Tiroides Ectópica Lingual: caso Clínico / Lingual Ectopic Thyroid: a clinical case

La tiroides ectópica lingual es una patología muy poco frecuente, producida por la detención en el descenso normal de la glándula durante el desarrollo embrio-nario. La localización lingual de tejido tiroideo es la más común entre las tiroides ectópicas o aberrantes. Esta enfermedad puede ser asintomática pero, cuan-do los signos y síntomas están presentes, guardan estrecha correlación con la localización de la lesión y son proporcionales a su tamaño. El diagnóstico debe realizarse clínicamente y con el complemento de es-tudios por imágenes y endocrinológicos. En los aná-lisis de laboratorio se debe incluir dosaje de las hor-monas TSH, T4 libre y T3, vinculadas con la función tiroidea. Las biopsias deben evitarse ya que causan desequilibrio en la producción hormonal de la glándu-la y peligro de profusas hemorragias. En este artículo se desarrolla una descripción de las generalidades de la tiroides ectópica lingual, y se presenta un caso clínico de un niño con un tumor lingual, que fue deri-vado por su médica pediatra a cirugía para realizar una biopsia. Asimismo, se comenta la importancia que tiene para el odontólogo conocer esta patología a fin de poder evitar sus posibles complicaciones (AU)

Lingual thyroid is a rare disorder produced by a failure in the descent of thyroid gland to its normal position during embryological development. Lingual localization of thyroid tissue is the most common among the ectopic or aberrant thyroids. This condition can be asymptomatic, although when symptoms take place, they are connected to the lesion location and depend on its size. Diagnosis should be made clinically and complemented with imaging and endocrine studies. Laboratory analysis must include dosage of TSH, free T4 and T3, thyroid function-linked hormones. Due to the possible imbalance in the gland hormone production and the risk of massive bleeding, biopsy should be avoided. In this article, a brief description of lingual ectopic thyroid generalities is developed and a clinical case of a 7-years old child is provided. Additionally, dentistry importance of knowing this condition is commented, in order to prevent its possible complications (AU)

Impact of the reduction in TSH cutoff level to 6 mIU/L in neonatal screening for congenital hypothyroidism in Santa Catarina: final results

ABSTRACT Oubjective: To assess the implications of changing the cutoff level of TSH from 10 to 6 mIU/L. Subjects and methods: The study population was constituted by 74.123 children screened for congenital hypothyroidism by the National Screening Program in Santa Catarina, from March 2011 to February 2012. The cutoff of TSH was 6 mIU/L. If TSH between 6-10 mIU/L, the newborn was recalled for a second TSH measurement on filter paper. If TSH > 6 mIU/L in the second sample, the child was sent for medical evaluation. In children with normal topic thyroid, levothyroxine was suspended for 1 month at the age of 3 years for identification of the etiology and evaluation of the need to continue treatment. Results: Among the children screened, 435 were recalled for presenting TSH between 6 and 10 mIU/L in the first sample, 28 remained TSH > 6 mIU/L in the second sample. Among these, 11 had a final diagnosis of dyshormonogenesis, two of ectopic thyroid, two of thyroid hypoplasia and one of transient hypothyroidism. Ten children presented normal TSH levels on the first medical evaluation and two lost follow-up. Conclusion: A decrease in the TSH cutoff level from 10 to 6 mIU/L in a neonatal screening program for congenital hypothyroidism reduced the number of false-negative results, increasing the sensitivity of the test, but increased the number of false-positive results and recalls. Since a TSH cutoff level of 6 mIU/L detects thyroid function abnormalities requiring treatment, the adoption of this cutoff level is justified.

Congenital Hypothyroidism in children – A cross-sectional study in a tertiary centre in Malaysia / Journal of the ASEAN Federation of Endocrine Societies

Introduction@#The causes of congenital hypothyroidism (CHT) are thyroid dysgenesis (TD), dyshormonogenesis (TDH) or transient hypothyroidism (TH).@*Methodology@#This is a cross-sectional study looking at data over a period of 16 years (2000-2016). Confirmed cases had thyroid scan at the age of 3-years-old and repeated TFT (after 6 weeks off medications). Relevant data was collected retrospectively.@*Results@#Forty (60% female) children with CHT were included in the study. Thirty (75%) children presented with high cord TSH. Nine (23%) presented after 2 weeks of life. Majority were diagnosed with TDH (42.5%) with TD and TH of 40% and 17.5% respectively. Median cord TSH of children with TD was significantly higher compared to TDH and TH (p=0.028 and p=0.001 respectively). L-thyroxine doses were not significantly different between TD, TDH and TH at diagnosis or at 3 years.@*Conclusions@#TDH is highly prevalent in our population. TD may present after 2 weeks of life. One in five children treated for CHT had TH. Differentiating TD, TDH and TH before initiating treatment remains a challenge in Malaysia. This study provides clinicians practical information needed to understand the possible aetiologies from a patient’s clinical presentation, biochemical markers and treatment regime. Reassessing TH cases may be warranted to prevent unnecessary treatment.

Caso Clínico: Tiroides Lingual Ectópica en Paciente Adulta Hipotiroidea. Diagnóstico Casual por Tomografía Computarizada. / Clinical Case: Ectopic Lingual Thyroid in Adult Hypothyroid Patient. Casual Diagnosis by Computed Tomography.

Introducción: Los casos de tiroides ectópica localizados en la base de la lengua son anormalidades congénitas raras y difíciles de diagnosticar. Razón de presentación del caso. Caso Clínico: El caso corresponde a una mujer de 41 años con tiroides en base de la lengua diagnosticada incidentalmente con tomografía computarizada (TC), con antecedentes de hipotiroidismo y cáncer de mama derecha. Al examen físico de cuello no se palpa glándula tiroidea ni se observa masa o protuberancia en cavidad bucal. Por control del cáncer de mama, se solicita tomografía por emisión de positrones (PET) y ecografía de cuello, reportándose captación del radiofármaco en la región cervical anterior y superior de cuello, y ausencia de tejido glandular tiroideo a nivel habitual, respectivamente. Por cuanto, se realiza TC simple y contrastada observándose a nivel de la raíz de la lengua una imagen nodular hipercaptante que mide 23x20x20 mm, bien definida, contornos regulares, no infiltra tejidos adyacentes, impronta luz de la orofaringe, sin individualizar la glándula tiroides a nivel habitual, corroborando así el diagnóstico de tiroides ectópica lingual. Conclusión: El diagnóstico de tiroides ectópica en paciente adulto hipotiroideo es raro, por lo que debe considerarse la realización de TC si al examen físico y ecográfico no es palpable ni observable

Introduction: Cases of ectopic thyroid located at the base of the tongue are rare and difficult to diagnose congenital abnormalities. Reason for presenting the case. Clinical case: The case corresponds to a 41-year-old woman with thyroid based on the tongue diagnosed incidentally with computed tomography (CT), with a history of hypothyroidism and right breast cancer. On the physical examination of the neck, the thyroid gland is not palpated, and no mass or bump is observed in the oral cavity. For breast cancer control, positron emission tomography (PET) and neck ultrasound are requested, radiopharmaceutical uptake is reported in the anterior and upper cervical neck region, and absence of thyroid glandular tissue at the usual level, respectively. As a simple and contrasted CT scan, a hypercapting nodular image measuring 23x20x20 mm, well defined, regular contours is observed at the root of the tongue, does not infiltrate adjacent tissues, oropharynx light imprint, without individualizing the thyroid gland to usual level, thus corroborating the diagnosis of lingual ectopic thyroid. Conclusion: The diagnosis of ectopic thyroid in an adult hypothyroid patient is rare, so CT should be considered if the physical and ultrasound examination is not palpable or observable.

A Case of Lateral Ectopic Thyroid Mimicking the Metastatic Lymphadenopathy / 대한이비인후과학회지

Ectopic thyroid means that thyroid tissue is present at an unusual area rather than at the orthotropic thyroid position. The most common form of ectopic thyroid is lingual thyroid, followed by thyroglossal duct cyst. Ectopic thyroid in the lateral neck area is extremely rare, with only a few case reports found in the literature review. Several studies recommended that metastasizing malignancy should be considered in lateral ectopic thyroid. Described here is a case of 60 year-old woman with lateral ectopic thyroid, which was newly found during a follow-up and was mistaken for metastatic lymphadenopathy.

Congenital hypothyroidism due to thyroglobulin deficiency: a case report with a novel mutation in TG gene

Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates and infants with an incidence of one in 2,000 to one in 4,000 newborns. Primary CH can be caused by thyroid dysgenesis and thyroid dyshormonogenesis. CH due to a TG gene mutation is one cause of thyroid dyshormonogenesis and can be characterized by goitrous CH with absent or low levels of serum thyroglobulin (Tg). In the present case, a 15-day-old neonate was referred to us with elevated thyroid stimulating hormone detected during a neonatal screening test. At the age of 34 months, extensive genetic testing was performed, including targeted exome sequencing for hypothyroidism, and revealed compound heterozygous mutations in the TG gene. Sanger sequencing of both parents’ DNA samples revealed a c.3790T> C (p.Cys1264Arg) mutation located at exon 17 inherited from the mother, and a c.4057C> T (p.Gln1353*) mutation located at exon 19 was inherited from the father. The c.4057C> T (p.Gln1353*) mutation located at exon 19 has never been reported and, therefore, is a new discovery. We report a case of primary permanent CH with compound heterozygous mutations of the TG gene, including a novel mutation.

TUBB1 mutation in children with congenital hypothyroidism and thyroid dysgenesis in Shandong, China / 中国当代儿科杂志

OBJECTIVE@#To study the types and characteristics of TUBB1 mutation in children with congenital hypothyroidism (CH) and thyroid dysgenesis (TD) in Shandong, China.@*METHODS@#Mutations of the whole coding region of the TUBB1 gene were analyzed for 289 children with CH and TD in Shandong. Whole-genome DNA was extracted from peripheral blood leukocytes. PCR multiplication was performed for the whole coding region of the TUBB1 gene. Sanger sequencing was performed for the PCR products, and a biological information analysis was performed.@*RESULTS@#Among the 289 children with CH and TD, 4 (1.4%) were found to have a c.952C>T(p.R318W) heterozygous mutation in the TUBB1 gene, resulting in the change of tryptophan into arginine at codon 318 of TUBB1 protein. This mutation was evaluated as "potentially pathogenic" based on the classification criteria and guidelines for genetic variation by American College of Medical Genetics and Genomics.@*CONCLUSIONS@#A novel mutation is detected in the exon of the TUBB1 gene in children with CH and TD in Shandong, suggesting that the TUBB1 gene may be a candidate pathogenic gene for CH children with TD.

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

ABSTRACT Objective: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Subjects and methods: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. Results: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Conclusions: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.

Tiroides ectópica dual hiperfuncionante: abordaje quirúrgico dual / Dual hyperfunctioning thyroid ectopia: dual surgical approach

RESUMEN Paciente de 36 años en tratamiento de leucemia mieloide crónica con nilotinib a quien se le diagnostica hipertiroidismo por síntomas clínicos y exámenes de laboratorio. Se inicia tratamiento con metimazol más propanolol. Los estudios imagenológicos muestran un tejido ectópico tiroideo cervical infrahiodeo lateralizado a la izquierda y un nódulo en la base de la lengua. Presentó toxicidad hepática atribuida al tratamiento por lo que se decide extirpación quirúrgica de tiroides ectópica dual. Por la edad de la paciente y preocupación acerca del resultado estético, se realiza una tiroidectomía videoasistida por via axilar de la tiroides ectópica cervical y una resección transoral de la tiroides ectópica lingual. La patología confirma tejido tiroideo en ambas localizaciones sin signos de malignidad. La paciente se recuperó sin complicaciones y sin cicatriz cervical.

ABSTRACT A 36-year-old female patient with chronic myeloid leukemia being treated with nilotinib who was diagnosed with hyperthyroidism both on clinical and laboratory examination is presented. Imaging studies found left lateralized ectopic thyroid tissue of infrahyoid localization and a nodule at the base of the tongue. Hepatic toxicity was attributed to medical treatment, surgical removal of the dual thyroid ectopia was proposed. Due to the patients age and cosmetical concerns, a minimally invasive surgery was undertaken thru a video assisted transaxillary thyroidectomy for the cervical thyroid ectopia and a video assisted trans oral approach for the lingual thyroid ectopia. Post op pathology confirmed thyroid tissue at both locations and also excluded malignancy. The patient fully recovered without any complicaction and witout a residual cervical scar.

Double ectopic thyroid gland in a 10-year-old Filipino boy

Objective@#To present a case of a double ectopic thyroid gland in a 10-year old boy and discuss the pros and cons of the different management options that were available. @*Methods@# Design: Case Report. Setting: Tertiary Hospital in Metro Manila. Subject: One (1). @*Results@#A 10-year-old boy presented with hoarseness and easy fatigability for 6 years. Rigid endoscopy and CT scan showed an infraglottic mass originating from the anterior tracheal wall causing obstruction. Biopsy revealed thyroid tissue with atypia. Thyroid scintigraphy showed uptake in the submental and midline anterior neck. Thyroid hormone levels were consistent with hypothyroidism. Levothyroxine returned hormone levels to normal and resulted in complete regression of the mass with no symptoms of dyspnea, stridor or bleeding.@*Conclusion@#The management of ectopic thyroid presents a challenge as there are no guidelines for optimal treatment. Thyroid hormone insufficiency is a frequent occurrence, and emphasis must be given to its monitoring. Surgery in a critical airway lesion such as this may be reserved for cases where the patient experiences dyspnea and stridor or lack of response to thyroid hormone treatment.

Anatomical variations and developmental anomalies of the thyroid gland in Ethiopian population: a cadaveric study / 대한해부학회지

Because of its embryonic origin, the thyroid gland is predisposed to multiple anatomical variations and developmental anomalies. These include the pyramidal lobe, the origin of levator glandular thyroidae, the absence of the isthmus, ectopic thyroid, accessory thyroid tissues, etc. These anatomical variations are clinically significant to surgeons, anatomists, and researchers. The present study was designed to report anatomical variations and developmental anomalies of the thyroid gland in Ethiopian population. The study was conducted on 40 cadavers used for routine dissection classes. The thyroid gland was exposed and observed for any variations and developmental anomalies. The length, width, and thickness of the lobes were measured using a vernier caliper. Differences in the incidence of pyramidal lobe and absence of the isthmus between sexes were tested using a Pearson chi-square test. The mean length, width, and thickness of the right lobe were 4.24 cm, 1.8 cm, and 1.6 cm, respectively, whereas it was 4.08 cm, 1.8 cm, and 1.6 cm, respectively for that of the left lobe. The pyramidal lobe was noted in 52.5% of the cadavers. The levator glandulae thyroidae were prevalent in 40% of the cadavers. The isthmus mainly overlies the 2nd to 4th tracheal rings and was absent in 7.5% of the cadavers. Accessory thyroid tissue and double pyramidal lobes were noted in 2.5% of the cadavers. Most of the variations of the thyroid gland were seen frequently in female but it was not statically significant. Different clinically important and rare variations of the thyroid gland were found.

A Case of Dual Ectopic Thyroid / 대한이비인후과학회지

Ectopic thyroid is an uncommon status characterized by the presence of thyroid tissue in a site other than in its usual region. It is rare for dual ectopic thyroid to have two ectopic foci simultaneously. Three cases of dual ectopic thyroid have been reported in the Korean literature. Clinically, most cases in ectopic thyroid were noted at adolescence or postpartum due to increased physiologic hormonal demands. Clinical manifestation, thyroid function test, and radiologic imaging should be employed to make a diagnosis and therapeutic plan of this disease. We present a patient with dual ectopic thyroid tissue in the suprahyoid and infrahyoid area without thyroid tissue in its normal thyroid bed.

Clinical Features of Patients with Congenital Hypothyroidism Due to Ectopic Thyroid

OBJECTIVE: This study aimed to describe the clinical features of patients with congenital hypothyroidism due to ectopic thyroid including locations of ectopic thyroid, thyroid function, age of treatment, and starting dose of medication. METHODS: A total of 71 children with congenital hypothyroidism due to ectopic thyroid diagnosed by thyroid ultrasonography (USG) or 99mTc-petechnetate thyroid scan in the department of pediatrics, Soonchunhyang University Seoul Hospital from 1992 to 2015 were enrolled and analyzed retrospectively. RESULTS: Among 71 patients, 26 patients (36.6%) were male and 45 patients (63.4%) were female as the gender ratio was 1:1.73. The locations of ectopic thyroid confirmed by USG or scan were found to be sublingual in 52 patients (73.2%), lingual in 17 patients (23.9%), prelaryngeal in 1 patient (1.4%), and combined in 1 patient (1.4%), respectively. The average value of serum thyroid stimulating hormone was 267.5 µIU/mL and free thyroxin was 0.63 ng/dL. The average value of thyroglobulin (TG) was 217.6 ng/mL. Fifty two patients (73.2%) started treatment within the 1 month of age and 19 patients (26.8%) started after the 1 month of age. The average of the medication starting dose was 12.2 µg/kg/day. There was no significant difference on TG value and starting medication dose. CONCLUSION: As the previous literatures, the presence of ectopic thyroid was more common in female than male. It was coincident with this study. It is generally accepted that lingual ectopic thyroid is most common ectopic location, but in this study, proportion of sublingual thyroid was most common.

Coexistence of resistance to thyroid hormone and ectopic thyroid: ten-year follow-up

SUMMARY Resistance to thyroid hormone (RTH) coexisting with ectopic thyroid is rare. Here we report a case of RTH with ectopic thyroid. A ten-year-old girl had been misdiagnosed as congenital hypothyroidism and treated with levothyroxine since she was born. Ten-year follow-up showed that the elevated thyrotropin was never suppressed by levothyroxine and no signs indicating hyperthyroidism or hypothyroidism despite elevated FT3 and FT4 levels. Therefore the girl developed no defects in physical and cognitive development. Pituitary adenoma was excluded by magnetic resonance imaging. Ultrasonography did not find the thyroid gland in the normal place, while the thyroid scan found a large lingual thyroid gland. The octreotide inhibition test showed a reduction in thyrotropin by 41.98%. No mutation was detected in the thyroid hormone receptor (THR) β, THRα, thyrotropin receptor (TSHR), and GNAS1 genes. To our knowledge, it is an interesting RTH case coexisting with lingual thyroid.

Importance of ectopic thyroid tissue detected in the midline of the neck: single center experience

Objective Ectopic thyroid tissue (ETT) is a rare abnormality of the thyroid gland and the true prevalence and importance is not known. The aim of this study was to evaluate ultrasonography (US) guided fine needle aspiration biposy (FNAB) results, sonographic features, and frequency of ETT detected in the midline of the neck. Subjects and methods Five thousand five hundred and twenty outpatients who were referred to our thyroid clinic between September 2010 and April 2012 and underwent thyroid US, were retrospectively analyzed. Patients with ETT, detected in the midline of the neck in US were included in the study. Thyroid functions, sonographic features, and US guided FNAB results were evaluated. Results There were 81 (81.8%) female and 18 (18.2%) male patients with a mean age of 50.9 ± 11.7. The ETT in the midline was present in 1.79% (99/5,520) of the patients. In the majority of the patients, benign sonographic features (isoechoic, regular margin, type 1 vascularization) were detected. There were 92 (92.9%) patients with a previous history of thyroidectomy and all were histopathologically benign. In 7 (7.1%) patients, there was no history of thyroid operation. FNAB results of ETT were benign. Conclusion This study evaluated the importance of ETT detected incidentally in the midline of the neck. Especially in patients with a history of thyroidectomy, the thyroid masses in the midline of the neck can be found as incidental with imaging methods. Our results suggests that the incidence of malignancy in this group is much lower than orthotopic thyroid nodules and they are often benign.

Abordaje inmunológico del síndrome por deleción 22q11 / Immunological approaches to 22q11 deletion syndrome

El síndrome por deleción 22q11 (SD22q11) es el síndrome por deleción cromosómica más frecuente en humanos y se caracteriza por la tríada clínica que incluye cardiopatía congénita, hipocalcemia e inmunodeficiencia primaria. El 85-90% de los pacientes tienen microdeleciones en el cromosoma 22q11.2. Tomando como punto cardinal la cardiopatía congénita, se diseñó una estrategia para tamización y diagnóstico de SD22q11 con énfasis en la evaluación inmune. Es imprescindible realizar una historia clínica detallada y, posteriormente, un análisis cuantitativo y funcional de las subpoblaciones de linfocitos en sangre periférica para clasificarlo en SD22q11 completo (<1%) o parcial (95-99%) e instaurar las pautas de tratamiento en aspectos como: aislamiento del paciente, vacunación, profilaxis contra microorganismos oportunistas, uso de productos sanguíneos irradiados y reconstitución inmunológica. Sin embargo, el abordaje del paciente debe ser multidisciplinario para detectar y prevenir complicaciones a largo plazo que pueden ser graves, especialmente en los pacientes con SD22q11 completo.

In humans, 22q11 deletion syndrome (22q11DS) is considered the most common chromosome deletion syndrome. It is characterised by a clinical triad that includes congenital heart disease, hypocalcaemia and primary immunodeficiency. Approximately 85-90% of patients with this syndrome exhibit microdeletions in chromosome 22q11.2. Using congenital heart disease as a starting point, we designed a strategy for the screening and diagnosis of 22q11DS with an emphasis on immunological evaluation. A detailed clinical history and the subsequent quantitative and functional analyses of the lymphocyte subpopulations in the peripheral blood is crucial to classify as complete (<1%) or partial (95-99%) the disease and to guide clinicians in terms of patient isolation, vaccination, prophylaxis for opportunistic infections, use of irradiated blood products and immunological reconstitution. However, multidisciplinary care is necessary to detect and prevent long-term complications that could be severe, particularly in cases of complete 22q11DS.

Estudo clínico, genético e molecular de pacientes com Disgenesia Tireoidiana

INTRODUÇÃO: Hipotireoidismo Congênito (HC), é uma das doenças metabólicas mais comuns na infância com incidência de 1:3.000 a 1:4.000 recém-nascidos. Um grupo de doenças relacionadas às alterações no desenvolvimento da tireoide, denominadas disgenesias tireoidianas (DT), responsabiliza-se por aproximadamente 85% de todos os casos de HC, sendo sua patogênese pouco conhecida. OBJETIVOS: Geral: Caracterização clínica e genética de pacientes com HC diagnosticados com disgenesia tireoidiana. Específicos: 1. Caracterizar clínica dos indivíduos com HC em acompanhamento na APAE/Salvador (Associação de Pais e Amigos dos Excepcionais); 2. Avaliar a existência de associação entre malformações tireoidianas e malformações cardiacos; 3. Pesquisar polimorfismos e mutações nos genes candidatos: PAX8, TSH-R, NKX2.5 e HES1, em pacientes diagnosticados com disgenesia tireoidiana; 4. Pesquisar o gene TSH-R numa coorte de pacientes com HC diagnosticados no programa de triagem neonatal da França. METODOLOGIA: Até o ano de 2016, 1.188 crianças foram diagnosticadas com HC e 773 estão em acompanhamento. Duzentos e dezoito crianças confirmadas com HC foram caracterizadas clinicamente através de testes de função da tireoide (TT4 e TSH), ultrassonografia e cintilografia, seguidas de dosagem de tireoglobulina. Toda a região codificantes dos genes PAX8, TSH-R, NKX2.5 e HES1 incluindo íntrons e éxons foram amplificados a partir do DNA genômico através da PCR (Reação em cadeia da Polimerase) utilizando-se técnicas padrão seguida de Sequenciamento direto. RESULTADOS: Sessenta e três pacientes foram diagnosticados com DT e 155 com glândula tópica normal. Hipoplasia representou 33,4% dos casos de DT, agenesia 19%, ectopia 27% e hemiagenesia 20,6%. Altos concentrações de TSH no teste do pezinho foram detectados no grupo das agenesias seguido das hipoplasias. Na análise genética/molecular, 31 (49,2%) dos pacientes foram identificados com o polimorfismo p.D727E em heterozigose e 4 (6,4%) em homozigose, no gene TSH-R; 4/63 pacientes tiveram o polimorfismo p.P52T em heterozigose; 14/63 apresentaram a variante polimórfica p.N181N e 2/63 apresentaram a substituição sinônima conhecida p.L645L, todos no gene TSH-R. o polimorfismo p.Glu21 foi encontrado em 54% dos pacientes e p.Gln181 encontrado em 1 paciente no gene NKX2.5. Nenhuma alteração foi encontrada no gene HES1, bem como em PAX8. CONCLUSÕES: Este é o primeiro estudo realizado na população de HC no Estado da Bahia. Análises clínicas revelaram um padrão distinto entre os subgrupos da DT quando comparados com glândula normal; 6 polimorfismos já descritos foram encontrados em dois genes candidatos. Nenhuma mutação patogênica foi encontrada. A descrição fenotípica é essencial para a correta avaliação genética e os mecanismos nela implicados, além de utilizados para predição da gravidade do HC. A identificação de novos genes ou eventos moleculares que controlam a função tireoidiana pós-natal seria de grande utilidade no esclarecimento das DT

INTRODUCTION: Congenital hypothyroidism (CH), is the most common metabolic diseases in childhood with incidence of 1: 3000-1: 4000 newborns. A group of diseases related to alterations in the development of the thyroid, called thyroid dysgenesis (TD), is responsible for approximated 85% of all HC cases, and the majority has unknown pathogenesis. OBJECTIVES: General: clinical and genetic characterization of CH patients diagnosed with TD. Specific: 1. CH clinical characterization in individuals followed at APAE/Salvador; 2. evaluating the association between thyroid abnormalities and other abnormalities or syndromes; 3. search polymorphisms and mutations in known candidate genes for TD: PAX8, TSH-R, NKX2.5 and HES1; 4. XX METHODS: Until the year 2016, 1.188 children were diagnosed for CH and 773 were actually follow in APAE-Salvador. A continuous series of 218 children with confirmed HC were characterized clinically through thyroid function tests (TT4 and TSH), thyroid ultrasound and scintigraphy, followed by serum thyroglobulin measurement. The entire coding region of the candidate genes (PAX8, TSH-R, NKX2.5 and HES1), including exon/intron boundaries, was amplified from genomic DNA by polymerase chain reaction (PCR) using standard techniques, followed by direct sequencing. Results: Sixty-three patients were diagnosed with DT and 155 with in situ thyroid gland (ISTG). Hypoplasia represented 33,4% of all cases of DT, agenesis (19%), ectopy (27%) and hemiagenesis (20,6%). The higher screening TSH levels was in the agenetic group followed by hypoplasia. In the genetic/molecular analysis, 31 (49,2%) patients were identified with a polymorphism of TSH-R gene (p.D727E); 4/63 patients had a heterozygous p.P52T; 14/63 patients showed p.N187N polymorphic variants of the gene; and 2/63 patients presented a known p.L645L synonimous substitution. The polymorphism p.Glu21was found in 54% of patients, and p.Gln181 found in only one patient in the NKX2.5 gene. None alteration was detected in HES1 gene. CONCLUSIONS: This is the first CH population-based study in State of Bahia, Brazil. Clinical analysis revealed distinct hormonal patterns in DT subgroup when compared with ISTG, with only 6 known polymorphisms identified in few cases of TD in TSH-R, PAX8, NKX2.5 and HES1 genes. No mutation was found in a candidate genes studied. A detailed description of phenotype might be essential to target the correct genetic and mechanism implicated, and useful to predict CH severity. The identification of additional genes or molecular events controlling early postnatal thyroid function would be helpful.

A Case of Mediastinal Ectopic Thyroid Cyst Inducing Severe Airway Compression / 대한이비인후과학회지

Ectopic thyroid gland is usually located along the development path of thyroid in the anterior midline of the neck. However, its occurrence within the mediastinum is very rare. Mediastinal ectopic thyroid cyst is usually benign and asymptomatic, but we experienced a case of the mediastinal ectopic thyroid cyst inducing a severe airway obstruction in a 45-year-old male. The mass had no connection to the cervical thyroid gland and histological examination revealed a mediastinal cyst of an ectopic thyroid. We present the case with a review of the related literatures.

The c.63A>G polymorphism in the NKX2.5 gene is associated with thyroid hypoplasia in children with thyroid dysgenesis

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.