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American Journal of Clinical Pathology Mar 2018Multinodular goiter (MNG) and well-differentiated thyroid carcinoma (WDTC) are emerging phenotypes of DICER1 syndrome.
OBJECTIVES
Multinodular goiter (MNG) and well-differentiated thyroid carcinoma (WDTC) are emerging phenotypes of DICER1 syndrome.
METHODS
Histologic and molecular findings of botryoid-type embryonal rhabdomyosarcoma (bERMS) and thyroid nodules from a 12-year-old DICER1 mutation carrier (p.Arg1060Ilefs*7) were investigated, providing interesting clues for understanding thyroid carcinogenesis.
RESULTS
The patient had bERMS at age 7 years. The thyroid was enlarged and multinodular (61 g). Histologically, some nodules were classified as adenomatous and others as tumors with "intermediate" nuclei. One displayed vascular invasion and was classified as WDTC not otherwise specified (NOS). Somatic DICER1 mutations were identified in bERMS, two tumors with "intermediate" nuclei and WDTC. No somatic DICER1 mutations were found in adenomatous nodules. No molecular alterations were detected in BRAF600, NRAS61, HRAS12/61, KRAS12/61, TERT promoter, RET/PTC1, RET/PTC3, and PAX8/PPARγ.
CONCLUSIONS
The findings obtained from this single case support the assumption that DICER1 syndrome-related WDTC NOS may develop on a background of MNG, via a stepwise process, involving DICER1 somatic mutations and additional molecular events, distinct from the classic pathways of papillary/follicular carcinoma.
Topics: Carcinogenesis; Child; DEAD-box RNA Helicases; Disease Progression; Female; Goiter, Nodular; Humans; Mutation; Rhabdomyosarcoma, Embryonal; Ribonuclease III; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy
PubMed: 29538609
DOI: 10.1093/ajcp/aqy004 -
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 -
Endocrine Practice : Official Journal... Oct 2014Although the use of oral cholecystographic agents (OCAs) had declined due to limited availability, there is literature to suggest it is an effective medication for... (Review)
Review
OBJECTIVE
Although the use of oral cholecystographic agents (OCAs) had declined due to limited availability, there is literature to suggest it is an effective medication for thyrotoxicosis in appropriate clinical situations.
METHODS
The authors performed a PubMed search and systematically reviewed all the English written case reports, original studies and reviews from 1953 to 2012. Additional information was supplemented from available online pharmacologic databases.
RESULTS
The off-label use of OCAs was reviewed for the management of neonatal and adult Graves' disease, subacute thyroiditis, amiodarone-induced thyroiditis (AIT), exogenous hyperthyroidism, toxic multinodular goiter (TMNG), thyrotropinoma, thyrotoxicosis during pregnancy, rapid pre-operative control of hyperthyroidism, and thyroid storm. Adverse effects were also reviewed.
CONCLUSION
OCAs generally are effective agents in treating thyrotoxicosis in the etiologies reviewed. OCAs are clinically relevant in patients who require rapid control, such as in the pre-operative state or patient who cannot tolerate a thyrotoxicosis state. OCA may also be beneficial in situations where other anti-thyroidal medication would be hazardous or ineffective, such as thionamide allergy or exogenous thyrotoxicosis. Given concern for long-term relapse, OCAs should be considered a short-term bridge to definitive therapy. OCAs are limited in TMNG and should be second line after glucocorticoids in AIT II. OCAs do not preclude the use of radioactive iodine, which can be performed one week after OCA therapy.
Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Female; Goiter, Nodular; Humans; Hyperthyroidism; Neoplasm Recurrence, Local; Pregnancy; Thyroiditis, Subacute; Thyrotoxicosis
PubMed: 25100369
DOI: 10.4158/EP14024.RA -
Diagnostics (Basel, Switzerland) Sep 2021Post-thyroidectomy hypocalcemia is a frequent complication with significant morbidity, and has been shown to increase hospital stay and readmission rates. The evaluation...
Post-thyroidectomy hypocalcemia is a frequent complication with significant morbidity, and has been shown to increase hospital stay and readmission rates. The evaluation of serum parathyroid hormone (PTH) levels after thyroidectomy represents a reliable method to predict post-thyroidectomy hypocalcemia, but it remains infrequently used. This retrospective study investigates serum PTH values 3 h after thyroidectomy as a predictor of hypocalcemia. In this study, we enrolled 141 patients aged between 27 and 71 years eligible for total thyroidectomy who presented with multinodular goiter, suspicious nodule on cytological examination, Graves' disease, or toxic multinodular goiter. Three hours after total thyroidectomy, 53 patients (37.6%) showed a reduction in serum PTH. Of these patients 75.5% developed hypocalcemia by 24 h after surgery and 100% were hypocalcemic after 48 h ( < 0.001). There was no significant difference attributable to the different thyroid diseases, nor to the age of the patients. PTH at 3 h after total thyroidectomy accurately predicts post-operative hypocalcemia. The early detection of patients at risk of developing post-operative hypocalcemia allows for prompt supplementation of calcium and Vitamin D in order to prevent symptoms and allows for a safe and timely discharge.
PubMed: 34574074
DOI: 10.3390/diagnostics11091733 -
Thyroid Research Dec 2022The debate on whether or not there is a difference in the incidence of thyroid cancer between the patients with Solitary thyroid Nodule (STN) and Multinodular Goiter... (Review)
Review
BACKGROUND
The debate on whether or not there is a difference in the incidence of thyroid cancer between the patients with Solitary thyroid Nodule (STN) and Multinodular Goiter (MNG) has been constantly present for the last few decades. With newer studies yielding mixed results, it was imperative to systematically compile all available literature on the topic.
METHODS
PubMed/MEDLINE, Cochrane Central, ScienceDirect, GoogleScholar, International Clinical Trials registry, and reference lists of the included articles were systematically searched for article retrieval. No filter was applied in terms of time, study design, language or country of publication. Rigorous screening as per PRISMA guidelines was undertaken by 2 independent reviewers in order to identify the articles that were most relevant to the topic.
RESULTS
Twenty-two studies spanning from 1992 to 2018 were included in this analysis and encompassed 50,321 patients, 44.2% of which belonged to the STN subgroup and 55.37% to the MNG subgroup. MNG was found to be associated with a significantly lower risk of thyroid cancer (OR = 0.76; 95% CI 0.61-0.96) when compared with STN. Papillary carcinoma was the most frequently occurring carcinoma across both groups, followed by follicular and medullary carcinomas. A subgroup analysis was performed to assess the efficacy of the two most commonly employed diagnostic tools i.e. surgery and fine needle aspiration cytology (FNAC), however it yielded nonsignificant results, indicating a comparable usefulness of the two. Another subgroup analysis run on the basis of the presumed iodine status of the participants also yielded nonsignificant results.
CONCLUSION
There is a higher incidence of thyroid cancer among patients of STN, however, given the low quality of existing evidence on the topic, it is crucial to conduct larger studies that can establish association with a greater precision.
PubMed: 36464691
DOI: 10.1186/s13044-022-00140-6 -
Przeglad Lekarski 2016Thyrotoxicosis is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormones. Including its subclinical form, it is... (Review)
Review
Thyrotoxicosis is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormones. Including its subclinical form, it is considered as one of the most frequent endocrine disorders in the general population. If not detected in a timely fashion, thyrotoxicosis can have serious health consequences. The most common forms of thyrotoxicosis include diffuse toxic goiter (Graves' disease), toxic multinodular goiter (Plummer's disease), and toxic adenoma (Goetsch's disease). The significant progress in the fields of hormonal assessment, imaging procedures and molecular biology made in recent years has brought about great improvement in the identification, differentiation and treatment of many other disorders associated with thyrotoxicosis. Therefore, this paper discusses the etiopathogenesis, clinical manifestation, biochemical abnormalities and management of thyrotropinoma, resistance to thyroid hormone, de Quervain's, silent, acute, posttraumatic and radiation-induced thyroiditis, Riedel's goiter, differentiated thyroid cancer, struma ovarii, thyrotoxicosis factitia, other forms of iatrogenic thyrotoxicosis, gestational trophoblastic disease, neonatal Graves's disease, familial nonautoimmune hyperthyroidism and McCune-Albright syndrome. On the basis of available studies, some of whom were carried out in the recent years, we provide practical guidelines for clinical endocrinologists dealing with the diagnosis and treatment of thyrotoxicosis.
Topics: Adult; Child; Disease Management; Female; Humans; Infant, Newborn; Pregnancy; Thyroid Hormones; Thyroid Neoplasms; Thyrotoxicosis
PubMed: 27526430
DOI: No ID Found -
Turkish Journal of Medical Sciences Nov 2017Background/aim: To evaluate the malignancy risk of thyroid nodules in different clinical thyroid diseases. Materials and methods: Patients who underwent thyroidectomy...
Background/aim: To evaluate the malignancy risk of thyroid nodules in different clinical thyroid diseases. Materials and methods: Patients who underwent thyroidectomy between 2007 and 2014 were grouped as euthyroid, hypothyroid, and hyperthyroid. Further classification was made depending on the presence of solitary/multiple thyroid nodules. Results: Among 2870 patients, 1719 (59.9%) were euthyroid, 962 (33.5%) were hyperthyroid, and 189 (6.6%) were hypothyroid. Overall malignancy was detected in 980 (34.1%) patients. Malignancy rates were 42.1%, 42.9%, and 18.3% in the euthyroid, hypothyroid, and hyperthyroid groups, respectively (P < 0.001). A total 41.4% of patients with euthyroid nodular goiter (ENG) and 46.3% of patients with euthyroid multinodular goiter (EMNG) had thyroid malignancy (P = 0.169). Mean tumor size and capsular and vascular invasion were significantly lower in EMNG than in ENG. Among hypothyroid patients, 45.7% with solitary and 42.2% with multiple nodules were malignant (P = 0.705). When toxic nodular goiter and toxic multinodular goiter were analyzed together, malignancy rate was 24.7% (104/421), and when Graves with nodule/nodules was considered, it was 19.7% (59/299). Conclusion: In hypothyroid or euthyroid patients who underwent thyroidectomy, malignancy rate was higher than 40%, and was lower in hyperthyroid patients. Patients with multiple nodules carry a similar risk of malignancy as patients with solitary nodules, independent of the functional status.
PubMed: 29151324
DOI: 10.3906/sag-1611-67 -
Cureus Dec 2021Primary amenorrhea is a serious medical condition. A thorough clinical assessment is necessary for a timely and correct diagnosis and management of this ailment to...
Primary amenorrhea is a serious medical condition. A thorough clinical assessment is necessary for a timely and correct diagnosis and management of this ailment to prevent long-term health and social problems. Turner's syndrome is considered one of the important causes of primary amenorrhea, with an incidence of one in 2,500 to one in 3,000 live-born girls. In this report, we present an interesting case involving multinodular goiter, hypothyroidism, and primary amenorrhea. A 24-year-old woman with a history of multinodular goiter and hypothyroidism attended an endocrine clinic with fine-needle aspiration cytology (FNAC) report of her bilateral thyroid nodules, which showed Bethesda category IV. She had a history of learning difficulties. During detailed history-taking, the patient also complained of primary amenorrhea. Clinical examination showed a lack of secondary sexual characters. Biochemical, imaging, and cytogenetic investigations were suggestive of absent ovaries and fallopian tubes, streaked uterus, hypergonadotropic hypogonadism, and X0 karyotyping. The learning objectives of this case report are as follows: firstly, in countries with a lack of awareness and limited health resources, patients may present with one of the manifestations of Turner's syndrome. Clinicians from all specialties should be aware of the clinical features of this relatively rare entity and should try to make the most of incidental clinical findings. Secondly, clinicians should be more vigilant and thorough in their clinical assessment of patients with learning difficulties to minimize the chances of missing a clinical diagnosis.
PubMed: 35018272
DOI: 10.7759/cureus.20285 -
International Archives of... Jan 2023The identification of thyroid cancer may be conducted through clinical detection, imaging method, and histopathological examination. Both solitary nodules and...
The identification of thyroid cancer may be conducted through clinical detection, imaging method, and histopathological examination. Both solitary nodules and multinodular goiter are associated with malignancy. To assess the risk factors for malignancy among patients with multinodular goiter submitted to total thyroidectomy. A series of 712 consecutive patients, submitted to total thyroidectomy between 2005 and 2016 with multinodular goiter regarding clinical, ultrasound, and pathological variables, was retrospectively evaluated. There were 408 cases of papillary carcinoma (57.3%), with the remaining being benign. Gender had no statistical significance ( = 0.169) for malignancy, unlike the Bethesda index, higher age group ( = 0.005), shorter clinical history time ( = 0.036), smaller number of nodules ( < 0.0001), and smaller nodule size ( < 0.0001), which were related to malignancy. The Bethesda index, older age group, shorter clinical history, smaller number of nodules, and smaller size of nodule were related to the diagnosis of papillary carcinoma.
PubMed: 36714905
DOI: 10.1055/s-0042-1748925 -
Thyroid : Official Journal of the... Feb 2024The optimal cutoff value of calcitonin (Ctn) levels measured using an electrochemiluminescence immunoassay (ECLIA) obtained from the washout fluid of fine needle...
The optimal cutoff value of calcitonin (Ctn) levels measured using an electrochemiluminescence immunoassay (ECLIA) obtained from the washout fluid of fine needle aspiration (FNA-Ctn) for the diagnosis of medullary thyroid carcinoma (MTC) is currently not established. We evaluated the diagnostic accuracy and clinical utility of FNA-Ctn for the diagnosis and location of MTC in patients with nodular or multinodular goiters. This was a case-control study nested on a prospective multicenter cohort of patients with nodular or multinodular goiter, normal or elevated serum Ctn, and thyroidectomy indications. Ctn and FNA-Ctn were measured using ECLIA methodology before surgery. From this nested cohort, MTC cases and controls (non-medullary pathology) were identified from the final pathological analysis. Cumulative incidence sampling of controls was randomly performed at a ratio of 1:2. Sensitivity, specificity, and area under the receiver operator curve (AUROC) were calculated for patients and the total number of thyroid nodules. From 1272 patients included in the prospective cohort, 50 MTC cases and 105 controls were included. In this study, 286 thyroid nodules were evaluated (63 MTC and 223 non-MTCs). The median serum Ctn value was significantly higher in cases (525 pg/mL [interquartile range (IQR), 162.5-1.200]) than in controls (1.6 pg/mL [IQR, 0.5-5.6]; < 0.001). The median FNA-Ctn value was significantly higher in MTC nodules (3.100 pg/mL [IQR, 450-45,200]) than in non-MTC nodules (0.5 pg/mL [IQR, 0.5-0.5]; < 0.0001). In 11 MTC patients with multinodular goiter, the FNA-Ctn value was significantly higher in non-medullary nodules located in the same lobe where an MTC nodule was diagnosed ( = 0.0002). Overall, the FNA-Ctn AUROC was 0.99 [95% confidence interval, 0.98-1.0], and a threshold of ≥220 pg/mL showed 100% sensitivity and 98% specificity for MTC diagnosis. The use of FNA-Ctn measured by ECLIA showed adequate diagnostic accuracy for MTC diagnosis. Moreover, it may be clinically useful for localization in multinodular goiter when lobectomy is considered. Clinicaltrials.gov NCT06067594.
Topics: Humans; Thyroid Nodule; Biopsy, Fine-Needle; Calcitonin; Case-Control Studies; Prospective Studies; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Goiter
PubMed: 38047535
DOI: 10.1089/thy.2023.0313