Validating the Modified McGill Thyroid Nodule Score for Assessment of Preoperative Risk of Pediatric Thyroid Malignancy.

OBJECTIVE: The McGill Thyroid Nodule Score (MTNS) is a preoperative tool used to predict the risk for well-differentiated thyroid cancer in adults. It was developed by a multidisciplinary team using established evidence-based risk factors for thyroid cancer. The modified McGill Thyroid Nodule Score (mMTNS) was developed to predict malignancy risk in children. A pilot study suggested the mMTNS was able to assess malignancy risk in children with indeterminate cytology on fine needle aspiration (FNA). This study seeks to validate these findings. METHODS: Retrospective chart review identified subjects who underwent FNA biopsy and subsequent resection. Each patient was assigned a score to compare to final pathology. Statistical analysis was performed with SPSS. All tests were 2-tailed and statistical significance defined p < 0.05. Logistic regression used to determine predictive values of scores. RESULTS: 46 patients ≤21 years of age underwent resection of a thyroid nodule. Female predominance of 85% (n = 39). 78% (n = 36) of patients had palpable nodule. 65% (n = 30) found to have benign pathology and 35% (n = 16) found to have malignancy. Malignant nodules associated with greater mean mMTNS compared to benign [13.63 vs 7.23]. An mMTNS greater >12 had sensitivity of 86.7%, specificity of 90.3%, positive predictive value of 81.3%, and negative predictive value of 93.3%. CONCLUSION: Our data suggests the mMTNS continues to be a useful adjunct in predicting malignancy risk of pediatric thyroid nodules. An mMTNS >12 has a high risk for malignancy, which can aid in counseling and clinical decision making, particularly when there is indeterminate cytology on FNA. LEVEL OF EVIDENCE: IV.

Fasting ketone levels vary by age: implications for differentiating physiologic from pathologic ketotic hypoglycemia.

OBJECTIVES: Ketone production is a physiological phenomenon that occurs during beta-oxidation of free fatty acids. Distinguishing physiologic ketosis from pathologic over-production/underutilization of ketones is critical as part of the diagnostic evaluation of disorders of carbohydrate metabolism, but there is limited literature on normal ketone production with fasting. Our aim is to measure fasting serum beta-hydroxybutyrate (BHB) concentrations in healthy children after an overnight fast. METHODS: Children ≤18 years of age were prospectively recruited from elective procedures through our surgery centers. Exclusion criteria included a history of diabetes, hypopituitarism, adrenal, metabolic or inflammatory disorders, dietary restrictions, trauma, or use of medications that might affect blood glucose. Serum glucose, cortisol, and BHB were assessed after an overnight fast. RESULTS: Data from 94 participants (mean 8.3 ± 5.7 years, 54 % male, 46 % female, were analyzed. Children ≤3 years of age (19) have significantly higher mean (0.40 ± 0.06 mmol/L) and median (0.4, IQR 0.2-0.6 mmol/L) BHB concentrations compared to children >3 years of age (75) with mean (0.21 ± 0.02 mmol/L) and median BHB (0.1, IQR 0.1-0.2 mmol/L) (p<0.0001). Fasting BHB levels of >1.0 mmol/L was rare (2 %, N=2) and 74 % (N=70) of participants had BHB levels <0.3 mmol/L. CONCLUSIONS: BHB concentrations are significantly higher in young children (≤3 years of age) compared to older children. Fasting BHB levels >1.0 mmol/L are rare within our population and therefore may identify a value above which there may a greater concern for pathologic ketotic hypoglycemia. It is imperative to establish the normative range in children to differentiate physiological from pathological ketotic hypoglycemia.

Venous thromboembolism in the setting of pediatric central diabetes insipidus: a systematic review of the literature and report of 2 cases.

OBJECTIVE: Central diabetes insipidus (DI) is frequently identified preoperatively and/or postoperatively in patients with sellar or parasellar lesions. Early diagnosis and effective perioperative management of central DI is critical to minimize disruptions in fluid homeostasis. In particular, although venous thromboembolism (VTE) is generally less common in pediatric patients than their adult counterparts, isolated reports suggest that VTE occurs at a higher frequency in pediatric patients with central DI. METHODS: Using the PubMed, Scopus, and Springer Link databases, the authors performed a systematic review of the literature with regard to the incidence of VTE in pediatric patients with central DI. Inclusion criteria were availability of the full text in English, diagnosis of central DI and VTE in the same patient, and pediatric age defined as ≤ 21 years. Data were reported as median and interquartile range for continuous variables and as frequencies and percentages for categorical variables. Risk of bias assessments of the individual studies were performed using the Joanna Briggs Institute Critical Appraisal Checklists for case series and case reports. RESULTS: Of 2094 search results, 12 articles met the inclusion criteria and described a total of 17 cases of VTE in pediatric patients with central DI. Two additional patients from the authors' institution were added to this cohort. The underlying pathologies included craniopharyngioma (n = 6), suprasellar germinoma (n = 4), epileptic encephalopathy (n = 2), pilocytic astrocytoma (n = 2), prolactinoma (n = 2), Cushing disease (n = 1), failure to thrive (n = 1), and congenital hypothalamic syndrome (n = 1). Thrombotic complications included deep vein thrombosis (n = 10 [53%]), cerebral venous sinus thrombosis (n = 6 [32%]), pulmonary embolism (n = 4 [21%]), inferior vena cava thrombosis (n = 2 [11%]), and disseminated intravascular coagulation (n = 1 [5%]). There was a 26% mortality rate. CONCLUSIONS: VTE is a rare but potentially devastating postoperative complication that appears to have a higher incidence among patients with central DI. Although this review was limited by heterogeneous information across limited reports, pediatric neurosurgical patients with DI may benefit from more aggressive VTE surveillance and prophylaxis.

Method comparison of beta-hydroxybutyrate point-of-care testing to serum in healthy children.

Ketone production is a physiological phenomenon that occurs to avoid irreversible neurological damage from hypoglycemia, thereby serving as a marker of metabolic stress. The primary ketone body, beta-hydroxybutyrate (BHB), guides the diagnostic evaluation and management of many hypoglycemic disorders. Serum and point-of-care (POC) BHB values were not been compared in children without diabetes or metabolic disorders. We aim at comparing the serum and point-of-care BHB values in healthy children after an overnight fast. Eligible participants were ≤18 years of age prospectively recruited from elective procedures through our surgery centers. Exclusion criteria included a history of diabetes, hypopituitarism, adrenal, metabolic or inflammatory disorders, dietary restrictions, trauma, or use of medications that might affect blood glucose. The main outcome measure was comparing serum and POC BHB levels after a period of fasting. Data from 94 participants (mean age 8.29 ± 5.68 years, 54.3% male, 45.7% female, BMI mean 19.28 ± 5.25 kg/m2) were analyzed. There was a strong correlation between serum BHB (mean 0.25 ± 0.23 mmol/L) and POC BHB (mean 0.18 ± 0.20 mmol/L) (r s = 0.803, p < 0.0001). The majority (96.81%) of values for serum BHB compared with POC BHB fell within 0.1 ± 0.1 mmol/L. The average of difference between serum and POC BHB (the bias) was 0.064 mmol/L (95% CI 0.047-0.081), and percentage error was 3.19%. Point-of-care BHB is accurate and comparable to serum BHB levels in our cohort of children after an overnight fast. SYNOPSIS: Point-of-care BHB agrees with serum values in healthy children.

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs.

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.

Telomerase expression marks transitional growth-associated skeletal progenitor/stem cells.

Skeletal progenitor/stem cells (SSCs) play a critical role in postnatal bone growth and maintenance. Telomerase (Tert) activity prevents cellular senescence and is required for maintenance of stem cells in self-renewing tissues. Here we investigated the role of mTert-expressing cells in postnatal mouse long bone and found that mTert expression is enriched at the time of adolescent bone growth. mTert-GFP+ cells were identified in regions known to house SSCs, including the metaphyseal stroma, growth plate, and the bone marrow. We also show that mTert-expressing cells are a distinct SSC population with enriched colony-forming capacity and contribute to multiple mesenchymal lineages, in vitro. In contrast, in vivo lineage-tracing studies identified mTert+ cells as osteochondral progenitors and contribute to the bone-forming cell pool during endochondral bone growth with a subset persisting into adulthood. Taken together, our results show that mTert expression is temporally regulated and marks SSCs during a discrete phase of transitional growth between rapid bone growth and maintenance.

McGill Thyroid Nodule Score in Differentiating Benign and Malignant Pediatric Thyroid Nodules: A Pilot Study.

Objective The McGill Thyroid Nodule Score (MTNS) is a preoperative tool used to predict the risk for well-differentiated thyroid cancer given a specific nodule in adults. We evaluated the clinical utility of a modified pediatric MTNS with children and adolescents. Study Design Case series with chart review. Setting Tertiary care children's hospital. Subjects and Methods This is a retrospective chart review of 46 patients ≤18 years of age presenting with a solitary or dominant thyroid nodule treated with surgical resection between September 2008 and December 2015. The cumulative MTNS for each nodule was calculated and compared with the final pathology. Results Of 46 patients, 10 (21.7%) were diagnosed with well-differentiated thyroid cancer (80% papillary thyroid carcinoma, 10% follicular variant of papillary thyroid carcinoma, 10% follicular thyroid carcinoma). Malignant nodules were associated with a greater mean MTNS (benign, 5.72 ± 3.03; malignant, 16 ± 3.13; P < .05). The sensitivity, specificity, and positive predictive value of malignancy were 100%, 94.4%, and 83.3% for scores ≥10 and 80%, 100%, and 100% for scores ≥11, respectively. In nodules with indeterminate cytology (Bethesda III and IV), the pediatric MTNS showed good differentiation between benign and malignant disease, with mean scores of 7.95 and 12.5, respectively ( P = .006). Conclusion This pilot study suggests that a comprehensive scoring system may help assess the risk of malignancy in pediatric thyroid nodules and differentiate nodules with indeterminate cytology into higher- and lower-risk categories. Given these findings, larger, multi-institutional studies are warranted.