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Purpose: To systematically review published studies on the prevalence of the thyroid foramen (TF), perform a meta-analysis to generate pooled prevalence estimates, and identify factors associated with its presence., Methods: A systematic literature search was conducted in Google Scholar, PubMed, and Journal Storage databases. Studies reporting the prevalence of the thyroid foramen were included without language or date restrictions. Quality assessment was performed using AQUA tool. A random-effects meta-analysis was performed with subgroup analyses. Heterogeneity was assessed using Higgins' I 2 statistics, and publication bias was evaluated using funnel plots and Egger's test., Results: Out of 271 entries, 38 studies met the inclusion criteria, comprising 3,030 subjects from various continents. The overall TF prevalence was 24.5% (95% CI: 19.2-29.8%, I 2  = 93.44%), with unilateral TF present in 16.9% and bilateral TF in 6.2%. Prevalence was highest in North America (31.4%,) and lowest in Africa (12.3%). No significant prevalence difference was found between adults and younger populations (p = 0.15). Publication bias, or the small-study effect, was detected (p < 0.01)., Conclusion: This meta-analysis reveals a 24.5% overall prevalence of TF, with significant heterogeneity primarily explained by geographical differences. The TF's clinical relevance necessitates awareness among surgeons and radiologists to avoid complications during laryngeal surgeries and prevent misdiagnosis in imaging studies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

The common carotid artery (CCA) typically bifurcates into the external and internal carotid arteries (ECA and ICA). In the head and neck area, the ECA gives off a few anterior branches from proximal to distal: the superior thyroid artery (STA), the lingual artery (LA), and the facial artery (FA). Occasionally, these branches can fuse into trunks, with the linguofacial trunk being the most common. During a computed tomography angiography (CTA) of a 67-year-old patient, a common arterial trunk, 11.3 mm proximal (prior) to the CCA bifurcation was recorded. The trunk was formed by the STA and the LA fusion and was characterized as a thyrolingual trunk (TLT). These trunks have been reported with a prevalence ranging between 0.3 and 1% and correspond to one of the rarest variants of the ECA anterior branches. Knowledge of the typical and variant anatomy of the carotid arteries and their branches is of paramount importance to surgeons and interventional radiologists., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

In most cases, the superior laryngeal artery (SLA) branches from the superior thyroid artery, which, in turn, leaves the external carotid artery. Few dissection studies found previously that the SLA could originate from the lingual artery. We report here probably the first evidence of such a rare anatomical variation found unilaterally in a retrospectively evaluated by computed tomography angiography adult male case. The left SLA left a suprahyoid coil of the lingual artery and continued over the greater hyoid horn to enter the larynx through the thyrohyoid membrane. On both sides, thyroid foramina were found, but only the right one used for the entry of the right SLA. Therefore, the rare SLA origin from the lingual artery can be documented on computed tomography angiograms, which could help during preoperative evaluations and prevent unwanted surgical complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Thyroid hemiagenesis is defined as a failure of one thyroid lobe development. This condition predominantly manifests as an incidental finding during radiological investigation. This paper repor ts the case o f a 53-year-ol d female, a known case of hypertension, who visited the ENT clinic at AKU, a ter tiary ca re centre in Karachi, Pak istan and was hospi talized from 12 th to 1 5th Septembe r 202 1. The patient presented with hemiagenesis of the right thyroid lobe with enlargement of the contralateral lobe resulting in airway compression. She was subjected to excision of the thyroid gland without any intra-operative or postoperative com plicati ons. There were n o complaints o f dyspnoea, stridor or hoarseness during the hospital stay. The patient was discharged and was found to be well on subsequent follow-ups.

The thyroid gland is an endocrine organ comprising two lobes connected by an isthmus. Thyroid isthmus agenesia (TIA) is a rare anatomical anomaly, which has only been documented in a limited number of case reports. This report presents the case of a 49-year-old female patient who was diagnosed with intraoperative TIA during diagnostic thyroid lobectomy. The patient was arranged for a diagnostic lobectomy of the right thyroid lobe after identifying an atypical nodule of undetermined significance, in the right lobe, which had been confirmed with two distinct biopsies. The patient was discovered to have isthmus agenesia during a neck exploration performed under general anesthesia. Owing to its rarity, the precise clinical and anatomical characteristics of TIA have not been defined, and its underlying cause is still not completely understood. The detection of TIA warrants the considerations of any other accompanying diseases. Prior identification and assessment of surgical approach are crucial for ensuring a secure surgical procedure and mitigating the risk of surgical complications. Nevertheless, caution must be exercised if TIA is detected during operation because preoperative identification is not always feasible. In summation, additional patient reports and studies are required to uncover the underlying cause of this pathological condition.

Purpose: Primary thyroid lymphoma (PTL) is a rare malignancy, and the literature is limited to small case series and case reports. This study aimed to assess the epidemiologic characteristics, survival, and prognostic factors of patients with PTL., Methods: We analyzed 2215 PTL patients from the Surveillance, Epidemiology, and End Results database medical records, between 1983 and 2015, as the training cohort. We enrolled 105 patients from the Cancer Hospital, Chinese Academy of Medical Sciences, for the external validation cohort. The nomograms for predicting the 1-, 5-, and 10-year overall survival (OS) and lymphoma-specific survival (LSS) were constructed., Results: PTL incidence steadily increased from 1977 to 1994, with an annual percentage change of 3.2% (95% confidence interval [CI]: 1.2-5.2, P < 0.05). The 1-, 5-, and 10-year OS and LSS rates were 84.66%, 71.61%, and 55.95%; and 90.5%, 85.7%, and 82.2%, respectively. Multivariate Cox regression analysis revealed that shorter OS association with age ≥ 60 years (hazard ratio [HR], 3.94; 95% CI 3.31-4.69; P < 0.001), unmarried status (HR, 1.55; 95% CI 1.37-1.75; P < 0.001), Ann Arbor stage III-IV (HR, 1.55; 95% CI 1.37-1.75; P = 0.020), diffuse large B-cell lymphoma (HR, 2.60; 95% CI 1.15-5.87; P = 0.022), and T cell non-Hodgkin lymphoma (HR, 3.53; 95% CI 1.12-11.10; P = 0.031). In the multivariate competing-risk analyzes, age, stages III-IV, year of diagnosis, surgery, radiation, chemotherapy, and histology were strongly predictive of PTL-specific risk of death. To estimate the 1-, 5-, and 10-year LSS and OS rates, respectively, nomograms were built. In the validation cohort, the results also confirmed the utility., Conclusions: This study presents the first prognostic model with an external validation that could help clinicians identify patients with high-risk PTL to improve their prognosis., (© 2021. The Author(s).)

Thyroid dysgenesis (TD) is a major cause of primary congenital hypothyroidism; however, the molecular mechanism underlying this process is unclear. Current knowledge regarding the morphogenesis of the thyroid gland and vascular anomalies affecting thyroid development is limited. To monitor the early stages of thyroid gland development, we generated double transgenic zebrafish embryos Tg(tg:mCherry/flk1:EGFP). We described the volume of the thyroid from 2 days postfertilization (dpf) to 5 dpf using 3D reconstruction images. We treated zebrafish embryos with the fibroblast growth factor (FGF) inhibitor PD166866 to better understand the impact of vascular defects on thyroid development and the effects of drug administration at specific time periods on different stages of thyroid development. The 3D reconstruction data revealed that the thyroid glands underwent significant transformation at critical time points. PD166866 treatment from 48 to 72 hours postfertilization (hpf) and from 72 to 96 hpf did not cause obvious reductions in thyroid volume but did result in observable abnormalities in thyroid morphology. The treatment also affected thyroid volume from 36 to 48 hpf, thus indicating that there are time-point-specific effects of drug administration during thyroid development. Three-dimensional image reconstruction provides a comprehensive picture of thyroid anatomy and can be used to complement anatomical fluorescence information. The effects of an FGF pathway inhibitor on thyroid development were determined to be time-point-dependent., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

In the present study, we assessed the negative effects of triphenyltin (TPT) on zebrafish (Danio rerio) by exposing embryos and early-stage larvae to various concentrations of TPT from 2 h after fertilization (haf) until 30 days after hatching (dah). Whether test groups were fed or fasted during ecotoxicity studies using fish models has varied historically, and whether this experimental condition influences test results is unknown. Here, we confirmed that the lethal concentration of TPT to embryo and early-stage larvae (i.e., 3 dah or younger) showed in fed (lowest observed effect concentration (LOEC); 6.34 μg/L) and fasted (LOEC; 6.84 μg/L) groups. In addition, 84% and 100% of the larvae in the 2.95 and 6.64 μg/L exposure groups, respectively, had uninflated swim bladders; all affected larvae died within 9 dah. This finding suggests that morphologic abnormalities in early larval zebrafish are useful as endpoints for predicting the lethality of chemical substances after hatching. We then assessed the expression of several genes in the thyroid hormone pathway, which regulates swim bladder development in many fish species, including zebrafish. Larvae exposed to 6.64 μg/L TPT showed significant increases in the mRNA expression levels of thyroid hormone receptor α (trα) and trβ but not of thyroid stimulating hormone β subunit. These findings suggest that TPT disrupts the thyroid system in zebrafish., (Copyright © 2020. Published by Elsevier Inc.)

Background: Congenital hypothyroidism due to thyroid dysgenesis is a frequent congenital endocrine disorder for which the molecular mechanisms remain unresolved in the majority of cases. This situation reflects, in part, our still limited knowledge about the mechanisms involved in the early steps of thyroid specification from the endoderm, in particular the extrinsic signaling cues that regulate foregut endoderm patterning. In this study, we used small molecules and genetic zebrafish models to characterize the role of various signaling pathways in thyroid specification. Methods: We treated zebrafish embryos during different developmental periods with small-molecule compounds known to manipulate the activity of Wnt signaling pathway and observed effects in thyroid, endoderm, and cardiovascular development using whole-mount in situ hybridization and transgenic fluorescent reporter models. We used the antisense morpholino (MO) technique to create a zebrafish acardiac model. For thyroid rescue experiments, bone morphogenetic protein (BMP) pathway induction in zebrafish embryos was obtained by manipulation of heat-shock inducible transgenic lines. Results: Combined analyses of thyroid and cardiovascular development revealed that overactivation of Wnt signaling during early development leads to impaired thyroid specification concurrent with severe defects in the cardiac specification. When using a model of MO-induced blockage of cardiomyocyte differentiation, a similar correlation was observed, suggesting that defective signaling between cardiac mesoderm and endodermal thyroid precursors contributes to thyroid specification impairment. Rescue experiments through transient overactivation of BMP signaling could partially restore thyroid specification in models with defective cardiac development. Conclusion: Collectively, our results indicate that BMP signaling is critically required for thyroid cell specification and identify cardiac mesoderm as a likely source of BMP signals.

Congenital hypothyroidism (CH) is a neonatal endocrine disorder that might occur as itself or be associated to congenital extra-thyroidal defects. About 85% of affected subjects experience thyroid dysgenesis (TD), characterized by defect in thyroid gland development. In vivo experiments on null mice paved the way for the identification of genes involved thyroid morphogenesis and development, whose mutation has been strongly associated to TD. Most of them are thyroid-specific transcription factors expressed during early thyroid development. Despite the arduous effort in unraveling the genetics of TD in animal models, up to now these data have been discontinuously confirmed in humans and only 5% of TD have associated with known null mice-related mutations (mainly PAX8 and TSHR). Notwithstanding, the advance in genetic testing represented by the next-generation sequencing (NGS) approach is steadily increasing the list of genes whose highly penetrant mutation predisposes to TD. In this review we intend to outline the molecular bases of TD, summarizing the current knowledge on thyroid development in both mice and humans and delineating the genetic features of its monogenetic forms. We will also highlight current strategies to enhance the insight into the non-Mendelian mechanisms of abnormal thyroid development., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Thyroid dysgenesis (TD) is the main cause of congenital hypothyroidism (CH), affecting nearly 1 in 2000-3000 newborns worldwide, as the most common neonatal endocrine disorder. Paired box gene 8 (PAX8), expressed during all stages of thyroid follicular cell, plays a key role in thyroid morphogenesis by a complex regulatory network. In conclusion, the genetic mechanism of PAX8 mutant in TD is still ambiguous; therefore, further research is needed., Material and Methods: Blood samples were collected from 289 TD patients in Shandong Province, China. Genomic DNA was extracted from peripheral blood. All the exons of PAX8 along with their exon-intro boundaries were amplified by PCR and analysed by Sanger sequencing., Results: We identified three novel PAX8 nonsense mutations in three patients by sequence analysis of PAX8: Patient 1 (c.285C>G, p.Tyr95Ter), Patient 2 (c.747T>G, p.Tyr249Ter), and Patient 3 (c.786C>A, p.Tyr262Ter). All the three patients carrying PAX8 variants had obvious clinical phenotypes of thyroid anomaly, such as hypoplasia and athyreosis., Conclusion: We conducted the largest worldwide PAX8 mutation screening so far in TD patients. Three presumably pathogenic PAX8 mutations were detected in 289 TD cases for the first time, showing the mutation rate of PAX8 is 1.04% in Chinese TD patients. In addition, our study expands the gene mutation spectrum of TD.

Background Preterm infants are at high risk of developing congenital hypothyroidism (CH) due to the immaturity of the hypothalamic-pituitary-thyroid (HPT) axis, loss of iodine supply from the mother and preterm health problems. Objectives To study the incidence and etiologies of CH in preterm infants who were born or admitted in our institute during 2010-2015. Methods The medical records of preterm infants diagnosed with CH as defined by the thyroid-stimulating hormone (TSH) level at the time of the first or second screening >10 mU/L and/or free T4 < 1.00 ng/dL were reviewed. Results Of 2777 preterm infants, 73 cases (2.6%) were diagnosed as CH. The average TSH levels at the first and second screenings were 20.85 and 15.42 mU/L, respectively. The patients were treated with thyroxine at an average initial dosage of 15 μg/kg/day. At 2-3 years of age, after thyroxine discontinuation for 6-10 weeks and regular thyroid function tests for 2 years, 58 patients (79.5%) were diagnosed as having transient CH and 15 patients (20.5%) were diagnosed as having permanent CH. We found no clinical or laboratory parameters in the neonatal period that could differentiate permanent from transient CH. Thyroid scintigraphy (99 m pertechnetate) revealed two patients (13.3%) with ectopic thyroid, one with thyroid hypoplasia (6.7%), eight with normal thyroid (53.3%) and four with enlarged thyroid (26.7%). Conclusions CH was common in preterm infants with an estimated incidence of 2.6%. Thyroxine should be given to preterm infants with higher initial values of TSH >10 mU/L in order to prevent delayed treatment of permanent CH that could be confirmed later.

Background: Defects in embryonic development of the thyroid gland are a major cause for congenital hypothyroidism in human newborns, but the underlying molecular mechanisms are still poorly understood. Organ development relies on a tightly regulated interplay between extrinsic signaling cues and cell intrinsic factors. At present, however, there is limited knowledge about the specific extrinsic signaling cues that regulate foregut endoderm patterning, thyroid cell specification, and subsequent morphogenetic processes in thyroid development. Methods: To begin to address this problem in a systematic way, we used zebrafish embryos to perform a series of in vivo phenotype-driven chemical genetic screens to identify signaling cues regulating early thyroid development. For this purpose, we treated zebrafish embryos during different developmental periods with a panel of small-molecule compounds known to manipulate the activity of major signaling pathways and scored phenotypic deviations in thyroid, endoderm, and cardiovascular development using whole-mount in situ hybridization and transgenic fluorescent reporter models. Results: Systematic assessment of drugged embryos recovered a range of thyroid phenotypes including expansion, reduction or lack of the early thyroid anlage, defective thyroid budding, as well as hypoplastic, enlarged, or overtly disorganized presentation of the thyroid primordium after budding. Our pharmacological screening identified bone morphogenetic protein and fibroblast growth factor signaling as key factors for thyroid specification and early thyroid organogenesis, highlighted the importance of low Wnt activities during early development for thyroid specification, and implicated drug-induced cardiac and vascular anomalies as likely indirect mechanisms causing various forms of thyroid dysgenesis. Conclusions: By integrating the outcome of our screening efforts with previously available information from other model organisms including Xenopus , chicken, and mouse, we conclude that signaling cues regulating thyroid development appear broadly conserved across vertebrates. We therefore expect that observations made in zebrafish can inform mammalian models of thyroid organogenesis to further our understanding of the molecular mechanisms of congenital thyroid diseases.

Objective: To review the patient characteristics and outcomes for children and undergoing central neck dissection for control of recurrent thyroglossal duct cysts and fistula following prior Sistrunk procedures and children requiring surgery for refractory infection., Methods: We performed a computerized review of all children who were evaluated for thyroglossal duct cysts during the years 1999-2018 by a single surgeon operating at an urban children's hospital and an outpatient surgical center. Those requiring a central neck dissection for control of recurrent disease or intractable infection were identified. Age at time of surgery, sex, surgical procedure, and postoperative complications were recorded. These data were combined with similar data from a published report by the same surgeon in the years 1990-1998 to complete a 28-year review., Results: 18 central neck dissections were performed including 13 for recurrent thyroglossal duct remnants after Sistrunk procedures and 5 primary surgeries for intractable infection. Ages ranged from 3 to 19 years (median = 10 years) and 13 of 18 were girls (72%). Four children had their first Sistrunk surgery performed by the senior author. Three children operated elsewhere had intact hyoid bones at the time of revision surgery, suggesting less-than-Sistrunk primary surgeries. Central neck dissection controlled disease in the lower neck in all cases. One child re-fistulized at the level of the hyoid., Conclusions: Central neck dissection in combination with a Sistrunk-type dissection of the tongue base is effective in the control of recurrent infection following unsuccessful Sistrunk surgery and aids in dissection for children with intractable infection. Although this technique reliably controls infrahyoid disease and improves access to the hyoid and posterior hyoid space, it does nothing to address the difficulties of following the thyroglossal tract into the tongue base.

The serine-threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) modulates important cellular functions during development, acting as a signal integrator of a wide variety of stress signals, and as a regulator of transcription factors and cofactors. We have previously demonstrated that HIPK2 binds and phosphorylates High-Mobility Group A1 (HMGA1), an architectural chromatinic protein ubiquitously expressed in embryonic tissues, decreasing its binding affinity to DNA. To better define the functional role of HIPK2 and HMGA1 interaction in vivo, we generated mice in which both genes are disrupted. About 50% of these Hmga1/Hipk2 double knock-out (DKO) mice die within 12 h of life (P1) for respiratory failure. The DKO mice present an altered lung morphology, likely owing to a drastic reduction in the expression of surfactant proteins, that are required for lung development. Consistently, we report that both HMGA1 and HIPK2 proteins positively regulate the transcriptional activity of the genes encoding the surfactant proteins. Moreover, these mice display an altered expression of thyroid differentiation markers, reasonably because of a drastic reduction in the expression of the thyroid-specific transcription factors PAX8 and FOXE1, which we demonstrate here to be positively regulated by HMGA1 and HIPK2. Therefore, these data indicate a critical role of HIPK2/HMGA1 cooperation in lung and thyroid development and function, suggesting the potential involvement of their impairment in the pathogenesis of human lung and thyroid diseases.

Background: Billing diagnoses are used for quality assurance, estimates of prevalence and resource allocation. Validity studies showed relevant limitations. In Germany, there are no population-based data on the agreement of outpatient billing diagnoses with clinical data of thyroid disorders., Objectives: The study investigated the agreement of ICD-diagnosed thyroid nodules, goitre, hyperthyroidism, hypothyroidism and thyroiditis with clinical and self-reported data from the population-based cohort study called the Study of Health in Pomerania (SHIP)., Materials and Methods: Billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were linked on an individual level for the period from 2002-2016 with data from SHIP. The agreement was evaluated using sensitivity, specificity and positive and negative predictive value (PPW, NPW). Data were weighted to ensure population representativeness., Results: The data of 5746 participants were analysed (46% male, average age 55 years, SD [standard deviation] ± 15, min: 20 years, max: 93 years). Based on clinical data, 63% (3451/5511, missing values n = 235) and based on billing data 25% (1421/5746) of the participants had thyroid disorders. The sensitivity was 12-36%, the specificity was 84-98%, the PPW was highest for thyroid nodules (75%) and hypothyroidism (70%) and the NPW was between 63 and 94%, depending on the investigated thyroid disorder., Conclusions: Thyroid disorders are common and often undiagnosed. Billing data have a low sensitivity to identify clinically relevant thyroid disorders.

Hypothyroidism is rarely included in the differential diagnosis for fetal sinus bradycardia. We report an infant with congenital hypothyroidism caused by ectopic thyroid tissue, who showed antenatal bradycardia. The baseline fetal heart rate was 100-110 bpm at 30 weeks of gestation, and fetal echocardiography revealed sinus bradycardia but no cardiac anomalies. Maternal thyroid function was normal (thyroid-stimulating hormone [TSH] 2.03 μIU/ml, free T3 2.65 pg/ml, and free T4 0.99 ng/dl) when measured at 31 weeks of gestation. Her serum anti SS-A and SS-B antibodies, anti-thyroglobulin, and microsomal antibodies were negative. A male infant without cardiac anomalies was delivered at 35 weeks and 4 days of gestation and admitted for prematurity and respiratory distress syndrome. The infant's heart rate was 70-110 bpm (normal: 120-160 bpm) on admission. On 8 days of age, thyroid function tests revealed that the infant had severe hypothyroidism (TSH 903.3 μIU/ml, free T3 1.05 pg/ml, and free T4 0.26 ng/dl). The prolonged jaundice assumed to be due to hypothyroidism. Oral levothyroxine sodium hydrate (10 μg/kg/day) was immediately started on day 8. After the treatment, the heart rate was gradually increased to 130-140 bpm as the infant's thyroid function was improved (TSH 79.8 μIU/ml, free T3 2.95 pg/dl, and free T4 1.66 ng/dl on day 22). The infant was diagnosed ectopic thyroid tissue because of the high thyroglobulin level (85.9 μg/l). In conclusion, congenital hypothyroidism should be included in the differential diagnosis in cases of fetal bradycardia without cardiac anomalies or maternal autoimmune diseases.

Background and objectives: Increased thyroid gland volume (TV) may bring about tracheal compression, which is one of the causes of respiratory distress. The aim of this study was to investigate the relationship between TV and the severity of tracheal compression independent of patients' symptoms using semiautomated three-dimensional (3D) volumetry (S3DV) reconstructed from computed tomography (CT) scans. Cut-off TVs leading to different levels of tracheal narrowing were evaluated. Materials and Methods: One hundred sixty-three contrast-enhanced head and neck CT examinations were retrospectively assessed. TVs were measured by S3DV. The degree of tracheal compression was measured at the point where the greatest percent reduction in the cross-sectional area of the trachea adjacent to the thyroid gland was observed. To determine the severity of compression, the tracheal compression ratio (TCR) was defined (TCR = A1 (the narrowest cross-sectional area of trachea)/A2 (the largest cross-sectional area of trachea)). Results : The mean tracheal narrowing was 15% (TCR = 0.85 ± 0.15) in the study population. Patients with more than 15% tracheal compression had significantly higher TV values than those with less than 15% tracheal compression ( p < 0.001). In addition, a significant correlation was found between TV and tracheal compression ( p < 0.001). Moreover, the receiver operating characteristic (ROC) curve analysis revealed that the cut-off levels for TV that predict a tracheal narrowing of 10%, 20%, 30%, and 40% were 19.75 mL, 21.56 mL, 24.54 mL, and 30.29 mL, respectively ( p < 0.05). Conclusions: This study objectively demonstrated that larger thyroid glands cause more severe compression on the trachea. The results may be helpful during the decision-making process for thyroidectomies to be performed due to compression symptoms.

Background: It is unknown whether the growth of thyroid nodules with a Bethesda category III cytology (atypia of undetermined significance [AUS]) is predictive of malignancy, especially in cases with architectural atypia (AUS-A). This study evaluated whether tumor growth rates can help distinguish malignant from benign nodules in the AUS-A subcategory., Methods: This retrospective, single-center cohort study included 172 patients who underwent diagnostic thyroid surgery because of a nodule with a cytological diagnosis of AUS-A. The growth kinetics of nodules was assessed by serial preoperative neck ultrasonography over a median follow-up of 52.6 months (range 12.7-198.3 months)., Results: Pathologic examinations showed that 112 (65%) and 60 (35%) patients had benign and malignant nodules, respectively. The largest diameter and volume of both benign and malignant nodules increased gradually (p < 0.001). However, there was no significant difference in the growth rates of benign and malignant nodules based on the largest diameter (p = 0.132) and volume (p = 0.200). The time to tumor growth curves and estimated median time to significant tumor growth from baseline were not significantly different in malignant nodules compared to benign nodules (p = 0.458 and p = 0.568, respectively). The relative risk (RR) of malignancy of growing and stable nodules did not differ significantly based on the largest diameter (RR = 0.5; p = 0.064) and volume (RR = 0.9; p = 0.748)., Conclusions: The size of thyroid nodules classified as AUS-A increased linearly, regardless whether these nodules were benign or malignant. These results suggest that growth kinetics on serial preoperative neck ultrasonography cannot predict malignancy in the AUS-A subcategory.

The thyroid is an endocrine gland composed of two lateral lobes connected by a strip of thyroid tissue called an isthmus. The thyroid gland is usually associated with extensive morphological variations and developmental anomalies. During the 4th intrauterine week, the thyroid gland begins to develop mainly from the invagination of the endodermal cells of the ventral floor of the primitive pharynx. One of the anomalies of the thyroid gland is the agenesis of the isthmus of the thyroid. It is a rare condition and very few cases have been reported in the literature. Another rare developmental abnormality is the presence of ectopic thyroid tissues, which are characterised by the presence of thyroid tissue in locations other than the anterolateral region of the second and fourth tracheal cartilages. Ectopic thyroid tissues are most commonly found in the lingual region but are also found in the other head/neck localisations as well. In this present case report, a 54-year-old female patient with the agenesis of the isthmus of the thyroid gland with accompanying tissues of multifocal and multicentric papillary thyroid carcinoma will be discussed. When an agenesis of the isthmus of the thyroid is detected, the agenesis of the thyroid lobes or the presence of an ectopic thyroid tissue must be considered. Especially in the patients who will undergo a thyroid surgery, it should not be forgotten that the identification of an agenesis of the isthmus as well as the other thyroid anomalies during the preoperative examination, will make a remarkable contribution in deciding the strategy of the surgery and will help in preventing the development of surgical complications. However, it is not always possible to detect the presence of these anomalies, during the preoperative examinations of the patients who will undergo thyroid surgeries; therefore, one must be careful with regard to these type of anomalies in the perioperative examinations. To the best of authors' information, the present case is considered to be the first in the literature in English, presenting with an agenesis of the isthmus of the thyroid gland in the presence of ectopic thyroid tissues associated with papillary carcinoma.

Objective: To assess clinical variables, including early thyroid scintigraphy, in predicting the outcome (permanent vs transient) in term infants with congenital hypothyroidism (CH)., Methods: In a retrospective study, 142 full-term infants with CH diagnosed between 2000 and 2012 were categorized into three groups: agenesis/ectopic thyroid and permanent CH; eutopic thyroid and permanent CH; and eutopic thyroid and transient CH. All underwent early thyroid scintigraphy and were under regular follow-up in our tertiary Pediatric Endocrine Institute., Results: Thyroid scan showed agenesis/ectopic thyroid in 58 (41%) and eutopic thyroid in 84 (59%) infants. Imaging findings were similar in eutopic-permanent and eutopic-transient groups. At initial evaluation, TSH levels were higher in the agenesis/ectopic group than in the eutopic-permanent and eutopic-transient groups (71.5 ± 11.2 mIU/L vs 49.1 ± 27.9 mIU/L and 42.5 ± 29.1 mIU/L, respectively; P < 0.001). Higher l-T4 doses were required from the third month in the agenesis/ectopic than in the eutopic-permanent group (P < 0.001) and from the sixth month in the eutopic-permanent than in the eutopic-transient group (P < 0.01). Initial TSH >63.5 mU/L (P < 0.001) and l-T4 dose >4.6 μg/kg/d at age >6 months (P < 0.001) were found to be predictors for an agenesis/ectopic gland using receiver operating characteristic analysis, as was an l-T4 dose >2.2 μg/kg/d at age >6 months (P < 0.01) for permanent CH in patients with a eutopic gland., Conclusions: Although early thyroid scintigraphy is reliable in predicting permanent CH when detecting agenesis or ectopic gland, it cannot differentiate between permanent and transient CH in cases with a eutopic thyroid. Confirmatory TSH at diagnosis and the l-T4 dose through treatment may better distinguish between permanent and transient CH.

Competing Interests: Competing interests: None declared.

Ectopic intrathyroidal thymic tissue is a benign lesion of nonthyroid origin occasionally found in the pediatric thyroid gland. Accurate diagnosis of such lesions is critical to avoid unnecessary biopsy or surgery. Twelve children referred to our center for the concern of thyroid nodules were found to have intrathyroidal thymic tissue. Most of the lesions had a classic sonographic appearance of a hypoechoic mass with sharp margins and multiple focal internal nonshadowing echogenicities identical to thymic tissue. Sonography and, in select cases, fine-needle aspiration can be used to diagnose benign thymic tissue within the thyroid and avoid unnecessary surgery., (© 2017 by the American Institute of Ultrasound in Medicine.)

Objective: The incidence of congenital hypothyroidism (CH) varies globally. This 5-year study aimed to determine the prevalence of permanent CH in the southwest of Iran., Materials and Methods: Between January 2007 and December 2009, all newborns in Ahvaz, the biggest city in the southwest of Iran, were screened for CH using a heel-prick sample for thyrotropin (TSH) levels. Subjects with TSH ≥ 5 mU/L were evaluated for T4-TSH. Infants with T4 < 6.5 µg/dL, TSH > 10 mU/L, and normal T4 but persistent (> 60 days) high TSH were considered to have CH. After the third birthday, treatment was discontinued, and T4-TSH was reevaluated; subjects with TSH ≥ 10 mU/L were investigated using thyroid Tc99 scintigraphy (TS). Based on TS, they were classified as normal, dysgenetic, or athyretic (agenesis)., Results: Screening was performed for 86,567 neonates, and 194 were confirmed to have CH (100 males; F/M = 0.94; overall incidence 1:446). After the third birthday, reevaluation was performed in all (except 18 that were not accessible). From 176 patients, 81 (46%) were diagnosed with permanent CH, and 95 were discharged as transient. Considering the same percentage in the lost cases, the prevalence of permanent CH was found to be 1:970. TS performed for 53 of the permanent subjects found agenesis/dysgenesis in 25 (F:M = 15:10) and a normal result in 28 (F:M = 11:17), indicating dyshormonogenesis as the cause in more than 50% of subjects., Conclusions: The incidence of CH in this area was found to be higher than that in other countries but less than the incidence rate reported in central Iran. The large number of transient cases of CH suggests environmental or maternal causes for the incidence rather than a genetic basis.

Thyroid hemiagenesis is a rare congenital abnormality in which one of the thyroid lobes is not developed. It can be associated with various thyroid diseases, such as Grave's disease, nodular goiter and thyroid neoplasm, rarely with hyperparathyroidism. We report a case of a 50-year old woman with left thyroid lobe agenesis diagnosed by ultrasonography and scintigraphy. Right thyroidectomy was performed and the histopathological examination showed diffuse hyperplasia, multinodular goiter and Hashimoto's thyroiditis. To our knowledge, this is the first description of multinodular goiter and Hashimoto's thyroiditis in a patient with thyroid hemiagenesis.

Background: Thyroid hemiagenesis (TH) is a rare congenital disease with absence of a thyroid lobe; most patients have no clinical symptoms. The etiology of TH remains unclear. In this paper, we describe a rare case of TH and congenital absence of the ipsilateral parathyroid gland, found during the operation, combined with the autoimmune disease Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis., Case Presentation: A 31-year-old woman was admitted to our hospital because of a mass in the right neck. Surgical exploration validated the absence of the left lobe of the thyroid and parathyroid glands, and pathological examination of the excised nodules confirmed Hashimoto's thyroiditis. Patients with TH might show accompanying absence of the ipsilateral parathyroid gland. The case described here, in which TH was combined with Hashimoto's thyroiditis, is rare in the medical literature. The operation should be ended at once if Hashimoto's thyroiditis is diagnosed during surgery., Conclusions: Absence of thyroid lobe may accompany with a congenital absence of the ipsilateral parathyroid gland and Hashimoto's thyroiditis. Fine needle aspiration is essential to diagnosis and decision-making of the treatment.

22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features including endocrine abnormalities. We aimed to characterize growth patterns, hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS. Anthropometric and laboratory measurements were obtained from the charts of 48 individuals (males=28, 8.0±6.8 visits/participant) followed at a national 22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3±4.9 years and age at last evaluation 11.2±7.2 years. Median height-SDS was negative at all ages. Height-SDS at last visit was correlated to the midparental height-SDS (r=0.52 P=0.002). Yet, participants did not reach their target height, with a difference of 1.06±1.07 SD (P <0.0001). Height-SDS at last visit of participants with a heart defect was lower compared to participants with a normal heart (-1.5±1.4 vs. -0.6±0.8, P=0.036), with lower height-SDS in the subgroup of participants with severe heart defects (-2.1±1.6, P=0.009). Mean IGF1-SDS was low (-0.99±1.68) but was not correlated with height-SDS. Thirteen patients (27%) had hypoparathyroidism: 10 presented during infancy and 3 during adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In conclusions, individuals with 22q11.2 DS have a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Hypoparathyroidism is common and may present during the neonatal period as well as later in life. Thyroid abnormalities may present during childhood, adolescence, or adulthood., (© 2017 Wiley Periodicals, Inc.)

Developmental anomalies of the thyroid gland, defined as thyroid dysgenesis, underlie the majority of cases of congenital hypothyroidism. Thyroid dysgenesis is predominantly a sporadic disorder although a reported familial enrichment, variation of incidence by ethnicity and the monogenic defects associated mainly with athyreosis or orthotopic thyroid hypoplasia, suggest a genetic contribution. Of note, the most common developmental anomaly, thyroid ectopy, remains unexplained. Ectopy may result from multiple genetic or epigenetic variants in the germline and/or at the somatic level. This review provides a brief overview of the monogenic defects in candidate genes that have been identified so far and of the syndromes which are known to be associated with thyroid dysgenesis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background/aims: Thyroid disease is a common comorbidity in individuals with Down syndrome (DS), but historical studies have multiple limitations. We assessed thyroid abnormalities in a large cohort of children with DS., Methods: Retrospective records review from a single institution. Calculated prevalence of common thyroid abnormalities and associations with common comorbidities., Results: Among 508 patients, 120 (24%) had a thyroid-related diagnosis, the majority having elevated thyrotropin treated with levothyroxine. A Kaplan-Meier estimate projects that 50% have thyroid disorder by adulthood, with 20% of hypothyroidism diagnosed before the age of 6 months. When tested, approximately 50% had positive antithyroid antibodies, though this rate was 100% in overt hypothyroidism. There was no association between congenital or acquired hypothyroidism and common comorbidities., Conclusion: Thyroid disease in DS is more common and occurs earlier than in the general population, and is often transient. Thyroid disease is unrelated to gender, obesity, or other comorbidities. Apart from overt hypothyroidism, much of hypothyroidism in DS appears unrelated to autoimmunity; we recommend checking of antithyroid antibodies only in select cases. An additional screen for thyroid disease between the newborn screen and the 6-month well-child visit will detect early cases of hypothyroidism who passed their newborn screen.
., (© 2017 S. Karger AG, Basel.)

Introduction: Acromegaly results from oversecretion of growth hormone and subsequently insulin growth factor-1. According to some authors, the disease can cause increased prevalence of nodular goitre and thyroid cancer (TC). However, the number of studies comparing acromegalic patients with control groups is low. We aimed to assess the prevalence of thyroid lesions in patients with acromegaly in comparison to an age- and sex-matched control group and to update the meta-analysis previously performed in our department by the same authors., Material and Methods: We searched medical documentation of patients with acromegaly treated in our department between 2003 and 2013. The prevalence of thyroid abnormalities was compared with the group of patients with hormonally inactive adrenal incidentalomas. To perform the meta-analytic part of the paper we also searched ten databases to find relevant papers., Results: Two hundred and five patients with acromegaly and 184 patients with incidentalomas were included. Any thyroid lesions were present in 77.6% of patients with acromegaly vs. 63.0% with incidentalomas (p = 0.002), multinodular goitre - 66.8% vs. 47.8% (p = 0.0002), and TC- 5.4% vs. 2.7% (p = 0.21) respectively. For thyroid lesions the pooled odds ratio (OR) was 3.1 (95% confidence interval [CI] 1.8-5.5), and for TCs the OR was 4.5 (95% CI 1.9-10.3)., Conclusions: According to our results thyroid lesions were significantly more common in patients with acromegaly; in case of TC the difference was not significant. The updated meta-analysis showed significantly increased prevalence of both disorders. In conclusion, systematic thyroid examination should be an important part of follow-up in case of acromegalic patients. (Endokrynol Pol 2017; 68 (1): 2-6).

Thyroid gland is the largest of all endocrine glands. It is composed of two lobes. These two lobes are joined by an isthmus and this resemble the letter "H". A wide range of morphological variations and developmental anomalies of the thyroid gland like hypoplasia, ectopy, hemiagenesis, and agenesis have been reported in literature. Out of these, the incidence of agenesis of the thyroid isthmus is rare, and very few cases have been reported. In our report, 28 year old male patient was found with agenesis of thyroid isthmus with papillary carcinoma in the right lobe of thyroid. During the operation it was seen that the right and left thyroid lobes were independent from each other and isthmus was absent. We will present a case of thyroid isthmus agenesis and discuss the clinical importance and the incidence of this case.

Hearing loss is a relatively common condition in children, occurring in approximately 2 out of every 1,000 births with approximately 50% of reported diagnoses having a primary genetic etiology. Given the prevalence and genetic component of hearing loss, coupled with a trend toward early diagnosis with the institution of universal newborn hearing screening, The Genetics of Hearing Loss Clinic was established at The Children's Hospital of Philadelphia to manage the diagnosis, testing, and genetic counseling for individuals and families. This paper described a cohort of 660 individuals with a diagnosis of hearing loss evaluated between July 2008 and July 2015 in the Genetics of Hearing Loss Clinic. To elucidate the cause of hearing loss in this cohort for better management and prognostication, testing included single nucleotide polymorphism chromosomal microarray, hearing loss next generation sequencing panel, and additional clinical tests inclusive of thyroid and renal function studies, temporal bone magnetic resonance imaging, and electrocardiogram. Of those evaluated, most had bilateral sensorineural hearing loss, occurring in 489/660 (74%). Additionally, 612/660 (93%) of patients presented with a nonsyndromic form of hearing loss (no other observed clinical findings at the time of exam), of which pathogenic mutations in GJB2 were most prevalent. Of the individuals with syndromic manifestations (48/660), Usher and Waardenburg syndrome were most commonly observed. A family history of hearing loss (first degree relative) was present in 12.6% of families with available information. Through molecular analyses, clinical examination, and laboratory testing, a definitive etiologic diagnosis was established in 157/660 (23.8%) of individuals. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Adaptor protein (AP) complexes function in the intracellular sorting and vesicular transport of membrane proteins. The clathrin-associated AP-1 complex functions at the trans-Golgi network and endosomes, and some forms of this complex are thought to mediate the sorting of proteins in plasma membranes of polarized epithelial cells. A null mutation of the mouse Ap1g1 gene, which encodes the gamma-1 subunit of the AP-1 complex, causes embryonic lethality when homozygous, indicating its critical importance in early development but precluding studies of its possible roles during later stages. Here, we describe our analyses of a new spontaneous mutation of Ap1g1 named "figure eight" (symbol fgt) and show that it is an in-frame deletion of 6 bp, which results in the elimination of two amino acids of the encoded protein. In contrast to Ap1g1 (-/-) null mice, mice homozygous for the recessive fgt mutation are viable with adult survival similar to controls. Although Ap1g1 is ubiquitously expressed, the phenotype of Ap1g1 (fgt) mutant mice is primarily restricted to abnormalities in sensory epithelial cells of the inner ear, pigmented epithelial cells of the retina, follicular epithelial cells of the thyroid gland, and the germinal epithelium of the testis, suggesting that impaired AP-1 sorting and targeting of membrane proteins in these polarized cells may underlie the observed pathologies. Ap1g1 (fgt) mutant mice provide a new animal model to study the in vivo roles of gamma-1 adaptin and the AP-1 complex throughout development and to investigate factors that underlie its associated phenotypic abnormalities.

Context: Congenital hypothyroidism (CH) may arise from dual foci thyroid ectopia., Objective: To ascertain the incidence of dual ectopia in CH and compare the phenotype to single ectopia or thyroid agenesis., Design and Setting: Single center, retrospective study of babies referred through UK Newborn Bloodspot Screening between 2006 and 2012., Patients: A total of 837 377 babies were screened for CH, with 730 referred for diagnostic confirmation (134 thyroid ectopia, 73 thyroid agenesis)., Intervention: Thyroid isotope scans were classified as single or dual ectopia. Biochemical, clinical, and sociodemographic data were collected., Main Outcome Measures: The incidence of thyroid dual ectopia and comparison of clinical parameters with single ectopia and agenesis., Results: Thyroid ectopia occurs with an incidence of 16 per 100 000 births. Twenty-one of 134 (15.7%) babies with thyroid ectopia had dual foci, an incidence of 2.5 per 100 000 births. Dual ectopia infants had lower mean bloodspot TSH compared to single ectopia and agenesis groups (P < .001). On venous sampling, the ectopia group differences were absent, but the difference with the agenesis group remained (TSH, P < .001; free T4, P < .001). There were no between-group differences for gestation, ethnicity, maternal age, or levothyroxine requirements at 12 months., Conclusions: Thyroid dual ectopia has an incidence of 2.5 per 100 000 births. Early functional activity in the ectopia groups with detectable serum free T4 concentrations is lost at 12 months when T4 requirements are the same as the agenesis group.

Background: Familial clustering in patients with permanent congenital hypothyroidism (CH) caused by thyroid dysgenesis (TD) has been reported in developed countries. There is no information on familial TD from developing countries., Methods: A total of 312 first degree relatives belonging to 80 families of children with TD (group 1) and 40 families of age-matched normal children (group 2) were screened by thyroid ultrasonography, serum total thyroxine (T4) and thyroid stimulating hormone (TSH)., Results: Thyroid scintigraphy revealed agenesis in 78.7% of the patients, ectopic gland in 15%, and hypoplasia in 6.2%. The mean thyroid volumes were similar in parents and siblings of both groups. Eight (10.6%) mothers in group 1 were identified to have thyroid hypoplasia as compared with none in group 2 (P=0.03). Serum TSH was significantly higher in group 1 than in group 2 (P=0.004). Sixteen (7.8%) subjects (6 mothers, 5 fathers, and 5 siblings) in group 1 were found to have subclinical hypothyroidism as compared to none in group 2 (P<0.05). Four families were identified to have thyroid developmental anomalies and abnormal thyroid functions accounting for 5% of cases of familial TD in our cohort., Conclusion: Thyroid developmental anomalies and thyroid function abnormalities are more frequent in first degree relatives of children with TD as compared with a control population. These findings suggest that possibly there is a genetic component of TD in Indian patients.

Background: Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism. Over time, forms of thyroid dyshormonogenesis can result in goiter, which can lead to difficult management decisions as the pathologic changes can both mimic or lead to thyroid cancer., Methods: Herein we describe the cases of two brothers diagnosed with congenital hypothyroidism, with initial findings consistent with thyroid dyshormonogenesis. One brother eventually developed multinodular goiter with complex pathology on biopsy, resulting in thyroidectomy., Results: Whole exome sequencing revealed the brothers carry a novel frameshift mutation in thyroperoxidase; the mutation, while not previously described, was likely both deleterious and pathogenic. Conlcusions: These cases highlight the complex pathology that can occur within thyroid dyshormonogenesis, with similar appearance to possible thyroid cancer, leading to complex management decisions. They also highlight the role that a genetic diagnosis can play in interpreting the impact of dyshormonogenesis on nodular thyroid development, and the need for long-term follow-up in these patients.

Primary posterior mediastinal ectopic goitre is an extremely rare entity; we report a case of a 28-year-old man who presented with dysphagia, respiratory distress and hoarseness of voice, gradually worsening over a period of 3 months. CT scan of the thorax revealed a giant posterior mediastinal ectopic goitre. The mass was removed through a right posterolateral thoracotomy. The patient's symptoms, respiratory distress and dysphagia disappeared immediately after surgery while his voice gradually returned to normal after 6 weeks., (2016 BMJ Publishing Group Ltd.)