Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 Oxidoreductase deficiency

Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. \ud \ud Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. \ud \ud Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. \ud \ud Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. \ud \ud Conclusion: Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR

Multifocal VEP (mfVEP) reveals abnormal neuronal delays in diabetes

This pilot study examined the diagnostic role of multifocal visually evoked potentials (mfVEP) in a small number of patients with diabetes. mfVEP, mfERG, and fundus photographs of both eyes of five patients with diabetes, three with nonproliferative diabetic retinopathy (NPDR) and two without NPDR were examined. Thirteen control subjects were also examined. Eighteen zones were constructed from the 60-element mfVEP stimulus array. mfVEP implicit time (IT) and amplitude (SNR) differences were tested between subject groups. We also examined whether there was a difference in function for patches with and without retinopathy in the NPDR group. Lastly, we compared mfVEP and mfERG results in the same patients. We found significant mfVEP IT differences between controls and all patients with diabetes, controls and diabetics without retinopathy, and between controls and diabetics with retinopathy. The subject groups did not differ significantly in terms of SNR. In the retinopathy group, ITs from zones with retinopathy were significantly longer than ITs from zones without retinopathy (P = 0.016). mfERG IT was more frequently abnormal than mfVEP IT. In addition, mfERG hexagons were twice as likely to be abnormal if the corresponding mfVEP zone was abnormal (P < 0.05). mfVEP implicit times are significantly delayed in patients with diabetes even when there is no retinopathy. These cortical response results are similar, albeit considerably less abnormal, than those previously reported for retinal (mfERG) responses in patients with diabetes. A correlation exists between the location of abnormal mfERG hexagons and abnormal mfVEP zones

Secular trends in growth in diabetes: are we winning?

Aim: To determine potential effects of modern treatment on growth in diabetic children. Methods: Retrospective analysis of growth in diabetic children stratified by their year of diagnosis between 1974 and 1995. A total of 451 children and adolescents attending the Diabetes Outpatient and Outreach Clinics of Royal Alexandra Hospital for Children in Sydney and rural NSW, Australia were studied. Standard deviation scores (SDS) for height and body mass index (BMI) were assessed at diagnosis, five years later (n = 451), and 10 years later (n = 111). Results: After five years of diabetes duration height SDS loss correlated with higher HbA(1c) and fewer injections. BMI SDS gain correlated with HbA(1c) and age at diagnosis. Although there was no significant difference in their height SDS or age at diagnosis, children diagnosed 1974–90 were significantly shorter than children diagnosed 1991–95 (height SDS 0.07 v 0.37) after five years diabetes duration. Furthermore, over 5 and 10 years, the 1979–90 group had lost significant height SDS (mean change -0.20 at 5 years, -0.29 at 10 years); this did not occur in the 1991–95 group (-0.01 at 5 years, -0.13 at 10 years). The BMI SDS increased significantly after 10 years in the 1974–90 group (mean change 0.37) but not in the 1991–95 group. There was no significant difference in the 174 females' age of menarche (13.0 v 12.8 years). Conclusions: Children with diabetes treated with modern regimens maintain their increased height from diagnosis better, and after five years diabetes duration, were taller than children diagnosed before 1991

Diabetes care, glycemic control, and complications in children with type 1 diabetes from Asia and the Western Pacific Region

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