Algorithm-Driven Electronic Health Record Notification Enhances the Detection of Turner Syndrome.

Early diagnosis of Turner syndrome enhances care, but in routine practice, even within larger referral centers, diagnosis is delayed. Our study examines the utility of an electronic health record algorithm in identifying patients at high risk for Turner syndrome. Six percent of those identified had missed diagnoses of Turner syndrome.

Expanding Genetic and Functional Diagnoses of IGF1R Haploinsufficiencies.

BACKGROUND: The growth-promoting effects of IGF-I is mediated through the IGF-I receptor (IGF1R), a widely expressed cell-surface tyrosine kinase receptor. IGF1R copy number variants (CNV) can cause pre- and postnatal growth restriction or overgrowth. METHODS: Whole exome sequence (WES), chromosomal microarray, and targeted IGF1R gene analyses were performed on 3 unrelated children who share features of small for gestational age, short stature, and elevated serum IGF-I, but otherwise had clinical heterogeneity. Fluorescence-activated cell sorting (FACS) analysis of cell-surface IGF1R was performed on live primary cells derived from the patients. RESULTS: Two novel IGF1R CNV and a heterozygous IGF1R nonsense variant were identified in the 3 patients. One CNV (4.492 Mb) was successfully called from WES, utilizing eXome-Hidden Markov Model (XHMM) analysis. FACS analysis of cell-surface IGF1R on live primary cells derived from the patients demonstrated a ∼50% reduction in IGF1R availability associated with the haploinsufficiency state. CONCLUSION: In addition to conventional methods, IGF1R CNV can be identified from WES data. FACS analysis of live primary cells is a promising method for efficiently evaluating and screening for IGF1R haploinsufficiency. Further investigations are necessary to delineate how comparable IGF1R availability leads to the wide spectrum of clinical phenotypes and variable responsiveness to rhGH therapy.

Adrenal Insufficiency after Chronic Swallowed Glucocorticoid Therapy for Eosinophilic Esophagitis.

OBJECTIVE: To establish the prevalence of adrenal insufficiency (AI) in children with eosinophilic esophagitis treated with swallowed fluticasone propionate (FP) or budesonide. STUDY DESIGN: Children treated with FP or budesonide for ≥ 6 months underwent a low-dose adrenocorticotropin stimulation test. Patients using systemic, inhaled, intranasal, or topical glucocorticoids were excluded. The primary outcome is AI, defined as peak serum cortisol <18 µg/dL (≤ 495 nmol/L). RESULTS: Of 58 patients (81% male), 67% were on FP (median age 13.7 years [range 4.3-19.1], dose 1320 µg/d [440-1760], treatment duration 4.0 years [0.6-13.5]). Thirty-three percent were on budesonide (median age 10.7 years [range 3.2-17.2], dose 1000 µg/d [500-2000], treatment duration 3.4 years [0.6-7.7]). The overall prevalence of abnormal peak cortisol response (≤ 20 µg/dL) was 15% (95% CI 6%-25%) (indeterminate [18-20 µg/dL] 5% [n = 3] vs AI [<18 µg/dL] 10% [n = 6]). All patients on budesonide had a normal response vs only 77% of patients on FP (P = .02), all of whom were taking FP at a dose >440 µg/d. CONCLUSIONS: AI was present in 10% of children treated with swallowed glucocorticoids for ≥ 6 months and was found only in those treated with FP >440 µg/d. We recommend low-dose adrenocorticotropin stimulation testing in children treated long term with high dose FP to allow early detection of AI.

Low incidence of pathology detection and high cost of screening in the evaluation of asymptomatic short children.

OBJECTIVE: To determine the incidence of pathology during routine screening of healthy short children, testing adherence to a consensus statement on the diagnosis and treatment of children with idiopathic short stature, and the cost per identified diagnosis resulting from comprehensive screening. STUDY DESIGN: Retrospective chart review of 1373 consecutive short stature referrals evaluated at the Cincinnati Children's Hospital Medical Center Pediatric Endocrinology Clinic between 2008 and 2011. We identified 235 patients with a height of <3rd percentile, negative history and review of systems, and normal physical examination. Outcome measures were incidence of pathology detection, diagnostic group characteristics, clinicians' adherence to testing guidelines, and screening costs. ANOVA and χ(2) were used to analyze the data. RESULTS: Nearly 99% of patients were diagnosed as possible variants of normal growth: 23% with familial short stature, 41% with constitutional delay of growth and maturation, and 36% with idiopathic short stature. The incidence of newly diagnosed pathology was 1.3%: 1 patient with biopsy-proved celiac disease, 1 with unconfirmed celiac disease, and 1 with potential insulin-like growth factor I receptor defect. On average, each patient had 64.3% of the recommended tests for age and sex; 2.1% of patients had all of the recommended testing. The total screening tests costs were $315321, yielding $105107 per new diagnosis entertained. CONCLUSIONS: Healthy short children do not warrant nondirected, comprehensive screening. Future guidelines for evaluating short stature should include patient-specific testing.

Endocrine dysfunction following traumatic brain injury in children.

OBJECTIVE: To identify the incidence of endocrine dysfunction in children following traumatic brain injury (TBI). STUDY DESIGN: This was a prospective evaluation of 31 children after TBI. Inclusion criteria included Glasgow Coma Scale score ≤ 12 and age 1.5-18 years. We evaluated thyroid function, insulin-like growth factor I, insulin-like growth factor-binding protein 3, and cortisol at 1, 3, 6, and 12 months after injury, and assessed prolactin at 3 and 6 months. At 6 months, we also assessed overnight spontaneous growth hormone secretion, nocturnal thyrotropin surge, adrenal reserve, and serum and urine osmolarity. RESULTS: The average patient age was 11.6 years, and mean Glascow Coma Scale score was 6. The incidence of endocrine dysfunction was 15% at 1 month, 75% at 6 months, and 29% at 12 months. At 12 months after injury, 14% had precocious puberty, 9% had hypothyroidism, and 5% had growth hormone deficiency. Endocrine dysfunction at 1 year did not correlate with the severity of injury. CONCLUSIONS: Endocrine dysfunction after TBI is common in children, but most cases resolve by 1 year. We recommend endocrine surveillance at both 6 and 12 months following moderate or severe TBI to ensure early intervention for persistent or late-occurring endocrine sequelae.