[Show abstract][Hide abstract] ABSTRACT: Context:
Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia (CAH) occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management.
To investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology.
A structured questionnaire was used to evaluate clinical, biochemical and imaging data. Genetic analysis was performed using Haloplex capture and next generation sequencing. Patients with CAH, adrenoleukodystrophy, autoimmune adrenal insufficiency or obvious syndromic PAI were excluded.
Nineteen tertiary pediatric endocrinology clinics.
Ninety-five children (48 females, age 0-18 years, 8 familial) with PAI of unknown etiology.
A genetic diagnosis was obtained in 77 (81%) patients. The range of etiologies was: MC2R (n= 25), NR0B1 (n=12), StAR (n=11), CYP11A1 (n= 9), MRAP (n= 9), NNT (n= 7), ABCD1 (n= 2), NR5A1 (n=1), AAAS (n=1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c.IVS3ds+1delG in MRAP. Several important clinical and molecular insights emerged.
This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (e.g. mineralocorticoid replacement), predicating co-morbidities (e.g. neurological, puberty/fertility), and for targeting clinical genetic testing in the future.
The Journal of Clinical Endocrinology and Metabolism 11/2015; DOI:10.1210/jc.2015-3250 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies performed on mice suggest that adropin is a peptide hormone playing a role in metabolic homeostasis and prevention of obesity-associated insulin resistance. Our study was conducted to investigate the role of adropin in children with obesity or metabolic syndrome. The study group consisted of 70 patients, including 42 obese and 28 with metabolic syndrome, and 26 healthy volunteers. After anthropometric variables and blood pressure of all participants were measured, serum lipids were analyzed, liver USG and oral glucose tolerance test were performed, and HOMA-IR values were calculated. Plasma adropin levels were collectively analyzed from collected plasma samples. In patient and control groups, no difference was observed in the levels of adropin (327.7±124.7 vs. 344.6±208.5 ng/L, respectively). The adropin levels of metabolic syndrome, obesity, and control groups also showed no difference (316±142.3, 335.8±112.5, and 344.6±208.5 ng/L, respectively). While the adropin levels of patients with and without hepatic steatosis were 319.6±123.7 and 347.8±128.7 ng/L, respectively, patients with HOMA-IR values of <3.16 and ≥3.16 had levels 342.3±124.8 and 296.5±136.7 ng/L, respectively. Although statistically insignificant, our findings are considered to support the hypothesis suggesting a nexus between adropin and obesity and metabolic syndrome. Small sample size in our study may have prevented our results to reach a more significant level. So, long-term follow-up studies with large population are needed to enlighten the role of adropin in metabolic homeostasis.
[Show abstract][Hide abstract] ABSTRACT: The previously reported activated intravascular coagulation system in the acute phase of respiratory distress syndrome (RDS) has not been evaluated in the long term. We assessed the activities of coagulation system of a cohort of premature infants with RDS in comparison with healthy premature infants (HPIs), healthy mature infants (HMIs), and pediatric laboratory controls over a 6-month period. Cord and venous blood samples were taken at birth, at the first month and sixth month. Protein C (PC), free protein S (f-PS), and antithrombin (AT) activities, thrombin-antithrombin (TAT) complex, prothrombin fragment 1 + 2 (PF1 + 2), and fibrinogen levels were measured. Mean PC, f-PS, d -dimer, and fibrinogen values were similar at all periods for HPI and RDS groups. Low neonatal anticoagulant proteins increased within 6 months in HMI and HPI groups. However, in RDS group, the AT activity remained significantly lower together with significantly higher TAT and PF1 + 2 levels both at the first month and at sixth month, suggesting a long-term consumption coagulopathy.
[Show abstract][Hide abstract] ABSTRACT: The prevalence of obesity among children and adolescents has been rapidly increasing in recent years. Obese individuals are at risk for vitamin D deficiency. The aim of this study was to investigate the relation of vitamin D deficiency with puberty and insulin resistance in obese children and adolescents. A total of 106 children and adolescents (48 prepubertal and 58 pubertal) between 8 and 16 years of age were included in the study. Fasting blood glucose, insulin, lipid profile, calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D [25(OH)D] levels, as well as blood glucose and insulin concentrations at 120 min of oral glucose tolerance test were measured. Insulin resistance was calculated using the homeostasis model assessment. Daily vitamin D intake was questioned. Serum 25(OH)D level was normal in only 3.8%, insufficient in 34.0%, and deficient in 62.2% of the subjects. There was a statistically significant rate of 25(OH)D deficiency in the pubertal group compared with that in the prepubertal group. Those subjects with 25(OH)D deficiency were found to have greater insulin resistance. Vitamin D deficiency is common among obese children and adolescents. Low vitamin D levels in obese individuals may accelerate the development of metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease by further increasing insulin resistance.