Rachel Kadakia

The Relationship of Insulin-Like Growth Factor 2 to Fetal Growth and Adiposity

Insulin-like growth factor 2 (IGF-2) is necessary for adequate human growth. Overexpression of the IGF2 gene is associated with fetal overgrowth and may play a role in the intrauterine programming of adipose tissue. As obesity in children is a major public health problem associated with early onset of comorbid metabolic diseases, identifying early life markers of obesity may serve as useful tool for counseling and implementation of preventive efforts before obesity develops. The relationship between IGF-2 and body composition is an emerging field of study and existing data are conflicting. In this review, we discuss the IGF2 gene and its function, highlight the proposed mechanisms for the effects of IGF-2 on adiposity, and examine the current literature studying the relationships between IGF-2 levels, changes within the IGF2 gene, weight, and adiposity. With additional study, IGF-2 may emerge as a useful marker of future obesity risk in infants.

Diabetes insipidus in infants and children

Diabetes insipidus, the inability to concentrate urine resulting in polyuria and polydipsia, can have different manifestations and management considerations in infants and children compared to adults. Central diabetes insipidus, secondary to lack of vasopressin production, is more common in children than is nephrogenic diabetes insipidus, the inability to respond appropriately to vasopressin. The goal of treatment in both forms of diabetes insipidus is to decrease urine output and thirst while allowing for appropriate fluid balance, normonatremia and ensuring an acceptable quality of life for each patient. An infants obligate need to consume calories as liquid and the need for readjustment of medication dosing in growing children both present unique challenges for diabetes insipidus management in the pediatric population. Treatment modalities typically include vasopressin or thiazide diuretics. Special consideration must be given when managing diabetes insipidus in the adipsic patient, post-surgical patient, and in those undergoing chemotherapy or receiving medications that alter free water clearance.

Neonatal adiposity increases with rising cord blood IGF-1 levels.

Infants with higher adiposity at birth may be at greater risk of developing obesity later in life. IGF‐1 is important for intrauterine growth and may be a useful early life marker of adiposity, and thus later obesity risk. The aim of this study was to determine the relationship between cord blood IGF‐1, neonatal anthropometrics and markers of neonatal adiposity.

Squamosal suture craniosynostosis due to hyperthyroidism caused by an activating thyrotropin receptor mutation (T632I)

BACKGROUND Congenital hyperthyroidism can be a cause of failure to thrive, hyperactivity, developmental delay, and craniosynostosis during infancy. Most commonly, the condition occurs in the setting of maternal autoimmune thyroid disease. Rarely, congenital hyperthyroidism can also occur secondary to activating mutations within the thyrotropin (TSH) receptor. PATIENT FINDINGS A Hispanic male infant presented at age 6 months with severe thyrotoxicosis. At the time of presentation he was being evaluated for squamosal suture synostosis and he was noted to have significant developmental delays. SUMMARY The patients thyrotoxicosis was initially treated with antithyroid medication, and he subsequently underwent craniosynostosis repair leading to neurodevelopmental improvement. DNA from the patient and his parents was submitted for mutational analysis of exons 9 and 10 of the TSH receptor. He was found to carry a monoallelic transition 1895C>T in exon 10 that resulted in the substitution of threonine at position 632 by isoleucine (T32I). This mutation resulted in constitutive activation of the TSH receptor. Neither parent carried this mutation indicating that the child has acquired a de novo germline mutation. CONCLUSIONS We report the first case of squamosal suture craniosynostosis in a patient with non-autoimmune hyperthyroidism. Squamosal suture craniosynotosis is rare, often has a subtle presentation, and should be considered in all patients with this condition because prompt treatment of hyperthyroidism and craniosynotosis repair can lead to normalization of neurodevelopment.

Maternal pre-pregnancy BMI downregulates neonatal cord blood LEP methylation

Neonatal adiposity has many determinants and may be a risk factor for future obesity. Epigenetic regulation of metabolically important genes is a potential contributor.

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma: Should it also be reclassified in children?

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (noniEFVPTC) has low risk of adverse outcome in adults, warranting reclassification as noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP). In children, thyroid nodules have higher risk of malignancy and it is unknown if encapsulated FVPTC (EFVPTC) and infiltrative FVPTC (IFVPTC) tumors have different behavior. We analyzed the clinicopathologic features of follicular variant of papillary thyroid carcinoma (FVPTC) subtypes in our pediatric population to determine if noniEFVPTC has an indolent course as reported in adults.

Cord Blood Metabolites Associated with Newborn Adiposity and Hyperinsulinemia

Objective To evaluate the association between cord blood amino acid and acylcarnitine profiles and measures of adiposity and hyperinsulinemia in healthy newborns. Study design A cross‐sectional study of 118 full‐term infants born to mothers without gestational diabetes was performed. Cord blood leptin, C‐peptide, acylcarnitine, and amino acid levels were measured. Body composition was measured by air displacement plethysmography. Multivariate linear regression and principal component analysis were used to analyze associations of cord blood metabolites with newborn anthropometrics, leptin, and C‐peptide. Results Acylcarnitines AC C2, AC C4‐DC/Ci4‐DC, and AC C8:1‐OH/C6:1‐DC were positively associated with leptin, and AC C14, AC C14:2, AC C16, AC C18, and AC C18:2 were negatively associated with C‐peptide (P ≤ .0016). Principal component analysis revealed a positive association between factor 1(AC C2, AC C3, AC C5, AC C4/Ci4, AC C4‐OH, AC C4‐DC/Ci4‐DC, glutamate/glutamine, and glycine) and adiposity measures. Conclusions The positive association of AC C2 and AC C4‐DC/Ci4‐DC levels with leptin may reflect excess fat stores, higher fatty acid oxidation rate, and mitochondrial dysfunction leading to accumulation of acylcarnitine intermediates. Principal component analysis revealed a positive association between branched chain amino acid and ketone body metabolites and adiposity, confirming prior findings in adults. Cord blood acylcarnitine profiles may identify at‐risk children before obesity or insulin resistance develops.

Pheochromocytoma and Paraganglioma in the Pediatric Population

Pheochromocytomas and paragangliomas are rare tumors in the pediatric population that arise from neural crest cells. Prompt recognition and treatment are necessary to limit morbidity. Compared to adults, pheochromocytoma and paraganglioma in children are more likely to be associated with an underlying genetic syndrome, and genetic testing should be pursued. These tumors can produce catecholamines and present with symptoms such as sweating, nausea, emesis, hypertension, or diarrhea, or they can be nonfunctional and present with symptoms related to mass effect. Evaluation is initiated with measurement of urine and plasma metanephrines and diagnosis confirmed with magnetic resonance imaging. Definitive treatment occurs via surgical excision. A multidisciplinary team specifically trained in the management of pediatric PHEO and PGL is necessary for optimal patient care.

Use of Metformin for Weight Management in Children and Adolescents With Obesity in the Clinical Setting

Use of metformin for weight loss for children in a clinical setting has not been well described; therefore, we aimed to identify characteristics of obese patients prescribed metformin in a clinical setting and evaluate changes in anthropometric measures. Records of obese patients aged 10 to 18 years without diabetes attending an academic endocrinology practice from 2009 to 2013 were reviewed. Analyses assessed changes in anthropometric measures (weight, body mass index [BMI], and BMI z-score) over 12 months between those prescribed metformin (n = 49) and those not prescribed metformin (n = 142). Outcomes were standardized before using multivariable linear regression models. Patients prescribed metformin were significantly older, more often female, and had larger baseline anthropometric measures (all P < .05). In the models, subjects prescribed metformin had significantly less gain in standardized weight, BMI, and BMI z-score over 6 and 12 months (all P < .05). Metformin may be a useful weight management aid in children in a clinical setting.