Objective We aimed to determine the reproducibility of TSH testing in pediatric patients referred to pediatric endocrinologists and to identify the threshold TSH levels that would predict the presence of antithyroid autoantibodies and inform decisions by pediatric endocrinologists to initiate or continue treatment with levothyroxine. Study Design We analyzed a retrospective case series of 325 children aged 1 to 18 years referred for hypothyroidism to the endocrinology clinic at a tertiary care children’s hospital. The receiver operating characteristic area under curve (AUC) determined the ability of the initial TSH level to predict pediatric endocrinologists’ treatment decisions, presence of thyroid autoantibodies, and reproducibility of elevated TSH on repeat testing. Results Of 325 patients, 191 were treated. The treated patients were more likely to have had a higher referral TSH, positive autoantibodies, and abnormal thyroid gland examination findings. An initial TSH of 5 had a specificity of only 14% for a repeat TSH of ≥5. An initial TSH level of 11 had a specificity of 90% for a repeat TSH of ≥11, with sensitivity of 90%. TSH was a relatively poor predictor (AUC, 0.711) of the presence of autoantibodies with optimal classification at TSH >8.8 mIU/L. It was better (AUC, 0.878) at predicting whether endocrinologists started or continued treatment with levothyroxine, with optimal classification at 8.2 mIU/L. TSH levels combined with antibody status and thyroid examination findings had the best ability to predict treatment (AUC, 0.930). Conclusions TSH levels slightly above the reference range should not prompt referral to pediatric endocrinologists unless another basis for clinical concern is present.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is rare in children and is hereditary (hMTC), caused by germline mutations in the RET proto-oncogene, in about 95% of cases. Very little is known about sporadic MTC (sMTC) when diagnosed in children/young adults. Our aim was to study the clinical presentation and long-term outcomes of a large cohort of sMTC seen at a tertiary cancer center and to compare sMTC with hMTC in young patients (pts). METHODS: Through a review of institutional databases, we identified pts diagnosed with MTC ≤ age 21 years (y.). Charts were retrospectively reviewed and data abstracted. The diagnosis of sMTC vs hMTC was determined based on germline RET testing and family history. RESULTS: We identified 146 pts (53% female), of whom 20 (14%) had sMTC and 126 (86%) had hMTC (80 MEN2a and 46 MEN2b), with a median follow-up of 10 y. (range: 0.08-58, IQR 4.8-18). In pts with sMTC, the stage at diagnosis was I-II in 3/15 (20%) and stage III-IV in 12/15 (80%). Somatic mutations were identified in 11/12 tumors tested (6 RET p.M918T, 1 RET p.G691S, 2 RET deletions p.L629_L633del and p.E632_L633del, 1 RET c.2698_2710delinsC, and 1 CCDC6-ALK fusion). In contrast to hMTC, pts with sMTC were diagnosed at an older age [mean 18.0 y. ± 3.4 (range: 10-21) vs 12.9 y. ± 5.4 (range: 1.5-21), p<0.001], had higher calcitonin [median 889 (IQR 528-2634) vs 16 (IQR 3-117) x Upper Limit of Normal, p<0.001] and CEA levels [median 186 (IQR 46-468) vs 11 (IQR 4-16) x Upper Limit of Normal, p<0.001], larger tumors [median 2.5 cm (IQR 2-3.7) vs. 0.8 cm (IQR 0.4-1.9), p<0.001], and were more likely to be stage IV at diagnosis [73% vs 28%, p<0.001]. sMTC pts were less likely to have bilateral tumors [27% vs 81%, p<0.001] and, at last follow-up, had more persistent structural disease [79% vs 46%, p=0.007] and distant metastases [74% vs 37%, p=0.005]. Death from MTC occurred in 15% of pts with sMTC vs 6% pts with hMTC; median overall survival was not significantly different [30.6 y. in sMTC vs 39.3 y. in hMTC]. CONCLUSION: In this largest reported series of MTC in children/young adults, and the only study to look at sMTC in this population, we identified sMTC in 14% of MTC cases, a higher prevalence than is traditionally recognized but one that is possibly confounded by a referral bias. Somatic mutations were identified in 92% of samples tested, allowing for targeted therapy in those with distant metastases if needed. Compared with hMTC, patients with sMTC presented at an older age with higher tumor markers, larger tumors, and more unilateral disease. At last follow-up, persistent structural disease and distant metastases were more common in sMTC. The differences in clinical presentation and long-term outcomes likely reflect a variable path to MTC diagnosis. In conclusion, sMTC in pts ≤ age 21 y. presents at an older age with more advanced disease, frequently has an actionable driver mutation, and may be more common than previously thought.

Background: Monitoring of blood glucose, ketones and/or adjustment of the daily insulin dose is usually required with intercurrent illness in children with type 1 diabetes (T1D). International Society for Pediatric and Adolescent Diabetes recommends sick day guidelines, including insulin adjustments, should be taught soon after diagnosis. At our center, caregivers of children with newly diagnosed T1D receive extensive inpatient education, including introduction to sick day management. However, there was no standardized education for calculation of extra insulin doses to treat ketosis, i.e. advanced ketone management. This resulted in increased calls for ketone management and potential readmissions to the hospital.Objectives: Through a quality improvement (QI) initiative, we aimed to (1) provide standardized education on advanced ketone management to 50% of patients with a new diagnosis of T1D, aged 5-18 years, at their initial outpatient visit within four weeks of diagnosis, and (2) decrease the number of telephone calls for management of ketosis without increasing calls for hypoglycemia.Methods: Baseline data for telephone calls pertaining to ketosis or hypoglycemia management, within four weeks of diagnosis, were collected retrospectively by chart review for all children with new onset T1D, aged 5-18 years, from April 2018 to September 2018 (n=23). Through a series of plan-do-study-act (PDSA) cycles, a standardized ketosis management patient education bundle and ketone dose calculation tool were created. A pre-assessment questionnaire was used to determine eligibility at the initial follow up visit, within four weeks of diagnosis. Advanced ketone management education was provided to eligible patients. A post-assessment questionnaire was used to assess retention of knowledge at the next follow-up visit. Results: Forty-two children were diagnosed with new onset diabetes from January 2019 to May 2019. Of these, 30 children (71%) qualified to participate in the QI project and were given pre-assessment questionnaires. Twenty children (67%) were eligible to receive education on advanced ketone management. Of these, 95% children received standardized education at their initial outpatient visit. One child did not receive education due to time constraints and education was provided at the next follow-up visit. 70% eligible children received post-assessment questionnaires and of these, 100% scored ≥70%. Telephone calls for ketosis management decreased (26% to 6%, p<0.001), but there was no change in calls for hypoglycemia (52% to 48%).Conclusion: Standardized education on advanced ketone management is feasible to be provided within four weeks of diagnosis of T1D. This can decrease telephone calls for sick day ketosis management without increasing calls for hypoglycemia. This can likely result in reduction of parental anxiety and diabetes related hospital readmissions.