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1.
Am J Physiol Endocrinol Metab ; 326(6): E832-E841, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38656129

RESUMO

Thyroid dysgenesis (TD) is the common pathogenic mechanism of congenital hypothyroidism (CH). In addition, known pathogenic genes are limited to those that are directly involved in thyroid development. To identify additional candidate pathogenetic genes, we performed forward genetic screening for TD in zebrafish, followed by positional cloning. The candidate gene was confirmed in vitro using the Nthy-ori 3.1 cell line and in vivo using a zebrafish model organism. We obtained a novel zebrafish line with thyroid dysgenesis and identified the candidate pathogenetic mutation TATA-box binding protein associated Factor 1 (taf1) by positional cloning. Further molecular studies revealed that taf1 was needed for the proliferation of thyroid follicular cells by binding to the NOTCH1 promoter region. Knockdown of TAF1 impaired the proliferation and maturation of thyroid cells, thereby leading to thyroid dysplasia. This study showed that TAF1 promoted Notch signaling and that this association played a pivotal role in thyroid development.NEW & NOTEWORTHY In our study, we obtained a novel zebrafish line with thyroid dysgenesis (TD) and identified the candidate pathogenetic mutation TATA-box binding protein associated Factor 1 (taf1). Further researches revealed that taf1 was required for thyroid follicular cells by binding to the NOTCH1 promoter region. Our findings revealed a novel role of TAF1 in thyroid morphogenesis.


Assuntos
Proliferação de Células , Transdução de Sinais , Fatores Associados à Proteína de Ligação a TATA , Glândula Tireoide , Fator de Transcrição TFIID , Peixe-Zebra , Animais , Peixe-Zebra/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Fator de Transcrição TFIID/genética , Fator de Transcrição TFIID/metabolismo , Transdução de Sinais/genética , Proliferação de Células/genética , Glândula Tireoide/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Disgenesia da Tireoide/genética , Disgenesia da Tireoide/metabolismo , Humanos , Histona Acetiltransferases
2.
Hum Mol Genet ; 31(23): 3967-3974, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35535691

RESUMO

Congenital hypothyroidism due to thyroid dysgenesis (TD), presented as thyroid aplasia, hypoplasia or ectopia, is one of the most prevalent rare diseases with an isolated organ malformation. The pathogenesis of TD is largely unknown, although a genetic predisposition has been suggested. We performed a genome-wide association study (GWAS) with 142 Japanese TD cases and 8380 controls and found a significant locus at 2q33.3 (top single nucleotide polymorphism, rs9789446: P = 4.4 × 10-12), which was replicated in a German patient cohort (P = 0.0056). A subgroup analysis showed that rs9789446 confers a risk for thyroid aplasia (per allele odds ratio = 3.17) and ectopia (3.12) but not for hypoplasia. Comprehensive epigenomic characterization of the 72-kb disease-associated region revealed that it was enriched for active enhancer signatures in human thyroid. Analysis of chromosome conformation capture data showed long-range chromatin interactions of this region with promoters of two genes, FZD5 and CCNYL1, mediating Wnt signaling. Moreover, rs9789446 was found to be a thyroid-specific quantitative trait locus, adding further evidence for a cis-regulatory function of this region in thyroid tissue. Specifically, because the risk rs9789446 allele is associated with increased thyroidal expression of FDZ5 and CCNYL1 and given the recent demonstration of perturbed early thyroid development following overactivation of Wnt signaling in zebrafish embryos, an enhanced Wnt signaling in risk allele carriers provides a biologically plausible TD mechanism. In conclusion, our work found the first risk locus for TD, exemplifying that in rare diseases with relatively low biological complexity, GWAS may provide mechanistic insights even with a small sample size.


Assuntos
Estudo de Associação Genômica Ampla , Disgenesia da Tireoide , Animais , Humanos , Peixe-Zebra/genética , Via de Sinalização Wnt/genética , Doenças Raras , Disgenesia da Tireoide/genética , Predisposição Genética para Doença
3.
BMC Endocr Disord ; 24(1): 16, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38287285

RESUMO

BACKGROUND: Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary architecture lacking the nuclear characteristics of papillary carcinoma. Herein, we present a case of follicular adenoma with papillary architecture originating from an ectopic thyroid gland, diagnosed from a mass in the submandibular region. CASE PRESENTATION: A 70-year-old woman was referred to our hospital with the chief complaint of a painless left submandibular mass that had been present for one year. The patient underwent left submandibular dissection for therapy and diagnosis. Microscopically, papillary lesions with fibrovascular cores were observed in the interior, and the epithelial cells were cylindrical in shape with eosinophilic cytoplasm, round or oval nuclei, with no pathological features, leading to a diagnosis of papillary carcinoma or follicular carcinoma. The mass was diagnosed as a follicular thyroid adenoma with papillary architecture. This is the first report of a follicular adenoma with a papillary architecture originating from an ectopic thyroid gland. CONCLUSION: This experience suggests that follicular adenoma should be included in the differential diagnosis of ectopic thyroid tumors.


Assuntos
Adenoma , Carcinoma Papilar , Disgenesia da Tireoide , Neoplasias da Glândula Tireoide , Feminino , Humanos , Idoso , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Disgenesia da Tireoide/diagnóstico , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Diagnóstico Diferencial
4.
J Pak Med Assoc ; 74(5): 987-989, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38783453

RESUMO

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.


Assuntos
Hipertrofia , Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Glândula Tireoide/anormalidades , Glândula Tireoide/diagnóstico por imagem , Tireoidectomia/métodos , Disgenesia da Tireoide/complicações , Disgenesia da Tireoide/cirurgia , Disgenesia da Tireoide/diagnóstico por imagem , Disgenesia da Tireoide/diagnóstico
5.
BMC Pediatr ; 23(1): 178, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072721

RESUMO

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


Assuntos
Carcinoma , Bócio Nodular , Disgenesia da Tireoide , Feminino , Criança , Humanos , Bócio Nodular/diagnóstico , Bócio Nodular/patologia , Disgenesia da Tireoide/diagnóstico , Carcinoma/diagnóstico , Pulmão/patologia
6.
J Paediatr Child Health ; 59(1): 129-133, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36303462

RESUMO

AIM: Recently, there has been debate about reducing newborn screening (NBS) thyroid-stimulating hormone (TSH) cut-offs to identify children with mild, but potentially clinically significant, thyroid deficiency. Once identified by NBS, these children will be referred to paediatric endocrinologists for further testing and possible treatment; however, variation in current clinical practice is not known. The aim of this study is to survey Paediatric Endocrinologists in Australia and New Zealand to gain insight into clinical practice for the treatment of mild thyroid deficiency. METHODS: A piloted questionnaire was sent to members of the Australasian Paediatric Endocrinologist Group. The survey asked the Australasian Paediatric Endocrinologist Group members about the investigations performed, treatment and follow-up for infants with different confirmatory serum TSH levels. RESULTS: There were 42 completed surveys, a response rate of 34%. When presented with four case studies, 7% of clinicians would treat a child with confirmatory serum TSH of 8.7 mU/L with thyroxine, 69% would treat a child with confirmatory serum TSH 21.4 mU/L, 76% would treat a child with confirmatory serum TSH 24.3 mU/L and 95% would treat a child with confirmatory serum TSH 44.7 mU/L. CONCLUSION: This contemporary survey of clinicians regarding the treatment of mild thyroid deficiency in children has shown that clinical practice varies extensively. International and national guidelines on the treatment of congenital hypothyroidism should be updated to incorporate new evidence and ensure consistency across clinical practice.


Assuntos
Hipotireoidismo Congênito , Disgenesia da Tireoide , Recém-Nascido , Lactente , Criança , Humanos , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/tratamento farmacológico , Tiroxina/uso terapêutico , Tireotropina/uso terapêutico , Triagem Neonatal , Inquéritos e Questionários
7.
Medicina (Kaunas) ; 59(10)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37893606

RESUMO

Congenital hypothyroidism (CH) may have major detrimental effects on growth and neurological development, but early intervention leads to excellent outcomes. CH is classified as transient or permanent, primary or secondary, with primary CH being the most common neonatal endocrine disorder. Most patients with CH do not present any typical signs and symptoms of hypothyroidism shortly after birth, partly due to transplacental maternal thyroid hormone transfer and residual neonatal thyroid function. This paper reports on two CH cases. During the initial Neonatal Intensive Care Unit (NICU) admission phase, CH was not suspected due to nonspecific signs. The distinct characteristics of our cases are as follows: both infants were admitted to the NICU for respiratory distress syndrome, requiring invasive mechanical ventilation, and both were born to diabetic mothers. Following extubation, they both showed similar neurological issues, including reduced muscle tone and feeding difficulties. Initially, those symptoms were attributed to delayed clearance of analgesic and sedative medication. However, symptoms progressively worsened over time. Subsequent tests revealed both meeting CH diagnostic criteria: an unusual ultrasound indicating thyroid agenesis and abnormal hormone levels. Guided by the pediatric endocrinology team, prompt hormonal treatment was started with improvements in neurocognitive function and feeding. Usually, CH screening involves blood samples from healthy newborns at 2-3 days of life. Abnormal results require confirmation, prompting treatment within two weeks. Certain NICU-admitted infants face higher diagnosis delays, as seen in those two cases where CH screening was postponed. Thus, for all neonates with persistent pathologies unresponsive to standard etiological treatment, conducting a comprehensive anamnestic evaluation of the medical history, along with maternal preconceptional and prenatal nutrition, is recommended.


Assuntos
Hipotireoidismo Congênito , Disgenesia da Tireoide , Lactente , Gravidez , Feminino , Humanos , Recém-Nascido , Criança , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/diagnóstico , Triagem Neonatal/efeitos adversos , Disgenesia da Tireoide/complicações , Disgenesia da Tireoide/diagnóstico , Disgenesia da Tireoide/patologia , Tireotropina , Tiroxina/uso terapêutico
8.
Medicina (Kaunas) ; 59(2)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36837515

RESUMO

Failure in the embryological development of the thyroid in adults is rarely seen. We present the case of a 79-year-old female patient who complained of dysphagia and progressive upper respiratory obstruction, which started 12 months prior to her admission. An ENT clinical exam revealed a tongue base, spherical, well-defined tumour covered by normal mucosa. Further assessments established the diagnosis of the tongue base ectopic thyroid tissue. Due to the patient's symptoms, a transhyoid tongue base tumour removal was performed. The selected patient gave consent for participation and inclusion in this paper, in compliance with the 1964 Helsinki declaration.


Assuntos
Coristoma , Doenças da Glândula Tireoide , Disgenesia da Tireoide , Neoplasias da Língua , Humanos , Adulto , Feminino , Idoso , Coristoma/patologia , Língua/patologia
9.
Medicina (Kaunas) ; 60(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38276049

RESUMO

Diagnosis of primary hyperparathyroidism (PHP) is based on blood assessments in terms of synchronous high calcium and PTH (parathormone), but further management, particularly parathyroid surgery that provides the disease cure in 95-99% of cases, requires an adequate localisation of the parathyroid tumour/tumours as the originating source, with ultrasound and 99m-Technetium (99m-Tc) sestamibi scintigraphy being the most widely used. We aimed to introduce an adult female case diagnosed with PHP displaying unexpected intra-operatory findings (ectopic thyroid tissue) in relation to concordant pre-operatory imaging modalities (ultrasound + dual-phase 99m-Tc pertechnetate and sestamibi scintigraphy + computed tomography) that indicated bilateral inferior parathyroid tumours. A sudden drop in PTH following the removal of the first tumour was the clue for performing an extemporaneous exam for the second mass that turned out to be non-malignant ectopic thyroid tissue. We overviewed some major aspects starting from this case in point: the potential pitfalls of pre-operatory imaging in PHP; the concordance/discordance of pre-parathyroidectomy localisation modalities; the need of using an additional intra-operatory procedure; and the clues of providing a distinction between pathological parathyroids and thyroid tissue. This was a case of adult PHP, whereas triple localisation methods were used before parathyroidectomy, showing concordant results; however, the second parathyroid adenoma was a false positive image and an ectopic thyroid tissue was confirmed. The pre-operatory index of suspicion was non-existent in this patient. Hybrid imaging modalities are most probably required if both thyroid and parathyroid anomalies are suspected, but, essentially, awareness of the potential pitfalls is mandatory from the endocrine and surgical perspectives. Current gaps in imaging knowledge to guide us in this area are expected to be solved by the significant progress in functional imaging modalities. However, the act of surgery, including the decision of a PTH assay or extemporaneous exam (as seen in our case), represents the key to a successful removal procedure. Moreover, many parathyroid surgeons may currently perform 4-gland exploration routinely, precisely to avoid the shortcomings of preoperative localisation.


Assuntos
Hiperparatireoidismo , Neoplasias das Paratireoides , Doenças da Glândula Tireoide , Disgenesia da Tireoide , Adulto , Humanos , Feminino , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/métodos , Pertecnetato Tc 99m de Sódio , Tecnécio , Hiperparatireoidismo/diagnóstico por imagem , Hiperparatireoidismo/cirurgia , Sensibilidade e Especificidade , Compostos Radiofarmacêuticos , Cintilografia , Tecnécio Tc 99m Sestamibi , Compostos de Organotecnécio , Disgenesia da Tireoide/cirurgia
10.
Chirurgia (Bucur) ; 118(1): 96-102, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36913422

RESUMO

Introduction: Ectopic thyroid tissue (ETT) is a rare cause of mediastinal masses, representing less than 1% of all mediastinal tumors (1). ETT could be detected anywhere along the path of the first embryonic descent of the thyroid gland from the primordial foregut floor to its usual pre-tracheal position. ETT mediastinal localization accounts for fewer than 1% of all ectopic thyroid cases (2,3). Various surgical methods for approaching mediastinal masses have been documented in the literature, including median sternotomy, posterolateral thoracotomy, and, video-assisted thoracoscopic surgery (VATS) (4). More recently, robotic-assisted thoracoscopic surgery (RATS) has been proposed for these masses. The aim of this article is to present the use of robotic-assisted thoracoscopic surgery (RATS) for a rare case of a mediastinal ETT. Case presentation: We present the case of a 40-year-old male with no significant medical history who discovered a mediastinal mass on a thoracic CT scan following COVID-19 infection. Symptoms were dysphagia and anterior thoracic pain with cervical extension. Scintigraphy confirmed the presence of ectopic thyroid tissue in the mediastinum as well as a normal cervical thyroid gland. ETT was histologically confirmed by endoscopic ultrasound guided biopsy. Robotic assisted surgery was the chosen approach to surgically treat this mass and the technical details are presented. The mass was extracted through the cervical incision. Total surgical time was 230 minutes, and the blood loss was 60 ml. The patient was discharged after 48 hours with follow up showing a full recovery with no residual pain or respiratory symptoms. Conclusion: Ectopic thyroid tissue (ETT) is a rare cause of mediastinal masses, and the diagnosis is always a challenge. Robotic assisted thoracoscopic surgery was proved to be safe and efficient in this rare case of ETT developed in the superior mediastinum.


Assuntos
COVID-19 , Procedimentos Cirúrgicos Robóticos , Disgenesia da Tireoide , Masculino , Humanos , Mediastino/patologia , Resultado do Tratamento , Disgenesia da Tireoide/diagnóstico por imagem , Disgenesia da Tireoide/cirurgia
11.
Radiology ; 305(1): 242-246, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36154285

RESUMO

HISTORY: A 61-year-old woman was admitted to our institution to characterize an incidentally found mass in the porta hepatis. An episode of pulmonary embolism (18 months ago) and a pulmonary abscess (15 months ago) were reported. The patient had no history of known liver disease, previous cancer diagnosis, or trauma. She underwent total thyroidectomy for goiter several years ago, with initial iatrogenic hypothyroidism treated with levo-thyroxine hormone replacement therapy. During follow-up, this therapy was adjusted (50 µg per day) to induce euthyroidism and to achieve a target serum thyroid-stimulating hormone concentration of 1-2 mIU/L. Physical examination findings were unremarkable. Admission laboratory data were entirely normal, including tumor markers, such as carcinoembryonic antigen and carbohydrate antigen 19-9. Unenhanced and multiphasic contrast-enhanced CT imaging was performed in arterial, portal venous, and delayed (3 minutes after injection) phases. Axial and coronal maximum intensity projection reconstructed CT images were obtained in the arterial and portal venous phases. Because of the imaging findings of the mass in the porta hepatis and concerns about malignancy, the patient underwent endoscopy. Therefore, endoscopic US-guided fine-needle biopsy was performed in the same session. The patient also underwent whole-body iodine 131 (131I) scintigraphy.


Assuntos
Bócio , Disgenesia da Tireoide , Carboidratos , Antígeno Carcinoembrionário , Feminino , Humanos , Pessoa de Meia-Idade , Tireotropina , Tiroxina
12.
Clin Endocrinol (Oxf) ; 96(4): 617-626, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34374102

RESUMO

OBJECTIVE: Congenital hypothyroidism (CH) is known to be due to thyroid dyshormonogenesis (DH), which is mostly inherited in an autosomal recessive inheritance pattern or thyroid dysgenesis (TD), whose inheritance pattern is controversial and whose molecular etiology remains poorly understood. DESIGN AND METHODS: The variants in 37 candidate genes of CH, including 25 genes related to TD, were screened by targeted exon sequencing in 205 Chinese patients whose CH cannot be explained by biallelic variants in genes related to DH. The inheritance pattern of the genes was analyzed in family trios or quartets. RESULTS: Of the 205 patients, 83 patients carried at least one variant in 19 genes related to TD, and 59 of those 83 patients harbored more than two variants in distinct candidate genes for CH. Biallelic or de novo variants in the genes related to TD in Chinese patients are rare. We also found nine probands carried only one heterozygous variant in the genes related to TD that were inherited from a euthyroid either paternal or maternal parent. These findings did not support the monogenic inheritance pattern of the genes related to TD in CH patients. Notably, in family trio or quartet analysis, of 36 patients carrying more than two variants in distinct genes, 24 patients carried these variants inherited from both their parents, which indicated that the oligogenic inheritance pattern of the genes related to TD should be considered in CH. CONCLUSIONS: Our study expanded the variant spectrum of the genes related to TD in Chinese CH patients. It is rare that CH in Chinese patients could be explained by monogenic germline variants in genes related to TD. The hypothesis of an oligogenic origin of the CH should be considered.


Assuntos
Hipotireoidismo Congênito , Disgenesia da Tireoide , China , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação/genética , Disgenesia da Tireoide/genética
13.
Am J Med Genet A ; 188(1): 89-98, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34545694

RESUMO

Thyroid dysgenesis (TD) accounts for 80% cases of congenital hypothyroidism, which is the most common neonatal disorder. Until now, the gene mutations have been reported associated with TD can only account for 5% cases, suggesting the genetic heterogeneity of the pathology. Nicotinamide nucleotide transhydrogenase (NNT) plays a crucial role in regulating redox homeostasis, patients carrying NNT mutations have been described with a clinical phenotype of hypothyroidism. As TD risk is increased in the context of several syndromes and redox homeostasis is vital for thyroid development and function, NNT might be a candidate gene involved in syndromic TD. Therefore, we performed target sequencing (TS) in 289 TD patients for causative mutations in NNT and conducted functional analysis of the gene mutations. TS and Sanger sequence were used to screen the novel mutations. For functional analysis, we performed western blot, measurement of NADPH/NADPtotal and H2 O2 generation, cell proliferation, and wounding healing assay. As a result, three presumably pathogenic mutations (c.811G > A, p.Ala271Ser; c.2078G > A, p.Arg693His; and c.2581G > A, p.Val861Met) in NNT had been identified. Our results showed the damaging effect of NNT mutations on stability and catalytic activity of proteins and redox balance of cells. In conclusion, our findings provided novel insights into the role of the NNT isotype in thyroid physiopathology and broaden the spectrum of pathogenic genes associated with TD. However, the pathogenic mechanism of NNT in TD is still need to be investigated in further study.


Assuntos
Hipotireoidismo Congênito , NADP Trans-Hidrogenases , Disgenesia da Tireoide , China , Hipotireoidismo Congênito/genética , Humanos , Proteínas Mitocondriais , Mutação , NADP Trans-Hidrogenase Específica para A ou B , NADP Trans-Hidrogenases/genética , NADP Trans-Hidrogenases/metabolismo , Disgenesia da Tireoide/genética
14.
J Craniofac Surg ; 33(3): 895-896, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34743156

RESUMO

ABSTRACT: A 44-year-old female without any systemic diseases had a slowly enlarging anterior neck mass for 1 year. She had received transcervical surgery for a left thyroid cyst 3 years ago. An enhanced computed tomography scan showed a hyper-dense, markedly enhancing, and homogenous mass at the level of the thyrohyoid membrane. under the impression of an ectopic thyroid gland, operation was scheduled. However, she worried about cosmesis pitfalls besides the existing scar from her previous thyroid surgery. Transoral vestibular robotic surgery was arranged to prevent an additional neck incision wound. The mass was removed and confirmed as an ectopic thyroid nodule by pathological examination. No recurrence was found at the 1-year follow-up, and the surgical and aesthetic outcomes were satisfied. The surgery can provide adequate surgical exploration with excellent cosmesis, whereas managing cervical masses. For the cosmetic concerns, this procedure is the potential alternative in other neck surgeries.


Assuntos
Procedimentos Cirúrgicos Robóticos , Disgenesia da Tireoide , Neoplasias da Glândula Tireoide , Adulto , Estética Dentária , Feminino , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Disgenesia da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos
15.
Int J Mol Sci ; 23(6)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35328834

RESUMO

Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis. The aim of the study was to reveal genetic factors responsible for thyroid maldevelopment in two siblings with THA. None of the family members presented with congenital heart defect. The samples were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Enrichment Kit, San Diego, CA 92121, USA). An ultra-rare variant c.839C>T (p.Pro280Leu) in NKX2-5 gene (NM_004387.4) was identified in both affected children and an unaffected father. In the mother, the variant was not present. This variant is reported in population databases with 0.0000655 MAF (GnomAD v3, dbSNP rs761596254). The affected amino acid position is moderately conserved (positive scores in PhyloP: 1.364 and phastCons: 0.398). Functional prediction algorithms showed deleterious impact (dbNSFP v4.1, FATHMM, SIFT) or benign (CADD, PolyPhen-2, Mutation Assessor). According to ACMG criteria, variant is classified as having uncertain clinical significance. For the first time, NKX2-5 gene variants were found in two siblings with THA, providing evidence for its potential contribution to the pathogenesis of this type of thyroid dysgenesis. The presence of the variant in an unaffected parent, carrier of p.Pro280Leu variant, suggests potential contribution of yet unidentified additional factors determining the final penetrance and expression.


Assuntos
Irmãos , Disgenesia da Tireoide , Criança , Exoma , Proteína Homeobox Nkx-2.5/genética , Humanos , Mutação , Disgenesia da Tireoide/genética , Disgenesia da Tireoide/patologia
16.
Vet Radiol Ultrasound ; 63(3): 298-305, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34918415

RESUMO

Radioactive iodine is frequently used for staging of human thyroid carcinomas. Iodine-124 scans performed using position emission tomography (PET) allow for more precise dosimetry of therapeutic radioiodine. The distribution of I-124 has not previously been described in veterinary medicine. The purpose of this prospective, exporatory, descriptive study is to evaluate the whole-body distribution of I-124 in dogs with suspected thyroid carcinoma. Ten dogs with either a cytologic diagnosis of a neuroendocrine neoplasm or biochemical hyperthyroidism were enrolled in a prospective clinical study. Whole-body I-124 PET/CT scans were performed and were evaluated for physiologic and pathologic uptake of I-124. The maximum and mean standardized uptake values (SUVmean) were recorded for several normal and abnormal tissues. Varying degrees of uptake were found in thyroid tumors (SUVmean = 66.37), ectopic thyroid masses (21.44), presumed metastatic lesions in lymph nodes (32.14), and the pulmonary parenchyma (4.50). In most dogs, physiologic uptake above background, measured in maximum SUV, was identified in parotid and mandibular salivary glands (14.00 and 1.57) the urinary tract (1.83), the gastrointestinal tract (19.90 stomach, 6.15 colon), the liver (1.41), and the heart (1.88). Occasionally, uptake was identified in the nasolacrimal duct (3.42), salivary duct (2.73), gallbladder (2.68), and anal gland (2.22). Physiologic uptake was also identified in normal thyroid glands and ectopic thyroid tissue. This study provides a baseline of pathologic and physiologic uptake of I-124 in dogs with thyroid carcinoma, to guide interpretation of future studies.


Assuntos
Doenças do Cão , Disgenesia da Tireoide , Neoplasias da Glândula Tireoide , Animais , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/tratamento farmacológico , Cães , Radioisótopos do Iodo/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/veterinária , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos , Disgenesia da Tireoide/tratamento farmacológico , Disgenesia da Tireoide/veterinária , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/veterinária , Distribuição Tecidual
17.
Vestn Otorinolaringol ; 87(2): 76-79, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35605277

RESUMO

In this clinical case, papillary carcinoma was detected in the ectopic area of the thyroid gland in the presence of an unchanged thyroid gland of natural localization. An extremely rare disease is presented and an examination algorithm is proposed that is recommended to exclude unusual pathology in the absence of a response to ongoing conservative treatment.


Assuntos
Carcinoma Papilar , Disgenesia da Tireoide , Neoplasias da Glândula Tireoide , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Humanos , Septo Nasal/patologia , Disgenesia da Tireoide/diagnóstico , Disgenesia da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
18.
Genet Med ; 23(10): 1944-1951, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34194003

RESUMO

PURPOSE: Congenital hypothyroidism (CH) is a common congenital endocrine disorder in humans. CH-related diseases such as athyreosis, thyroid ectopy, and hypoplasia are primarily caused by dysgenic thyroid development. However, the underlying molecular mechanisms remain unknown. METHODS: To identify novel CH candidate genes, 192 CH patients were enrolled, and target sequencing of 21 known CH-related genes was performed. The remaining 98 CH patients carrying no known genes were subjected to exome sequencing (ES). The functions of the identified variants were confirmed using thyroid epithelial cells in vitro and in zebrafish model organisms in vivo. RESULTS: Four pathogenic GBP1 variations from three patients were identified. In zebrafish embryos, gbp1 knockdown caused defective thyroid primordium morphogenesis and hypothyroidism. The thyroid cells were stuck together and failed to dissociate from each other to form individual follicles in gbp1-deficient embryos. Furthermore, defects were restored with wild-type human GBP1 (hGBP1) messenger RNA (mRNA) except for mutated hGBP1 (p.H150Y, p.L187P) overexpression. GBP1 promoted ß-catenin translocation into the cytosol and suppressed the formation of cellular adhesion complexes. Suppression of cell-cell adhesion restored the thyroid primordium growth defect observed in gbp1-deficient zebrafish embryos. CONCLUSION: This study provides further understanding regarding thyroid development and shows that defective cellular remodeling could cause congenital hypothyroidism.


Assuntos
Hipotireoidismo Congênito , Proteínas de Ligação ao GTP , Disgenesia da Tireoide , Glândula Tireoide/crescimento & desenvolvimento , Animais , Hipotireoidismo Congênito/genética , Modelos Animais de Doenças , Proteínas de Ligação ao GTP/genética , Humanos , Morfogênese , Mutação , Regulação para Cima , Peixe-Zebra/genética
19.
BMC Cancer ; 21(1): 718, 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34147083

RESUMO

BACKGROUND: Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear. METHODS: Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET. RESULTS: In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells. COCLUSION: MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.


Assuntos
Neoplasias Colorretais/genética , Exossomos/genética , MicroRNAs/genética , Animais , Proliferação de Células , Neoplasias Colorretais/patologia , Hipotireoidismo Congênito , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Humanos , Camundongos , Camundongos Nus , Disgenesia da Tireoide
20.
Neuroradiology ; 63(10): 1739-1742, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34032885

RESUMO

Ectopic thyroid tissue is a rare entity, resulting from developmental abnormality during the migration of the embryonic thyroid germ from the floor of the primitive foregut to its final pre-tracheal position. Although ectopic thyroid tissue may be located anywhere, its location at the skull base is extremely rare. We report a case of ectopic thyroid tissue at the skull base in a 19-year-old man with multimodality imaging findings.


Assuntos
Disgenesia da Tireoide , Adulto , Humanos , Base do Crânio/diagnóstico por imagem , Disgenesia da Tireoide/diagnóstico por imagem , Adulto Jovem
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