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Frontiers in Endocrinology 2016Patients with large benign goiters often present local compressive symptoms that require surgical treatment, including dysphagia, neck tightness, and airway obstruction.... (Review)
Review
Patients with large benign goiters often present local compressive symptoms that require surgical treatment, including dysphagia, neck tightness, and airway obstruction. In contrast, patients with such goiters who remain asymptomatic may be observed after exclusion of malignancy. The use of levothyroxine (LT4) to reduce the volume of the goiter is still a controversial treatment for large goiters, and the optimal surgical procedure for multinodular goiter is still debatable. Radioiodine is a safe and effective treatment option when used alone or in combination with recombinant human TSH. This review discusses current therapeutic options to treat diffuse and multinodular non-toxic benign goiters.
PubMed: 27242669
DOI: 10.3389/fendo.2016.00048 -
Endocrinology, Diabetes & Metabolism... Jun 2022Mass effect from a goiter is a serious complication with potentially life-threatening consequences. In rare instances, a goiter can compress nearby vessels, compromising...
SUMMARY
Mass effect from a goiter is a serious complication with potentially life-threatening consequences. In rare instances, a goiter can compress nearby vessels, compromising cerebral blood flow, which can lead to an ischemic stroke. Ischemic strokes generally occur due to atherogenic or embolic phenomenon, albeit a rare etiology can be due to a mechanical obstruction of great vessels of the neck that provide blood supply to the brain. An unusual example of a similar obstruction is the mass effect of an expansive goiter on the carotid artery (CA) in the neck. We present a rare case of a 90-year-old female who had a historically untreated goiter for 13 years. She presented with symptoms of acute stroke, including right-sided weakness and dysarthria. CT angiogram of the neck revealed a massively enlarged thyroid gland causing compression and intermittent obstruction of the blood flow in the left common CA. Subsequently, the patient underwent a total thyroidectomy. Postoperatively, she had a remarkable recovery of her symptoms of right-sided weakness and dysarthria. Acknowledging stroke as a grave mechanical complication of a large multinodular goiter is crucial for timely and appropriate management to avoid serious consequences.
LEARNING POINTS
The natural history of euthyroid multinodular goiters include abnormal enlargement of the thyroid gland, which results in local compression of structures in the neck causing neurovascular injury. Timely diagnosis and surgical management of an enlarging goiter compressing the CA can reduce morbidity from an ischemic stroke. Ischemic stroke is a rare and dangerous complication of a giant multinodular goiter.
PubMed: 36103594
DOI: 10.1530/EDM-22-0247 -
Analytical Cellular Pathology... 2023This study aimed to examine the incidence of incidental papillary microcarcinoma (PMC) and papillary thyroid carcinoma (PTC) in patients with benign multinodular goiter...
INTRODUCTION
This study aimed to examine the incidence of incidental papillary microcarcinoma (PMC) and papillary thyroid carcinoma (PTC) in patients with benign multinodular goiter (MNG) and to compare their relationship with some prognostic factors from a new perspective.
METHODS
Bilateral total thyroidectomy (BTT) was used to evaluate the data of 716 patients who underwent a surgery for MNG. The prognostic data for these tumors and the relationship between patients with bilateral and multifocal tumors were evaluated using statistical tests.
RESULTS
Papillary carcinomas were detected in 201 patients, PMC in 134 of them, and PTCs in 67. Bilaterality was more common in patients with PTCs than in those with PMC. The incidence of bilaterality in male patients with PTC was statistically more common. The presence of intra-tumoral lymphocytes was higher in multifocal PTC cases than in unifocal PTC cases.
CONCLUSION
The results revealed that the number of PMC s was high in incidental tumors, and patients with PTC with male sex, bilaterality, multifocality, and tumor capsule invasion were associated with poor prognosis.
Topics: Humans; Male; Thyroid Cancer, Papillary; Thyroid Neoplasms; Carcinoma, Papillary; Goiter; Retrospective Studies
PubMed: 36691406
DOI: 10.1155/2023/2768344 -
Thyroid : Official Journal of the... Apr 2022Multinodular goiter (MNG) is the most common disorder of the thyroid gland. Aging and genetic mutations that impair thyroid hormone (TH) production have been implicated...
Multinodular goiter (MNG) is the most common disorder of the thyroid gland. Aging and genetic mutations that impair thyroid hormone (TH) production have been implicated in the development of MNG. XB130 is an adaptor/scaffold protein predominantly expressed in the thyroid gland. XB130 deficiency leads to transient postnatal growth retardation in mice due to congenital hypothyroidism. We studied the formation of MNG and possible mechanisms in elderly mice. Thyroid glands of male and female knockout (), heterozygous (), and wild-type () mice at the ages of 12-20 months were harvested for visual examination, histopathological, and immunohistological analyses. Blood and thyroid samples were collected after feeding elderly mice with a low iodine diet for I uptake and perchlorate discharge assay. The activity of thyroperoxidase (Tpo) was examined by spectrophotometric evaluation of iodide oxidation. While moderate MNG was seen in and mice, severe MNG, characterized by multiple nodules intermixed with dilated colloid-rich macrofollicles, was found only in mice at 18 months. Thyrocyte cytoskeletal structure and cell adhesion molecules were disorganized, and TH production was significantly reduced. Reduced iodide organification was seen in elderly mice and further enhanced in mice. In mice, Tpo shows high affinity with hydrogen peroxide (HO) throughout aging, but reduced affinity with iodide in an age-dependent manner. By contrast, in elderly mice, the affinity of Tpo for iodide remained high, but the affinity of Tpo for HO was reduced. The pathophysiological features in the thyroid glands of aged mice closely resemble the features of MNG in humans. Moderate MNG in elderly mice was dramatically aggravated by XB130 deficiency. Reduced affinity of Tpo for HO may contribute to MNG development via oxidative stress. This could be specific to XB130 deficiency but also could be a common mechanism in MNG. Its clinical relevance should be further investigated.
Topics: Aged; Animals; Congenital Hypothyroidism; Female; Goiter; Humans; Hydrogen Peroxide; Iodide Peroxidase; Iodides; Male; Mice; Thyroid Hormones
PubMed: 34915750
DOI: 10.1089/thy.2021.0458 -
Laryngoscope Investigative... Apr 2018In a retrospective study, the authors analyzed the surgical approach to the intrathoracic goiter to avoid sternotomy or thoracotomy.
OBJECTIVE
In a retrospective study, the authors analyzed the surgical approach to the intrathoracic goiter to avoid sternotomy or thoracotomy.
METHODS
We selected 70 intrathoracic cases of multinodular goiter out of 988 cases of thyroidectomy and compared them with cervical goiter cases. Surgical technique, results, and postsurgical complications were assessed.
RESULTS
The analyzed cases presented the retrosternal goiter (n = 53; 75.7%), the retrotracheal goiter (n = 9; 12.8%), and the retroesophageal goiter (n = 8; 11.4%). Complaining of chest pressure or discomfort was specific for intrathoracic cases (50%; 35 of 70). All goiters except one were removed via cervical incision. The surgeons used head reclination and isthmus dissection when removing sizable goiters. Mean weight of goiters was 180 g. The recurrent laryngeal nerve was more often temporarily damaged in intrathoracic cases in comparison with cervical cases (4.3% vs. 2.8%, = .04), but the difference in permanent injury was less significant ( = .09). The incidence of temporary hypoparathyroidism was significantly higher in intrathoracic cases ( = .01).
CONCLUSION
In cases of multinodular goiter the goiters of various extensions can be successfully removed via the cervical incision in most of the cases even if they occupy the retrosternal, retrotracheal, or retroesophageal position. The transthoracic approaches and sternotomy might be justified in malignant cases.
LEVEL OF EVIDENCE
4.
PubMed: 29721546
DOI: 10.1002/lio2.146 -
Revista Da Associacao Medica Brasileira... Mar 2022Thyroid neoplasm incidence has increased worldwide, mostly due to the advancements in medical imaging and screening rates. The aberrant Wnt/β-catenin pathway has been...
OBJECTIVE
Thyroid neoplasm incidence has increased worldwide, mostly due to the advancements in medical imaging and screening rates. The aberrant Wnt/β-catenin pathway has been identified as a key mechanism, and it has also been related to the metastatic activity of differentiated thyroid cancer. We aimed to verify the difference in the expression of Wnt3a, a canonical activator of the β-catenin signaling, and CDX-2, a transcription factor upregulated by Wnt/β-catenin pathway, in multinodular goiter and differentiated thyroid cancer and to determine their prognostic value.
METHODS
We included 194 thyroid tissue surgical specimen and their clinicopathological data: study group (differentiated thyroid cancer, n=154) and control group (multinodular goiter, n=40). Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded tissue by the primary antibodies Wnt3a and CDX-2.
RESULTS
High Wnt3a expression was significantly associated with differentiated thyroid cancer (p=0.031). CDX-2 was negative in all differentiated thyroid cancer cases (100%) and also in multinodular goiter. Wnt3a expression was significantly associated with tumors ≤20 mm (p=0.044) and with the absence of capsule invasion (p=0.031). The multivariate analyses suggested that older age (≥55), independent of capsular invasion and tumor size, was an independent prognostic factor for Wnt3a expression (p=0.058).
CONCLUSIONS
Wnt3a expression but not CDX-2 is correlated with differentiated thyroid cancer samples in comparison to multinodular goiter. Although its prognostic value was limited to tumor size and capsule invasion, a combined model in a panel of immune markers can add accuracy in the classification of challenging thyroid follicular-derived lesions.
Topics: Adenocarcinoma; CDX2 Transcription Factor; Goiter; Humans; Thyroid Neoplasms; Wnt Signaling Pathway; Wnt3A Protein; beta Catenin
PubMed: 35442371
DOI: 10.1590/1806-9282.20211132 -
BMC Surgery 2012Thyroid disease is common in the elderly population. The incidence of hypothyroidism and multinodular goitre gradually increases with age. In view of a growth of aging... (Review)
Review
BACKGROUND
Thyroid disease is common in the elderly population. The incidence of hypothyroidism and multinodular goitre gradually increases with age. In view of a growth of aging population, we performed a literature review about the feasibility of thyroid surgery in the elderly.
METHODS
We conducted a literature search in the PubMed database in September 2012 and all English-language publications on thyroidectomy in geriatric patients since 2002 were retrieved. The potential original articles mainly focusing on thyroidectomy in elderly patients were all identified and full texts were obtained and reviewed for further hand data retrieving.
RESULTS
We retrieved five papers based on different primary end-point. Four were retrospective non randomized studies and one was prospective non randomized study. At last 65, 70, 75 and 80 years were used as an age cut-off. All studies evaluate the indications of thyroidectomy in geriatric patients, postoperative morbility and mortality. Only one study specifically assesses the rate of the rehospitalization after thyroidectomy among the elderly.
CONCLUSIONS
Thyroid nodules are particularly important in elderly patients, as the incidence of malignancy increases and they are usually more aggressive tumors. An age of at least 70 years is an independent risk factor for complications after general surgery procedures. Thyroid surgery in patients aged 70 years or older is safe and the relatively high rate of thyroid carcinoma and toxic goiter may justify an aggressive approach. A programmed operation with a careful pre-operative evaluation and a risk stratification should make the surgical procedures less hazardous, specially in 80 years old patients with an high ASA score.
Topics: Age Factors; Aged; Aged, 80 and over; Goiter; Humans; Postoperative Complications; Risk Factors; Thyroid Diseases; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome
PubMed: 23173919
DOI: 10.1186/1471-2482-12-S1-S16 -
Modern Pathology : An Official Journal... Apr 2011Thyroid carcinomas can be sporadic or familial. Familial syndromes are classified into familial medullary thyroid carcinoma (FMTC), derived from calcitonin-producing C... (Review)
Review
Thyroid carcinomas can be sporadic or familial. Familial syndromes are classified into familial medullary thyroid carcinoma (FMTC), derived from calcitonin-producing C cells, and familial non-medullary thyroid carcinoma, derived from follicular cells. The familial form of medullary thyroid carcinoma (MTC) is usually a component of multiple endocrine neoplasia (MEN) IIA or IIB, or presents as pure FMTC syndrome. The histopathological features of tumors in patients with MEN syndromes are similar to those of sporadic tumors, with the exception of bilaterality and multiplicity of tumors. The genetic events in the familial C-cell-derived tumors are well known, and genotype-phenotype correlations well established. In contrast, the case for a familial predisposition of non-medullary thyroid carcinoma is only now beginning to emerge. Although, the majority of papillary and follicular thyroid carcinomas are sporadic, the familial forms are rare and can be divided into two groups. The first includes familial syndromes characterized by a predominance of non-thyroidal tumors, such as familial adenomatous polyposis and PTEN-hamartoma tumor syndrome, within others. The second group includes familial syndromes characterized by predominance of papillary thyroid carcinoma (PTC), such as pure familial PTC (fPTC), fPTC associated with papillary renal cell carcinoma, and fPTC with multinodular goiter. Some characteristic morphologic findings should alert the pathologist of a possible familial cancer syndrome, which may lead to further molecular genetics evaluation.
Topics: Adenocarcinoma, Follicular; Adenomatous Polyposis Coli; Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary, Follicular; Carcinoma, Renal Cell; Female; Genetic Predisposition to Disease; Goiter, Nodular; Hamartoma Syndrome, Multiple; Humans; Kidney Neoplasms; Male; Multiple Endocrine Neoplasia; Multiple Endocrine Neoplasia Type 2a; Neoplastic Syndromes, Hereditary; Thyroid Neoplasms
PubMed: 21455198
DOI: 10.1038/modpathol.2010.147 -
Journal of Endocrinological... Feb 2022Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and...
Gene expression profile in functioning and non-functioning nodules of autonomous multinodular goiter from an area of iodine deficiency: unexpected common characteristics between the two entities.
PURPOSE
Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and non-functioning nodules, characterized by increased proliferation but opposite functional activity, may coexist in the same gland. To understand the distinct molecular pathology of each entity present in the same gland, the gene expression profile was evaluated by using the Affymetrix technology.
METHODS
Total RNA was extracted from nodular and healthy tissues of two patients and double-strand cDNA was synthesized. Biotinylated cRNA was obtained and, after chemical fragmentation, was hybridized on U133A and B arrays. Each array was stained and the acquired images were analyzed to obtain the expression levels of the transcripts. Both functioning and non-functioning nodules were compared versus healthy tissue of the corresponding patient.
RESULTS
About 16% of genes were modulated in functioning nodules, while in non-functioning nodules only 9% of genes were modulated with respect to the healthy tissue. In functioning nodules of both patients and up-regulation of cyclin D1 and cyclin-dependent kinase inhibitor 1 was observed, suggesting the presence of a possible feedback control of proliferation. Complement components C1s, C7 and C3 were down-regulated in both types of nodules, suggesting a silencing of the innate immune response. Cellular fibronectin precursor was up-regulated in both functioning nodules suggesting a possible increase of endothelial cells. Finally, Frizzled-1 was down-regulated only in functioning nodules, suggesting a role of Wnt signaling pathway in the proliferation and differentiation of these tumors. None of the thyroid-specific gene was deregulated in microarray analysis.
CONCLUSION
In conclusion, the main finding from our data is a similar modulation for both kinds of nodules in genes possibly implicated in thyroid growth.
Topics: Cell Proliferation; Complement System Proteins; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Gene Expression Profiling; Gene Expression Regulation; Goiter, Nodular; Humans; Hyperthyroidism; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Tissue Array Analysis; Wnt Signaling Pathway
PubMed: 34405392
DOI: 10.1007/s40618-021-01660-y -
The Journal of Clinical Investigation Mar 2020BACKGROUNDDICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset... (Clinical Trial)
Clinical Trial
BACKGROUNDDICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset lesions. Other susceptibility genes for familial forms of MNG likely exist.METHODSWhole-exome sequencing of a kindred with early-onset MNG and schwannomatosis was followed by investigation of germline pathogenic variants that fully segregated with the disease. Genome-wide analyses were performed on 13 tissue samples from familial and nonfamilial DGCR8-E518K-positive tumors, including MNG, schwannomas, papillary thyroid cancers (PTCs), and Wilms tumors. miRNA profiles of 4 tissue types were compared, and sequencing of miRNA, pre-miRNA, and mRNA was performed in a subset of 9 schwannomas, 4 of which harbor DGCR8-E518K.RESULTSWe identified c.1552G>A;p.E518K in DGCR8, a microprocessor component located in 22q, in the kindred. The variant identified is a somatic hotspot in Wilms tumors and has been identified in 2 PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the DGCR8 locus, was found in all 13 samples harboring c.1552G>A;p.E518K. miRNA profiling of PTCs, MNG, schwannomas, and Wilms tumors revealed a common profile among E518K hemizygous tumors. In vitro cleavage demonstrated improper processing of pre-miRNA by DGCR8-E518K. MicroRNA and RNA profiling show that this variant disrupts precursor microRNA production, impacting populations of canonical microRNAs and mirtrons.CONCLUSIONWe identified DGCR8 as the cause of an unreported autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter with schwannomatosis.FUNDINGCanadian Institutes of Health Research, Compute Canada, Alex's Lemonade Stand Foundation, the Mia Neri Foundation for Childhood Cancer, Cassa di Sovvenzioni e Risparmio fra il Personale della Banca d'Italia, and the KinderKrebsInitiative Buchholz/Holm-Seppensen.
Topics: Amino Acid Substitution; Child; Chromosomes, Human, Pair 22; Female; Gene Dosage; Genetic Predisposition to Disease; Genome-Wide Association Study; Goiter, Nodular; HEK293 Cells; Humans; Male; Mutation, Missense; Neoplasm Proteins; Neurilemmoma; Neurofibromatoses; RNA-Binding Proteins; Skin Neoplasms; Exome Sequencing
PubMed: 31805011
DOI: 10.1172/JCI130206