malignancy. CONCLUSIONS: MK/FT4 and MK/TG may have diagnostic utility for evaluation of papillary thyroid carcinomas, particularly for cytologically indeterminate thyroid nodules.

T cell exhaustion is associated with the risk of papillary thyroid carcinoma and can be a predictive and sensitive biomarker for diagnosis.

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has been steadily increasing over the past decades. Hashimoto's thyroiditis (HT) is the most common autoimmune disease, and is related to the pathogenesis of PTC. Programmed death-1 (PD-1) is currently used for the treatment of PTC, but there are very few studies on the clinical value of PD-1 in the diagnosis and targeted therapy of PTC. METHODS: The expression of T, B, NK cells and PD-1 in the peripheral blood of 132 patients with PTC (PTC group), 48 patients with nodular goiter (NG group) and 63 healthy subjects (HP group) were detected by flow cytometry. The expression of plasma T3, T4, FT3, FT4, TSH, TGAb and TPO was detected by chemiluminescence immunoassay. Among 132 PTC, 49 PTC&HT and 83 PTC&noHT were included. Among 48 NG, 10 NG&HT and 38 NG&noHT were included. The expressions of programmed death- ligand1(PD-L1) in tumor tissues of PTC group and thyroid tissues of NG group, PD-1 and CD3 in tumor infiltration lymphocyte (TIL) were detected by immunohistochemistry. RESULTS: The expression of FT3, TGAb, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC and NG was significantly higher than that in the HP group. Moreover, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ expression had significant differences between the PTC group and the NG group. In addition, the expression of TGAb, TPO, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC&HT group was significantly higher than that in the PTC&noHT group. While, the expression of B cells, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC&HT group was higher than that in NG&HT group. PD-1 showed a significant correlation with PTC lymph node metastasis. CD3+PD-1+ and CD3+CD4+PD-1+ was higher in N1 stage than in N0 stage. Immunohistochemical results showed that the expression of PD-1, CD3 and PD-L1 in PTC was significantly higher than that in NG. CONCLUSIONS: T cell exhaustion might act as a biomarker for the differential diagnosis of PTC and NG. Patients with PTC&HT have obvious T cell exhaustion and increased expression of PD-1, PD-L1.Targeting the PD-1/PD-L1 pathway could be a new approach to prevent malignant transformation from HT to PTC&HT in the future.

Clinical profile and management of primary thyroid cancer in patients with nodular goitre at the Douala General Hospital, Cameroon.

INTRODUCTION: thyroid cancer (TC) is considered to have become the fastest growing cancer in terms of incidence worldwide. Despite literature reporting a prevalence of 5-10% in clinically identified thyroid nodules, Cameroon still has limited data on the profile of TCs in patients with Nodular Goitres (NGs). The Objective were to describe the epidemiological, diagnostic and therapeutic profiles of TCs in patients with nodular goitres at the Douala General Hospital (DGH). METHODS: this was a retrospective cross-sectional analysis of patient records with diagnoses of NGs, over 11 years (2006 to 2016) at the DGH. RESULTS: overall, 187 patients (mean age= 46.8±13.9 years, men=27 (14.4%)) were included; 43 (23%) cancers were identified. The most common histological type was papillary cancer (50%). Nodule size of >4cm and hypoechogenicity were independently associated with malignancy. Most patients presented with TNM stage II (47.4%) and well-differentiated cancers were considered to be predominantly at low-risk according to MACIS (55%) and AMES (74%) scores. Surgery was offered to 95.3% of patients. CONCLUSION: TCs are frequent in patients with NGs with papillary cancer dominating. A high index of suspicion should be held if a nodule is >4cm and/or is hypoechogenic. Prognostic studies are needed to describe the outcome of TCs in our setting.

Poorly Differentiated Thyroid Carcinoma Coexisting with Graves' Disease Involving T3 Thyrotoxicosis due to Increased D1 and D2 Activities.

Background: Poorly differentiated thyroid carcinoma is rare and patients are typically euthyroid. We report a novel rare case of poorly differentiated thyroid carcinoma with triiodothyronine (T3) thyrotoxicosis. Patient's Findings: A 77-year-old man presented to Kuma Hospital due to a neck tumor. A thyroid ultrasonography revealed a 220-mL mass in the right lobe. Laboratory data showed low serum thyrotropin (TSH), low free thyroxine (fT4), and high free T3 (fT3) levels. Anti-TSH receptor antibodies and thyroid-stimulating antibodies were positive. 131I scintigraphy showed diffuse uptake only in the left thyroid lobe. The patient underwent a total thyroidectomy and histological examination identified as poorly differentiated thyroid carcinoma. He was diagnosed with poorly differentiated thyroid carcinoma coexisting with Graves' disease. The tumor showed elevated type 1 iodothyronine deiodinases (D1) and type 2 iodothyronine deiodinases (D2) activities compared with that of the left thyroid lobe. Summary and Conclusions: Increased D1 and D2 activities in poorly differentiated carcinoma resulted in T3 toxicosis with a high serum fT3/fT4 ratio.

Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model.

Purpose: Slc26a4-/- mice exhibit severer defects in the development of the cochlea and develop deafness, while the underlying mechanisms responsible for these effects remain unclear. Our study was to investigate the potential mechanism linking SLC26A4 deficiency to hearing loss. Materials and Methods: RNA sequencing was applied to analyze the differential gene expression of the stria vascularis (SV) from wildtype and Slc26a4-/- mice. GO and KEGG pathway analysis were performed. Quantitative RT-PCR was applied to validate the expression of candidate genes affected by Slc26a4. ELISA and immunofluorescence technique were used to detect the homocysteine (Hcy) level in serum, brain, and SV, respectively. Results: 183 upregulated genes and 63 downregulated genes were identified in the SV associated with Slc26a4 depletion. Transcriptomic profiling revealed that Slc26a4 deficiency significantly affected the expression of genes associated with cell adhesion, transmembrane transport, and the biogenesis of multicellular organisms. The SV from Slc26a4-/- mice exhibited a higher expression of Bhmt mRNAs, as well as altered homocysteine (Hcy) metabolism. Conclusions: The altered expression of Bhmt results in a dramatic change in multiple biochemical reactions and a disruption of nutrient homeostasis in the endolymph which may contribute to hearing loss of Slc26a4 knockout mouse.

Proteomic analysis of thyroid tissue reveals enhanced catabolic activity in Graves' disease compared to toxic multinodular goitre.

Graves' disease (GD) and toxic multinodular goitre (TMNG) are the most common thyroid diseases which mainly lead to thyrotoxicosis, however, the underlying mechanism of distinct clinical presentations remains unclear. Protein extracts from the thyroid tissue specimens of the patients with GD and TMNG were subjected to Difference Gel Electrophoresis (DIGE). Differentially regulated protein spots were determined by image analysis, and the spots displaying statistically significant differences were identified by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometer (MALDI-TOF) followed by MASCOT search. Western blot analysis was used to verify changes occurring at the protein levels. The identified proteins were classified based on their functions in metabolic pathways using bioinformatics algorithms. Fifteen proteins showed significant alterations in abundance between the two disease groups. Bioinformatic analysis revealed the differentially regulated proteins were particularly related to catabolism, oxidative stress and especially energy utilization pathways, including glycolysis, proteolysis, ketone body catabolism and other energy metabolism-related pathways. SIGNIFICANCE OF THE STUDY: Previously, GD has been the subject of many studies that performed the proteomics approaches in the orbital tissue samples or tear. This is one of the very few studies that investigate the changes in the proteome of thyroid tissue in GD. We demonstrated mainly the upregulation of catabolic activity-related proteins in patients with GD compared to TMNG. Although it remains to be elucidated, some of these proteins can be used as markers for GD or have a role in the pathogenesis of the disease. Our study contributes the increasing data over time by providing new biomarker candidates for GD.

Features of Lymph Node Metastasis and Structural Recurrence in Papillary Thyroid Carcinoma Located in the Upper Portion of the Thyroid: A Retrospective Cohort Study.

Background: This study aims to reveal the features of lymph node metastasis (LNM) and recurrence in papillary thyroid carcinoma (PTC) tumors located in the upper portion of the thyroid. Methods: A total of 1075 PTC patients were retrospectively reviewed, including 314 patients with a tumor in the upper portion of the thyroid. Another 103 PTC patients with upper portion diagonsis from three clinical centers were included for external validation. Results: The results showed no difference between the patients with a tumor in the upper portion of the thyroid and those with a tumor in the non-upper portion in terms of overall LNM rates. However, patients with a tumor in the upper portion were significantly more prone to LLNM and exhibited a significantly worse recurrence outcome than those with a tumor in other subregions. Multivariate analysis showed that four factors-age no more than 40, maximum tumor diameter no less than1.0 cm, the presence of thyroid capsular invasion, and tumor with ipsilateral nodular goiter-were independent risk factors for LLNM of the tumor in the upper thyroid. A predictive risk-scoring model was established based on these factors. Conclusions: Patients with PTC located in the upper portion may have an exclusive lymphatic drainage pathway to the lateral neck region and are more prone to suffer from LLNM and tumor recurrence than those with a tumor located in other subregions. A new postoperative strategy selection flow chart was established based on our newly created risk-scoring model that can effectively predict the individualized possibility of LLNM for PTC patients with a tumor in the upper portion.

Mice Hypomorphic for Keap1, a Negative Regulator of the Nrf2 Antioxidant Response, Show Age-Dependent Diffuse Goiter with Elevated Thyrotropin Levels.

Background: Familial nontoxic multinodular goiter (MNG) is a rare disease. One of the associated genes is Kelch-like ECH-associated protein 1 (KEAP1), which encodes the main inhibitor of nuclear factor erythroid 2-related transcription factor 2 (Nrf2), a central mediator of antioxidant responses. The association of KEAP1 with familial MNG is based on only two loss-of-function mutations identified in two families, only one of which included proper phenotyping and adequate demonstration of co-segregation of the phenotype and the mutation. There is no experimental evidence from model organisms to support that decreased Keap1 levels can, indeed, cause goiter. This study used mice hypomorphic for Keap1 to test whether decreased Keap1 expression can cause goiter, and to characterize the activation status of Nrf2 in their thyroid. Methods: C57BL/6J Keap1flox/flox (Keap1 knock-down [Keap1KD]) mice were studied at 3 and 12 months of age. Plasma and thyroid glands were harvested for evaluation of thyroid function tests and for gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Results: Keap1KD mice showed diffuse goiter that began to develop in early adult life and became highly prominent and penetrant with age. The goiter was characterized by a markedly increased size of thyroid follicles, most notably of the colloid compartment, and by absence of thyroid nodules or hyperplasia. Keap1KD mice also showed decreased T4 levels in early adult life that were eventually well compensated over time by increased thyrotropin (TSH) levels. Nrf2 was activated in the thyroid of Keap1KD mice. Despite a known stimulatory effect of Nrf2 on thyroglobulin (Tg) gene transcription and Tg protein abundance, the expression levels were decreased in the thyroid of Keap1KD mice. No clear patterns were observed in the expression profiles of other thyroid hormone synthesis-specific factors, with the exception of Tg-processing and Tg-degrading cathepsins, including an increase in mature forms of cathepsins D, L, and S. Conclusions: Keap1KD mice develop age-dependent diffuse goiter with elevated TSH levels. The precise mechanism accounting for the thyroidal phenotype remains to be elucidated, but it may involve enhanced Tg solubilization and excessive lysosomal Tg degradation.