A Case of Salt-Wasting Congenital Adrenal Hyperplasia with Triple Homozygous Mutation: Review of Literature.

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency represents a group of autosomal recessive disorders characterized by impaired cortisol production due to altered upstream steroid conversions, subclassified as classic and nonclassic forms. The genotype-phenotype correlation is possible in the most frequent case but not in all. Despite in literature many mutations are known, there is the possibility of finding a new genetic pattern in patients with CAH.

Comparison of triptorelin acetate vs triptorelin pamoate in the treatment of Central precocious puberty (CPP): a retrospective study.

The aim of this study is to compare the clinical and biochemical outcomes of triptorelin acetate (TPA) versus triptorelin pamoate (TPP) treatment in girls with central precocious puberty. A total of 60 patients with idiopathic CPP were retrospectively recruited. Thirty girls were treated with triptorelin acetate 3.75 mg/month (TPA group) and thirty girls in a second group received triptorelin pamoate 3.75 mg/4 weeks (TPP group). Patient follow-up at 12 and 24 months included GnRH Test at 12 months and baseline LH at 24 months. Patients were monitored with pelvic ultrasound, X-Ray of the hand and wrist and anthropometric evaluations. A total of 60/60 girls showed a good response to both formulations. Significant reductions in basal and LH peaks, estradiol values, breast pubertal stage, progression of bone age and growth velocity rate after 12 months treatment were obtained in both groups, demonstrating the equivalence of the two formulations in regulating the hypothalamic-pituitary-gonadal (HPG) axis. Triptorelin pamoate provided a more effective and significant reduction in LH peak after 12 months in comparison with triptorelin acetate more effective in reducing ovarian volume and endometrial thickness. Both formulations were equivalent, even though the LH peak was significantly lower in girls treated with triptorelin pamoate.

Gelastic seizures not associated with hypothalamic hamartoma: A long-term follow-up study.

OBJECTIVE: The objective of the study was to describe the electroclinical features, seizure semiology, and the long-term evolution of gelastic seizures (GS) not associated with hypothalamic hamartoma (HH). METHODS: We reviewed video-electroencephalogram (video-EEG) recordings from pediatric patients with GS without HH admitted to 14 Italian epilepsy centers from 1994 to 2013. We collected information about age at onset, seizures semiology, EEG and magnetic resonance imaging (MRI) findings, treatment, and clinical outcome in terms of seizure control after a long-term follow-up. RESULTS: A total of 30 pediatric patients were stratified into two groups according to neuroimaging findings: group 1 including 19 children (63.3%) with unremarkable neuroimaging and group 2 including 11 children with structural brain abnormalities (36.7%). At the follow-up, patients of group 1 showed better clinical outcome both in terms of seizure control and use of AED polytherapy. Our patients showed remarkable clinical heterogeneity, including seizure semiology and epilepsy severity. Electroencephalogram recordings showed abnormalities mainly in the frontal, temporal, and frontotemporal regions without relevant differences between the two groups. Overall, carbamazepine showed good efficacy to control GS. CONCLUSIONS: Patients with nonlesional GS have a more favorable outcome with better drug response, less need of polytherapy, and good long-term prognosis, both in terms of seizure control and EEG findings.

Pharmacokinetic considerations for anti-epileptic drugs in children.

INTRODUCTION: Epilepsy is a chronic and debilitating neurological disease, with a peak of incidence in the first years of life. Today, the vast armamentarium of antiepileptic drugs (AEDs) available make even more challenging to select the most appropriate AED and establish the most effective dosing regimen. In fact, AEDs pharmacokinetics is under the influence of important age-related factors which cannot be ignored. Areas covered: Physiological changes occurring during development age (different body composition, immature metabolic patterns, reduced renal activity) can significantly modify the pharmacokinetic profile of AEDs (adsorption, volume of distribution, half-life, clearance), leading to an altered treatment response. We reviewed the main pharmacokinetic characteristics of AEDs used in children, focusing on age-related factors which are of relevance when treating this patient population. Expert opinion: To deal with this pharmacokinetic variability, physicians have at their disposal two tools: 1) therapeutic drug concentration monitoring, which may help to set the optimal therapeutic regimen for each patient and to monitor eventual fluctuation, and 2) the use of extended-release drug formulations, when available. In the next future, the development of 'ad-hoc' electronic dashboard systems will represent relevant decision-support tools making the AED therapy even more individualized and precise, especially in children.

Investigational small molecules in phase II clinical trials for the treatment of epilepsy.

INTRODUCTION: Epilepsy is a neurological disorder that significantly impacts the quality of life of affected persons. Despite advances in research, nearly a third of patients have refractory or pharmacoresistant epilepsy. Even though numerous antiepileptic drugs (AEDs) have been approved over the past decade, there are no agents that halt the development of epilepsy. Thus, new and improved AEDs to prevent these conditions are necessary. AREAS COVERED: We highlight recent advances in new and innovative drugs for epilepsy disorders. We review three small molecule drugs in phase II clinical trials: Cannabidivarin, BGG492 (Selurampanel) and Ganaloxone. EXPERT OPINION: The full potential of Cannabidivarin will be realized by testing in other types of treatment-resistant seizures; if they are beneficial, larger phase III clinical trials would probably be undertaken in the same patient population. About BGG492, the challenge will be to find 'superselective' AMPAR antagonists targeting only calcium-permeable receptors, with specific mechanisms, that may be attractive partners for drugs in polytherapy. Moreover, there is anew interest surrounding Ganaloxone because of a new submicron formulation that improves its absorption and pharmacokinetic profile, but new studies are necessary before progressing. Further clinical innovations will define the future for these small molecule-type drugs in epilepsy therapeutics.

Thirty-year persistence of obesity after presentation to a pediatric obesity clinic.

BACKGROUND: Few large, long-term studies are available on the relationship between childhood and adult obesity. AIM: The present study examined the 30-year association between childhood and adult obesity in a large sample of girls with essential and uncomplicated obesity. SUBJECTS AND METHODS: 318 girls who had visited our Pediatric Obesity Clinic between January 1972 and December 1974 were re-contacted between January 2002 and December 2005. All had undergone an assessment of weight, height and pubertal status at the baseline visit. Anthropometry was performed again on those who agreed to take part in the follow-up visit. The women's general practitioners were also asked to compile a health questionnaire. Hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes were defined according to current guidelines. Rates are expressed as number of cases per 1000 person-years (PY). Multivariable Poisson regression was used to identify predictors of persistent obesity. RESULTS: 224 (70%) of the 318 girls took part to the 30-year follow-up study. They had the same baseline anthropometry of those not available at follow-up. Sixteen per cent of them were still obese at the 30-year follow-up, giving a persistence rate of obesity of 5.2 x 1000 PY. Tanner stages > or = 1 [rate = ratios (RR) from 4.73 to 7.74 for different stages, p < or = 0.021] and Z-score of BMI (RR = 2.72 for one SDS, p = 0.019) were independent predictors of obesity persistence. Having a university degree vs. an elementary degree was instead protective (RR = 0.32, p = 0.009). The most prevalent complication was hypertriglyceridemia (8.8 x 1000 PY), followed by hypercholesterolemia (rate = 8.4 x 1000 PY), hypertension (rate = 5.2 x 1000 PY) and diabetes mellitus (rate = 1.0 x 1000 PY). CONCLUSION: The study reinforces the notion that obesity should be prevented at an early age and shows that adolescents with severe obesity and low educational degree are at greater risk of becoming obese adults.

Early activation of vascular endothelial cells and platelets in obese children.

Obesity in adulthood is combined with vascular endothelial cell and platelet activation. In this study we evaluated whether or not such activation is already present in obese children. Forty obese (10.3 +/- 2.5 yr) and 40 nonobese (10.3 +/- 2.3 yr) children were studied. Circulating levels of soluble (s) intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, as indices of vascular endothelial cell activation, were assessed in both groups. Plasma concentrations of sP-selectin and sCD40 ligand, as indices of platelet activation, were also measured. Circulating levels of highly sensitive C-reactive protein (hs-CRP) and the lipid peroxidation product 8-iso-prostaglandin (PG)F(2alpha) were evaluated because of their ability to promote vascular endothelial cell and platelet activation. Circulating levels of all of the assessed markers were higher in obese than in nonobese children (sICAM-1, +38.8 +/- 13.3%; sVCAM-1, +26.5 +/- 13.7%; sE-selectin, +31.3 +/- 17.3%; sP-selectin, +31.7 +/- 16.9%; sCD40 ligand, +36.9 +/- 22.1%; total 8-iso-PGF(2alpha), +24.0 +/- 20.2%; hs-CRP, +76.6 +/- 12.9%; P < 0.0001). Significant correlations (P < 0.004) between plasma total 8-iso-PGF(2alpha) levels and circulating sICAM-1 (r = 0.485), sVCAM-1 (r = 0.506), sP-selectin (r = 0.449), sCD40 ligand (r = 0.498), and hs-CRP (r = 0.520) concentrations were found in obese children. In conclusion, an early activation of vascular endothelial cells and platelets was present in obese children. Increased lipid peroxidation was also present in these children and likely contributed to the observed proinflammatory phenotype.