Thyroid Carcinoma In Children Research Articles

Clinicopathological characteristics and prognostic analysis of medullary thyroid carcinoma in children and adolescents

Clinicopathological characteristics and prognostic analysis of medullary thyroid carcinoma in children and adolescents

Medullary thyroid carcinoma in children: current state of the art and future perspectives.

Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.

Calcitonin and complementary biomarkers in the diagnosis of hereditary medullary thyroid carcinoma in children and adolescents.

Medullary thyroid carcinoma (MTC) is a rare malignancy that is effectively curable by surgery. Unlike in adults, hereditary MTC has a predominant role in children. A fast and safe diagnosis is important to assure the good prognosis for the patients. A major cornerstone is the assessment of biomarkers, but the interpretation must respect their pre-, post- and analytical features. Especially calcitonin (Ctn) is a challenging biomarker in daily laboratory diagnostics. However, Ctn is of particular relevance for the diagnostic in MTC. The American Thyroid Association recommends thyroidectomy if the upper reference range of Ctn is exceeded. Interestingly, age-dependent reference ranges for children and adolescents have become available only recently for Ctn assays. With this review, we aim to highlight the importance of a timely diagnosis of MTC in children and adolescents. Recent developments in pediatric biochemical diagnostics of MTC were summarized. This includes guidance on interpretation of RET, Ctn, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 19-9, and chromogranin A. Currently, Ctn is the most investigated biomarker in the diagnosis of MTC in children and adolescents. Other biomarkers as PCT suggest complementary evidence about pediatric MTC but their interpretation based largely on adult's data. A successful treatment of MTC requires, besides results of biomarkers, information about medical history, RET gene analysis and recent guideline knowledge. More research is required to validate complementary biomarkers of Ctn in children. Additionally, the effect of different confounder on pediatric Ctn levels has to be further clarified.

Management of papillary thyroid carcinoma in children

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Prevalence and Spectrum of DICER1Mutations in Adult-Onset Thyroid Nodules

Abstract Context: DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Objective: Determine 1) the prevalence of DICER1 hotspot mutations in thyroid nodules; 2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; 3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Design: Population-based study of 14,993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot-positive cases, we selected 61, matched to DICER1 hotspot-negative nodules. We performed full sequencing of all exons and exon-intron boundaries of DICER1. Setting: Commercial and university-based laboratories in the United States and Canada Results: Among 14,993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot-positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot-negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot-negative nodules (32/61) than in DICER1 hotspot-positive nodules (4/59) (p<0.0001). Conclusions: DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

Differentiated thyroid carcinoma in children: A retrospective analysis of 125 pediatric cases from a single institution in India.

Thyroid carcinoma (TC) is extremely rare in children. We assessed the clinicopathological features, outcomes, recurrence pattern, and associated risk factors of differentiated thyroid carcinoma (DTC). Children aged ≤14years, pathologically diagnosed as DTC at a tertiary cancer institute between January 1998 and December 2015 were retrospectively analyzed. Survival outcomes were estimated using the Kaplan-Meier method. During 18years, 125 children with DTC were treated with a male:female ratio of 1:2.3. The median age was 12years (2-14years). Anterior neck swelling was the commonest presentation (72.8%). Histopathology revealed papillary thyroid carcinoma (PTC) in 123 children (98.4%). Extrathyroidal extension was seen in 32 children (25.6%). Sixty-eight children (54.4%) had nodal metastases and seven had distant metastasis. Relapse developed in 12 children. All were salvaged with subsequent surgery and radioiodine therapy. Eight children had persistent disease and one had a second malignant neoplasm. The median follow-up period was 9years 1month (1-20years). Five-year recurrence-free survival (RFS) was 94.8% and 5-year overall survival was 100%. Larger tumors (p-value=.001), extrathyroidal extension (p-value=.001), and nodal metastasis (p-value=.022) were significant predictors for RFS in univariate analysis. Pediatric DTC showed aggressive behavior characterized by a high rate of extrathyroidal extension and nodal and pulmonary metastasis. Persistent disease should be distinguished from recurrent disease as DTCs with metastatic disease remain stable for long time and usually respond well to radioiodine therapy. Our study reaffirmed favorable prognosis despite aggressive presentation and even after relapse.

Familial Non-Medullary Thyroid Carcinoma in Pediatric Age: Our Surgical Experience

BackgroundThe purpose of the article was to evaluate the existence of significant clinical, pathological and prognostic differences between familial and sporadic form of pediatric non-medullary thyroid carcinoma, in order to tailor the therapeutic strategy to be adopted for patients with family history.MethodsWe analyzed the records of 76 pediatric patients that underwent surgery for differentiated thyroid cancer from 2014 to 2019 at the Surgical Pathology Department of the University of Pisa, Italy. Among these, 20 (26,3%) had positive family history (familial non-medullary thyroid carcinoma—FNMTC group) while 56 (73.7%) were affected by sporadic forms (sporadic non-medullary thyroid carcinoma—SNMTC group).ResultsIn our study, the correlation between the FNMTC and the SNMTC group showed no difference in terms of tumor features like multifocality, bilaterality, capsular/extracapsular invasion and the presence of vascular emboli. A statistical significance, on the other hand, was revealed by observation of clinical outcomes, such as distant metastasis (p = 0,022), persistence of disease (p = 0,054) and necessity of radioiodine sessions (p = 0,005).ConclusionsThese findings suggest that family history may have an independent role on the outcome, expressing its action through an intrinsic more aggressive biological behavior. Therefore, familial non-medullary thyroid carcinoma in children represents a nosological entity that requires an accurate pre-operative evaluation, an adequate surgical strategy and a careful follow up.

Risk Factors and Prediction Model for Lateral Lymph Node Metastasis of Papillary Thyroid Carcinoma in Children and Adolescents.

PurposePapillary thyroid carcinoma (PTC) in children and adolescents is prone to lateral lymph node metastasis (LNM), which is a high-risk factor for recurrence. However, few studies focused on identifying risk factors and establishing prediction models for lateral LNM of PTC in children and adolescents.Patients and MethodsWe retrospectively reviewed consecutive cases of children and adolescents with PTC undergoing thyroidectomy and cervical lymph node dissection between January 2009 and December 2019. The demographics and clinicopathologic features were collected and analyzed.ResultsA total of 102 children and adolescents with PTC were enrolled in our study; 51 of whom had lateral LNM (50%). After adjusting for other risk factors, the independent risk factors for lateral LNM were multifocality (odds ratio [OR]: 6.04; 95% confidence interval [CI]: 1.653–22.092; p=0.007), tumor size (OR: 1.752; 95% CI: 1.043–2.945; p=0.034), and the number of central LNM (OR: 1.23; 95% CI: 1.028–1.472; p=0.023). The formula of the combined predictor is: Multifocality + 0.31 × Tumor size + 0.115 × Number of central LNM. The area under the receiver operating characteristic curve of multifocality, tumor size, number of central LNM, and the combined predictor was 0.706, 0.762, 0.748, and 0.855, respectively. When the value of the combined predictor was ≥2.2744, lateral LNM could be predicted. The sensitivity and specificity of the predicted value were 82.4% and 74.5%, respectively.ConclusionThe independent risk factors for lateral LNM in children and adolescents with PTC were multifocality, tumor size, and the number of central LNM. The prediction model can better predict the presence of lateral LNM.

Timely diagnosis of multiple endocrine neoplasia 2B by identification of intestinal ganglioneuromatosis: a case series

BackgroundMedullary thyroid carcinoma (MTC) in childhood is rare and has an unfavorable prognosis. To improve outcome, early diagnosis is essential. In patients with multiple endocrine neoplasia type 2B (MEN2B), MTC can occur already before the age of 1 year. Recognition of non-endocrine features of MEN2B may lead to timely diagnosis.PurposeTo describe how early recognition of non-endocrine features can lead to a timely diagnosis of MEN2B as well as the effect of recognition of premonitory symptoms on prognosis.MethodsA retrospective case series from the University Medical Center Utrecht/Wilhelmina Children’s Hospital, a Dutch national expertise center for MEN patients. All eight MEN2B patients in follow-up between 1976 and 2020 were included and medical records reviewed.ResultsIntestinal ganglioneuromatosis (IGN) as the cause of gastrointestinal (GI) symptoms was detected in seven patients. In three of them within months after birth. This led to early diagnosis of MEN2B, which allowed subsequent curative thyroid surgery. On the contrary, a MEN2B diagnosis later in childhood—in three patients (also) triggered by oral neuromas/neurofibromas—led to recurrent, persistent, and/or progressive MTC in five patients.ConclusionsNeonatal GI manifestations offer the most important window of opportunity for early detection of MEN2B. By accurate evaluation of rectal biopsies in patients with early onset severe constipation, IGN can be timely detected, while ruling out Hirschsprung’s disease. MEN2B gene analysis should follow detection of IGN and—when confirmed—should prompt possibly still curative thyroid surgery.

Thyroid cancer incidence in children and adolescents

Clinically detected thyroid cancer is rare in children, with one to three cases per 1 million children per year. The disease—a papillary carcinoma in most cases—is frequently more extensive at diagnosis in children than in adults, particularly in children aged younger than 10 years who often have large thyroid tumours with lymph node and lung metastases. 1 Hay ID Johnson TR Kaggal S et al. Papillary thyroid carcinoma (PTC) in children and adults: comparison of initial presentation and long-term postoperative outcome in 4432 patients consecutively treated at the Mayo Clinic during eight decades (1936–2015). World J Surg. 2018; 42: 329-342 Crossref PubMed Scopus (41) Google Scholar The overall prognosis is favourable even in cases of metastatic disease, but the treatment burden can be substantial, and thyroid cancer related deaths that are extremely rare during childhood and adolescence have been reported several decades after initial diagnosis, at an adult age. 2 Schlumberger M De Vathaire F Travagli JP et al. Differentiated thyroid carcinoma in childhood: long term follow-up of 72 patients. J Clin Endocrinol Metab. 1987; 65: 1088-1094 Crossref PubMed Scopus (221) Google Scholar The incidence of clinical thyroid cancer increases with age, and the extent of disease is usually less in adolescents and young adults, who have excellent long-term prognoses. Global patterns and trends in incidence and mortality of thyroid cancer in children and adolescents: a population-based studyThe pattern of thyroid cancer incidence in children and adolescents mirrors the pattern seen in adults, suggesting a major role for overdiagnosis, which, in turn, can lead to overtreatment, lifelong medical care, and side effects that can negatively affect quality of life. We suggest that the existing recommendation against screening for thyroid cancer in the asymptomatic adult population who are free from specific risk factors should be extended to explicitly recommend against screening for thyroid cancer in similar populations of children and adolescents. Full-Text PDF

Prevalence and Spectrum of DICER1 Mutations in Adult-onset Thyroid Nodules with Indeterminate Cytology.

DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Determine (1) the prevalence of DICER1 hotspot mutations in thyroid nodules; (2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; (3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Population-based study of 14 993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot-positive cases, we selected 61, matched to DICER1 hotspot-negative nodules. We performed full sequencing of all exons and exon-intron boundaries of DICER1. Commercial and university-based laboratories in the United States and Canada. Among 14 993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot-positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot-negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot-negative nodules (32/61) than in DICER1 hotspot--positive nodules (4/59) (P < .0001). DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

Histopathological profile of childhood thyroid carcinoma in Ibadan, Southwestern Nigeria.

Thyroid carcinoma is a common endocrine malignancy. It is however rare in childhood and often occurs as a result of radiation exposure or inherited genetic mutations. Most childhood thyroid carcinomas are well differentiated. There are very few epidemiological studies of this disease in Nigeria and our study aimed to determine the frequency in a subset of our population. The study aimed to determine the prevalence and histopathological characteristics of childhood thyroid carcinoma in our environment. This was a retrospective review of histopathologically diagnosed thyroid carcinoma in children less than 18 years of age in the Department of Pathology, University College Hospital, Ibadan over a 40-year period. Histopathological diagnosis, age, sex and other relevant clinical information were extracted from the hospital records and surgical pathology records of the department. All cases of patients under18 years old had their slides re-examined and reclassified by two pathologists according to the World Health Organization histopathological classification of thyroid tumours. There were 25 cases of thyroid carcinomas seen in children within the study period. Papillary thyroid carcinoma was the most common, accounting for 80% of the cases. Follicular carcinoma accounted for 12%, and medullary and anaplastic carcinoma accounted for 4% each. The mean age at presentation was 13 years. There was a female preponderance with females accounting for 60% of cases. Tumours with distant metastasis made up 20% of the cases. Childhood thyroid carcinomas are rare in our environment, with a minority of cases presenting with metastases.

Papillary thyroid carcinoma in children with Hashimoto's thyroiditis - a review of the literature between 2000 and 2020.

Thyroid cancer is the most common pediatric endocrine neoplasm representing 3% of all malignancies in children. Hashimoto's thyroiditis (HT) is also a common disorder in the pediatric age range. Patients with HT frequently develop enlarged thyroid with nodules. We aimed to provide a literature review on the frequency of papillary thyroid carcinoma (PTC) in patients with HT. A literature search of the PubMed database between 2000 and 2020 was performed, using the relevant keywords "papillary thyroid carcinoma," "Hashimoto's thyroiditis" and "children". We followed the PRISMA statement guidelines during the preparation of this review. Six studies (n=2,065 patients with HT) were retained for the final analysis. The follow-up of the patients with HT was from 2 to 10 years. PTC was diagnosed in 0.67-7.87% of the HT patients included in these studies. In patients with HT and nodules, the percentage of PTC varied between 5.13 and 35%. The overall occurrence of PTC in patients with HT was 3.07%. The number of patients developing thyroid nodules in relation to HT was increased. The development of PTC in children with HT appeared to be higher than in the normal population.

Papillary Thyroid Carcinoma in Children: Clinicopathological Profile and Outcomes of Management.

We aim to analyze the clinicopathological profile and outcomes of management for children with papillary thyroid carcinoma (PTC). Relevant clinical data of children ≤ 18years of age managed for PTC between January 2006 and July 2018 as well as details of their follow-up till December 2019 were retrospectively collected and analyzed. There were 82 children with PTC that were managed during the study period. At presentation, 39 (47.6%) had cervical lymphadenopathy, while 9 (11%) had systemic metastasis. Majority of patients 39 (47.6%) underwent total thyroidectomy with a selective neck dissection, while total thyroidectomy alone was performed in 26 (31.7%). Following surgery, hypocalcemia was seen in 39 (47.6%): 28 (34.1%) were temporary, while 11 (13.4%) were permanent. Twenty-eight (34%) developed persistent disease after surgery and 131I therapy. Significant risk factors for persistence and metastatic disease were metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014), respectively. The mean duration of follow-up was 60.3 (range 12-150) months with a mean overall disease-free survival of 60months (95% CI 57.11, 77.95). Children with papillary thyroid cancers present with aggressive disease, 47.6% with cervical nodal metastasis and 11% with distant metastasis in this cohort. The rate of post-thyroidectomy hypocalcemia in this study is substantial, and efforts to reduce it are actively being pursued. The presence of metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014) were the only significant risk factors for persistent and metastatic disease, respectively, in this study.

Long-term follow-up of differentiated thyroid carcinoma in children and adolescents.

Objectives The aims were to analyze the clinical features, response to treatment, prognostic factors and long-term follow-up of children and adolescents with differentiated thyroid carcinoma (DTC). Methods Eighty patients with DTC were studied retrospectively. All underwent total or near-total thyroidectomy, and in 75 cases, ablative iodine therapy was recommended. Patients were assessed periodically by tests for serum thyroglobulin levels and whole-body iodine scans. Age, gender, initial clinical presentation, histology, tumor stage, postoperative complications, radioiodine treatment protocol, treatment response, thyroglobulin (Tg), recurrence and long-term disease progression were evaluated. Results Seventy patients completed >2 years of follow-up (23 males, 47 females; median age: 14 years; range: 3-18years). Sixty-two patients showed papillary DTC and eight, follicular DTC. Sixty-five percent presented nodal metastasis and 16%, pulmonary metastasis at diagnosis. Six months after first radioiodine treatment, 36.2% of patients were free of disease. Seven recurrences were documented. At the end of follow-up, overall survival was 100%, and 87.2% of patients were in complete remission. Nine patients had persistent disease. We found a significant association between stage 4 and persistent disease. Hundred percent of patients with negative Tg values at 6months posttreatment were documented free of disease at the end of the follow-up. The analysis of disease-free survival based on radioiodine treatment protocols used showed no statistically significant differences. Conclusions DTC in children and adolescents is frequently associated with presence of advanced disease at diagnosis. Despite this, complete remission was documented after treatment in most cases, with a good prognosis in the long-term follow-up. Negative posttreatment thyroglobulin and stage 4 at diagnosis were significant prognostic variables.

Medullary Thyroid Carcinoma in Children

The vast majority of medullary thyroid carcinomas (MTC) in children are inherited as part of the multiple endocrine neoplasia (MEN) syndromes MEN2A and MEN2B, and the related variant, familial MTC. Prophylactic surgery in infants and children identified through genetic screening leads to the highest survival in these patients. This article summarizes the current recommendations for screening, treatment, and surveillance of children with MTC to provide a concise clinically relevant review for pediatric practitioners.

Thyroid carcinoma in children, adolescents, and young adults in Brazil: A report from 11 population-based cancer registries.

The increasing incidence of thyroid cancer has been described worldwide. Overdiagnosis, improved imaging, and increased environmental risk factors have contributed to the rising incidence. The objective of this study was to analyze the population incidence rate and trends during the period of 2000-2013 in children, adolescents and young adults (AYAs) in Brazil. Data were extracted from 11 population-based cancer registries (PBCRs) encompassing the five geographic regions of Brazil. Incidence rates per million in children (0-14) and AYAs (15-39) according to world population were analyzed according to sex, age, and type of carcinoma. Incidence trends were evaluated using joinpoint regression. During 2000 to 2013, we identified 11,081 children and AYAs (0-39 years) with thyroid carcinoma in 11 PBCRs, with an age-adjusted incidence rate (AAIR) of 42 cases per million. Females had a higher AAIR of 66 cases per million versus 14 cases per million in males. Age-specific incidence rate (ASR) increased with age. Geographic variation was also observed; the Midwest and Southeast regions had the highest ASR in all age groups. The lowest ASR in all age groups was seen in the North region. Papillary subtype was the most common. Overall, the incidence rates in children and AYAs significantly increased from 0.2 in 2000 to 2.8 in 2013 and from 47.1 to 115.3, respectively, with an annual average percent change of 18.8 [8.1; 30.6] for children and 7.9 [CI 5.6; 10.3] for AYAs. Rates of thyroid cancer, particularly the papillary subtype, are steadily increasing in children and AYAs, especially among females. There are variations among geographic areas. This increased incidence is unlikely to be explained by screening, as children less than 14 years of age do not typically undergo medical surveillance. Environmental risk factors must be investigated.

Differentiated thyroid carcinoma in children: Clinical characteristics and long-term follow-up.

Differentiated thyroid cancer (DTC) is rare in children, but it still remains the most common endocrine malignancy in children. The aim of this study was to analyze treatment response to radioactive iodine (RAI) therapy, clinical outcomes, recurrences, survival analysis, and long-term follow-up. We retrospectively reviewed the medical records of 43 pediatric patients (≤17 years of age) with DTC diagnosis after thyroidectomy who were treated with RAI. The follow-up protocol consisted of detailed clinical examination, testing of thyroid function, determination of serum thyroglobulin (Tg), and anti-Tg antibodies, and neck ultrasonography application. Forty-three pediatric patients (34 females and 9 males) treated with RAI for DTC in our institute. The median follow-up period was 54 months. The histologic classification was papillary thyroid cancer in 41 patients and the remaining 2 patients had follicular thyroid cancer. After the long-term follow-up, complete remission, partial remission, and recurrent-persistent disease were observed in 37 patients, 3 patients, and 3 patients, respectively. Among the series, 1 death occurred due to multiple metastases. The mortality rate is 2.56%. Total thyroidectomy followed by RAI appears to be the most effective treatment for patients with pediatric DTC in terms of reducing the rate of relapse and improving surveillance for recurrent disease.

Pediatric Differentiated Thyroid Carcinoma: Outcome in Response to Initial Treatment

Introduction: Though the differentiated thyroid carcinoma in children is a common pediatric endocrine malignancy, its prognosis is excellent with a proper initial treatment. Objectives: This is to evaluate the initial treatment patern for a good prognosis with longterm outcome in pediatric DTC patients. Methods: This study is a prospective one done in BSMMU during a period of 10 years in 52 post-operative pediatric DTC patients after excluding the follow-up missing patients. These patients are yet in a regular follow-up were outcome evaluated with clinical, pathological &amp; imaging studies. Results: All the patients got initial treatment of total thyroidectomy. About half of the group had undergone neck dissection along with total thyroidectomy. Forty six patients had taken 131-I therapy. The survival is 100%. Conclusion: The life expectancy for children with DTC is excellent. However, many patients experience adverse effects from thyroid surgery, resulting in life long complications. Bangladesh J of Otorhinolaryngology; October 2018; 24(2): 143-148

Metabolomics as a potential method for predicting thyroid malignancy in children and adolescents.

To identify potential metabolic biomarkers for distinguishing malignant and benign thyroid nodules in children and adolescents using a metabolomics approach. A total of 96 consecutive patients (median age 14.29 ± 2.31years, range 9-18years) who underwent thyroidectomy and 40 healthy controls were enrolled. Patients were assigned to the papillary thyroid carcinoma and benign thyroid adenoma groups according to postoperative pathologic biopsy. Plasma samples were preoperatively collected, and multivariate analysis was performed to identify differential metabolites. Papillary thyroid carcinoma could be distinguished not only from healthy serum but also from benign thyroid adenoma according to the metabolic profiles. A total of 17 metabolites were identified. Compared with those from benign thyroid adenoma patients and healthy controls, the metabolites from papillary thyroid carcinoma patients, including leucine, lactate, alanine, glycine, acetate, lysine and choline, were increased, while glucose was decreased. The metabolomics method based on proton nuclear magnetic resonance has great potential for identifying papillary thyroid carcinoma in children and adolescents. Lactate and glycine may be used as potential serum markers for the diagnosis of papillary thyroid carcinoma.