No abstract

Laboratory measurements of hemoglobin A1c above 6.5% were approved as an additional diagnostic criteria for diabetes mellitus by the American Diabetes Association in 2010. Several recent pediatric studies have cast HbA1c measurement in children in an unfavorable light in the pediatric population, by comparing HbA1c measurements to results on oral glucose tolerance test (OGTT) or fasting plasma glucose (FPG). However, many of these studies do not recognize that diabetes diagnostic criteria are based upon long-term health outcomes. In this sense, OGTT and FPG have themselves never been validated in the pediatric population. Studies to validate diagnostic tests for diabetes in pediatric populations may take a substantial period of time, and may prove unfeasible. However, studies that tie diagnostic results as a child to diagnostic results as an adult may be more feasible and may provide the data needed to determine which pediatric diagnostic criteria to use. Thus, for the time being, except for cases of hemoglobinopathy, cystic fibrosis, and a few other exceptions, describing HbA1c as ‘lacking in sensitivity or specificity’ in the pediatric population because of lack of correlation with OGTT is not scientifically sound.

Proximal interstitial 6q deletion involving Single-minded 1 (SIM1) gene causes a syndromic form of obesity mimicking Prader-Willi syndrome. In addition to obesity, Prader-Willi syndrome includes several other endocrinopathies, such as hypothyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. The endocrine phenotype of interstitial 6q deletion remains largely unknown, although clinical similarities between Prader-Willi syndrome and interstitial 6q deletion suggest endocrine abnormalities also may contribute to the interstitial 6q deletion phenotype. This report describes the endocrine phenotype in a propositus with the Prader-Willi-like syndrome associated with an interstitial 6q deletion including the SIM1 gene. Detailed endocrine evaluation of the propositus during childhood and adolescence revealed hypopituitarism, though initial endocrine evaluations during infancy were unremarkable. Our patient raises the possibility that hypopituitarism may be part of the phenotype, especially short stature, caused by interstitial 6q deletion. SIM1 plays an important role in the development of neuroendocrine lineage cells, implicating SIM1 haploinsufficiency in the pathophysiology of hypopituitarism seen in our propositus. Early identification of endocrine abnormalities can improve clinical outcome by allowing timely introduction of hormone replacement therapy. Hence, we suggest that detailed endocrine evaluation and longitudinal endocrine follow up be performed in individuals with proximal interstitial 6q deletion involving SIM1.

Objective: We hypothesized that most patients with 22q11.2 deletion and a history of hypocalcemia have inadequate parathyroid function, manifested by intact parathyroid hormone levels below normal. We aimed to evaluate intact parathyroid hormone levels both during normocalcemia and at hypocalcemia, in this population.Study Design: Retrospective chart review of 103 patients with 22q11.2 deletion born since 1997 and cared for at the Children's Hospital of Philadelphia. Calcium and intact parathyroid hormone drawn simultaneously were recorded, along with clinical presentation at hypocalcemia. Results: Forty-seven simultaneous Ca/intact parathyroid hormone values were available. Seventy-nine percent of calcium levels and 81% of parathyroid hormone levels were within normal range. There were 19 patients with a history of symptomatic hypocalcemia, for whom any available simultaneous Ca/parathyroid hormone levels, before, during, or after hypocalcemia were analyzed. In this subgroup, 59% of calcium and 76% of parathyroid hormone levels were normal. None had an intact parathyroid hormone of Ͼ39.2 pg/mL at hypocalcemia. Seventy-three percent of hypocalcemic events had a precipitating stressor. Conclusions: Hypoparathyroidism in 22q11.2 deletion is mild, manifesting as a phenomenon of decreased parathyroid hormone reserve. Subjects are normocalcemic most of the time, but are unable to mount elevated intact parathyroid hormone levels, and therefore unable to correct hypocalcemia, in response to stressors. Genet Med 2008:10(3):224 -228.Key Words: parathyroid hormone, PTH, calcium, Digeorge, 22q11.2, hypocalcemia, hypoparathyroidism, intact PTH Microdeletion of chromosome 22q11 occurs with an incidence of approximately 1/4000 -7000 live births. [1][2][3] This deletion results in failure of development of the derivatives of the 3rd and 4th pharyngeal pouches, with anomalous migration of the cells derived from the cephalic neural crest. 4 Clinical expression varies from one patient to another. Features can include congenital cardiac defects, hypocalcemia, short stature, immunodeficiency from thymic hypoplasia, palate abnormalities, cognitive impairment, and minor facial dysmorphism. 5 Hypocalcemia due to hypoparathyroidism in this population was described originally by Digeorge. 6 The parathyroids are derivatives of the 3rd and 4th pharyngeal pouches, and therefore hypoparathyroidism in this syndrome is not unexpected. It has been documented by aplasia or hypoplasia of parathyroid glands at surgery or autopsy. 7 Our center previously reported hypocalcemia in 77 of 158 (49%) patients. 8,9 Brauner et al. 10 combined a cross-sectional study with historical review to reveal abnormal parathyroid gland function in 69% of patients. However, hypoparathyroidism in 22q11.2 deletion syndrome has been difficult to characterize. The varying degrees of parathyroid dysfunction in the 22q11.2 deletion population, and even intra-individual variation in parathyroid function, have been described by multiple authors. 1,5,10 -15 We hypothesiz...

The modified CDC score chart is suitable for growth tracking of children with normal and extreme growth patterns; the measures correlate well with the %BMI and the chart can be incorporated easily into existing electronic health record systems for clinical use.

Diagnostic criteria for diabetes in children have not been established with nearly the rigor as that employed in adults. Recently revised American Diabetes Association (ADA) criteria allowed utilization of hemoglobin A(1c) (HbA1c) ≥ 6.5 % for diagnosis of diabetes. A recent series of pediatric studies appear to show that HbA1c has lower sensitivity than Fasting plasma glucose (FPG) or oral glucose tolerance test (OGTT). However, FPG and OGTT have themselves never been validated in children. Studies to validate diagnostic thresholds in children appear unlikely to take place. Thus, accepting the major ADA diagnostic criteria appears to be the best course of action for the pediatric community. One area in which correlation studies between HbA1c and FPG or OGTT might shed light is in the definition of criteria for intervention in 'pre-diabetes,' as the Diabetes Prevention Program Trial did not use HbA1c. However, such treatment, and the exact diagnostic thresholds at which it should be initiated in children, remains unproven.

A procedure is presented for evaluating and comparing the biological activity of biofilms attached to various biofilrn caniers by measurement of the glucose consumption rate. 1111S technique allows for the economical design and selection of small particulate biofilm carriers that will maximize substrate removal when used in industrial-scale fluidized bioreactors. Methods for ensuring reproducible results are described. To support the glucose consumption rate findings, biofilm dty weights were obtained at the conclusion of activity rate experiments, and scanning electron micrographs were taken to evaluate the presence of biofilm and to view surface characteristics. Fourteen different biofilm carriers were evaluated ranging from commercially available products to novel carriers designed specifically for this study. Carriers that exhibited the highest reaction rates in descending order included: Syntrex 1220 (Kinetico. Inc.), Kaldnes Carrier Element·····Modified (Kaldnes North America, Inc.), Kaldnes Carrier Element······Original (Kaldnes North America, Inc.), Macrolite Modified CEPP-02 (Kinetico, Inc.), Macrolite 357 (Kinetco, Inc.), and Virgin Foam Cubes (BB Bradley Co.). Results showed that the accumulation of biofilrn depended most strongly on carrier surface properties, such as surface roughness and specific surface area. The bioillm activity as measured by glucose consumption rate correlated well with activity determinations made by COD measurements when a complex carbohydrate was used as substrate in place of glucose. Substrate consumption rates in microreactors were within ±43% of those measured in a 3-L bioreactor. The method presented here produced highly reproducible results and may be used to accurately and economically screen a large number of newly-designed carriers for application in industrial bioreactor processes.

Objective: Inhaled corticosteroids (ICS) are exogenous glucocorticoids that typically have minimal systemic effects at standard doses. They are metabolized by the cytochrome P450 (CYP450) enzyme pathway in the liver; thus, they can cause unwanted side effects when used in conjunction with medications affecting this system. Here, we present a case of adrenal suppression (AS) secondary to combined usage of ICS and posaconazole, a known CYP450 inhibitor.Methods: Clinical and laboratory data were isolated and are presented.Results: A 9-year-old Caucasian female with history of hyper IgE syndrome. On chronic fluticasone and posaconazole for Aspergillus infection, she presented with fatigue and "facial puffiness" (cushingoid features). Low morning cortisol (0.3 μg/dL) prompted further evaluation. Low-dose (1 μg) adrenocorticotropic hormone (ACTH)stimulation test with peak cortisol level <1 μg/dL. Other causes of hypocortisolism were ruled out. Started on physiologic hydrocortisone (10 mg/m 2 /day) and fluticasone discontinued. After weaning hydrocortisone, repeat low-dose ACTH-stimulation test with peak cortisol of 21.8 μg/dL, consistent with resolution of AS. Conclusion:Cushingoid features, growth failure, and AS can all be side effects of exogenous corticosteroids. The risk of AS increases when ICS are paired with CYP450 inhibitors, such as triazoles. Patients on ICS are not routinely screened for hypocortisolism. AS should be considered in symptomatic patients on moderate-high doses of ICS for prolonged periods. AS is a high-risk condition; thus, providers must have high level of suspicion and be aware of this potentially life-threatening complication.