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Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Objective
The American Thyroid Association (ATA) Pediatric Guidelines recommend selective, prophylactic central neck dissection (pCND) for patients with papillary thyroid carcinoma (PTC) based on tumor focality, tumor size, and the surgeon’s experience. With the expansion of pre-surgical somatic oncogene testing and continued controversy over the benefits of pCND, oncogenic alteration data may provide an opportunity to stratify pCND. This study compared lymph node (LN) involvement in pediatric patients with PTC between tumors with low- and high-invasive-associated alterations to explore the potential utility of preoperative oncogenic alterations in the stratification of pCND.
Methods
This is retrospective cohort study of pediatric patients who underwent somatic oncogene testing post thyroidectomy for PTC between July 2003 and July 2022.
Results
Of 192 eligible PTC patients with postoperative somatic oncogene data, 19 tumors harbored somatic alterations associated with low-invasive disease (19/192, 10%), and 128 tumors harbored a BRAFV600E alteration (45/192, 23%) or an oncogenic fusion (83/192, 43%). Tumors with low-invasive alterations were less likely to present malignant preoperative cytology (2/18, 11%) than those with high-invasive alterations (97/124, 78%; P < 0.001). Twelve patients with low-invasive alterations had LNs dissected from the central neck (12/19, 63%) compared to 127 patients (127/128, 99%) with high-invasive alterations. LN metastasis was identified in two patients with low-invasive alterations (2/19, 11%) compared to 107 patients with high-invasive alterations (107/128, 84%; P < 0.001).
Conclusion
Pediatric patients with low-invasive somatic oncogenic alterations are at low risk for metastasis to central neck LNs. Our findings suggest that preoperative knowledge of somatic oncogene alterations provides objective data to stratify pediatric patients who may not benefit from pCND.
Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
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Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
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Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
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Introduction
Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility.
Objective
The aim was to analyze the association between RAI and serum AMH level in women treated with RAI.
Methods
We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured.
Results
The study included 47 patients with a mean age of 25.1 years (12.4–50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30–1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01–7.81); the level was 1.57 ng/mL (0.01–7.81) after multiple RAI doses and 2.99 ng/mL (0.01–6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39–7.81) than those who received more (1.0 ng/mL, 0.01–6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55–52.2, P = 0.014) after age adjustments.
Conclusion
Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.
Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
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Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands
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Amsterdam Public Health, Amsterdam, The Netherlands
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Department of Endocrinology and Metabolism, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
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Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
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Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
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Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
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Department of Pediatrics, Division of Metabolic Disorders, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
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Department of Laboratory Medicine, Amsterdam UMC, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands
Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
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Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
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Objective
Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007–2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model.
Methods
Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed.
Results
The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model’s performance.
Conclusions
The PPV improved significantly (26–48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.
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At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.
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Endocrinology Department, Instituto Nacional do Cancer do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
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Objective
A sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease presentation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influence of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors.
Design and methods
Clinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff.
Results
Postpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher risk of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status.
Conclusion
Our study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.
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Department of Pediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
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Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
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Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.
