Hypothalamic-pituitary function following childhood brain tumors: Analysis of prospective annual endocrine screening.

BACKGROUND: Outcomes for childhood brain tumors are now associated with a five-year survival rate of 75%. Endocrine effects of brain tumors are common, occurring in 43% of patients by 10 years from tumor diagnosis. Optimal timing of screening for endocrinopathies remains undefined. We aim to identify incidence and timing of endocrinopathies following brain tumor diagnosis, to better refine screening guidelines. METHODS: Retrospective chart review of patients referred to our hospital's neuro-oncology clinic for evaluation and treatment of brain tumors. Inclusion criteria were a positive history for brain tumor diagnosis and evaluation at our center. Data collection included demographics, tumor diagnosis, tumor therapy, and endocrinopathy diagnosis and timing. Laboratory data and clinical documentation were reviewed. RESULTS: Four hundred nineteen subjects were included for analysis. Tumor locations included supratentorial 158 (38%), posterior fossa 145 (35%), suprasellar 96 (23%), and upper spinal cord 20 (5%). Only 61% had undergone endocrine screening. Forty-five percent of screened patients had endocrinopathies. Endocrinopathy diagnosis typically occurred within six years after tumor diagnosis. Tumor recurrence and repeated therapies increased the risk for endocrinopathies within the subsequent six years after tumor therapy. Higher rates of endocrinopathies were identified in patients who had received cranial irradiation for posterior fossa, supratentorial, or suprasellar tumors. CONCLUSION: Endocrine screening should occur in childhood brain tumor survivors, particularly those who have received irradiation. Our study suggests that in children with brain tumors, the highest yield for finding a pituitary deficiency is within the first six years after tumor diagnosis and treatment. Screening should continue annually beyond six years, but with special attention in the subsequent six years after therapy for tumor recurrence. Prospective screening and endocrinology referral should be implemented in childhood brain tumor survivors.

Hypothyroidism and Iodine Deficiency in Children on Chronic Parenteral Nutrition.

BACKGROUND AND OBJECTIVES: Iodine is an essential trace element for maintenance of normal thyroid function. Normal thyroid function is a prerequisite for neurocognitive development and growth in children. In the United States, iodine is not routinely added as a trace element in parenteral nutrition (PN). Our objective was to determine the prevalence of iodine deficiency and hypothyroidism in children on chronic PN. METHODS: This was a cross-sectional study of children <17 years of age and using PN for >6 months at a tertiary children's hospital. Primary outcomes were spot urine iodine concentration (UIC), serum thyrotropin, and free thyroxine levels. RESULTS: Twenty-seven patients were identified (74% male). The median age at screening was 48 months (range: 7-213 months). The median duration on PN was 27 months (range: 11-77 months). Seventeen out of 20 patients (85%) were iodine deficient (spot UIC <100 µg/L), whereas 11 out of 20 patients (55%) were severely iodine deficient (spot UIC <20 µg/L). The prevalence of acquired hypothyroidism (elevated thyrotropin, low free thyroxine, and UIC <100 µg/L) was 33% (n = 8). None of the children with hypothyroidism screened for autoimmune thyroiditis had positive test results. There was no statistically significant association between duration of PN use and development of iodine deficiency (P = .08) or hypothyroidism (P = .96). CONCLUSIONS: Children on chronic PN are at risk for developing iodine deficiency and resultant hypothyroidism; hence, these children should be screened for these outcomes. Further studies are needed to define the temporal onset of iodine deficiency and timing to thyroid dysfunction related to PN.

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.

Severe Hypothyroidism From Iodine Deficiency Associated With Parenteral Nutrition.

Parenteral nutrition is crucial for supply of nutrients in children who cannot tolerate a full enteral diet. In the United States, it is not standard of care to give iodine to children dependent on parenteral nutrition, hence iodine is not routinely included in the micronutrient package. Herein, we present a case of a boy with hypothyroidism secondary to iodine deficiency after prolonged exclusive use of parenteral nutrition. Our case highlights the importance of screening for iodine deficiency and administering timely iodine supplementation in these at-risk children to prevent iatrogenic hypothyroidism.

Comparison of the immunogenicity of intramuscular versus subcutaneous administration of trivalent inactivated influenza vaccine in individuals with neuromuscular diseases.

Individuals with neuromuscular disease show a wide spectrum of muscle pathology. To test the hypothesis that the immune response to trivalent inactivated influenza vaccine is potentially inadequate when given intramuscularly into a fibrosed muscle, this prospective randomized study compared the immunogenicity and safety of the standard intramuscular versus subcutaneous administration of the influenza vaccine in 22 nonambulatory subjects, of whom 10 have been on glucocorticoid therapy. Analysis of hemagglutination inhibition antibody titers showed high prevalence of seroprotection (prevaccination of 82% H1N1, 72% H3N2, 31% B; postvaccination of 100% H1N1, 77% H3N2, 59% B). Geometric mean titer ratios for each antigen showed no significant difference (P > .5) between intramuscular and subcutaneous routes. Seroprotection was not adversely affected by glucocorticoid therapy. Local tolerance was better with subcutaneous route. Larger studies are needed to confirm these preliminary results.