ESPE Abstracts

Context: Puberty timing is highly heritable. Recent genome-wide association studies, comparing timing of menarche in girls to timing of voice-break and facial hair in boys, revealed a largely overlapping genetic architecture of female and male pubertal timing. However, it is also known that genetic heterogeneity between sexes exists for some loci.Objectives: We hypothesized that self-reported relative parental pubertal t...

Background: Aromatase (CYP19A1) a member of cytochrome P450 protein family is a major steroid metabolizing enzyme which converts androgens to estrogens. Mutations in aromatase can lead to autosomal recessive aromatase deficiency. An R192H mutation in CYP19A1 described earlier caused severe phenotype of aromatase deficiency with regressive virilization of the 46,XX new-born, but without signs of androgen excess during pregnancy. Computational studies suggested that R192H disrup...

Background: Cytochromes P450 proteins metabolize several steroid hormones, drugs and xenobiotics. All cytochromes P450s in the endoplasmic reticulum require P450 oxidoreductase (POR) for their catalytic activities. Earlier it has been shown that mutations in POR cause metabolic disorders of steroid hormone biosynthesis and also affect some drug metabolizing P450 activities. We aimed to characterize the mutations identified in nonclinical samples to access their effects on ster...

Background: Thyroid imaging is recommended to determine the aetiology of congenital hypothyroidism (CHT). Currently scintigraphy is the gold standard imaging modality. Negative scinitigraphy despite the presence of thyroid tissue may lead to a spurious diagnosis of athyreosis. Few centres routinely perform both scinitgraphy and ultrasound so that the incidence of misclassified athyreosis is unknown.Aim: To describe the incidence of sonographically normal...

Background: The steroidogenic enzyme aromatase (CYP19A1) is a protein located in endoplasmic reticulum (ER) that catalyzes the conversion of androgens to estrogens. Both deficiency and excess of aromatase activity lead to disease states implicating its role in human biology. Cytochrome P450 (CYP) enzymes in ER use reduced nicotinamide adenine dinucleotide phosphate through cytochrome P450 oxidoreductase (POR) for their metabolic activities. Mutations in POR cause disorders of ...

Background: It is well known that growth hormone (GH) brings about several effects, involving bone, body composition, lipids and glucose homeostasis. However, the complex interplay between these parameters is rather poorly studied in children with childhood-onset-GH deficiency (CO-GHD).Objective and hypotheses: To investigate lipids, adipokines (leptin- adiponectin- resistin) and glucose homeostasis and their relationship with bone and body composition i...

Background: GH treatment is effective in improving adult height (AH) in short children born Small for Gestational Age. If SGA children are short at the start of puberty, they could benefit from combined GH/GnRH Analogue (GnRHa) treatment.Objective and hypotheses: To determine the timing and progression of pubertal development in short SGA children, comparing GH treatment with combined GH/GnRHa treatment.Method: For the present stud...

Background: A broad spectrum of human diseases including abnormalities in steroidogenesis is caused by mutations in the NADPH P450 oxidoreductase (POR). POR transfers electrons from NADPH to several small molecules, non-P450 redox partners and all microsomal cytochrome P450 proteins. POR disruption affects all partners with disastrous consequences and POR knock-out mice are embryonically lethal. A number of POR mutations and polymorphisms have been characterized from patients ...

Background: Severe obesity due to hypothalamic involvement has major impact on prognosis in long-term survivors of childhood-onset craniopharyngioma. The long-term effects of rehabilitation efforts on weight development and obesity in these patients are not analysed up to now.Method: 108 patients with childhood-onset craniopharyngioma recruited in HIT Endo before 2001 were included in the study. Long-term weight development (BMI SDS after ...

Background: As a result of hypothalamic involvement and/or treatment-related hypothalamic damage, up to 75% of childhood craniopharyngioma patients develop hypothalamic obesity.outcome is important for optimization of treatment.Method: Eating behaviour was analysed in 101 survivors of childhood craniopharyngioma, recruited from 1980 to 2001 in the HIT-Endo multicentre study, and in 85 BMI-matched healthy controls using the Inventory for eating behavior a...