Clinically detectable thyroid nodules are less common in children than adults. However, they are associated with an increased risk of malignancy. Therefore, thorough evaluation of paediatric thyroid nodules is necessary, and an understanding of the features associated with a higher risk of malignancy is important to guide management and referral. Thyroid cancer in children differs significantly from that seen in adults in terms of genetics, presentation, response to treatment and prognosis. Children often present with more advanced disease, but the vast majority have excellent long‐term prognosis. Evaluation and management of thyroid nodules and thyroid cancer require a multidisciplinary team approach and involvement of specialists with experience in this field. This review summarises investigative pathways for thyroid nodules in children and outlines current management strategies for paediatric thyroid nodules and cancer.

Aims/hypothesis: We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control. Methods: This was a prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of the Adolescent Cardio-Renal Intervention Trial (AdDIT). Participants were classified as ‘high ACR’ or ‘low ACR’ (lowest and middle ACR tertiles) using baseline standardised log₁₀ ACR. The primary outcome, 3DR, was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable Cox regression for the effect of high ACR, with HbA_1c, BP, LDL-cholesterol and BMI as covariates; diabetes duration was the time-dependent variable. Results: At baseline mean ± SD age was 14.3 ± 1.6 years and mean ± SD diabetes duration was 7.2 ± 3.3 years. After a median of 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high ACR (HR 2.1 [1.3, 3.3], p=0.001), higher mean IFCC HbA_1c (HR 1.03 [1.01, 1.04], p=0.001) and higher baseline diastolic BP SD score (HR 1.43 [1.08, 1.89], p=0.01) were independently associated with 3DR risk. Conclusions/interpretation: High ACR is associated with greater risk of 3DR in adolescents, providing a target for future intervention studies. Trial registration: isrctn.org ISRCTN91419926. Graphical

OBJECTIVE: Cardiac autonomic neuropathy (CAN) may contribute to vascular complications in diabetes. We hypothesized that adolescents with CAN are at greater risk of diabetic retinopathy and early kidney dysfunction.RESEARCH DESIGN AND METHODS: In this prospective longitudinal study of 725 adolescents with type 1 diabetes without retinopathy and albuminuria at baseline, early CAN was defined as one or more abnormalities in seven heart rate tests derived from a 10-min electrocardiogram. Retinopathy was defined as the presence of one or more microaneurysms, early kidney dysfunction as an albumin excretion rate (AER) >7.5 μg/min, and albuminuria as an AER >20 μg/min. Multivariable generalized estimating equations were used to examine the association between CAN and retinopathy or early kidney dysfunction. Cox proportional hazards regression analysis was used to assess cumulative risks of incident retinopathy and albuminuria.RESULTS: At baseline, the mean age of the sample was 13.6 ± 2.6 years, 52% were male, and mean diabetes duration was 6.1 ± 3.3 years. Over a median follow-up of 3.8 (interquartile range 2.2–7.5) years, the complication rate 27% for retinopathy, 16% for early kidney dysfunction, and 3% for albuminuria. The mean study HbA1c was 72.3 ± 16 mmol/mmol (8.6 ± 1.4%). CAN predicted incident retinopathy (odds ratio 2.0 [95% CI 1.4, 2.9]) and early kidney dysfunction (1.4 [1.0, 2.0]) after adjusting for HbA1c and diabetes duration. CAN also predicted retinopathy (hazard ratio 1.57 [95% CI 1.09, 2.26]) and albuminuria (2.30 [1.05, 5.04]) independently of HbA1c.CONCLUSIONS: CAN predicted incident retinopathy and kidney dysfunction in adolescents with type 1 diabetes, likely reflecting autonomic microvascular dysregulation contributing to complications. Therefore, screening and interventions to reduce CAN may influence the risk of complications.

Purpose of Review: Paediatric thyroid cancer management traditionally relied on extrapolation from adult data and, despite good survival outcomes, often involved extensive surgical approaches and radioactive iodine (RAI) therapy with potentially life‐long complications. Increasing understanding of paediatric diagnostic techniques, molecular tumour drivers and targeted therapies will allow a more nuanced, disease‐specific comprehensive model of care. This review summarises recent developments in paediatric thyroid cancer biology, diagnosis and models of care.Methods: Review of relevant literature from the last 5 years to inform a narrative summary by a multidisciplinary team of clinician experts in paediatric thyroid cancer management.Findings: Standardised risk scoring systems will likely improve the objectivity and accuracy of paediatric thyroid nodule risk stratification on ultrasound, but further studies are needed to validate these. Identification of somatic and germline gene variants is playing a rapidly increasing role in paediatric thyroid cancer diagnosis and planning of surgical approaches and neoadjuvant and adjuvant therapies. There is growing recognition that lobectomy may achieve comparable outcomes, with reduced risk of complications, to total thyroidectomy in patients with low‐risk disease. Molecularly targeted therapies are now available for the management of advanced disease as an adjuvant, and likely neo‐adjuvant, therapy for medical debulking of large tumours and resensitisation of RAI‐resistant disease.Conclusions: The management pathways for paediatric thyroid cancer are rapidly evolving due to the increasing availability of paediatric‐specific data. As management options become more complex, interdisciplinary collaboration and shared decision‐making are ever more important.

Background: The understanding of the molecular basis of paediatric thyroid carcinoma has expanded rapidly in the last decade. Most carcinomas are associated with de novo somatic gene alterations that confer distinct clinicopathological characteristics. In comparison to adults, paediatric carcinomas are less commonly associated with point mutations and more commonly with gene fusions, which are characterised by more-invasive disease. Cancer predisposition genes play an important role in a small percentage of tumours, and the family history and the recognition of other syndromic features are key to identifying these patients. Molecular testing platforms for clinical use have been developed and validated in adults, and their use is becoming established in the management of indeterminate thyroid nodules, where they significantly reduce the rates of diagnostic lobectomy. Paediatric data are more limited than adult data, and the role of molecular testing in paediatric thyroid carcinoma management is evolving. Methods: This review describes the current knowledge of molecular alterations in paediatric thyroid carcinomas, evidence supporting molecular testing in clinical practice, and future directions for research. Results and Conclusions: A molecular diagnosis enables the use of molecularly targeted therapies for children and adolescents with advanced or radioiodine-refractory disease. There is also great potential for molecular testing to improve the accuracy of the risk-stratification of paediatric thyroid nodules, reducing surgical intervention and complications without negatively impacting outcomes, and data to support such an approach are emerging.

Aim: Data on the impact of metabolic dysfunction‐associated fatty liver disease (MAFLD) on diabetes complications in youth with type 1 diabetes are lacking. However, MAFLD is well known to contribute to cardiovascular disease (CVD) in people with type 2 diabetes. We aimed to investigate markers of MAFLD in youth with type 1 diabetes and their relationship with chronic complications. Methods: A prospective study of 102 adolescents (mean age 14.7 ± 1.9 years) with type 1 diabetes underwent repeated annual diabetes complications assessments, including annual measures of liver enzymes. Early cardiac autonomic nerve dysfunction (CAN) was defined as ≥1 abnormality in seven heart rate variability parameters derived from a 10‐min resting electrocardiogram. Multivariate generalized estimating equations explored predictors of CAN and other microvascular complications (retinopathy and early kidney dysfunction). Results: After a median follow‐up of 3.5 years (IQR 2.7–4.6), there were significant increases in the mean alanine transaminase level (ALT) and systolic blood pressure (SBP) percentiles. Upper ALT and gamma‐glutamyl transferase (GGT) tertiles (T3 vs. T1‐2: odds ratio [OR], 95% confidence interval [CI], 2.05 [1.20, 3.48], and 2.99 [1.61, 5.58], respectively) predicted CAN development (23%, n = 24) independent of HbA1c and diabetes duration. They were not associated with retinopathy or early kidney dysfunction. Conclusion: Higher ALT and GGT associate with early CAN in adolescents with type 1 diabetes, suggesting hepatic inflammation may compound the impact of the diabetes milieu on systemic endothelial dysfunction.