Clinical presentation and outcome of children with central diabetes insipidus associated with a self-limited or transient pituitary stalk thickening, diagnosed as infundibuloneurohypophysitis.

OBJECTIVE: Despite lymphocytic or autoimmune infundibuloneurohypophysitis (INH) is an increasingly recognized aetiology in children with central diabetes insipidus (CDI); clinical data on epidemiology (clinical evolution, predisposing factors, complications), diagnosis and management of this entity are limited and mostly based on published case reports. The aim of this study was to gain a broader insight in the natural history of this disease by analysing the clinical presentation, radiological pituitary stalk changes, associated autoimmunity and hormonal deficiencies in children with CDI and a self-limiting or transient stalk thickening (ST), diagnosed as autoimmune infundibuloneurohypophysitis, during the last 15 years in four Belgian university hospitals. DESIGN AND PATIENTS: The medical files of nine CDI patients with a ST at initial presentation and no signs of Langerhans cell histiocytosis or germinoma at presentation and/or during follow-up of more than 1.5 years were reviewed. RESULTS: Age at presentation ranged from 3 to 14 years. Two patients had a positive family history of autoimmunity. Three children presented with associated growth failure, two with nausea and one with long-standing headache. Median maximal diameter of the stalk was 4.6 mm (2.7-10 mm). Four patients had extra-pituitary brain anomalies, such as cysts. One patient had central hypothyroidism, and another had a partial growth hormone deficiency at diagnosis. Within a mean follow-up of 5.4 (1.5-15) years, stalk thickening remained unchanged in two patients, regressed in one and normalized in six children. CDI remained in all, while additional pituitary hormone deficiencies developed in only one patient. CONCLUSIONS: In this series of children INH with CDI as initial presentation, CDI was permanent and infrequently associated with anterior pituitary hormone deficiencies, despite a frequent association with nonstalk cerebral lesions.

Evaluation of the hypothalamic-pituitary-adrenal axis and its relationship with central respiratory dysfunction in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi Syndrome (PWS) have been considered at risk for central adrenal insufficiency (CAI). Hypothalamic dysregulation has been proposed as a common mechanism underlying both stress-induced CAI and central respiratory dysfunction during sleep. OBJECTIVE: To evaluate CAI and sleep-related breathing disorders in PWS children. PATIENTS AND METHODS: Retrospective study of cortisol response following either insulin tolerance test (ITT) or glucagon test (GT) in 20 PWS children, and comparison with 33 non- Growth Hormone deficient (GHD) controls. Correlation between sleep related breathing disorders and cortisol response in 11 PWS children who received both investigations. RESULTS: In PWS children, the cortisol peak value showed a significant, inverse correlation with age (Kendall's τ = -0.411; p = 0.012). A similar though non-significant correlation was present between cortisol increase and age (τ = -0.232; p = 0.16). Similar correlations were found in controls. In only 1 of 20 PWS children (5 %), ITT was suggestive of CAI. Four patients had an elevated central apnea index but they all exhibited a normal cortisol response. No relationship was found between peak cortisol or cortisol increase and central apnea index (respectively p = 0.94 and p = 0.14) or the other studied polysomnography (PSG) parameters. CONCLUSIONS: CAI assessed by ITT/GT is rare in PWS children. Our data do not support a link between CAI and central respiratory dysregulation.

Thoracic duct ligation as treatment of chylothorax due to vena cava superior thrombosis.

Thrombosis is a well known complication of subclavian vein catheterization. As collateral circulation develops, consequences are usually limited to the fact that this vein is no longer usable as an access route. However, one of the possible complications of a superior vena cava thrombosis is the development of a chylothorax. We describe an infant developing a chylothorax caused by a SVC thrombosis after subclavian vein catheterization for parenteral nutrition. The chylothorax did not resolve following conservative management, but was successfully treated by surgical ligation of the thoracic duct.

Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization.

UNLABELLED: Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations. 1. Screening for HeFH should be performed only in children older than 2 years when HeFH has been identified or is suspected (based on a genetic test or clinical criteria) in one parent.2. The diagnostic procedure includes, as a first step, the establishment of a clear diagnosis of HeFH in one of the parents. If this precondition is satisfied, a low-density-lipoprotein cholesterol (LDL-C) levelabove 3.5 mmol/L (135 mg/dL) in the suspected child is predictive for differentiating affected from non-affected children. 3. A low saturated fat and low cholesterol diet should be started after 2 years, under the supervision of a dietician or nutritionist.4. The pharmacological treatment, using statins as first line drugs, should usually be started after 10 years if LDL-C levels remain above 5 mmol/L (190 mg/dL), or above 4 mmol/L (160 mg/dL) in the presence of a causative mutation, a family history of early cardiovascular disease or severe risk factors. The objective is to reduce LDL-C by at least 30% between 10 and 14 years and, thereafter, to reach LDL-C levels of less than 3.4 mmol/L (130 mg/dL). CONCLUSION: The aim of this consensus statement is to achieve more consistent management in the identification and treatment of children with HeFH in Belgium.

Adult final height after GH therapy for irradiation-induced GH deficiency in childhood survivors of brain tumors: the Belgian experience.

OBJECTIVES: The treatment of brain tumors in childhood is frequently complicated by growth retardation with a high proportion of irradiation (Irr)-induced GH deficiency (GHD) resulting in reduced adult final height (AFH) even after GH therapy (GHT). In order to optimize future GHT protocols, more information on the factors influencing the growth response to GH in these children is needed. This retrospective study evaluated AFH and influencing auxological and treatment factors of a standardized daily biosynthetic GHT in childhood survivors of brain tumors with documented GHD after brain Irr. DESIGN AND METHODS: From the Belgian GH Registry, 57 children survivors of a brain tumor outside the hypothalamo-pituitary area with available AFH were stratified into two groups depending on cranial (C-Irr; n=25) or craniospinal (CS-Irr; n=32) Irr. RESULTS: In the C-Irr patients, results showed an AFH of -0.8 (-2.5, 1.4) SDS (median (range)) and in the CS-Irr patients, results showed a significantly (P<0.001) lower AFH of -1.8 (-4.2, 0.0) SDS. AFH SDS corrected for mid-parental height (MPH) in the C-Irr group was -0.5 (-2.2, 0.9) and -1.5 (-3.6, 0.0) SDS in the CS-Irr group. AFH was positively correlated with age at end of tumor therapy, height SDS at start GHT, height gain SDS first year GHT, and negatively correlated with CS-Irr. CONCLUSIONS: GHT failed to restore adult height to MPH in nearly half of Irr-induced GHD patients for brain tumor, especially those receiving CS-Irr, irradiated at a younger age or shorter at start GHT.

Ghrelin and the growth hormone secretagogue receptor in growth and development.

The pancreas is a major source of ghrelin in the perinatal period, whereas gastric production progressively increases after birth. Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth. However, ghrl(-/-) or ghsr(-/-) mice fed a high fat diet starting soon after weaning are resistant to diet-induced obesity, suggesting that ghrelin affects the maturation of the metabolic axes involved in energy balance. In addition, animal and human studies suggest that GHSR plays a physiological role in linear growth. In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake. In humans, a mutation of the GHSR gene that impairs the constitutive activity of the receptor was found in two families with short stature. Administration of acylated ghrelin to rat pups directly does not affect weight gain. In contrast, administration of ghrelin to pregnant or lactating rats results in greater fetal weight and postnatal weight gain, respectively, suggesting that maternal ghrelin may stimulate perinatal growth. These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.

Percutaneous endoscopic gastrostomy in cystic fibrosis: patient acceptance and effect of overnight tube feeding on nutritional status.

BACKGROUND: Malnutrition remains a common problem in cystic fibrosis (CF) patients, despite pancreatic enzymes and hypercaloric diet advice. When oral supplementation fails, additional overnight gastrostomy tube-feeding is a therapeutic option. METHODS: In our centre gastrostomy tube feeding is proposed when weight for height drops below 85% despite intensive dietetic counselling. All the CF patients at our centre (n = 11) receiving gastrostomy tube feeding were evaluated for changes in nutritional status and pulmonary function. Complications of percutaneous endoscopic gastrostomy were inventarised and patients older than 7 years and all the parents were asked to fill in a questionnaire concerning subjective well-being with gastrostomy supplemental feeding. RESULTS: The patients received 40% of the recommended daily allowances (RDA) for energy by tube feeding. Total daily energy intake increased by 30%. Within 3 months this resulted in a significant improvement in nutritional status expressed as percentage of ideal weight for height or body mass index z-score. After 6 months a significant catch-up growth was detectable. Pulmonary function remained stable. The complications were local irritation (n = 4), night sweating (n = 1) and bed-wetting (n = 1). The gastrostomy was well accepted. CONCLUSION: Gastrostomy appears to be a good and safe way to improve nutritional status, growth and mood of the CF child. As decreased pulmonary function plays a crucial role in the growth of the CF child, full normalisation of growth pattern is not achieved despite catch-up. Gastrostomy tube feeding should perhaps be used earlier to optimalise growth.

Cystic fibrosis: an unusual cause of chronic pancreatitis.

Chronic pancreatitis is most frequently associated with alcohol abuse. This should however not always automatically be accepted as the presumed cause. When the history is doubtful, uncommon etiologies must be considered as is illustrated by the present case. A 38 years old man was in the past 20 years treated for chronic pancreatitis ascribed to ethylisme although he always denied this. When the diagnosis was eventually questioned, new investigations showed slightly elevated sweat electrolyte concentrations and a delta F508/R117H genotype compatible with cystic fibrosis (CF). Demonstration of mild respiratory abnormalities, obstructive azoospermia and CF in his brother supported this diagnosis. Although rarely, pancreatitis typically develops in the kind of CF patients with milder genotypes and less severe symptoms. Systematic analysis for genetic mutations in patients with idiopathic chronic pancreatitis (ICP) revealed however that this mild form of CF is a less exceptional cause than thought. As CF patients increasingly survive into adulthood this disease should be considered as a possible etiology in the differential diagnosis of pancreatitis at all ages.

Influence of vaccine medium and vaccination schedules on the induction of active immunity against Aujeszky's disease in maternally immune pigs.

Active immunity against Aujeszky's disease virus (ADV) was compared at the end of the fattening period in pigs which had been vaccinated with the attenuated Bartha strain according to different schedules in the presence of different levels of maternal immunity. The percentage of seropositive pigs at the end of the fattening period varied from 21 to 94 per cent. The percentage was significantly higher when the vaccination schedules were applied to pigs from mothers vaccinated with an attenuated strain compared to pigs from mothers vaccinated with a subunit vaccine or from infected-immune mothers. Additionally, this percentage was two to three times lower when pigs were vaccinated once at 10 weeks old compared to pigs either revaccinated at 14 weeks or vaccinated once at 14 weeks old. When the virus strain used for vaccination had been suspended either in saline or in an oil-in-water emulsion, significant differences were not found in the serological response after vaccination and in the reduction of virus excretion upon subsequent challenge. In challenge experiments, a significantly longer duration of virus excretion was observed in vaccinated pigs which had not seroconverted than in vaccinated but seropositive pigs. The vaccination schedules for sows and fattening pigs in view of the eradication of ADV are discussed.

Field experiments to evaluate the feasibility of eradication of Aujeszky's disease virus by different vaccination schedules.

In the present report, the extent of the reduction in Aujeszky's disease virus (ADV) dissemination achieved when pigs were intensively vaccinated with gI-deleted vaccines under field circumstances, was examined. On widely dispersed breeding-fattening farms, a gI-negative status was most rapidly obtained and the rate of new waves of infections was lowest when the attenuated Bartha strain was administered to both the sows and the fatteners. It was more difficult not only to reach but also to keep a gI-negative status on farms on which the sows were vaccinated with an inactivated vaccine and the fatteners with the attenuated Bartha strain or when the fattening pigs were not vaccinated at all. In a densely populated area, 9 of the 17 farms had gI-positive fatteners at the start of the intensive vaccination programme in which the attenuated Bartha strain was given to both the sows and the fatteners. Antibodies were not detected in the sera of the fatteners of each farm at some time during the experiments, but the fatteners on 7 of the 18 farms still showed antibodies against gI after 20 months of vaccination. At the end of the experiment, the percentage of fatteners with antibodies on these farms was markedly reduced compared with the percentage at the start of the experiment. Therefore, elimination of field virus may be feasible if intensive vaccination is carried out over a sufficiently long period of time. However, the high rate of reinfections experienced either due to reintroduction of the virus or to recrudescence should be a warning against too much optimism, particularly in regions with a dense swine population.

Extent and duration of virulent virus excretion upon challenge of pigs vaccinated with different glycoprotein-deleted Aujeszky's disease vaccines.

Different deleted Aujeszky's disease vaccines were compared for their ability to induce an immunity which suppresses virus excretion optimally upon infection. Groups of pigs were vaccinated once with attenuated deleted Aujeszky's disease vaccine (gI, gX or gp63 negative), suspended in phosphate buffered saline. Two additional groups were vaccinated with a gI deleted vaccine virus suspended in an oil-in-water emulsion. Other groups were vaccinated twice with gI deleted inactivated vaccines. The three control groups included were: pigs immune after infection, unvaccinated pigs and pigs receiving vaccine without known deletion in the envelope. Experimental challenge took place 3 or 4 weeks after the only or the last vaccination. The number of excreting pigs, the duration of excretion and the virus titers excreted, were determined for all the groups. All the pigs vaccinated with glycoprotein deletion vaccines suspended in phosphate buffered saline, excreted virus for 2 to 6 days after challenge. A 100 to 1000 fold reduction in excreted virus titers was obtained in vaccinated pigs compared to unvaccinated ones. Some vaccines suppressed virus excretion better than others, but no correlation could be made between the type of deletion (gI, gX or gp63) and the degree of reduction in virus excretion. Similar results were obtained with two applications of inactivated vaccines. The lowest number of excreting pigs, the lowest duration of excretion and the lowest titers were obtained in groups vaccinated with the attenuated vaccine suspended in an oil-in-water emulsion. No vaccine suppressed virus excretion totally.