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Nature Communications Apr 2024The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar...
The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.
Topics: Animals; Mice; Hepatocyte Growth Factor; Zebrafish; Cadherins; Thyroid Dysgenesis; Proto-Oncogene Proteins c-met
PubMed: 38605010
DOI: 10.1038/s41467-024-47363-9 -
Progress in Orthodontics Mar 2024Mutations in one or multiple genes can lead to hypodontia and its characteristic features. Numerous studies have shown a strong genetic influence on the occurrence of... (Observational Study)
Observational Study
BACKGROUND
Mutations in one or multiple genes can lead to hypodontia and its characteristic features. Numerous studies have shown a strong genetic influence on the occurrence of hypodontia, and identified several genes, including AXIN2, EDA, FGF3, FGFR2, FGFR10, WNT10A, MSX1, and PAX9, that are directly associated with dental agenesis and carcinogenesis. The objective of this study was to investigate the occurrence and pattern of tooth agenesis, microdontia, and palatally displaced canine (PDC) in women diagnosed with papillary thyroid cancer (PTC), compared to a control group of women without any malignancy or thyroid disease.
MATERIALS AND METHODS
This case-control study was carried at the Department of Orthodontics, School of Dental Medicine University of Zagreb, and Department of Oncology and Nuclear Medicine Sestre Milosrdnice University Hospital Centre. The study involved a clinical examination and evaluation of dental status, panoramic X-ray analysis, and assessment of medical and family history of 116 female patients aged 20-40 with PTC, as well as 424 females in the control group who were of similar age.
RESULTS
The prevalence of hypodontia, microdontia, and PDC was statistically higher in women with PTC than in the control group. The prevalence rate of hypodontia was 11.3% in the experimental group and 3.5% in the control group. The experimental group showed a higher occurrence of missing upper lateral incisors, lower left central incisors, and all the third molars (except the upper left) compared to the control group. Women with PTC showed the prevalence of PDC significantly higher than the control group (3.5%, 0.7%, p = 0.002). The probability of hypodontia as a clinical finding increases 2.6 times, and microdontia occurs 7.7 times more frequently in women with PTC.
CONCLUSION
Our study suggests a possible link between odontogenesis and PTC. The absence of permanent teeth may increase the likelihood of PTC in women. Leveraging the age-7 orthopantomogram to identify women at high risk for PTC within a critical early detection window could significantly improve oral health outcomes and PTC prognosis through proactive interventions.
Topics: Female; Humans; Anodontia; Case-Control Studies; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms; Tooth Abnormalities; Young Adult; Adult
PubMed: 38523193
DOI: 10.1186/s40510-024-00511-9 -
International Journal of General... 2024Congenital hypothyroidism (CH) is indeed a prevalent neonatal endocrine disorder, affecting approximately 1 in 2000-3000 newborns worldwide, and 1 in 2400 newborns in...
BACKGROUND AND OBJECTIVE
Congenital hypothyroidism (CH) is indeed a prevalent neonatal endocrine disorder, affecting approximately 1 in 2000-3000 newborns worldwide, and 1 in 2400 newborns in China. Despite its high incidence, the genetic causes of CH, particularly those related to thyroid dysgenesis (TD), are still not well understood. However, previous studies have suggested that JAG1 may be a potential susceptibility gene for congenital thyroid defects. To explore the association between and CH, we screened variants in a large cohort of 813 CH patients.
METHODS
We performed genetic analysis of using next-generation sequencing in 813 CH cases. The pathogenicity of the variants was assessed by bioinformatics softwares, protein sequence conservation analysis, and hydrophobic analysis. Further genetic analysis was conducted targeting 20 CH-related genes in these 25 variant carriers.
RESULTS
We identified 10 pathogenic missense mutations (p.V45L, p.V272I, p.P552L, p.G610E, p.G852D, p.A891T, p.E1030K, p.R1060W, p.A1131T, p.P1174L) carried by 25 patients, the mutation rate of in CH was 3.08%. Among these 25 patients, 16 with 1 variant, 6 with 2 variants, and the other 3 with 3 variants. Our findings indicated that variants confer genetic susceptibility to both TD and DH, but with different inheritance models. variants lead to TD mainly through monogenic model, while for DH cases, both monogenic mechanisms and oligogenic mechanisms play a pivotal role. Oligogenicity may contribute to the disease severity of DH.
CONCLUSION
is a shared genetic factor in TD and DH, with a detection rate of 3.08% in Chinese individuals with CH. A comparison between the oligogenic and monogenic groups suggests a gene dosage effect in CH. Patients with the same mutation exhibit diverse clinical phenotypes, indicating complex mechanisms underlying phenotypic heterogeneity.
PubMed: 38468821
DOI: 10.2147/IJGM.S445557 -
BMC Endocrine Disorders Jan 2024Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary...
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.
Topics: Female; Humans; Aged; Carcinoma, Papillary; Thyroid Neoplasms; Thyroid Dysgenesis; Adenoma; Diagnosis, Differential
PubMed: 38287285
DOI: 10.1186/s12902-024-01547-y -
Frontiers in Endocrinology 2023Although thyroid abnormalities are observed less frequently in children than in adults, the increased incidence of thyroid cancer makes it mandatory for all pediatric...
Thyroid diseases in children and adolescents requiring surgical treatment-indications, techniques, results, and complications based on 10 years of the single center's own experience.
INTRODUCTION
Although thyroid abnormalities are observed less frequently in children than in adults, the increased incidence of thyroid cancer makes it mandatory for all pediatric surgeons to be knowledgeable about the disorders of this gland. Thyroid abnormalities can be associated with hyperthyroidism or hypothyroidism and euthyroidism and/or symmetric or asymmetric enlargement of the gland.
AIM
The present study was undertaken to retrospectively analyze the indications, surgical techniques used, results obtained, and complications found in the surgical treatment of thyroid diseases in children and adolescents in a surgical center for the macro-region of western Poland.
METHODS
The data of 148 patients undergoing total or partial thyroidectomy between 2013 and 2022 were analyzed from the medical records of the Department of Pediatric Surgery, Traumatology, and Urology of the Medical University of Poznan, Poland.
RESULTS
A total of 95 children underwent subtotal thyroidectomy and 64 underwent total thyroidectomy, of which the procedure was widened to include prophylactic removal of neck lymph nodes in 45 patients. There were 113 girls (76%) in the analyzed group, and the average age of the patients at the time of surgical treatment was 15 years. The average time from the diagnosis of thyroid disease to surgery was 4 months, ranging from 2 weeks to 3 years. Of the 64 patients undergoing total thyroid resection, 35 (54.69%) were diagnosed with thyroid cancer.
CONCLUSIONS
Collaboration within a multidisciplinary team ensures optimal surgical outcomes in children and adolescents with thyroid disease. With extreme caution, thyroid removal is a safe procedure with few complications, but the experience of the surgeon performing thyroid surgery in children remains crucial. Despite the absence of such a diagnosis in the first fine-needle aspiration biopsy, the high percentage of thyroid carcinomas in the analyzed group may be because the initial biopsy was performed in a less experienced center, also in terms of histopathological laboratory. Hence, we point out the necessity of performing a repeat fine-needle aspiration biopsy (according to the Bethesda classification) in a more experienced center before the final decision of thyroidectomy.
Topics: Adult; Child; Female; Humans; Adolescent; Retrospective Studies; Thyroid Diseases; Thyroid Neoplasms; Biopsy, Fine-Needle; Thyroid Dysgenesis
PubMed: 38283745
DOI: 10.3389/fendo.2023.1301191 -
Cellular and Molecular Life Sciences :... Jan 2024Loss of GLI-Similar 3 (GLIS3) function in mice and humans causes congenital hypothyroidism (CH). In this study, we demonstrate that GLIS3 protein is first detectable at...
Loss of GLI-Similar 3 (GLIS3) function in mice and humans causes congenital hypothyroidism (CH). In this study, we demonstrate that GLIS3 protein is first detectable at E15.5 of murine thyroid development, a time at which GLIS3 target genes, such as Slc5a5 (Nis), become expressed. This, together with observations showing that ubiquitous Glis3KO mice do not display major changes in prenatal thyroid gland morphology, indicated that CH in Glis3KO mice is due to dyshormonogenesis rather than thyroid dysgenesis. Analysis of GLIS3 in postnatal thyroid suggested a link between GLIS3 protein expression and blood TSH levels. This was supported by data showing that treatment with TSH, cAMP, or adenylyl cyclase activators or expression of constitutively active PKA enhanced GLIS3 protein stability and transcriptional activity, indicating that GLIS3 activity is regulated at least in part by TSH/TSHR-mediated activation of PKA. The TSH-dependent increase in GLIS3 transcriptional activity would be critical for the induction of GLIS3 target gene expression, including several thyroid hormone (TH) biosynthetic genes, in thyroid follicular cells of mice fed a low iodine diet (LID) when blood TSH levels are highly elevated. Like TH biosynthetic genes, the expression of cell cycle genes is suppressed in ubiquitous Glis3KO mice fed a LID; however, in thyroid-specific Glis3 knockout mice, the expression of cell cycle genes was not repressed, in contrast to TH biosynthetic genes. This indicated that the inhibition of cell cycle genes in ubiquitous Glis3KO mice is dependent on changes in gene expression in GLIS3 target tissues other than the thyroid.
Topics: Animals; Mice; DNA-Binding Proteins; Gene Expression Regulation; Repressor Proteins; Thyroid Gland; Thyroid Hormones; Thyrotropin; Trans-Activators; Transcription Factors
PubMed: 38281222
DOI: 10.1007/s00018-024-05113-6 -
Medicina (Kaunas, Lithuania) Dec 2023Diagnosis of primary hyperparathyroidism (PHP) is based on blood assessments in terms of synchronous high calcium and PTH (parathormone), but further management,...
Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue.
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.
Topics: Adult; Humans; Female; Parathyroid Neoplasms; Parathyroidectomy; Sodium Pertechnetate Tc 99m; Technetium; Hyperparathyroidism; Sensitivity and Specificity; Radiopharmaceuticals; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Organotechnetium Compounds; Thyroid Diseases; Thyroid Dysgenesis
PubMed: 38276049
DOI: 10.3390/medicina60010015 -
Cureus Nov 2023Congenital abnormalities in the development of the thyroglossal duct are a common pathology in the pediatric population. The exact frequency of hemiagenesis of the...
Congenital abnormalities in the development of the thyroglossal duct are a common pathology in the pediatric population. The exact frequency of hemiagenesis of the thyroid gland is not known because the condition is rarely manifested clinically and is almost always discovered incidentally. Papillary carcinoma of thyroglossal cysts is relatively uncommon, has a good prognosis if promptly detected and treated and occurs mainly in adults. The case we present here is an extremely rare occurrence: a patient with papillary thyroid carcinoma of the thyroglossal duct cyst and thyroglossal duct cyst carcinoma (TDCa). So far, only two such adult patients (women aged 24 and 35) have been described in the world medical literature. The patient we present is a 14-year-old female and is the first described adolescent with papillary carcinoma of the thyroglossal duct cyst and thyroid hemiagenesis (THA). The disease didn't have any clinical manifestations, and the patient was brought in by her parents to improve her aesthetic appearance. Neither the physical examination nor the radiological evaluation showed any signs of malignancy. The diagnosis was reached by our team only after the patoanatomical examination. In this patient's case, due to its early diagnosis, the spread of the disease was limited only to the borders of the thyroglossal duct cyst and the absence of regional and distant metastasis. Surgical removal led to a complete cure, without any postoperative data suggestive of residual disease. The functions of the thyroid gland in her case were not affected, despite her left-lobe agenesis, to which there are multiple proofs, namely the normal blood concentration of the examined thyroid markers: free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (TG), thyroid stimulating hormone (TSH), anti-TG (thyroid antibody test (TAT)), anti-thyroid peroxidase (TPO) (microsomal antibody test (MAT)), and normal physical and psychological development.
PubMed: 38161947
DOI: 10.7759/cureus.49712 -
Indian Journal of Endocrinology and... 2023Congenital hypothyroidism (CH) is the most common cause of preventable intellectual disability. Newborn screening (NBS) for CH has been in vogue in many parts of the...
BACKGROUND
Congenital hypothyroidism (CH) is the most common cause of preventable intellectual disability. Newborn screening (NBS) for CH has been in vogue in many parts of the world since 1970, but despite its well-known benefits, many developing countries including India have not been able to establish universal NBS for CH till date.
OBJECTIVE
The aim of this study was to review the clinical aspects of congenital hypothyroidism in a tertiary care university referral teaching hospital, focusing on aetiology of CH, predictors of permanence, optimal targeted dose strategies based on aetiology and the effect of newborn screening on the time to diagnosis.
MATERIAL AND METHODS
The electronic medical records of 233 children with CH referred to our centre between January 2009 and December 2019 were analysed. A partial NBS was established in the state in 2012.
RESULTS
Dyshormonogenesis (57.5%) was the most common aetiology of CH. The incidence of transient CH in children with a gland (GIS) was 35%. Levothyroxine (LT-4) dose of >2.75 μg/kg/day (sensitivity 76.5, specificity 72), >2.15 μg/kg/day (sensitivity 82.4, specificity 61.9) and >1.85 μg/kg/day (sensitivity 76.5, specificity 61.9) at years 1, 2 and 3, respectively, were predictors of permanent CH. An initial LT-4 dose ≥8 μg/kg was sufficient and very seldom led to undertreatment in children with dyshormonogenesis. On the contrary, even doses ≥13 mcg/kg/day led to frequent undertreatment in children with thyroid dysgenesis. After the introduction of newborn screening, the median age at diagnosis came down from 45 days (IQR 14-180 days) to ten days (IQR 3-12 days).
CONCLUSION
Targeted dosing based on aetiology of CH may be more appropriate to optimise outcomes. The time to diagnosis of CH reduced significantly after the adoption of even a partial NBS program highlighting the urgent need for implementation of the same in resource poor settings.
PubMed: 38107726
DOI: 10.4103/ijem.ijem_314_22 -
Frontiers in Endocrinology 2023Ectopic thyroid gland (ETG) is an uncommon clinical condition, presenting various challenges and limitations in its regulate diagnosis and treatment currently. This...
BACKGROUND
Ectopic thyroid gland (ETG) is an uncommon clinical condition, presenting various challenges and limitations in its regulate diagnosis and treatment currently. This study aims to enhance our understanding of ETG and improve the strategies for its diagnosis and treatment.
METHODS
The retrospective single-center study was conducted, encompassing clinical data from ETG patients screened at our institution between 2013 and 2022. Patients were categorized based on the location of the disease, and follow-ups were performed on each.
RESULTS
This study included a total of 47 patients who were confirmed to hav confirmed to have ETG. Among them, we found 29 cases of accessory thyroid and 18 cases of aberrant thyroid. Furthermore, 42 cases exhibited the single ETG, while 5 cases displayed the double ETG. The distribution of the ETG was as follows: 20 were lingual, 10 were submandibular, 10 were lateral cervical, 4 were thoracic mediastinal, 1 was esophageal, and 7 were ovarian. Of these cases, 22 patients underwent surgery, 18 received thyroid hormone replacement therapy, and 7 were placed under observation. All patients were followed up for 59.4 (12-117) months. No significant abnormalities were detected at the conclusion of the follow-up period.
CONCLUSION
ETG is frequently observed in the head and neck, particularly in lingual. Accessory thyroid glands are commonly reported, with most cases being single ETG. Notably, these glands usually do not manifest specific clinical symptoms. Therefore, the appropriate and comprehensive examinations during the initial diagnosis are crucial to avoid misdiagnosis. Treatment should be individualized, and long-term follow-up is essential for managing ETG effectively.
Topics: Humans; Follow-Up Studies; Retrospective Studies; Thyroid Dysgenesis; Treatment Outcome; Thyroid Gland; Laryngoscopy; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 38075053
DOI: 10.3389/fendo.2023.1278734