Publications

Brief summary: In this cross-sectional study, the growth pattern from birth until diagnosis of premature adrenarche (PA) was assessed in 82 children (16 boys) compared to 63 controls (15 boys). PA children were taller, heavier and had an accelerated linear growth. PA children also showed earlier adiposity rebound (AR) irrespective of whether they had obesity or not. A sex dimorphism was observed. The authors hypothesized that both earlier AR and accelerated linear growth may trigger adrenal androgen production and PA.

Transsphenoidal resection of adrenocorticotrophic hormone (ACTH)-producing pituitary adenomas has the potential of curing most patients with Cushing's disease. However, transsphenoidal exploration of the pituitary is not always curative, and patients who have remission of hypercortisolism following surgery occasionally develop a recurrence. Whether repeat pituitary surgery should be performed for recurrent or persistent Cushing's disease has not been evaluated previously. To determine the efficacy of transsphenoidal surgery in recurrent or persistent Cushing's disease, we performed transsphenoidal surgery in 31 patients (22 women and nine men) who had previously undergone a transsphenoidal operation and two female patients who had had previous pituitary irradiation only. In 24 (73%) of the 33 patients, remission of hypercortisolism was achieved by surgery. Although preoperative computerized tomography (CT) scanning identified an adenoma in only three of the 33 patients, in 20 patients a discrete adenoma was identified at pituitary exploration. The incidence of hypercortisolism was greatest if an adenoma was identified at surgery and the patient received selective adenomectomy (19, or 95% of 20 patients), if there was evidence at surgery or by preoperative CT scanning that the previous surgical exposure of the pituitary was incomplete (seven, or 78% of nine patients), if an adenoma was seen on preoperative CT scanning (three of three patients), or if the patient had had prior pituitary irradiation without surgery (two of two patients). In contrast, only five (42%) of 12 patients who received subtotal or total hypophysectomy had remission of hypercortisolim. Surgically induced hypopituitarism occurred in six (50%) of these 12 patients, but in only one (5%) of the 20 patients who underwent selective adenomectomy. Three (13%) of the 24 patients who were in remission from hypercortisolims following repeat surgery developed recurrent hypercortisolism 10 to 47 months postoperatively. Repeat transsphenoidal exploration of the pituitary and treatment limited to selective adenomectomy should be considered in patients with hypercortisolism despite previous pituitary treatment. If an adenoma is identified during surgery, the chance of remission of Cushing's disease is high and the risk of hypopituitarism is low; however, if no adenoma can be found and partial or complete hypophysectomy is performed, remission of hypercortisolism is less likely and the risk of hypopituitarism is about 50%.

In primates, ovine and human CRH cause ACTH- and cortisol secretion in a dose-dependent fashion. Ovine CRH has a half-life, which is about three times longer than that of human CRH and results in long lasting ACTH- and cortisol responses. Plasma ACTH- and cortisol rises after administration of human CRH mimic the spontaneously occurring secretory episodes of these hormones in man. Pulsatile administration of human CRH restores the diurnal secretory pattern of ACTH and cortisol to normal in patients with apparent CRH deficiency. Facial and upper body flush occur in about 20% of patients receiving intravenously a 1 microgram/kg dose of CRH. Higher doses result in hypotension due to a decrease in peripheral vascular resistance. The latter is primarily due to dilatation of the superior mesenteric vessels. In in vitro models desensitization of the pituitary corticotroph by continuous, high-dose CRH administration occurs. No down-regulation of ACTH- and cortisol secretion has been shown in vivo, however. Pituitary-adrenal responsiveness to CRH can be modulated by many factors. These factors are involved in the basal regulation of the hypothalamic-pituitary-adrenal axis and in its activation during the stress response. Such factors include AVP, morphine, DAMME, and drugs modulating the endogenous serotoninergic and GABA/benzodiazepine system. Glucocorticoid feedback inhibition of the pituitary is one of the most important factors modulating ACTH- and cortisol responses to CRH. A negative correlation exists between the net ACTH- and cortisol response to exogenous CRH and the basal cortisol plasma concentration. Replacement doses of glucocorticoid result in a drastic decrease of basal plasma concentrations of cortisol and adrenal androgens.(ABSTRACT TRUNCATED AT 250 WORDS)

Myasthenia Gravis (MG) is an autoimmune disease that affects neuromuscular junctions and is characterized by muscle weakness as a result of autoantibodies against certain proteins. As a heterogeneous disorder, MG presents with different types, including neonatal, ocular and generalized in both juveniles and adults. Different types of antibodies serve a role in how MG presents. The main biological characteristic of MG is the production of antibodies against the muscular acetylcholine receptor; however, other types of antibody have been associated with the disorder. The role of the thymus gland has been established and thymectomy is a possible treatment of the disease, along with traditional medication such as pyridostigmine bromide (Mestinon) and immunosuppresants. In recent years, steps have been made towards developing more sensitive diagnostic methods. Additionally, novel treatments have demonstrated promising results. Developing new assays may lead to an increased understanding of the disease and to unravelling the genetic pathway that leads to the development of neuromuscular diseases.

Overweight of children and adolescents continues to be an important and alarming global public health problem. As the adolescent's time spent online has increased, problematic internet use (PIU) potentially leads to negative health consequences. This study aimed to examine the relation between PIU and overweight/obesity among adolescents in seven European countries and assess the effect of demographic and lifestyle factors recorded in the European Network for Adolescent Addictive Behaviour (EU NET ADB) survey (www.eunetadb.eu).A cross-sectional school-based survey of 14- to 17-year-old adolescents was conducted in seven European countries: Germany, Greece, Iceland, the Netherlands, Poland, Romania and Spain. Anonymous self-completed questionnaires included sociodemographic data, internet usage characteristics, school achievement, parental control and the Internet Addiction Test. Associations between overweight/obesity and potential risk factors were investigated by logistic regression analysis, allowing for the complex sample design.The study sample consisted of 10 287 adolescents aged 14-17 years. 12.4% were overweight/obese, and 14.1% presented with dysfunctional internet behavior. Greece had the highest percentage of overweight/obese adolescents (19.8%) and the Netherlands the lowest (6.8%). Male sex [odds ratio (OR) = 2.89, 95%CI: 2.46-3.38], heavier use of social networking sites (OR = 1.26, 95%CI: 1.09-1.46) and residence in Greece (OR = 2.32, 95%CI: 1.79-2.99) or Germany (OR = 1.48, 95%CI: 1.12-1.96) were independently associated with higher risk of overweight/obesity. A greater number of siblings (OR = 0.79, 95%CI: 0.64-0.97), higher school grades (OR = 0.74, 95%CI: 0.63-0.88), higher parental education (OR = 0.89, 95%CI: 0.82-0.97) and residence in the Netherlands (OR = 0.49, 95%CI: 0.31-0.77) independently predicted lower risk of overweight/obesity.The results indicate an association of overweight/obesity with PIU and suggest the importance of formulating preventive public health policies that target physical health, education and sedentary online lifestyle early in adolescence with special attention to boys.

The potency and specificity of the 44-amino acid human pancreatic tumor GRF were tested in six adult female rhesus monkeys and in a perifusion system containing a suspension of rat pituicytes. In vivo, plasma GH levels were elevated in a dose-dependent fashion, with an ED50 of approximately 5 µg/kg, a value of the same order of magnitude as other hypothalamic releasing hormones. The magnitude of the GH response after GRF treatment was similar to that observed during insulininduced hypoglycemia, with peak plasma GH concentrations occurring 5–15 min after GRF administration. High doses of GRF slightly stimulated PRL release, but had no effect on arterial blood pressure, heart rate, or plasma cortisol or glucose concentrations. In vitro, GRF released GH in a dose-dependent manner, but no PRL was released even at the highest GRF concentrations employed (100 nM). It thus appears that stimulation of PRL in vivo may be an indirect effect of GRF. Alternatively, there may be species differences in responsiveness to GRF.

Background:Asthma is characterized by chronic airway inflammation involving mainly increased numbers of eosinophils, mast cells and T-lymphocytes. “Airway remodeling” refers to structural changes, one of which is thickening of reticular basement membrane (RBM). Aim: To assess whether RBM thickness is associated with age, atopic status, lung function and other parameters in asthmatic children. Methods:Fifteen children with asthma underwent bronchoscopy and bronchial mucosa biopsy. Formalin fixed, paraffin-embedded tissues of the bronchial biopsies were used for the measurement of RBM thickness with the micrometric lens adjusted on photomicroscope. Immunohistochemistry was performed on paraffin section for the detection of B- cell [CD20/L-26] and T-cell [CD3/PS-1] markers. Atopic status was assessed by measuring total IgE and specific IgE antibodies to common allergens. Results:Fifteen children (7 atopic, 8 non- atopic) with asthma were studied, aged 5-11 years. RBM thickness ranged from 2 to 5μ and was >3μ in 9/15 subjects. There was no difference in RBM thickness between atopic and non-atopic children (p=0.217). Moreover, there was no association of RBM thickness with age (p=0.819), FEV1 (p=0.906), eosinophilia vs no eosinophilia in bronchial mucosa (p=0.402), eosinophilia vs no eosinophilia in blood (p=0.415) and the use of inhaled corticosteroids (median dose 250-500 mcg fluticazone /24h) (p=0.143). Biopsies of asthmatic children with atopy showed a trend for an increased number of CD3+ T lymphocytes in lamina propria of the bronchial mucosa. Conclusions:In our series, there was no significant correlation of RBM thickness with the severity of asthma, possibly because the most participants had mild to moderate disease.