Search

Exposure to asbestos is known to induce lung cancer, and our previous studies have suggested that specific chromosomal regions, such as 19p13, are preferentially aberrant in lung tumours of asbestos-exposed patients. Here, we further examined the association between the 19p region and exposure to asbestos using array comparative genomic hybridization and fluorescence in situ hybridization (FISH) in lung tumours and FISH characterization of asbestos-induced micronuclei (MN) in human bronchial epithelial BEAS 2B cells in vitro. We detected an increased number of 19p losses in the tumours of asbestos-exposed patients in comparison with tumours from non-exposed subjects with similar distribution of tumour histology in both groups (13/33; 39% versus 3/25; 12%, P = 0.04). In BEAS 2B cells, a 48 h exposure to crocidolite asbestos (2.0 μg/cm2) was found to induce centromere-negative MN-harbouring chromosomal fragments. Furthermore, an increased frequency of rare MN containing a 19p fragment was observed after the crocidolite treatment in comparison with untreated controls (6/6000 versus 1/10 000, P = 0.01). The results suggest that 19p has significance in asbestos-associated carcinogenesis and that asbestos may be capable of inducing specific chromosome aberrations. [ABSTRACT FROM AUTHOR]

Objective: Levothyroxine (LT 4 ) monotherapy is the current recommended approach for treating pediatric patients post-total thyroidectomy (TT) based on the assumption that peripheral conversion of thyroxine (T 4 ) to triiodothyronine (T 3 ) normalizes thyroid hormone levels. In adults, approximately 15% of post-TT patients on LT4 monotherapy have altered T 4 :T 3 ratios with ongoing debate in regard to the clinical impact with respect to health-related quality of life (hrQOL). The ability to normalize T 3 and T 4 levels on LT 4 monotherapy for pediatric patients' post-TT is important but not previously described. This study reports data on T 3 levels in athyreotic pediatric patients to determine if a similar cohort of patients exists on LT4 monotherapy targeting normalization of TSH (LT4 replacement) or suppression (LT4 suppression)., Methods: Thyroid function tests (TFTs) were retrospectively extracted from medical charts for patients <19 years old who underwent TT for definitive treatment of Graves' disease (GD) or differentiated thyroid cancer (DTC) between 2010-2021. LT4 dosing was selected to normalize the TSH in GD patients (LT4 replacement) or suppress TSH in DTC patients (LT4 suppression). Pre- and post-surgical TSH, T3 and T4 levels were compared., Results: Of 108 patients on LT 4 replacement (n=53) or LT 4 suppression (n=55) therapy, 94% (102/108) of patients demonstrated T 3 levels in the normal range post-TT. However, the majority of patients on LT 4 replacement (44/53; 83%) and LT 4 suppression (31/55; 56%) displayed post-TT T 3 levels in the lower half of the normal range despite 50% (22/44) and 48% (15/31) of these patients, respectively, having post-TT fT 4 levels above the upper limit of the normal range., Conclusion: A significant number of pediatric patients do not achieve similar T 3 and T 4 :T 3 levels pre- and post-TT. Future multi-center, prospective studies evaluating LT 4 monotherapy in comparison to combined LT 4 /LT 3 therapy are warranted to determine the potential clinical impact of altered T3 levels in athyreotic pediatric patients., Competing Interests: AB is a consultant for IBSA Pharm and Rare Thyroid Therapeutics/Egetis Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baran, Isaza, Bojarsky, Alzoebie, Song, Halada, Sisko, Gonzales, Mostoufi-Moab and Bauer.)

Introduction: Childhood cancer survivors (CCS) are at risk for radiotherapy (RT) late effects, including second malignancies. Optimal screening for differentiated thyroid cancer (DTC) in CCS post-RT remains controversial. We assessed the outcome of thyroid ultrasound (US) surveillance in CCS exposed to RT., Methods: 306 CCS were surveilled with thyroid US between 2002-2021. Surveillance was dependent on age at the time of primary diagnosis, interval from receipt of RT, and individual provider. Thyroid US, clinicopathologic features, and outcomes were described. Cutpoints of CCS RT age associated with varying risk of nodule presentation were explored. The selected cutpoints were used to define age categories, which were then used to compare thyroid nodule-related outcomes. Risk factors for thyroid nodule(s) were evaluated using multivariate logistic regression (odds ratio [OR] [95% confidence interval])., Results: The most common CCS diagnoses were leukemia (32%), CNS tumor (26%), and neuroblastoma (18%). Patients received TBI (45%) and/or RT to craniospinal (44%), chest (11%), and neck regions (6%). About 49% (n = 150) of patients had thyroid nodule(s). Forty-four patients underwent surgery, and 28 had DTC: 19 with American Thyroid Association (ATA) low-risk classification, 2 with ATA intermediate-risk, and 7 with ATA high-risk disease. Age cutpoint analyses identified cutpoints 3 and 10; hence, ≤3, &gt;3 to ≤10, and &gt;10 years were used. Of the 9 patients with intermediate- or high-risk disease, 8 were ≤10 years and 1 was &gt;10 years at the time of RT. Female sex (OR = 1.62 [1.13-2.12] p = 0.054) and greater interval between RT and first US (OR = 1.10 [1.04-1.16] p = 0.001) were independent risk factors for nodule presentation., Conclusions: Thyroid US surveillance may be beneficial for CCS exposed to RT at younger ages (≤10 years) for earlier detection of DTC, prior to developing advanced metastatic disease., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Radiation-induced lung injury is a rare complication of radioactive iodine therapy (RAIT) in pediatric thyroid cancer treatment. In this case report, we describe a pediatric patient with an ERC1::RET-positive classic papillary thyroid carcinoma who developed progressive respiratory symptoms and chest imaging abnormalities following RAIT for lymph node and pulmonary disease., Case Presentation: A pediatric patient with ERC1::RET-positive classic papillary thyroid carcinoma was hospitalized for pulmonary decompensation 3 months following one empiric dose of RAIT. Testing revealed no evidence of infection or progression of pulmonary metastases, and there was no improvement with empiric antibiotic therapy for pneumonia. Despite empiric anti-inflammatory therapies, the patient remains symptomatic from a respiratory standpoint with requirement for supplemental oxygen and evidence of fibrotic changes on chest imaging., Conclusions: This patient's pulmonary condition is consistent with radiation-induced pulmonary injury including development of pulmonary fibrosis. With the availability of RET fusion-targeted inhibitors, this case highlights a rare pulmonary side effect of radioactive iodine for clinicians to recognize. Upfront targeted therapy protocols may help avoid radioactive iodine-associated adverse reactions., (© 2023 S. Karger AG, Basel.)

Context: The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission., Objective: This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates., Methods: Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate., Results: Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015., Conclusion: Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Pediatric thyroid cancer (TC) incidence rates are increasing, yet TC has one of the highest survival rates. Despite increased prevalence, little is known about youth adjustment to TC, particularly compared to other pediatric cancers., Objective: The current study sought to describe health-related quality of life (HRQoL) in pediatric TC patients early after diagnosis compared to other pediatric cancer patients and healthy youth and examine predictors of HRQoL., Methods: Pediatric TC patients (ages 8.5-23.4 years) and their caregivers from a pediatric thyroid center completed psychosocial questionnaires as part of a clinic-based screening program around time of surgery. TC HRQoL was compared to other pediatric cancer and healthy youth reported norms. Clinical and demographic data extracted from the medical record were examined for predictors of HRQoL. The main outcome measures included the Pediatric Quality of Life Inventory (PedsQL) and Distress Thermometer., Results: Findings evidenced significantly higher HRQoL for TC patients than other pediatric cancers for all but emotional and school functioning. Compared to healthy youth, TC patients reported significantly lower functioning, except comparable social functioning. No significant differences in HRQoL were identified based on disease severity, thyroid disease history, or treatment. Patient distress was associated with HRQoL., Conclusion: The findings suggest general resilience in TC patients compared to youth with other cancers, yet worse HRQoL than peers. Early universal screening is warranted due to a short TC treatment regimen. If administrative barriers preclude comprehensive screening, the single-item Distress Thermometer may identify patients for further comprehensive screening., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Pediatric Graves' disease (GD) is associated with hyperthyroid symptoms that impact psychosocial and physical functioning. Total thyroidectomy (TT) is a definitive treatment option that replaces antithyroid medication. While studies have examined health-related quality of life (QOL) in adults, there are no data describing impacts of TT in pediatrics. In this prospective longitudinal study, we explored the impact of TT on disease-specific QOL and satisfaction with TT and scar appearance in adolescent patients with GD undergoing TT. Methods: Patients 12-19 years old pursuing TT for GD and their parents were recruited to complete surveys before and at least 6 months after TT. Surveys assessed motivations for pursuing TT, QOL, perceived stigmatization, self-esteem, scar appearance, and surgery satisfaction. Paired scores were compared using Wilcoxon signed-rank tests, and subscore associations were assessed using Spearman association tests. Results: Thirty-seven patient-parent dyads completed baseline surveys, including 20 patient-parent dyads completing pre- and post-TT surveys. At baseline, patients reported physical and cognitive symptomology, including tiredness, anxiety, and emotional susceptibility through ThyPRO . Psychosocial functioning at school was low through PedsQL . Disease-specific QOL significantly improved after TT, with notable improvements associated with resolution of goiter ( median change = - 26.14 , p  = 0.003), hyperthyroid symptoms ( median change  =  - 43.75, p  = 0.002), tiredness ( median change  =  - 26.79 , p  = 0.017), cognitive impairment ( median change  =  - 14.58 , p  = 0.035), anxiety ( median change  =  - 33.33, p  = 0.010), and emotional susceptibility ( median change  =  - 28.99 , p  = 0.035). Physical ( median change  = 18.75 , p  = 0.005) and school-related functioning ( median change  = 30.00 , p  = 0.002) also significantly improved post-TT. Reported GD-associated eye symptomology (thyroid eye disease) was the second lowest scoring ThyPRO subscore at baseline and improved after surgery ( median change  = 14.06, p  = 0.03). Families reported median recovery by two months, high satisfaction with the outcomes of TT, and minimal concerns over scar appearance. No permanent surgical complications (i.e., recurrent laryngeal nerve damage or hypoparathyroidism) were sustained. Conclusions: In the setting of a high-volume surgeon with low complication rates, TT for GD in pediatric populations may have substantial beneficial effects on disease-specific QOL and psychosocial functioning, with minimal adverse complaints about scar appearance.

Introduction: Risk of malignancy for pediatric thyroid nodules classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is not well defined. Correlations between risk of malignancy and ancillary clinical data remain inconclusive. We report a single institutional experience of fine-needle aspiration (FNA) to improve upon current management paradigm of thyroid nodules., Methods: A retrospective chart review of 575 thyroid nodules was performed of 324 patients who underwent 340 FNAs between 2008 and 2018 at the Children's Hospital of Philadelphia. Demographics, ultrasound (US) characteristics, FNA cytology, surgical pathology, and ancillary data were reviewed., Results: The rate of malignancy according to TBSRTC was 0.0% for category I, 0.8% for category II, 15.6% for category III, 54.5% for category IV, 100.0% for category V, and 100.0% for category VI. The cumulative Thyroid Imaging Reporting and Data System (TI-RADS) score was significantly correlated with benign and malignant nodules on pathology (p < 2.2e-16). Distribution of TI-RADS for cytologically indeterminate nodules with benign or malignant pathology revealed significant differences for composition (p = 3.20e-8) and echogenic foci (p = 0.005) but not for echogenicity (p = 0.445), shape (p = 0.160), margins (p = 0.220), and size (p = 0.105). Distributions of thyroid-stimulating hormone levels between benign and malignant patients was significant (p = 1.58e-3)., Conclusions: Nodules with TI-RADS scores >3 should undergo FNA, irrespective of size; surgical resection is recommended for nodules classified as TBSRTC category IV and V due to high risk of malignancy. US surveillance instead of FNA can be performed for nodules with TI-RADS scores ≤3., (© 2021 S. Karger AG, Basel.)