The thyroid foramen: a systematic review and meta-analysis.

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' I2 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%, I2 = 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.

An ectopic thyrolingual trunk arising from the common carotid artery: a rare variant.

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.

Superior laryngeal artery originating from the lingual artery.

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.

Thyroid hemiagenesis with compensatory hypertrophy of the remaining lobe: A case report.

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.

Prognostic evaluation models for primary thyroid lymphoma, based on the SEER database and an external validation cohort.

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.

Molecular defects in thyroid dysgenesis.

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.

Fetal Sinus Bradycardia Is Associated with Congenital Hypothyroidism: An Infant with Ectopic Thyroid Tissue.

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.

[Prevalence of thyroid abnormality: a comparison of ambulatory claims data with data from a population-based study]. / Schilddrüsenveränderungen: Ein Vergleich ambulanter Abrechnungsdaten mit Daten einer populationsbasierten Studie.

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.

Determining the Thyroid Gland Volume Causing Tracheal Compression: A Semiautomated 3D CT Volumetry Study.

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.

Ectopic Intrathyroidal Thymic Tissue Mimicking Thyroid Nodules in Children.

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.

Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.

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.

Thyroid hemiagenesis and Hashimoto's thyroditis-diagnostic and treatment pitfalls.

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.

Thyroid hemiagenesis associated with multinodular goiter and Hashimoto's thyroiditis.

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.

A hypomorphic mutation of the gamma-1 adaptin gene (Ap1g1) causes inner ear, retina, thyroid, and testes abnormalities in mice.

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.

Outcomes of evaluation and testing of 660 individuals with hearing loss in a pediatric genetics of hearing loss clinic.

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.

Thyroid Isthmus Agenesis in a Patient with Papillary Carcinoma of Thyroid.

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.

[The clinical definition and etiology of Pendred syndrome (a review of the literature and clinical observations)]. / Sindrom Pendreda (obzor literatury i klinicheskie nablyudeniya).

The aim of this work was a clinical study of the patients with mutations in the SLC26A4 gene and clinical diagnosis of the Pendred syndrome. The Pendred syndrome is a hereditary autosomal recessive disorder characterized by combined pathology of the inner ear and the thyroid gland. CT of the temporal bones demonstrates the Mondini-type structural anomaly in the inner ear and enlarged vestibular aqueduct. Examination of the thyroid gland reveals hypothyroidism and euthyroid goiter. A total of 20 unrelated children at the age from 2 to 16 years presenting with the hearing loss of different severity were available for the examination. High-resolution CT of the temporal bones demonstrated abnormal development of the inner ear including the Mondini-type structural anomaly and enlarged vestibular aqueduct. Five children with congenital hypothyroidism suffered from bilateral sensorineural impairment of hearing. The routine methods of audiological and molecular genetic examination were used throughout the study. RESULTS: As a result of molecular genetic studies, four out of the 20 patients were found to carry six recessive mutations of the SLC26A4 gene in the compound heterozygous and one such gene in the homozygous state which confirmed the hereditary nature of the disease. The children suffered the hearing loss of varying severity diagnosed at different age. The thyroid hypofunction in one child was identified when it was 2 years of age, and in two children at the age of 8 and 9 years. CONCLUSION: The first step in the diagnosis of the Pendred syndrome among children with congenital hearing loss was a CT scan of the temporal bones that showed incomplete separation of the curls of the cochlea and enlarged vestibular aqueduct. It is necessary to continue to study epidemiology, clinical and molecular genetics of the Pendred syndrome in the Russian population.

Atypical fibrodysplasia ossificans progressiva diagnosed by whole-exome sequencing.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of connective tissue that begins during the first decade of life. Our patient presented with intrauterine growth retardation, respiratory distress, neonatal onset soft tissue masses, bilateral hallux valgus, and congenital anomalies of the thyroid and uterus. She was initially diagnosed with atypical infantile myofibromatosis based on clinical and pathological findings. She underwent whole-exome sequencing (WES) as part of the FORGE study to identify the gene for infantile myofibromatosis; however a de novo dominant mutation in ACVR1 (NM_001105.4:c.617G>A) revised the diagnosis to FOP. This patient highlights the utility of WES as an early diagnostic tool in the investigation of patients with unusual presentations of rare diseases, thereby providing clinicians with accurate molecular diagnoses and the opportunity to tailor clinical management to improve patient care.

Segregation of S292F TPO gene mutation in three large Tunisian families with thyroid dyshormonogenesis: evidence of a founder effect.

UNLABELLED: We aimed to identify causal mutation(s) in 13 patients with thyroid dyshormonogenesis (TD) from three consanguineous Tunisian families. A 12-year clinical follow-up showed phenotypic variability ranging from the presence to the absence of goiter, sensorineural deafness, and mental retardation. Genetic analysis using microsatellite markers within two candidate genes (TPO and PDS) gave evidence of linkage with the TPO gene. Sequencing of its 17 exons and their flanking intron-exon junctions revealed the previously described c.875C>T (p.S292F) mutation in homozygous state. No additional mutations were found in either a 900 bp of the TPO gene promoter or PDS gene. In silico analysis showed that p.S292F mutation might reduce the catalytic cavity of the TPO which would restrict access of a potential substrate to the catalytic pocket. Using 4SNPs and one microsatellite marker in the TPO gene, an associated haplotype: G-C-G-G-214 was found, giving evidence of a founder mutation. CONCLUSION: This is the first description of a TD causing mutation in Tunisia and thus may help to develop a genetic screening protocol for congenital hypothyroidism in the studied region. Although structural modeling suggested a pathogenic effect of this mutation, functional studies are needed. Additional causing and/or modifier genes, together with late diagnosis could explain the clinical variability observed in our patients.