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Background: Ectopic thyroid tissue (ETT) is a rare congenital anomaly caused by the abnormal embryonic migration of thyroid tissue, leading to its presence outside its usual pretracheal location. This condition can lead to diagnostic challenges, especially when located within the airway, as it mimics other respiratory disorders such as asthma., Case Presentation: We report the case of a 69-year-old man with endotracheal ETT presenting with severe dyspnea, and the lesion was initially suspected to be malignant. The diagnosis of ETT was confirmed through bronchoscopy and histopathological examination. The patient underwent successful endoscopic interventional therapy, resulting in significant symptom improvement and complete resolution of the airway lesion., Conclusion: Although rare, ETT should be considered in the differential diagnosis of unexplained respiratory symptoms to prevent misdiagnosis and permit effective, minimally invasive treatment options such as endoscopic resection, which can significantly improve patient outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was not required because this is a case report. This study was conducted in compliance with the Declaration of Helsinki. Written informed consent was obtained from the individual participant included in the study. Consent for publication: Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

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.

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.)

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.

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.

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.

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.

Competing Interests: Competing interests: None declared.

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.

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.

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.)

Surgeries of the anterior neck include thyroid surgery, open or percutaneous dilatational tracheotomy, bronchoscopy, mediastinoscopy and oesophagoscopy. These are potentially safe surgeries with mortality rates less than 1%. Today, the most common cause of death following a tracheotomy is haemorrhage and, following thyroid surgery, the causes are haemorrhage, giant goitres and upper airway complications. Bronchoscopies and mediastinoscopies are almost never fatal. While operating around the trachea, no major vessel is encountered in the surgical field. We report a case in which an aberrant innominate artery was encountered crossing anterior to the trachea just below the thyroid isthmus. As it is an uncommon finding, even minor complacency can lead to torrential bleeding culminating in death. Thus, we recommend surgeons to be vigilant for any aberrant artery in the surgical field rather than finding it accidentally; thereby preventing any complications in a potentially safe surgery., (2016 BMJ Publishing Group Ltd.)

Objective: To search for genetic alteration in NKX2.5 gene in patients presenting both congenital heart disease (CHD) and TD., Subjects and Methods: Individual phenotypes were carefully analyzed in 86 children with thyroid dysgenesis (TD) using thyroid function tests, scintigraphy, ultrasound and echocardiography. DNA was extracted and NKX2.5 gene coding region was amplified by polymerase chain reaction (PCR) and sequenced., Results: CHD were found in 8.1% of patients with TD. The mutation screening revealed two known polymorphisms in patients with isolated TD or TD associated with CHD. None of them are predicted to result in codon change in conserved domain. The c.63A>G polymorphism was detected in 54/86 patients (49 with isolated TD and 5 with TD combined with CHD). There was a significant association of c.63A>G polymorphism with hypoplasia (p < 0.036). The c.541G>A polymorphism was observed in only one patient with isolated thyroid hypoplasia., Conclusion: NKX2.5 mutations were not found. The c.63A>G polymorphism might be associated with thyroid hypoplasia.

Background: The aim of this study was to evaluate abnormalities in thyroid function according to tests and the humoral immune systems of patients from Eastern China with pediatric vitiligo., Material and Methods: A total of 145 pediatric patients with vitiligo were investigated in this study, along with 59 children without autoimmune diseases as controls. Laboratory tests of thyroid function were conducted, and these tests examined free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab), antinuclear antibodies (ANAs), immunoglobulins (IgA, IgM, and IgG), and complements (C3 and C4)., Results: A total of 63 patients (43.4%), including 39 boys (44.3%) and 24 girls (42.1%), displayed abnormalities in thyroid function according to the tests. This finding indicated that patients with vitiligo differed significantly from those in the control group (P<0.001), particularly in terms of FT3 and TSH abnormalities (P<0.05). However, these groups did not deviate significantly with respect to FT4, Tg-Ab, and TPO-Ab abnormalities (P>0.05). Thirteen patients (8.9%) and 1 (1.7%) control were positive for ANA. All 12 specific antibodies were detected in 8 patients. Anti-SSA/Ro-60 and anti-SSA/Ro-52 were the most prevalent antibodies, followed by anti-dsDNA and then by anti-SmD1 and CENB-P. The serum levels of IgA and IgG decreased more significantly in the vitiligo group than in the control group (P<0.001). However, no significant difference was observed in terms of IgM levels (P>0.05). C4 serum levels also decreased more significantly in the vitiligo group than in the control group (P=0.035)., Conclusions: Results suggest that the incidence of abnormalities in the thyroid functions of children and adolescents is significantly higher in those with vitiligo than that in those in the control group. In addition, immunological dysfunction is common in the vitiligo group.

Thyroid hemiagenesis is an infrequent congenital disorder which is rarely associated with hyperparathyroidism. We present a case of an adult woman who presented with hyperparathyroidism and ipsilateral thyroid hemiagenesis. Parathyroid adenoma was excised by minimal invasive parathyroidectomy.

Background: Thyroid hemiagenesis is a rare congenital anomaly, and still more rarely associated with primary hyperparathyroidism (pHPT). Due to the embryologic pathways of the thyroid and parathyroid glands, it remains unclear whether or not thyroid hemiagenesis may be linked to ipsilateral parathyroid agenesis, and consequently, surgical strategy for thyroid hemiagenesis associated pHPT (THAP) does not only depend on preoperative localization but also on the thyroid anomaly., Methods: Including the present case report, a total of nine cases with THAP retrieved from the literature were reviewed. Seven of nine cases had thyroid hemiagenesis on the left side, three out of nine showed a parathyroid adenoma on the contralateral side to the thyroid hemiagenesis., Conclusions: Based on these cases, it can be concluded that the embryologic pathways of the thyroid and parathyroid glands are different, and in cases of THAP, parathyroid exploration should follow standard recommendations for pHPT surgery.

Introduction: Lingual thyroid gland is a rare anomaly of thyroid gland development, occurring more frequently in females. If it causes local symptomatology such as dysphagia, dysphonia or dyspnea it is diagnosed in childhood, however, if it is asymptomatic it is usually diagnosed in adulthood., Case Outline: We present a 23-year-old female patient in whom we diagnosed lingual thyroid gland coincidentally during diagnostic procedures of a concomitant disease. The application of 131I scintigraphy showed an oval field of intensive accumulation of radio markers in the zone of medial face line, around tongue base, with the absence of thyroid gland in its physiological position. Functional testing proved primary hypothyroidism and we started the application of substitution therapy. The application of levothyroxine resulted in reaching euthyroid state and the reduction of thyroid gland size., Conclusion: We present a very rare anomaly of the thyroid gland, and so far there have been no clear attitudes about further treatment. The general condition of the patient, age, the size of ectopic thyroid gland and the existence of local symptomatology or complications represent the factors that have influence on the choice of treatment method.

A 12-year-old girl presented with dysphagia and a feeling of fullness in the throat. On examination a midline smooth, rubbery and reddish mass was seen at the base of the tongue, which moved with deglutination and protrusion of the tongue. A thyroid function test was within normal limits. On ultrasonography, absences of thyroid gland in its normal position with a smooth-contoured, round-shaped nodular mass at the tongue base with internal vascularity within. The mass was hyperdense and homogeneously enhancing on postcontrast. A clinical diagnosis of ectopic lingual was made based on the ultrasonography and CT scan features., (2014 BMJ Publishing Group Ltd.)

Thyroid hemiagenesis can be associated with various thyroid pathologies such as papillary thyroid cancer or nodular goiter. However, we did not encounter any publication in the literature in which hemiagenesis could be observed together with retrosternal goiter. In this report, a thyroid hemiagenesis associated with a benign nodular goiter extending retrosternally is reported. A 59-year-old male patient presented to the surgery clinic because of swelling in the neck. A mass was observed in the right thyroid lobe extending to the retrosternal region. On ultrasonography, a nodule in the right thyroid lobe measuring 63 mm was determined, which was extended retrosternally. However, the left lobe of the thyroid could not be visualized. Scintigraphy and Computerized Tomography confirmed hemiagenesis. Total thyroidectomy was performed without sternotomy. In conclusion, thyroid hemiagenesis can be associated with a retrosternally located nodular goiter.

Background: Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation. One important challenge in understanding the epidemiology of CH is that some newborns will have transient CH, a temporary depression of thyroid hormone concentrations that can last from several days to several months. Studies from other countries have reported that 10 to 15% of children treated for CH ultimately prove not to need treatment past 3 years of age to maintain normal hormone concentrations, and thus have transient hypothyroidism. The purpose of this study was to determine the prevalence of permanent and transient congenital hypothyroidism in Fayoum, Egypt., Methods: Cases detected by Fayoum neonatal screening program (NSP) between January 2003 and December 2011, and followed up at health insurance center were included. Permanent or transient CH was determined using results of thyroid function tests., Results: Of the 248 patients diagnosed primarily with CH by NSP; 204 (82.3%) patients were diagnosed to have permanent CH (prevalence 1/3587 live birth), and 44 (17.7%) patients were diagnosed to have transient CH (prevalence 1/16667 live birth). Initial TSH levels were higher in permanent CH cases than transient cases (p<0.004). Female to male ratio was 0.8 and 0.7 in permanent and transient CH respectively. 161 (65%) patients had thyroid dysgenesis (107 ectopic thyroid gland, 28 athyreosis and 26 thyroid hypoplasia). 87 (35%) patients had intact gland in thyroid scan and were considered to have dyshormonogenesis. Of these 87 patients 44 proved to have transient CH and 43 had permanent CH., Conclusion: The preliminary data from our study revealed that the incidences of CH as well as the permanent form were similar to worldwide reports. Although the high incidence of transient CH in our study could be explained by iodine deficiency further studies are needed to confirm the etiology and plan the treatment strategies.

Background: Morphological alterations of thyroid gland are common and result because of disturbed embryogenesis. These may vary from hypoplasia, ectopy to hemiagenesis and genesis of the gland. The authors strive to report an unusual morphological alteration of the left lobe of the thyroid gland. The current study presents a case of unusual extension of the thyroid gland discovered incidentally while dissecting the anterior cervical region of an adult Indian male cadaver. The left lobe displayed medial extension from its inferior angle which overlapped the common carotid artery (CCA). The isthmus was absent; instead a fibrous strand was interposed in between the two lobes with ramification into both the lobes. The relevance of diagnosing such extensions of thyroid gland is immense. It may alter the topographical relationship of thyroid gland with other adjacent cervical structures. Further, it may present abnormal signals upon scintillation scans and may be confused with a tumor mass on MRI scans. Lastly, the presence of lobar extension along with absence of isthmus is a gross morphological variant and in our opinion not to be overlooked by anatomists, ultrasonologists as well as thyroid surgeons. Additionally, the study presents possible embryological explanation for these gross anatomical variations.

The presence, position, extent, relationships to neighboring structures and size of the human pyramidal lobe were investigated in 58 human post-mortem specimens in order to determine the variability of this structure. The pyramidal lobe is found in 55.2% of cases as a single conical extension of the thyroid gland. It was present more often in male (53.1%) than in female (46.9%) specimens and located slightly more often on the left side of the midsagittal plane (53.1%). According to the origin and location of its base, we defined five types of pyramidal lobe, with the left-sided types (Types III and IV) being predominant. The pyramidal lobe was 22.6 mm long, 11.2 mm wide and 3.6 mm thick (mean values). The means of all measured parameters were higher in female than in male specimens (pyramidal lobe was 2.3 mm longer, 1.6 mm wider and 0.4 mm thicker in female specimens) but these differences were not significant. In addition, we found that the size of the pyramidal lobe was dependent on the presence of a fibrous or muscular band that may represent a fibrous remnant of the thyroglossal duct or the levator glandulae thyroideae muscle. The pyramidal lobe was four times longer and its base was two and a half times wider and three times thicker when it was associated with this band. We believe that our data can be used to perform safer and more effective partial thyroidectomy in order to preserve thyroid function after surgical treatment.

The right and left lobes of the thyroid gland are connected by an isthmus. The isthmus lies at the level of the second and third tracheal rings. Occasionaly, the isthmus may be absent. We hereby, report the absence of isthmus in a 52-year-old male cadaver of unknown origin. Both the right and left lobes were normal but they were separated. Both the right and left lobes of the thyroid gland measured 4.3 cm vertically. The separation distance between right and left glands was noted at the upper, middle and lower parts. The upper end of medial border of both lobes were separated by a distance of 1 cm while the separation distance was 0.7 cm and 1.5 cm at the middle and lower parts, respectively. The anatomical and clinical significance of absence of isthmus is important for medical personnel and the surgeons operating on the thyroid gland. The present case report is a an attempt to highlight such.

Objective: The main objective was to assess iodine status (thyroid volume (Tvol) and urinary iodine concentration (UIC)) and their determinants in Saharawi refugee women., Design: A cross-sectional survey was performed during January-February 2007. Tvol was measured by ultrasound and iodine concentration was analysed in spot urine samples and in household drinking water. Anthropometry and Hb concentration were measured and background variables were collected using pre-coded questionnaires., Setting: The survey was undertaken in four long-term refugee camps in the Algerian desert., Subjects: Non-pregnant women (n 394), 15-45 years old, randomly selected., Results: Median (25th percentile-75th percentile (P25-P75)) UIC was 466 (294-725) μg/l. Seventy-four per cent had UIC above 300 μg/l and 46 % above 500 μg/l. Median (P25-P75) Tvol was 9·4 (7·4-12·0) ml and the goitre prevalence was 22 %. UIC was positively associated with iodine in drinking water and negatively associated with breast-feeding, and these two variables explained 28 % of the variation in UIC. The mean (sd) Hb level was 11·8 (2·4) g/dl. In total 46 % were anaemic with 14 %, 25 % and 7 %, classified with respectively mild, moderate and severe anaemia., Conclusions: The Saharawi women had high UIC, high levels of iodine in drinking water and increased Tvol and probably suffered from iodine-induced goitre. The high prevalence of anaemia is considered to be a severe public health concern. To what extent the excessive iodine intake and the anaemia have affected thyroid function is unknown and should be addressed in future studies.

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.

Objective: Developmental defects of the thyroid gland are the most frequent causes of permanent congenital hypothyroidism. This study aimed to investigate the epidemiological features of patients with thyroid dysgenesis (TD)., Methods: Medical records of 234 patients with TD followed between the years 2008 and 2010 were evaluated retrospectively. Diagnosis was made by ultrasonography., Results: Of 234 patients, 120 (51.3%) were male and 114 (48.7%) were female. Male to female ratio was 1.08 and there were no significant differences in epidemiologic and clinical findings between girls and boys. One hundred eighty-three patients (78.2%) were diagnosed as hypoplasia, 35 (14.9%) as thyroid agenesis, 4 as ectopic thyroid gland and 12 as hemiagenesis. The mean maternal age of the group was 28.9 ± 0.4 years (range 18 to 45 years), which is significantly higher than the recently reported mean maternal ages for Turkish women., Conclusions: Advanced maternal age was more prevalent in patients with TD. Our clinical and epidemiologic findings suggested no evidence of sexual dimorphism.

Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1(-/-) mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1(-/-) mouse embryos showed a significantly smaller total thyroid surface area (-40 to -60%) compared to wild type mice at all study time points (E9.5-E16.5). In both Hes1(-/-) and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1(-/-) mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1(-/-) thyroids revealed a significantly decreased labelling area for T4 (-78%) and calcitonin (-65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (-69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

Background: The transcription factor Nkx2-1 (also known as TTF-1, Titf1 or T/EBP) contains two apparently redundant activation domains and is post-translationally modified by phosphorylation. We have generated mouse mutant strains to assess the roles of the two activation domains and of phosphorylation in mouse development and differentiation., Results: Mouse strains expressing variants of the transcription factor Nkx2-1 deleted of either activation domain have been constructed. Phenotypic analysis shows for each mutant a distinct set of defects demonstrating that distinct portions of the protein endow diverse developmental functions of Nkx2-1. Furthermore, a mouse strain expressing a Nkx2-1 protein mutated in the phosphorylation sites shows a thyroid gland with deranged follicular organization and gene expression profile demonstrating the functional role of phosphorylation in Nkx2-1., Conclusions: The pleiotropic functions of Nkx2-1 are not all due to the protein as a whole since some of them can be assigned to separate domains of the protein or to specific post-translational modifications. These results have implication for the evolutionary role of mutations in transcription factors.

The thyroid develops from the foregut endoderm. Yet uncharacterized inductive signals specify endoderm progenitors to a thyroid cell fate that assembles in the pharyngeal floor from which the primordium buds and migrates to the final position of the gland. The morphogenetic process is regulated by both cell-autonomous (e.g. activated by NKX2-1, FOXE1, PAX8, and HHEX) and mesoderm-derived (e.g. mediated by TBX1 and fibroblast growth factors) mechanisms acting in concert to promote growth and survival of progenitor cells. The developmental role of TSH is limited to thyroid differentiation set to work after the gross anatomy of the gland is already sculptured. This review summarizes recent advances on the molecular genetics of thyroid morphogenesis put into context of endoderm developmental traits and highlights established and novel mechanisms of thyroid dysgenesis of potential relevance to congenital hypothyroidism in man.

Thyroid is particularly prone to morphogenetic variability. Developmental failure of the thyroid gland is in 85% of cases the underlying cause of congenital hypothyroidism, diagnosed at birth with a frequency of 1:3000-1:4000 newborns. However, the incidence of less severe developmental variants of the thyroid is much higher. Determination of the aetiology of congenital hypothyroidism is crucial for predicting its severity and outcome as well as impacts dose of L-thyroxine during substitution. Thyroid imaging is necessary to establish diagnosis, and it involves mainly thyroid ultrasound examination and scintiscan. Awareness of both the advantages and limitations of sonographic and scintigraphic imaging are central to the successful interpretation of their results and reasonable recommendation of these procedures for patients with thyroid developmental anomalies of different age and clinical picture. Hence, the aim of this review is to provide the most important and up-to-date information on the place of radionuclide scanning and ultrasonography in visualization of different thyroid developmental abnormalities.

Thyroid hemiagenesis (TH) is characterized by the congenital absence of one thyroid lobe. The aim of this study was to evaluate the calcium-phosphate balance in TH. Twenty patients with TH and 20 controls with a bilobed thyroid were studied. Serum concentrations of total calcium, parathormon and calcitonin were measured. Additionally, the immunohistochemical expression of calcitonin, chromogranin A (chA), neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP) was evaluated in surgical specimens from patients with TH and controls. There were no significant differences in biochemical parameters between TH and controls. Positive staining for calcitonin was demonstrated in 3/8 thyroid sections from three patients with TH, but only in 2/33 sections from four controls (p < 0.005). All sections from patients with TH positive for calcitonin also expressed chA, NSE and CGRP. Two sections from controls positive for calcitonin presented an additionally positive reaction for chA, and one of them also for NSE. None presented positive staining for CGRP. Of three TH sections, in one, hyperplasia of C cells of medium grade, and in another hyperplasia of C cells of high grade, could be detected. In the controls, hyperplasia of C cells of low and medium grade was observed. TH was associated with slightly enhanced C cells hyperplasia compared to controls, which might indicate compensatory proliferation. However, the calcium-phosphate balance does not seem to be significantly affected.

The case of a patient with primary hyperparathyroidism with the incidental finding of left thyroid hemiagenesis with isthmus involvement is presented. Thyroid hemiagenesis is a rare congenital abnormality. There have been approximately 310 cases reported in the literature to date. It has been reported as an incidental finding with a wide range of associated pathological conditions. It is important to consider this in patients being prepared for thyroid lobectomy due to the inevitability of postoperative hypothyroidsm. Due to the female predominance of thyroid disease, hemiagenesis was first thought to be more common in women. Left lobe cases accounts for the majority of instances and isthmus is absent in half the cases. Ultrasonography is the diagnostic tool of choice.

Background: Non-recurrent laryngeal nerve, a rare anomaly, passes transversely into larynx with or without its recurrent branches directly arising from the vagus nerve. The paper investigates clinical significance of non-recurrent laryngeal nerve during thyroid surgery. Clinical data from 5 cases of non-recurrent laryngeal nerve and related literature reviews were made to acknowledge its incidence, variant types and matters concerned during thyroid operations., Case Report: 821 recurrent laryngeal nerves were anatomized during 2496 thyroid operations, from which 5 were confirmed to hold non-recurrent laryngeal nerves (0.61%). 3 patients were found to have non-recurrent laryngeal nerves during re-operation because of voice horse after the first operation which improved much after re-operation. The other two patients were recognized during the first operation. All 5 cases were not diagnosed preoperatively., Conclusions: Non-recurrent laryngeal nerve, a rare anomaly, is very vulnerable during thyroid surgery. It is helpful to avoid injuring non-recurrent laryngeal nerve that identification of the non-recurrent laryngeal nerve and its types.

We report here the mapping of a chromosomal region responsible for strain-specific development of congenital hypothyroidism in mice heterozygous for null mutations in genes encoding Nkx2-1/Titf1 and Pax8. The two strains showing a differential predisposition to congenital hypothyroidism contain several single-nucleotide polymorphisms in this locus, one of which leads to a nonsynonymous amino acid change in a highly conserved region of Dnajc17, a member of the type III heat-shock protein-40 (Hsp40) family. We demonstrate that Dnajc17 is highly expressed in the thyroid bud and had an essential function in development, suggesting an important role of this protein in organogenesis and/or function of the thyroid gland.

In human thyroid, caveolin-1 is localized at the apex of thyrocytes, but its role there remains unknown. Using immunohistochemistry, (127)I imaging, transmission electron microscopy, immunogold electron microscopy, and quantification of H(2)O(2), we found that in caveolin-1 knockout mice thyroid cell homeostasis was disrupted, with evidence of oxidative stress, cell damage, and apoptosis. An even more striking phenotype was the absence of thyroglobulin and iodine in one-half of the follicular lumina and their presence in the cytosol, suggesting that the iodide organification and binding to thyroglobulin were intracellular rather than at the apical membrane/extracellular colloid interface. The latter abnormality may be secondary to the observed mislocalization of the thyroid hormone synthesis machinery (dual oxidases, thyroperoxidase) in the cytosol. Nevertheless, the overall uptake of radioiodide, its organification, and secretion as thyroid hormones were comparable to those of wild-type mice, suggesting adequate compensation by the normal TSH retrocontrol. Accordingly, the levels of free thyroxine and TSH were normal. Only the levels of free triiodothyronine showed a slight decrease in caveolin-1 knockout mice. However, when TSH levels were increased through low-iodine chow and sodium perchlorate, the induced goiter was more prominent in caveolin-1 knockout mice. We conclude that caveolin-1 plays a role in proper thyroid hormone synthesis as well as in cell number homeostasis. Our study demonstrates for the first time a physiological function of caveolin-1 in the thyroid gland. Because the expression and subcellular localization of caveolin-1 were similar between normal human and murine thyroids, our findings in caveolin-1 knockout mice may have direct relevance to the human counterpart.

Stüve-Wiedemann syndrome (SWS) is an autosomal recessive bone dysplasia (OMIM #601559) characterized by bowing of long bones, camptodactyly, respiratory insufficiency, hyperthermic episodes, and neonatal death from hyperthermia or apnea. We describe two female siblings with SWS born from consanguineous Gypsy parents. For a further delineation of SWS, we report hypothyroidism and ectopic thyroid as part of its phenotypic spectrum. Molecular study in the leukemia inhibitory factor receptor (LIFR) gene (OMIM *151 443) demonstrated the presence of a mutation. We observed that in one of our patients, oropharyngeal disruption in the swallowing process caused repetitive aspiration pneumonias, life-threatening events, and finally death. We emphasize that these features represent dysautonomic manifestations of SWS, and are probably related to pharyngoesophageal dyskinesia due to abnormal autonomic control of the anterior rami of cervical roots C1-C5.

We aim to determine long-term intellectual outcome of adolescents with early high-dose treated congenital hypothyroidism (CH). Sixty-three prospectively followed children with CH were assessed at age of 14 y with the Wechsler Intelligence Scale for Children-Revised and compared with 175 healthy controls. Median age at onset of treatment was 9 d (range 5-18 d) and median starting dose of levothyroxine (L-T4) was 14.7 microg/kg/d (range 9.9-23.6 microg/kg/d). Full-scale intelligence quotient (IQ) was significantly lower than in controls after adjustment for socioeconomic status (SES) and gender (101.7 versus 111.4; p < 0.0001). Children with athyreosis had a lower performance IQ than those with dysgenesis (adjusted difference 7.6 IQ scores, p < 0.05). Lower initial thyroxine (T4) levels correlated with poorer IQ (r = 0.27, p = 0.04). Lower SES was associated with poorer IQ, in particular in children with CH (interaction, p = 0.03). Treatment during childhood was not related to IQ at age 14 y. Adolescents with CH manifest IQ deficits when compared with their peers despite early high-dose treatment and optimal substitution therapy throughout childhood. Those adolescents with athyreosis and lower SES are at particular risk for adverse outcome. Therefore, early detection of intellectual deficits is mandatory in children with CH.

Thyroid hemiagenesis is a rare congenital anomaly in which one of the thyroid lobes with or without isthmus fails to develop. Here we present a woman patient with thyroid hemiagenesis, Graves' disease and ophthalmopathy with nodular goiter. Fine needle aspiration biopsy of the dominant nodule was suspicious of malignancy. The patient was referred for surgery for total thyroidectomy. Histopathological examination of the surgical material revealed benign features. The present case confirms that, although rare, a number of concomitant thyroid disorders can exist in a single patient with thyroid hemiagenesis just as it is seen for a normally developed thyroid gland.

Hesx1 has been shown to be essential for normal pituitary development. The homeobox gene Six3 is expressed in the developing pituitary gland during mouse development but its function in this tissue has been precluded by the fact that in the Six3-deficient embryos the pituitary gland is not induced. To gain insights into the function of Six3 during pituitary development we have generated Six3+/- ;Hesx1Cre/+ double heterozygous mice. Strikingly, these mice show marked dwarfism, which is first detectable around weaning, and die by the 5th-6th week of age. Thyroid and gonad development is also impaired in these animals. Analysis of Six3+/- ;Hesx1Cre/+ compound embryos indicates that hypopituitarism is the likely cause of these defects since pituitary development is severely impaired in these mutants. Similar to the Hesx1-deficient embryos, Rathke's pouch is initially expanded in Six3+/- ;Hesx1Cre/+ compound embryos due to an increase in cell proliferation. Subsequently, the anterior pituitary gland appears bifurcated, dysmorphic and occasionally ectopically misplaced in the nasopharyngeal cavity, but cell differentiation is unaffected. Our research has revealed a role for Six3 in normal pituitary development, which has likely been conserved during evolution as SIX3 is also expressed in the pituitary gland of the human embryo.