Circulating matrix metalloproteinases in children with diabetic ketoacidosis.

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) mediate blood-brain barrier dysfunction in inflammatory disease states. Our objective was to compare circulating MMPs in children with diabetic ketoacidosis (DKA) to children with type 1 diabetes mellitus without DKA. RESEARCH DESIGN AND METHODS: This was a prospective study performed at five tertiary-care pediatric hospitals. We measured plasma MMP-2, MMP-3, and MMP-9 early during DKA (time 1; within 2 h of beginning intravenous fluids) and during therapy (time 2; median 8 h; range: 4-16 h). The primary outcome was MMP levels in 34 children with DKA vs. 23 children with type 1 diabetes without DKA. Secondary outcomes included correlations between MMPs and measures of DKA severity. RESULTS: In children with DKA compared with diabetes controls, circulating MMP-2 levels were lower (mean 77 vs. 244 ng/mL, p < 0.001), MMP-3 levels were similar (mean 5 vs. 4 ng/mL, p = 0.57), and MMP-9 levels were higher (mean 67 vs. 25 ng/mL, p = 0.002) early in DKA treatment. MMP-2 levels were correlated with pH at time 1 (r = 0.45, p = 0.018) and time 2 (r = 0.47, p = 0.015) and with initial serum bicarbonate at time 2 (r = 0.5, p = 0.008). MMP-9 levels correlated with hemoglobin A1c in DKA and diabetes controls, but remained significantly elevated in DKA after controlling for hemoglobin A1c (ß = -31.3, p = 0.04). CONCLUSIONS: Circulating MMP-2 levels are lower and MMP-9 levels are higher in children during DKA compared with levels in children with diabetes without DKA. Alterations in MMP expression could mediate BBB dysfunction occurring during DKA.

Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene.

BACKGROUND: Lipoprotein Lipase (LPL) deficiency is a rare autosomal recessive disorder with a heterogeneous clinical presentation. Several mutations in the LPL gene have been identified to cause decreased activity of the enzyme. FINDINGS: An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. Genomic DNA analysis identified lipoprotein lipase deficiency due to compound heterozygosity including a novel p.Q240H mutation in exon 5 of the lipoprotein lipase (LPL) gene. His severe hypertriglyceridemia, including xanthomas, resolved with dietary long-chain fat restriction. CONCLUSIONS: We describe a novel mutation of the LPL gene causing severe hypertriglyceridemia and report the response to treatment. A review of the current literature regarding LPL deficiency syndrome reveals a few potential new therapies under investigation.

Underweight, overweight, and pediatric bone fragility: impact and management.

Skeletal health is modulated by a variety of factors, including genetic makeup, hormonal axes, and environment. Across all ages, extremes of body weight may exert a deleterious effect on bone accretion and increase fracture risk. The incidence of both anorexia nervosa and obesity, each involving extreme alterations in body composition, is rising among youth, and secondary osteoporosis is increasingly being diagnosed among affected children and adolescents. Compared with the elderly, the definition of osteoporosis that stems from any underlying condition differs for the pediatric population and special precautions are required with regard to treatment of young patients. Early recognition and management of both underweight and overweight youth and the accompanying consequences on bone and mineral metabolism are essential for preservation of skeletal health, although prevention of bone loss and optimization of bone mineral accrual remain the most important protective measures.

Anastrozole Improves Final Adult Height in Severe Hypothyroidism With Rapid Pubertal Progression.

Severe prolonged hypothyroidism due to Hashimoto thyroiditis may lead to rapid pubertal progression and compromised adult height after initiation of levothyroxine (LT4) therapy. There are no reports of aromatase inhibitor use to augment height in these patients. We describe a patient with severe hypothyroidism and growth failure who experienced rapid pubertal and bone age maturation on initiation of LT4 therapy. Anastrozole was added after 2 years to delay epiphyseal fusion. A boy aged 12 years and 1 month presented to the endocrine clinic with short stature and a markedly delayed bone age of 6 years. Brain magnetic resonance imaging showed a 1.5 × 1.0 × 1.2-cm enlarged lobular anterior pituitary. On examination, his height was -3.5 SD score (SDS) and weight was -2.87 SDS. Laboratory studies showed elevated thyrotropin (TSH) 850.6 µIU/mL, low free thyroxine 0.25 ng/dL, and elevated antithyroid antibodies. LT4 was initiated with normalization of TSH after 6 months. After 2 years of treatment he demonstrated catch-up growth with rapid bone age maturation, and his predicted adult height was compromised at 164.6 cm vs a midparental target height of 175.4 cm. Anastrozole 1 mg once daily was initiated. After 1.5 years of anastrozole treatment, the rate of his bone age advancement had slowed and his linear growth remained robust. The patient's near-final height (167 cm) was 2.4 cm taller than his height prediction prior to starting anastrozole. Anastrozole slowed the rate of bone age advancement in a patient with severe hypothyroidism and rapidly progressive puberty during treatment with LT4, leading to improvement in near-final height.

Recipe for Disaster: Homemade Formula Leading to Severe Complications in 2 Infants.

Families and physicians alike benefit from the advances and ease of the Internet. Similarly, both can be unaware of harmful misinformation circulating the Web. In this article, we describe the presentation of 2 unrelated infants, within 1 week of each other, with vitamin D deficiency rickets and severe extraskeletal manifestations of hypocalcemia, including seizures and cardiac arrest, from homemade, vegan formula found through Pinterest (San Francisco, CA). Despite good parental intentions this formula did not meet macronutrient and micronutrient standards, particularly regarding vitamin D, phosphorus, and calcium content, and led to rare, life-threatening complications in both cases. Before presentation, both patients followed appropriately with their pediatrician and discussed feeding in detail, although neither family disclosed the use of homemade formula. Pediatricians must be aware of these dangerous homemade alternative formulas, consider the manner and depth of their feeding history questioning, and continue to counsel against homemade formula to prevent further harm to children.

The Incidence of Erosive Esophagitis as a Complication of Pediatric Diabetic Ketoacidosis.

INTRODUCTION: Gastrointestinal (GI) symptoms commonly occur during diabetic ketoacidosis (DKA) and typically resolve with treatment. However, GI complications can persist after DKA resolves. The incidence of upper GI bleeding during DKA in adults has been described, with erosive esophagitis one of the most common lesions. The incidence of GI bleeding or erosive esophagitis in children with DKA has not been previously reported. We performed a retrospective chart review of DKA admissions in children 0 to <18 years with type 1 diabetes mellitus (T1DM) at a pediatric hospital between January 2009 and July 2016. Among 395 episodes of DKA over 7.5 years, erosive esophagitis occurred during two DKA admissions (0.5%) and there were no episodes of GI bleeding. Case presentations. Both episodes of erosive esophagitis occurred in adolescent males with known T1DM who presented with severe DKA. Both developed odynophagia after resolution of DKA and were readmitted for DKA recurrence. Upper endoscopy for both patients showed erosive esophagitis. Biopsies were negative for infection, though candida was found during one patient's endoscopy. Both had resolution of their esophagitis symptoms with medication management; neither has had recurrence. CONCLUSION: Erosive esophagitis, a rare complication of pediatric DKA, can manifest with odynophagia or substernal chest pain. This complication can lead to DKA recurrence, likely due to increased insulin resistance from inflammation and pain and from reduced oral intake and insulin administration. Patients with odynophagia associated with DKA should be monitored closely to allow timely evaluation and treatment of esophagitis.

SIADH in Systemic JIA Resolving After Treatment With an IL-6 Inhibitor.

Interleukin-6 (IL-6) is implicated in the pathogenesis of both systemic juvenile idiopathic arthritis (SJIA) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but the 2 have not been previously described as occurring together. We report a case of a 6-year-old girl with symptoms of arthralgia, daily fevers, evanescent rash, lymphadenopathy, and laboratory evaluation showing elevated inflammatory markers, consistent with SJIA. At presentation, the patient had hyponatremia with a sodium level of 128 mEq/L. She had low serum osmolality with elevated urine osmolality, consistent with SIADH. Hyponatremia improved temporarily during times of fluid restriction as expected in SIADH, but did not resolve until SJIA was treated successfully with tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity. The positive response to treatment with tocilizumab supports the role of IL-6 in the pathogenesis of both SJIA and SIADH. Patients with SJIA should be monitored for SIADH to avoid complications of untreated hyponatremia.

Pediatric Diabetes Outpatient Center at Rhode Island Hospital: The impact of changing initial diabetes education from inpatient to outpatient.

BACKGROUND: This study compared outcomes and costs for new-onset Type 1 diabetes mellitus (T1DM) patients educated at the outpatient versus inpatient settings. METHODS/DESIGN: Retrospective study examining the following variables: 1) hemoglobin A1c (HbA1c), 2) severe hypoglycemia, 3) admissions for diabetic ketoacidosis (DKA) or ER visits, and 4) healthcare cost. RESULTS: 152 patients with new-onset T1DM from September 2007-August 2009. There were no differences between outpatient group (OG) and inpatient group (IG) in mean HbA1c levels at 1, 2 and 3 years post-diagnosis (OG 8%, 8.5%, 9.3%; IG 8.3%, 8.9%, 9%, p=0.51). Episodes of severe hypoglycemia, DKA, and ER visits were not different between the two groups. Mean total hospital costs for OG and pure OG were significantly less than IG (OG: $2886 vs. IG: $4925, p<0.001), (pure OG: $1044 vs. IG: $4925, p<0.0001). CONCLUSION: Our study demonstrates that outpatient- based pediatric diabetes education lowers healthcare cost without compromising medical outcomes. [Full article available at http://rimed.org/rimedicaljournal-2017-02.asp].

Screening and Treatment of Common Lipid Disorders in Adolescents.

Cardiovascular disease remains a substantial health care burden in the adult population, the roots of which begin in childhood. Universal screening for dyslipidemia in all children and adolescents has been implemented to identify cases of FH that are otherwise missed by conventional screening because untreated FH can result in early CVD and untimely death. Recommendations for medical therapy did not change with the 2011 NHLBI guidelines. LDL levels targeted for therapy usually are elevated because of primary genetic disorders such as FH. Although these recommendations remain controversial, the benefit of universal screening and subsequent treatment of high-risk patients far outweighs the risk of not screening, although more investigation is warranted to understand the long-term outcomes of CVD risk in youth.

Rare complications of pediatric diabetic ketoacidosis.

The incidence of type 1 diabetes (T1D) among youth is steadily increasing across the world. Up to a third of pediatric patients with T1D present with diabetic ketoacidosis, a diagnosis that continues to be the leading cause of death in this population. Cerebral edema is the most common rare complication of diabetic ketoacidosis in children. Accordingly, treatment and outcome measures of cerebral edema are vastly researched and the pathophysiology is recently the subject of much debate. Nevertheless, cerebral edema is not the only sequela of diabetic ketoacidosis that warrants close monitoring. The medical literature details various other complications in children with diabetic ketoacidosis, including hypercoagulability leading to stroke and deep vein thrombosis, rhabdomyolysis, pulmonary and gastrointestinal complications, and long-term memory dysfunction. We review the pathophysiology, reported cases, management, and outcomes of each of these rare complications in children. As the incidence of T1D continues to rise, practitioners will care for an increasing number of pediatric patients with diabetic ketoacidosis and should be aware of the various systems that may be affected in both the acute and chronic setting.