Anastasios Papadimitriou

Regulation of the Hypothalamic-Pituitary-Adrenal Axis

Glucocorticoids (GCs) are essential for the maintenance of homeostasis and enable the organism to prepare for, respond to and manage stress, either physical or emotional. Cortisol, the principal GC in humans, is synthesized in the adrenal cortex. It is released in the circulation in a pulsatile and circadian pattern. GC secretion is governed by hypothalamus and pituitary. The hypothalamus senses changes in the external and internal environment that may disrupt the homeostatic balance of the organism (i.e. stressors), and responds by releasing corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from parvocellular neurons projecting from the paraventricular nucleus to the median eminence. These neurohormones are released into the anterior pituitary where they act synergistically via specific receptors (CRH-R1 and V1B receptor, respectively) to trigger the release of the adrenocorticotropic hormone (ACTH) from the corticotrope cells into the systemic circulation. In turn, ACTH exerts its actions on the adrenal cortex via specific receptors, type 2 melanocortin receptors (MC2-R), to initiate the synthesis of cortisol, which is released immediately into the systemic circulation by diffusion. Hypothalamic CRH and AVP, pituitary ACTH and adrenal GCs comprise the hypothalamic-pituitary-adrenal (HPA) axis. In this brief review, the HPA axis and the various factors that regulate its function are described.

Determinants of menarche

Menarche is a milestone in a womans life as it denotes the start of reproductive capacity. Aim of this report is to review the recent developments and the current knowledge in the neuroendocrinology of pubertal onset and the factors, genetic and environmental, that influence menarcheal age. We also review the implications of early or late menarcheal age on a young womans life.

Adherence to the Mediterranean type of diet is associated with lower prevalence of asthma symptoms, among 10―12 years old children: the PANACEA study

To cite this article: Arvaniti F, Priftis KN, Papadimitriou A, Papadopoulos M, Roma E, Kapsokefalou M, Antracopoulos MB, Panagiotakos DB. Adherence to the Mediterranean type of diet is associated with lower prevalence of asthma symptoms, among 10–12 years old children: the PANACEA study. Pediatr Allergy Immunol 2011; 22: 283–289.

Prevalence of Obesity in Elementary Schoolchildren Living in Northeast Attica, Greece

Objective: To assess the prevalence of obesity and obesity trend in schoolchildren living in Northeast Attica, Greece.

Dysregulation of the stress response in asthmatic children

The stress system co‐ordinates the adaptive responses of the organism to stressors of any kind. Inappropriate responsiveness may account for increased susceptibility to a variety of disorders, including asthma. Accumulated evidence from animal models suggests that exogenously applied stress enhances airway reactivity and increases allergen‐induced airway inflammation. This is in agreement with the clinical observation that stressful life events increase the risk of a new asthma attack. Activation of the hypothalamic–pituitary–adrenal (HPA) axis by specific cytokines increases the release of cortisol, which in turn feeds back and suppresses the immune reaction. Data from animal models suggest that inability to increase glucocorticoid production in response to stress is associated with increased airway inflammation with mechanical dysfunction of the lungs. Recently, a growing body of evidence shows that asthmatic subjects who are not treated with inhaled corticosteroids (ICS) are likely to have an attenuated activity and/or responsiveness of their HPA axis. In line with this concept, most asthmatic children demonstrate improved HPA axis responsiveness on conventional doses of ICS, as their airway inflammation subsides. Few patients may experience further deterioration of adrenal function, a phenomenon which may be genetically determined.

The hypothalamic-pituitary-adrenal axis in asthmatic children

Reduced responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in patients with various chronic allergic inflammatory disorders and a blunted HPA axis response of poorly controlled asthmatics before long-term treatment with inhaled corticosteroids (ICS) have been reported. It seems that pro- and anti-inflammatory cytokines might be involved in the attenuation of cortisol and adrenocorticotropic hormone (ACTH) responses to stress in these patients. Although long-term ICS treatment might produce mild adrenal suppression in some asthmatic children, improvement of adrenal function has been detected in the majority of cases. We postulate that the anti-inflammatory effects of ICS result both in asthma remission and HPA axis improvement. Adrenal suppression of some asthmatic patients on maintenance ICS seems to be a separate phenomenon, possibly constitutionally or genetically determined.

A Novel Monocarboxylate Transporter 8 Gene Mutation as a Cause of Severe Neonatal Hypotonia and Developmental Delay

Monocarboxylate transporter 8 acts as a specific cell membrane transporter for thyroxine and especially triiodothyronine into target cells. It is expressed in brain neurons and in many other tissues. The monocarboxylate transporter 8 gene resides on chromosome Xq13.2. An 11-month-old male infant was referred because of severe hypotonia from early life and global developmental delay. Thyroid-function tests showed normal thyrotropin levels and the characteristic for the disorder, including high serum triiodothyronine and low thyroxine concentrations. Molecular analysis of the monocarboxylate transporter 8 gene showed that the patient was hemizygous for a novel missense mutation P537L. This case highlights the importance of determining thyroid hormone levels, especially triiodothyronine, in infants with severe neonatal hypotonia.

Maturational tempo differences in relation to the timing of the onset of puberty in girls.

Aim: To determine maturational tempo differences related to the timing of pubertal onset in girls.

Breakfast cereal is associated with a lower prevalence of obesity among 10-12-year-old children: the PANACEA study.

BACKGROUND AND AIM Eating behaviours and obesity status among children have already been evaluated in several studies, with conflicting results. The aim of this study is to assess the correlation of breakfast cereal with childhood obesity. METHODS AND RESULTS A representative sample of 700 children (323 male) selected from 18 schools located in Athens greater area were enrolled. Children and their parents completed questionnaires that evaluated dietary habits and physical activity. We also retrieved information about the type of breakfast most frequently consumed. Height and weight of the children was measured and body mass index (BMI) was calculated. Simple and multiple logistic regression methods were used in order to determine the relationship between cereal intake for breakfast and obesity. Some boys (8.6%) and girls (9.0%) were obese, whereas 33.9% of boys and 22.1% of girls were overweight. For boys, the adjusted odds ratio for breakfast cereal intake for being overweight or obese was 0.54 (95% confidence interval (CI): 0.45-1.29), while for girls it was 0.41 (95% CI: 0.21-0.79). Moreover, the odds ratio of overweight/obesity for boys who ate daily breakfast was 0.51 (95% CI: 0.25-1.05), and for girls was 0.27 (95% CI: 0.12-0.64), adjusted for physical activity and other potential confounders. CONCLUSION These data provide evidence that breakfast cereal as a most frequent choice, and daily consumption of breakfast, are inversely associated with the prevalence of overweight or obesity in 10-12-year-old children.

The effect of inhaled budesonide on adrenal and growth suppression in asthmatic children

The present authors evaluated adrenal reserve in asthmatic children on long-term inhaled corticosteroids and whether possible adrenal suppression could be predicted by growth retardation. Low-dose synacthen test (0.5 µg·1.73 m−2) was performed in 72 asthmatic children with a median age of 9.4 (range 4.2–15.7) yrs on long-term treatment (median 18 (range 6–84) months) with low-to-moderate doses (median 363 (range 127–1012) µg·m−2) of inhaled budesonide, as well as in 30 controls. Adrenal suppression was considered as a peak serum cortisol <495 nmol·L−1. The current authors calculated height standard deviation score (HSDS) at the time of testing and height velocity SDS (HVSDS) in the preceding year. Mean HSDS was 0.06±1.3 and HVSDS was −0.9±2.3. Adrenal suppression was disclosed in 15 asthmatic children (20.8%). There were no differences in HSDS and HVSDS between children with and without adrenal suppression. There was no correlation between peak cortisol response and dose or duration of treatment. However, a positive relationship between HVSDS and duration of treatment was noted. These data suggest that long-term treatment of asthmatic children with low and moderate doses of inhaled budesonide may result in mild adrenal suppression that cannot be predicted by growth deceleration. The negative influence of inhaled corticosteroids on growth becomes less the longer the duration of treatment.