Search Results (52)

Background: Thyroid disorders are significant endocrine conditions in pediatric populations, sometimes requiring surgical intervention. While surgical outcomes are well-documented, the broader impact on quality of life (QoL) remains insufficiently synthesized. This systematic review aimed to evaluate the effects of thyroid surgery on QoL in pediatric patients, focusing on physical, emotional, and social dimensions. Methods: Following the PRISMA guidelines, we searched PubMed, EMBASE, and SCOPUS from inception to January 2025. Studies reporting health-related QoL outcomes in pediatric patients undergoing thyroid surgery were included. Quality assessment was conducted using the Newcastle–Ottawa Scale. Data synthesis focused on emotional and psychological outcomes, social functioning, physical health, and surgical-approach-specific effects. Results: Five studies (ranging from 37 to 92 participants) met the inclusion criteria. Unilateral thyroidectomy was associated with better QoL outcomes compared to bilateral procedures, particularly in emotional and physical domains. Post-surgical anxiety significantly improved. However, male survivors reported higher levels of depression and reduced motivation. Employment status emerged as a significant factor influencing physical functioning scores. Thyroid cancer patients demonstrated better social functioning than peers with other cancers, yet they lagged behind healthy controls. Long-term follow-up highlighted ongoing challenges in physical functioning and fatigue. Conclusions: Thyroid surgery impacts multiple dimensions of QoL in pediatric patients, with variations depending on surgical approach and patient characteristics. These findings underscore the need for comprehensive post-operative care, including routine QoL assessments and tailored psychological support. Future research should aim to standardize assessment timing and develop targeted interventions for high-risk groups. Full article

Background/Objectives: Cowden syndrome (or PTEN hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. Methods: Next-generation sequencing and Sanger sequencing were used to search for PTEN genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. Results: A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the PTEN pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the PTEN gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. Conclusions: Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS. Full article

Cowden syndrome (CS) is a rare hereditary disorder characterized by benign overgrowth in various tissues and a high risk of breast and thyroid cancer. CS is closely associated with pathogenic variants (PVs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene. PVs in PTEN are usually inherited and estimates of de novo frequencies remain inconclusive. The diagnosis of PTEN-associated syndromes remains a challenge in clinical practice, due to patients showing seemingly unrelated symptoms. We report on the clinical management of a now 18-year-old female CS patient, who initially presented with macrosomia, motor development delay and later, lipomas on the abdominal wall. Genetic testing revealed a de novo PTEN PV c.1003C>T(p.Arg335X). The PV was detected in leukocyte DNA of the patient. Using direct DNA sequencing, as well as NGS, the PV was not found in any of the tissues derived from immediate family members. However, the PV was detected in multiple samples representing other germ layers of the affected patient, which renders constitutional mosaicism unlikely. This case constitutes the first description of a de novo PTEN PV, in which constitutional mosaicism was systematically ruled out and underscores the importance of timely genetic testing of patients and their relatives. The diagnosis of a PTEN PV in early childhood allows for the implementation of a comprehensive, lifelong care plan that addresses both pediatric and adult medical needs as well as cancer risk surveillance and family planning. This not only accounts for the affected patients, but also their close family members who might be susceptible to the same PV. Full article

Background/Objectives: Thyroid cancer incidence has risen in both the United States and Canada, despite differing healthcare systems. While overdiagnosis likely partly explains this trend in adults, its impact on younger populations is unclear. We used the North American Association of Central Cancer Registries, which included 133,808 thyroid cancer cases from the United States and Canada, to assess incidence trends among pediatric, adolescent, and young adult (PAYA) populations. Methods: Age-adjusted incidence rates (AAIR) per 100,000 person-years (PY) were compared using rate ratios (RR), stratified by sex, age, race/ethnicity (United States only), and histology. Joinpoint regression estimated annual percentage changes (APC) and average APCs (AAPC) in AAIRs. From 1995 to 2014, thyroid cancer incidence increased by 137%. Significant increases occurred across all age groups (0–14, 15–24, 25–34, 35–39 years). The rate increase was highest for papillary thyroid cancer (AAPC = 5.50, 95% CI 5.06, 5.94), and among individuals aged 35–39 years (AAPC = 5.99, 95% CI 4.84, 7.15). Of racial/ethnic groups in the United States, non-Hispanic White individuals had the highest AAIR (6.22 per 100,000 PY). Mortality has changed minimally. Conclusions: Over the past two decades, thyroid cancer incidence has increased in individuals under 40. While evidence suggests that overdiagnosis primarily accounts for this trend, other contributing factors cannot be ruled out. Further research and surveillance of the drivers of increased incidence are critical. Full article

Background: Differentiated thyroid cancer (DTC) in children and adolescents is a rare but significant malignancy, often presenting at more advanced stages compared to adults, although it is associated with favorable long-term outcomes. This study aimed to identify prognostic factors and perform risk stratification with the goal of identifying low-risk patients who would benefit from a less radical treatment approach. Methods: This retrospective cohort study included patients aged 21 years and younger with DTC treated at the Institute for Oncology and Radiology of Serbia between 1980 and 2024. Results: The study analyzed 99 patients (39 children, 60 adolescents) with a median follow-up of 15.6 years (range: 0.6–43.6 years). No significant differences in long-term outcomes were observed between children and adolescents. Multivariate regression analysis identified a total number of more than 10.5 positive lymph nodes and extrathyroidal tumor extension as independent predictors of adverse events and event-free interval (EFI). Using these prognostic factors, patients were stratified into three groups: low-risk (no risk factors), intermediate-risk (one of two risk factors), and high-risk (both risk factors). Statistically significant differences in EFI were observed among the three groups. Notably, none of the patients in the low-risk group had evidence of disease after treatment. Patients classified as having no evidence of disease after treatment demonstrated significantly better EFI compared to those with evidence of disease. Conclusions: Our findings highlight the importance of meticulous risk stratification in predicting long-term outcomes and might serve as a basis for developing personalized therapeutic strategies. Identifying low-risk patients who may benefit from a less aggressive treatment approach while ensuring optimal treatment and follow-up for high-risk patients remains a central objective in the modern management of DTC. Full article

Background: Autoimmune thyroiditis (AIT) is a common thyroid disorder in children, linked to an increased risk of papillary thyroid carcinoma (PTC). Characteristic ultrasonographic features of AIT can obscure PTC, delaying diagnosis. Case Presentation: An 11-year-old girl with a two-year history of AIT presented with persistently elevated thyroid-stimulating hormone (TSH) levels despite levothyroxine therapy. Examination revealed a firm, slightly enlarged right thyroid lobe. Serial thyroid ultrasounds showed typical AIT features, with no apparent tumor. However, a cervical lymph node ultrasound detected a suspicious lymph node with pathological vascularization. Fine-needle aspiration suggested possible PTC metastasis. The patient underwent total thyroidectomy with central and right lateral neck dissection. Histopathology confirmed multifocal PTC with cervical lymph node metastases (pT3aN1bM0). Postoperative radioactive iodine therapy resulted in undetectable thyroglobulin levels, indicating a biochemical response. Conclusions: Children with AIT may harbor occult PTC even without thyroid gland abnormalities suggestive of malignancy. Comprehensive ultrasound evaluation, including cervical lymph nodes, is vital for early detection and timely treatment. Full article

The prevalence of goiter, thyroid nodules, and thyroid cancers in the pediatric population has increased. In some rare cases, local conditions such as juvenile desmoid-type fibromatosis (JDTF) can mimic specific thyroid pathology, complicating the diagnostic process. A 17-year-old obese adolescent girl was admitted to the Endocrinology Department with progressive swelling on the left side of the neck, persisting for approximately one year, recently accompanied by dysphonia and inspiratory dyspnea, and ultimately diagnosed as a unilateral nodular goiter associated with compressive phenomena. Despite her euthyroid status, the thyroid ultrasound identified a suspected, large, non-homogeneous, hypoechogenic nodule with calcifications in the left thyroid lobe (TI-RADS score of 4), confirmed by a cervical-region MRI. The biopsy specimens obtained through fine-needle aspiration were classified as Bethesda III (“atypia of undetermined significance” or “follicular lesion of undetermined significance”). Left thyroid lobe removal was performed by a specialized surgeon in thyroid pathology, with histopathological analysis revealing a diagnosis of JDTF in the thyroid gland. Post-surgery, the patient showed favorable progress without any relapse. Pediatric endocrinologists face challenges in diagnosing and managing thyroid nodules in children due to their higher malignancy potential. Familiarity with similar conditions, such as JDTF, is crucial in accurate diagnosis and appropriate pediatric management. Full article

Background/Objectives: Pediatric populations with well-differentiated thyroid cancer typically have favorable prognoses. However, the role of radioactive iodine (RAI) ablation in these patients remains uncertain. This investigation evaluates the national trends, therapeutic practices, and the impact of RAI on clinical outcomes. Methods: Patients aged 21 years or younger with differentiated thyroid cancer, identified from the SEER database between 2000 and 2019, were analyzed. We compared the treatment approaches and survival outcomes of patients who underwent RAI ablation with those who did not. Results: This retrospective cohort study encompassed 5318 pediatric patients, with 55.9% (n = 2973) who underwent RAI ablation. RAI utilization declined from 65% to 38.4% in 2019. Compared with those who did not undergo RAI, RAI patients presented with a larger tumor size (mean size: 27.7 vs. 20.4 mm), a higher T3/T4 stage (35.8% vs. 15.3%), nodal metastases (60.7% vs. 28.8%), and distant metastases (2.7% vs. 0.9%) (all p < 0.001). Despite this, RAI was not an independent predictor of recurrence, second malignancy, or mortality. The analysis showed no significant differences in long-term survival between the RAI and non-RAI groups (p > 0.05), with African American patients having an increased risk of mortality (HR = 3.81; p = 0.038). Cancer-directed surgery emerged as a protective factor (HR = 0.08; p = 0.018), while RAI treatment did not significantly affect mortality risk (p = 0.09). Conclusions: Excellent pediatric thyroid cancer outcomes were achieved regardless of RAI use. Further research should clarify appropriate RAI indications while addressing racial outcome inequities. Full article

Objective: To assess racial and sex variances in second primary thyroid malignancy (SPTM) cumulative incidence and temporal trends and the radiation exposure effect in pediatric SPTM. Materials and Methods: A retrospective cohort study, a non-experimental epidemiologic design, was used to assess the cumulative incidence (CmI) and temporal trends as well as the exposure effect of radiation in SPTM among children, 0–19 years, in the Surveillance, Epidemiology, and End Results (SEER) registry, National Cancer Institute (NCI), USA. Percent change (PC) and annual percent change (APC) were used to examine CmI rates and temporal trends, while chi-square statistics and binomial regression models were used to examine variable distribution by race and to determine the exposure effect of radiation on SPTM as well as mortality, respectively. Results: The frequency of pediatric thyroid cancer was (n = 3457) between 1973 and 2013/14, while the PC was 151.2 for all races but 99.8 among whites. Of all pediatric thyroid cancers diagnosed during this period, SPTM accounted for 3% (n = 99). Compared to whites, blacks/AA were 60% less likely to present with SPTM, adjusted risk ratio, aRR = 0.40, 99% CI 0.06–2.47, while other races were 18% more likely to develop SPTM, aRR = 1.18, 99% CI 0.48–2.87. Additionally, females relative to males were 63% less likely to be diagnosed with SPTM, aRR = 0.37, 99% CI 0.22–0.61. With respect to urbanicity, compared to children in rural areas, those in urban areas were 21% less likely to develop SPTM, aRR = 0.79, 99% CI, 0.12–5.35, while children in metropolitan areas were 40% less likely to develop SPTM, aRR = 0.60, 99% CI, 0.10–3.59. Although imprecise, there was a 5% increased risk of SPTM, with radiation as an exposure effect, aRR = 1.05, 99% CI 1.01–1.75. Conclusions: There are increasing temporal trends in pediatric SPTM with blacks relative to whites having observed lower incidence, despite an increasing percent change among blacks/AA, indicative of the disproportionate burden of this malignant neoplasm. SPTM risk was higher among males and in rural areas, while radiation as a risk for SPTM was clinically and biologically meaningful, albeit an observed statistically insignificant inference due to sampling variability, requiring intervention mapping in radiation exposure margination among children. Full article

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies –with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer). Full article

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening. Full article

Background: Many epigenetic factors, including microRNAs, are involved in the process of changing gene expressions. Small non-coding RNA molecules, called miRNAs, are responsible for regulating gene translation by silencing or degrading target mRNAs. It is acknowledged that for many diseases, they may be novel diagnostic and prognostic biomarkers. Patients with autoimmune thyroid diseases are more likely to develop nodules in the thyroid tissue, and Hashimoto’s thyroiditis and Graves’ disease predispose patients to thyroid cancer. We evaluated the concentrations of microRNA molecules (miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p, miR-150-5p) in the blood of children with thyroid disorders. In addition, we wished to identify molecules whose change in concentration predisposes to the development of thyroid cancer. Aim: The aim of this study is to evaluate selected epigenetic elements by analyzing the levels of miR-15a-5p, miR-126-3p, miR-142-5p, miR-150-5p and miR-21-5p in the blood of pediatric patients with Graves’ disease (n = 25), Hashimoto’s thyroiditis (n = 26) and thyroid nodular disease (n = 20) compared to a control group of healthy children (n = 17). Materials and Methods: The study consists of groups of children and adolescents aged 10–18 years with autoimmune thyroid disease, with thyroid nodular disease compared to a control group. The miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p and miR-150-5p molecules were determined through an immunoenzymatic assay using BioVendor reagents. Results: There is a statistically significant decrease in the expression of the miR-15a-5p in children with Graves’ disease (21.61 vs. 50.22 amol/μL, p = 0.03) and in patients with thyroid nodular disease compared to controls (20.23 vs. 50.22 amol/μL, p = 0.04). Higher levels of the miR-142-5p molecule are found in patients with thyroid disease (with GD-3.8 vs. 3.14 amol/μL, p = 0.01; with HT-3.7 vs. 3.14 amol/μL, p = NS, with thyroid nodular disease-4.16 vs. 3.14 amol/μL, p = 0.04). Lower levels of miR-126-3p were noted in the GD group compared to the control group (7.09 vs. 7.24 amol/μL, p = 0.02). No statistically significant changes in the expressions of miR-150-5p and miR-21-5p molecules were observed in the study groups. Conclusions: 1. The overexpression of the miR-142-5p molecule occurs in children and adolescents with thyroid diseases. 2. Decreased blood levels of miR-15a-5p predispose patients to the formation of focal lesions in the thyroid gland. 3. Identifying a lower expression of the miR-126-3p molecule in the blood of children with GD requires careful follow-up for the development of focal lesions in the thyroid gland and evaluation for their potential malignancy. Full article

Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan–Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12–15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans. Full article

The association between Hashimoto’s thyroiditis (HT) and pediatric thyroid cancer is controversial. Most studies examining this connection have been based on adults, and larger studies in children are lacking. We performed a retrospective study of all sequential pediatric patients who underwent a thyroidectomy for a neoplasm at our institution over a twenty-year period in order to explore the link between HT and pediatric thyroid cancer. A total of 153 patients, median age 16.5 (interquartile range [IQR] 14.2–18.3) years, underwent thyroid surgery for a neoplasm. Patients were mainly female (80%) and White (84%). Median follow-up was 58.6 (IQR 20.7–105.4) months. Thirty-five (23%) patients had HT. Patients who underwent thyroid surgery and had HT were more likely to harbor a malignant neoplasm (p = 0.05); specifically, papillary thyroid carcinoma (PTC, p = 0.02). There was a difference in the distribution of HT among the subtypes of PTC (p = 0.03). Despite this, there was no difference in terms of survival between patients with/without HT. In conclusion, children with a thyroid malignancy, specifically, PTC, are more likely to have HT. The association between HT and pediatric PTC appears to be subtype-specific but does not seem to affect patient survival. Full article

While thyroid nodules are less common in children than in adults, they are more frequently malignant. However, pediatric data are scarce regarding the performance characteristics of imaging and cytopathology classification systems validated to predict the risk of malignancy (ROM) in adults and select those patients who require fine-needle aspiration (FNA) and possibly surgical resection. We retrospectively reviewed the electronic medical records of all patients 18 years of age or younger who underwent thyroid FNA at our institution from 1 July 2015 to 31 May 2022. Based on surgical follow-up from 74 of the 208 FNA cases, we determined the ROM for the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) ultrasound risk stratification system and The Bethesda System for Reporting Thyroid Cytopathology and added our results to those of pediatric cohorts from other institutions already published in the literature. We found the following ROMs for 1458 cases using ACR TI-RADS (TR): TR1. Benign: 2.2%, TR2. Not Suspicious: 9.3%, TR3. Mildly Suspicious: 16.6%, TR4. Moderately Suspicious: 27.0%, and TR5. Highly Suspicious 76.5%; and for 5911 cases using the Bethesda system: Bethesda I. Unsatisfactory: 16.8%, Bethesda II. Benign: 7.2%, Bethesda III: Atypia of Undetermined Significance: 29.6%, Bethesda IV. Follicular Neoplasm: 42.3%, Bethesda V. Suspicious for Malignancy: 90.8%, and Bethesda VI. Malignant: 98.8%. We conclude that ACR TI-RADS levels imply higher ROMs for the pediatric population than the corresponding suggested ROMs for adults, and, in order to avoid missing malignancies, we should consider modifying or altogether abandoning size cutoffs for recommending FNA in children and adolescents whose thyroid glands are smaller than those of adults. The Bethesda categories also imply higher ROMs for pediatric patients compared to adults. Full article