RESUMO
The integration of genomic testing into clinical care enables the use of individualized approaches to the management of rare diseases. We describe the use of belzutifan, a potent and selective small-molecule inhibitor of the protein hypoxia-inducible factor 2α (HIF2α), in a patient with polycythemia and multiple paragangliomas (the Pacak-Zhuang syndrome). The syndrome was caused in this patient by somatic mosaicism for an activating mutation in EPAS1. Treatment with belzutifan led to a rapid and sustained tumor response along with resolution of hypertension, headaches, and long-standing polycythemia. This case shows the application of a targeted therapy for the treatment of a patient with a rare tumor-predisposition syndrome. (Funded by the Morin Family Fund for Pediatric Cancer and Alex's Lemonade Stand Foundation.).
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Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Indenos/uso terapêutico , Paraganglioma/tratamento farmacológico , Policitemia/tratamento farmacológico , Adolescente , Neoplasias das Glândulas Suprarrenais/genética , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/sangue , Cromograninas/sangue , Feminino , Mutação com Ganho de Função , Humanos , Indenos/efeitos adversos , Imageamento por Ressonância Magnética , Normetanefrina/sangue , Paraganglioma/genética , Policitemia/genética , Transdução de Sinais , Síndrome , Sequenciamento Completo do GenomaRESUMO
On March 30, 2022, the U.S. FDA issued a drug safety communication recommending that infants and young children through 3 years of age undergo monitoring of thyroid function within 3 weeks of intravascular administration of iodine-based contrast media. This article considers the literature that was referenced for this decision and provides an outlook on thyroid monitoring after diagnostic imaging from pediatric radiology and pediatric endocrinology perspectives.
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Iodo , Radiologia , Humanos , Lactente , Criança , Pré-Escolar , Recém-Nascido , Glândula Tireoide/diagnóstico por imagem , Iodo/efeitos adversos , Meios de Contraste/efeitos adversosRESUMO
INTRODUCTION: Ultrasound screening for thyroid cancer is recommended in familial adenomatous polyposis (FAP). This study investigated the prevalence of thyroid neoplasia in children with FAP. METHODS: Cross-sectional study of children with FAP at an academic hospital. Clinical and ultrasound data were analyzed for the prevalence of thyroid nodules and cancer. RESULTS: Of 37 children with FAP, 8 (22%) had thyroid nodules and 2 (5%) had thyroid cancer. Nodules (30%) and cancer (9%) were more common among female subjects and rare among male subjects. DISCUSSION: Thyroid ultrasound screening in adolescence may benefit female subjects with FAP but has limited utility in male subjects.
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Polipose Adenomatosa do Colo , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Polipose Adenomatosa do Colo/diagnóstico por imagem , Polipose Adenomatosa do Colo/epidemiologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/epidemiologiaRESUMO
Background The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) is a recognized tool for management of thyroid nodules in adults but has not been validated in pediatric patients. Purpose To assess the performance of the ACR TI-RADS criteria for guiding decisions on whether to biopsy thyroid nodules in pediatric patients in a single referral center. Materials and Methods In this retrospective study, a database of thyroid nodules in patients younger than 19 years who underwent fine-needle aspiration (FNA) biopsy between January 2004 and July 2017 was analyzed. ACR TI-RADS criteria were applied to each nodule, and an ACR TI-RADS score was created to determine how the nodule would be managed. The number of nodules that would be biopsied with FNA on the basis of ACR TI-RADS was compared with the total number of nodules biopsied with FNA in this clinic to determine if the use of ACR TI-RADS would have changed the rate of FNA (eg, decreased the number of procedures) and whether that change would have affected the timely diagnosis of cancer. Results A total of 314 patients (mean age, 14.9 years; age range, 2-18 years; 28 prepubertal patients; 286 postpubertal patients; 260 female patients) were evaluated. In these 314 patients, 404 thyroid nodules were scored, of which 19.1% (77 of 404) were malignant. Most cancers were papillary carcinoma (68 [88.3%] of 77). The use of ACR TI-RADS criteria for management of nodules in this pediatric study sample would have resulted in 17 (22.1%) of 77 cancers being missed at the patient's initial visit. Conclusion Use of the current American College of Radiology Thyroid Imaging Reporting and Data System criteria for management of pediatric thyroid nodules is inadequate because a high percentage of cancers would be missed at the initial encounter. © RSNA, 2019.
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Sistemas de Informação em Radiologia/estatística & dados numéricos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pediatria , Radiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sociedades Médicas , Glândula Tireoide/diagnóstico por imagem , Estados UnidosRESUMO
Nephrolithiasis, a condition in which urinary supersaturation leads to stone formation in the urinary system, affects about 5%-10% of individuals worldwide at some point in their lifetime and results in significant medical costs and morbidity. To date, mutations in more than 30 genes have been described as being associated with nephrolithiasis, and these mutations explain about 15% of kidney stone cases, suggesting that additional nephrolithiasis-associated genes remain to be discovered. To identify additional genes whose mutations are linked to nephrolithiasis, we performed targeted next-generation sequencing of 18 hypothesized candidate genes in 348 unrelated individuals with kidney stones. We detected biallelic mutations in SLC26A1 (solute carrier family 26 member 1) in two unrelated individuals with calcium oxalate kidney stones. We show by immunofluorescence, immunoblotting, and glycosylation analysis that the variant protein mimicking p.Thr185Met has defects in protein folding or trafficking. In addition, by measuring anion exchange activity of SLC26A1, we demonstrate that all the identified mutations in SLC26A1 result in decreased transporter activity. Our data identify SLC26A1 mutations as causing a recessive Mendelian form of nephrolithiasis.
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Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Mutação/genética , Nefrolitíase/etiologia , Sequência de Aminoácidos , Proteínas de Transporte de Ânions/química , Bicarbonatos/metabolismo , Imunofluorescência , Glicosilação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Immunoblotting , Nefrolitíase/patologia , Conformação Proteica , Dobramento de Proteína , Transporte Proteico , Reação em Cadeia da Polimerase em Tempo Real , Homologia de Sequência de Aminoácidos , Transportadores de Sulfato , Sulfatos/metabolismoRESUMO
The incidence of nephrolithiasis continues to rise. Previously, we showed that a monogenic cause could be detected in 11.4% of individuals with adult-onset nephrolithiasis or nephrocalcinosis and in 16.7-20.8% of individuals with onset before 18 years of age, using gene panel sequencing of 30 genes known to cause nephrolithiasis/nephrocalcinosis. To overcome the limitations of panel sequencing, we utilized whole exome sequencing in 51 families, who presented before age 25 years with at least one renal stone or with a renal ultrasound finding of nephrocalcinosis to identify the underlying molecular genetic cause of disease. In 15 of 51 families, we detected a monogenic causative mutation by whole exome sequencing. A mutation in seven recessive genes (AGXT, ATP6V1B1, CLDN16, CLDN19, GRHPR, SLC3A1, SLC12A1), in one dominant gene (SLC9A3R1), and in one gene (SLC34A1) with both recessive and dominant inheritance was detected. Seven of the 19 different mutations were not previously described as disease-causing. In one family, a causative mutation in one of 117 genes that may represent phenocopies of nephrolithiasis-causing genes was detected. In nine of 15 families, the genetic diagnosis may have specific implications for stone management and prevention. Several factors that correlated with the higher detection rate in our cohort were younger age at onset of nephrolithiasis/nephrocalcinosis, presence of multiple affected members in a family, and presence of consanguinity. Thus, we established whole exome sequencing as an efficient approach toward a molecular genetic diagnosis in individuals with nephrolithiasis/nephrocalcinosis who manifest before age 25 years.
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Sequenciamento do Exoma , Mutação , Nefrocalcinose/genética , Nefrolitíase/genética , Adolescente , Idade de Início , Criança , Pré-Escolar , Progressão da Doença , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Hereditariedade , Humanos , Lactente , Masculino , Nefrocalcinose/diagnóstico por imagem , Nefrocalcinose/epidemiologia , Nefrolitíase/diagnóstico por imagem , Nefrolitíase/epidemiologia , Linhagem , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto JovemRESUMO
Purpose To determine the relationship between demographic and sonographic characteristics of thyroid nodules and malignancy in a pediatric population. Materials and Methods All thyroid nodules in patients younger than 19 years that underwent ultrasound (US)-guided fine-needle aspiration biopsy between January 2004 and July 2017 were retrospectively identified. Age, sex, and background appearance of the thyroid gland were recorded for each patient, and sonographic characteristics and pathologic diagnosis were recorded for each nodule. Demographic and sonographic characteristics were assessed to determine which were associated with malignancy. Categorical and continuous variables and interobserver variability were assessed. Results A total of 404 nodules in 314 patients (82.8% female) (age range, 2-18 years; mean age, 14.9 years) were analyzed. A total of 77 nodules (19.1%) were malignant, the majority of which were papillary thyroid carcinoma (n = 68 [88.3%]). The likelihood of malignancy did not differ between boys and girls (27.8% vs 22.7%, P = .64), nor did it differ between prepubertal and pubertal patients (18.8% vs 19.1%, P > .99). The cancer rate in patients with a solitary nodule was higher than that in patients with multiple nodules (29.4% vs 14.2%, P = .003). Sonographic characteristics associated with malignant nodules included larger size, solid parenchyma, taller-than-wide shape, presence of speckled calcifications, lack of a smooth margin, and presence of abnormal lymph nodes. Interobserver variability for assessment of sonographic characteristics ranged from moderate to very strong. Conclusion In children with thyroid nodules, solitary nodules, larger nodule size, solid parenchyma, taller-than-wide shape, speckled calcifications, irregular margins, and abnormal lymph nodes raise concern for malignancy.
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Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia de Intervenção/métodos , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Variações Dependentes do Observador , Estudos Retrospectivos , Sensibilidade e Especificidade , Câncer Papilífero da Tireoide , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologiaRESUMO
OBJECTIVE: To assess whether adding liothyronine (LT3) to levothyroxine (LT4) monotherapy normalizes serum thyrotropin (TSH) and thyroxine (T4) concentrations in children with congenital hypothyroidism and central resistance to thyroid hormone. STUDY DESIGN: We retrospectively studied 12 patients with congenital hypothyroidism and central resistance to thyroid hormone (6 treated with LT3+LT4 combined therapy and 6 treated with LT4 monotherapy). In patients receiving combined therapy, we compared serum concentrations of TSH, T4, and triiodothyronine before and after addition of LT3. We used repeated measures analysis to compare thyroid function in participants receiving combined therapy vs monotherapy, while accounting for age and intrasubject correlation. RESULTS: In patients receiving combined therapy, the addition of LT3 was associated with normalization of mean TSH (9.2 vs 4.5 mIU/L, P = .002), a lower proportion of TSH values greater than 10 mIU/L (35% vs 8%, P = .03), and a decrease in mean serum T4 by 23 ± 9% (P < .001). Compared with patients receiving LT4 monotherapy, patients receiving combined therapy had lower mean TSH (8.5 ± 0.9 vs 4.3 ± 0.4, P < .001), lower odds of TSH elevation greater than 10 mIU/L (OR 0.20, 95% CI 0.10-0.41, P < .001), and lower odds of T4 elevation (OR 0.21, 95% CI 0.04-1.09, P = .06). LT3 treatment did not increase serum T3 levels significantly. CONCLUSION: The addition of LT3 to LT4 monotherapy facilitates normalization of both serum TSH and T4 in patients with congenital hypothyroidism and central resistance to thyroid hormone. Larger prospective studies are needed to confirm these findings and to determine the effect of combined therapy on neurodevelopmental outcomes.
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Hipotireoidismo Congênito/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Tiroxina/uso terapêutico , Tri-Iodotironina/uso terapêutico , Biomarcadores/sangue , Hipotireoidismo Congênito/sangue , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Estudos Retrospectivos , Tireotropina/sangue , Tiroxina/sangue , Resultado do TratamentoRESUMO
Nephrolithiasis is a prevalent condition with a high morbidity. Although dozens of monogenic causes have been identified, the fraction of single-gene disease has not been well studied. To determine the percentage of cases that can be molecularly explained by mutations in 1 of 30 known kidney stone genes, we conducted a high-throughput mutation analysis in a cohort of consecutively recruited patients from typical kidney stone clinics. The cohort comprised 272 genetically unresolved individuals (106 children and 166 adults) from 268 families with nephrolithiasis (n=256) or isolated nephrocalcinosis (n=16). We detected 50 likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 14.9% (40 of 268) of all cases; 20 of 50 detected mutations were novel (40%). The cystinuria gene SLC7A9 (n=19) was most frequently mutated. The percentage of monogenic cases was notably high in both the adult (11.4%) and pediatric cohorts (20.8%). Recessive causes were more frequent among children, whereas dominant disease occurred more abundantly in adults. Our study provides an in-depth analysis of monogenic causes of kidney stone disease. We suggest that knowledge of the molecular cause of nephrolithiasis and nephrocalcinosis may have practical implications and might facilitate personalized treatment.
Assuntos
Nefrocalcinose/genética , Nefrolitíase/genética , Adulto , Criança , Estudos de Coortes , Análise Mutacional de DNA , Humanos , Mutação de Sentido IncorretoRESUMO
In a retrospective analysis of childhood thyroid nodules, 18% were radiographic incidentalomas and 41% were discovered by a clinician's palpation; 40% were discovered by patients' families. The latter group had the largest nodules and highest rates of thyroid cancer metastasis, suggesting opportunities for earlier detection through annual well-child visits.
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Nódulo da Glândula Tireoide/diagnóstico , Adolescente , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Humanos , Achados Incidentais , Masculino , Metástase Neoplásica , Exame Físico/estatística & dados numéricos , Radiografia , Estudos Retrospectivos , Autoexame/estatística & dados numéricos , Distribuição por Sexo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico por imagemRESUMO
IMPORTANCE: Handoff miscommunications are a leading cause of medical errors. Studies comprehensively assessing handoff improvement programs are lacking. OBJECTIVE: To determine whether introduction of a multifaceted handoff program was associated with reduced rates of medical errors and preventable adverse events, fewer omissions of key data in written handoffs, improved verbal handoffs, and changes in resident-physician workflow. DESIGN, SETTING, AND PARTICIPANTS: Prospective intervention study of 1255 patient admissions (642 before and 613 after the intervention) involving 84 resident physicians (42 before and 42 after the intervention) from July-September 2009 and November 2009-January 2010 on 2 inpatient units at Boston Children's Hospital. INTERVENTIONS: Resident handoff bundle, consisting of standardized communication and handoff training, a verbal mnemonic, and a new team handoff structure. On one unit, a computerized handoff tool linked to the electronic medical record was introduced. MAIN OUTCOMES AND MEASURES: The primary outcomes were the rates of medical errors and preventable adverse events measured by daily systematic surveillance. The secondary outcomes were omissions in the printed handoff document and resident time-motion activity. RESULTS: Medical errors decreased from 33.8 per 100 admissions (95% CI, 27.3-40.3) to 18.3 per 100 admissions (95% CI, 14.7-21.9; P < .001), and preventable adverse events decreased from 3.3 per 100 admissions (95% CI, 1.7-4.8) to 1.5 (95% CI, 0.51-2.4) per 100 admissions (P = .04) following the intervention. There were fewer omissions of key handoff elements on printed handoff documents, especially on the unit that received the computerized handoff tool (significant reductions of omissions in 11 of 14 categories with computerized tool; significant reductions in 2 of 14 categories without computerized tool). Physicians spent a greater percentage of time in a 24-hour period at the patient bedside after the intervention (8.3%; 95% CI 7.1%-9.8%) vs 10.6% (95% CI, 9.2%-12.2%; P = .03). The average duration of verbal handoffs per patient did not change. Verbal handoffs were more likely to occur in a quiet location (33.3%; 95% CI, 14.5%-52.2% vs 67.9%; 95% CI, 50.6%-85.2%; P = .03) and private location (50.0%; 95% CI, 30%-70% vs 85.7%; 95% CI, 72.8%-98.7%; P = .007) after the intervention. CONCLUSIONS AND RELEVANCE: Implementation of a handoff bundle was associated with a significant reduction in medical errors and preventable adverse events among hospitalized children. Improvements in verbal and written handoff processes occurred, and resident workflow did not change adversely.
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Comunicação , Internato e Residência , Erros Médicos/prevenção & controle , Admissão do Paciente , Transferência da Responsabilidade pelo Paciente/normas , Boston , Criança , Criança Hospitalizada , Registros Eletrônicos de Saúde , Feminino , Hospitais Pediátricos , Humanos , Masculino , Equipe de Assistência ao Paciente , Estudos Prospectivos , Carga de TrabalhoRESUMO
Thyroid cancer is rare in children but its incidence is increasing. Recent data have clarified important similarities and differences between thyroid cancers originating in childhood and in adulthood. The genetic drivers of pediatric thyroid cancers are similar to those in adult tumors but comprise more gene fusions and fewer point mutations. Clinically, despite frequent metastatic spread, pediatric thyroid cancer has an excellent prognosis and mortality is rare. Therefore, treatment approaches must weigh carefully the morbidity of thyroid cancer treatments against their benefits. Current key questions include which children require total thyroidectomy rather than more limited-and safer-lobectomy, and in which children does the benefit of radioactive iodine therapy outweigh its risk of inducing a secondary malignancy. Finally, molecular therapies targeting genetic drivers of thyroid cancer now provide effective treatment for children with progressive, radioiodine-refractory disease, as well as opportunities to explore novel neoadjuvant uses that facilitate therapeutic surgery or radioactive iodine.
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Neoplasias da Glândula Tireoide , Adulto , Humanos , Criança , Neoplasias da Glândula Tireoide/patologia , Radioisótopos do Iodo/uso terapêutico , Resultado do Tratamento , Prognóstico , TireoidectomiaRESUMO
ABSTRACT: Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Prompt diagnosis by newborn screening (NBS) leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet established in all countries globally. Seventy percent of neonates worldwide do not undergo NBS.The initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism.Newborn screening alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.
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Hipotireoidismo Congênito , Recém-Nascido , Lactente , Humanos , Criança , Pré-Escolar , Tiroxina , Tireotropina , Testes de Função Tireóidea , Triagem NeonatalRESUMO
Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet practiced in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The recommended initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and with free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding the detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.
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Hipotireoidismo Congênito , Recém-Nascido , Lactente , Humanos , Criança , Pré-Escolar , Tiroxina , Tireotropina , Testes de Função Tireóidea , Triagem NeonatalRESUMO
PURPOSE: Multigene panels allow simultaneous testing of genes involved in cancer predisposition. Thyroid cancer (TCa) is a component tumor of several cancer predisposition syndromes, but the complete landscape of germline variants predisposing to TCa remains to be determined. METHODS: Clinical information and genetic test results were reviewed from over 170,000 individuals who had multigene panel testing for hereditary cancer at a single diagnostic laboratory. Germline pathogenic and likely pathogenic variants ("pathogenic variants") were examined among individuals with TCa. A cohort with breast cancer (BCa) was examined to serve as a comparison group and to determine the added contribution of TCa to the ascertainment of genetic risk. RESULTS: Of 3134 individuals with TCa, 291 (9.3%) were found to have one or more pathogenic variant(s). Among 904 individuals with TCa alone, 7.5% had one or more pathogenic variant(s), similar to those with BCa alone (8.4%). In all groups, CHEK2 was the gene with the highest number of pathogenic variants identified, with a significantly increased frequency among individuals with a history of both thyroid and BCa compared to BCa alone. CONCLUSIONS: A high prevalence of germline pathogenic variants was observed among individuals with TCa referred for hereditary cancer genetic testing, even in the absence of other cancer diagnoses. These data suggest that TCa may be an under-recognized component of cancer predisposition syndromes.
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Mutação em Linhagem Germinativa , Neoplasias da Glândula Tireoide , Predisposição Genética para Doença , Testes Genéticos/métodos , Células Germinativas , Humanos , Síndrome , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genéticaRESUMO
BACKGROUND: Thyroid nodules with atypia of undetermined significance (AUS) are challenging to manage because of their intermediate risk of malignancy. Subclassification of atypia can refine malignancy risk in adult AUS nodules but has not been evaluated in children. METHODS: This was a retrospective cohort study of pediatric patients (<19 years old) who underwent fine-needle aspiration (FNA) of a thyroid nodule with resulting AUS cytology. Atypia was subclassified as nuclear only, architectural only, nuclear and architectural, or oncocytic. The primary outcome was the association between atypia subtype and malignancy. A secondary outcome was the association of atypia subtype with repeat FNA cytology. RESULTS: Sixty-eight AUS nodules in 61 patients were analyzed. The median age at FNA was 16.2 years (range, 9.8-18.9 years). Twenty-four nodules (35%) were malignant. Nuclear atypia only was present in 17 nodules (25%), architectural atypia only was present in 27 nodules (40%), nuclear and architectural atypia was present in 20 nodules (29%), and predominantly oncocytic features were present in 4 nodules (6%). The presence of nuclear atypia was associated with a significantly increased rate of malignancy (22 of 37 [59%] vs 2 of 31 [6.5%]; P < .001), whereas architectural atypia was not associated with malignancy (P = .8). Repeat FNA was performed in 42 of 68 nodules (62%). In nodules with initial nuclear and architectural atypia, benign repeat cytology had a high false-negative rate (3 of 6; 50%). CONCLUSIONS: Pediatric AUS nodules with nuclear atypia have a high rate of malignancy, but architectural atypia is not associated with malignancy. In nodules with nuclear atypia, repeat FNA may inform clinical decisions regarding the need for resection. In the absence of suspicious clinical features, nodules without nuclear atypia might be considered for observation rather than resection or repeat FNA.
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Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Adenocarcinoma Folicular/patologia , Adulto , Biópsia por Agulha Fina/métodos , Criança , Citodiagnóstico , Humanos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/patologia , Adulto JovemRESUMO
Background: It is uncertain whether the presence of autoimmune thyroiditis (AIT) increases the risk of thyroid cancer in children with thyroid nodules. This study evaluated the association between AIT and thyroid cancer in pediatric patients with thyroid nodules. Methods: A cross-sectional study was performed of pediatric patients (<19 years old) with a thyroid nodule (≥1 cm) who underwent fine-needle aspiration in an academic pediatric thyroid center. AIT was defined by the presence of thyroid autoantibodies or diffusely heterogeneous sonographic echotexture. The primary outcome was diagnosis of thyroid cancer. The association of AIT with thyroid cancer was evaluated with univariable and multivariable logistic regression. Associations of AIT with subject and nodule characteristics were also assessed. Results: Four hundred fifty-eight thyroid nodules in 385 patients (81% female) were evaluated at a median age of 15.5 years (interquartile range 13.5-17.0). Thyroid cancer was present in 108 nodules (24%). AIT was present in 95 subjects (25%) and was independently associated with an increased risk of thyroid cancer (multivariable odds ratio [OR] 2.19, 95% confidence interval [CI] 1.32-3.62). Thyroid cancer was also independently associated with younger age, nodule size, and solitary nodules, but was not associated with serum thyrotropin concentration. AIT was not associated with the likelihood of subjects undergoing thyroid surgery (p = 0.17). AIT was less commonly associated with follicular thyroid carcinoma than with papillary thyroid carcinoma (OR 0.22, CI 0.05-1.06). Among papillary thyroid carcinomas, AIT was strongly associated with the diffuse sclerosing variant (OR 4.74, CI 1.33-16.9). AIT was not associated with the extent of local, regional, or distant disease at thyroid cancer diagnosis. Conclusions: AIT is independently associated with an increased risk of thyroid cancer in children with thyroid nodules. These findings suggest that the evaluation of thyroid autoantibodies and thyroid echotexture may inform thyroid cancer risk assessment and surgical decision-making in children with thyroid nodules.
Assuntos
Doença de Hashimoto , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Tireoidite Autoimune , Adolescente , Autoanticorpos , Estudos Transversais , Feminino , Doença de Hashimoto/complicações , Humanos , Masculino , Estudos Retrospectivos , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/complicações , Nódulo da Glândula Tireoide/diagnóstico por imagem , Tireoidite Autoimune/complicações , TireotropinaRESUMO
CONTEXT: Proteinuria can cause or exacerbate hypothyroidism, possibly due to urinary loss of protein-bound thyroid hormone. However, the precise relationship between proteinuria and hypothyroidism remains unclear. OBJECTIVE: This work aimed to determine the prevalence of hypothyroidism in patients with proteinuria and the relationship between hypothyroidism and degree of proteinuria. DESIGN: A retrospective cohort study was conducted from December 1979 to March 2015. SETTING: This study was conducted at a large academic hospital. PATIENTS: All paired samples of urine protein and serum thyrotropin (TSH), measured within 24 hours, were obtained from adults (age >â 18 years) with at least one instance of urine protein greater than 0.2 g/day or mg/mg creatinine. MAIN OUTCOME MEASURES: Samples were stratified by urine protein tertile. Mean TSH and risk of TSH elevation were compared among tertiles using analysis of covariance and generalized estimating equations controlled for age, sex, samples per patient, and levothyroxine treatment. RESULTS: A total of 2676 samples were identified from 2136 patients. Meanâ ±â SE TSH (mIU/L) was increased in the highest tertile of urine protein (>â 1.75g/day) compared to the lower 2 tertiles (2.09â ±â 0.07 vs 1.59â ±â 0.07, 1.59â ±â 0.06, Pâ <â .001). The highest tertile had a greater prevalence of TSH greater than 5 mIU/L (17.2% vs 10.5%, 11.9%, Pâ <â .001) but a similar risk of TSH greater than 5 mIU/L (odds ratio [OR] 1.44; 95% CI, 0.67-3.09, Pâ =â .35). The highest tertile also had a higher prevalence (6.2% vs 3.4%, 2.6%, Pâ =â .003) and risk (OR 1.72; 95% CI, 1.05-2.84, Pâ =â .008) of TSH greater than 10 mIU/L. Similar results were observed when comparing samples with nephrotic-range proteinuria (>â 3.5g/day) to those with lesser proteinuria. CONCLUSION: Hypothyroidism is common among adults with proteinuria, and the risk of hypothyroidism is directly related to the severity of proteinuria.
Assuntos
Hipotireoidismo/epidemiologia , Proteinúria/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , História do Século XX , História do Século XXI , Humanos , Hipotireoidismo/etiologia , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Prevalência , Proteinúria/complicações , Proteinúria/patologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Testes de Função Tireóidea , Adulto JovemRESUMO
CONTEXT: Thyroid function may be assessed in children before cardiac surgery because of concerns that hypothyroidism or thyrotoxicosis might adversely affect cardiac function perioperatively. However, the relationship between preoperative thyroid dysfunction and surgical outcomes is unknown. OBJECTIVE: Determine the relationship between preoperative thyroid dysfunction and outcomes of pediatric cardiac surgery. METHODS: Retrospective cohort study (January 2005 to July 2019). SETTING: Academic pediatric hospital. PATIENTS: All patients <19 years old who underwent cardiac surgery with cardiopulmonary bypass and had thyrotropin (TSH) measured within 14 days preoperatively. Exclusion criteria included neonates (≤30 days), preoperative extracorporeal life support, salvage operations, or transplantation procedures. MAIN OUTCOME MEASURES: Subjects were stratified by preoperative TSH concentration (mIU/L): low (<0.5), normal (0.5-5), mildly high (5.01-10), or moderately high (>10). Outcomes were compared among subjects with normal TSH (control) and each group with abnormal TSH concentrations. The primary outcome was 30-day mortality. Secondary outcomes included time to extubation, intensive care unit and hospital length of stay, and operative complications. RESULTS: Among 592 patients analyzed, preoperative TSH was low in 15 (2.5%), normal in 347 (58.6%), mildly high in 177 (29.9%), and moderately high in 53 (9.0%). Free thyroxine was measured in 77.4% of patients and was low in 0 to 4.4% of subjects, with no differences among TSH groups. Thirty-day mortality was similar among TSH groups. There were no differences in any secondary outcome between patients with abnormal TSH and patients with normal TSH. CONCLUSION: Preoperative mild to moderate subclinical hypothyroidism was not associated with adverse postoperative outcomes in children undergoing cardiopulmonary bypass procedures.