Jesse Vanbesien

Inhaled budesonide induced Cushing's syndrome in cystic fibrosis patients, due to drug inhibition of cytochrome P450

Two CF patients developed Cushings syndrome during administration of inhaled budesonide (400 microg/d) with oral itraconazole in one and with clarithromycin in the other patient. Clinical features appeared respectively after 2 and 6 weeks of drug co-administration, with prolonged adrenal suppression, and a slow recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere with the metabolism of corticosteroids. Combination of these drugs even with moderate doses of budesonide should be closely monitored.

Rapidly developing Cushing syndrome in a 4-year-old patient during combined treatment with itraconazole and inhaled budesonide.

A 4-year-old boy with cystic fibrosis developed hypertension, rapid weight gain and a moon face 2 weeks after starting a combined treatment of oral itraconazole and inhaled budesonide for a suspected allergic bronchopulmonary aspergillosis. Adrenal suppression was documented and found to persist 3 months after stopping this combined treatment. Conclusion:to the best of our knowledge, this is the first time that an iatrogenic Cushing syndrome in a young child with cystic fibrosis after such combined treatment is reported. The inhibition of cytochrome P4503A by intraconazole and a higher glucocorticoid tissue sensitivity is suggested as the underlying mechanism.

Trabecular Bone Mineral Density and Bone Geometry of the Distal Radius at Completion of Pubertal Growth in Childhood Type 1 Diabetes

Aim: To identify disease-related risk factors for an altered bone mineral density (BMD) and geometry at young adulthood in patients with diabetes mellitus type 1 (DM1). Methods: Fifty-six DM1 patients (23 females, 33 males) with prepubertal onset of diabetes were studied after completion of skeletal growth. Bone parameters at the distal radius were investigated by peripheral quantitative computed tomography. Disease-related parameters, in particular average HbA1c during the 2 years around peak height velocity, were analyzed. Forty-seven healthy controls (32 females, 15 males) were studied. Results: Trabecular BMD was similar between DM1 patients and controls. The mean (±SD) cross-sectional bone area (CSA) was smaller in DM1 patients compared to controls (282.5 ± 45.4 vs. 326.7 ± 52.2 mm2, p = 0.002 and males 391.0 ± 61.3 vs. 423.4 ± 81.9 mm2, p = 0.1). In female DM1 patients, the CSA z-score correlated negatively with the body mass index z-score (r = -0.52, p = 0.01) and positively with the height z-score (r = 0.49, p = 0.02). Conclusions: DM1 patients are at risk for smaller bone sizes at the distal radius at the end of pubertal growth, especially females with increased adiposity. Diabetes-specific parameters seem to have a low impact on forearm volumetric apparent mineral density.

Variability among five different commercial IGF-1 immunoassays in conditions of childhood-onset GH deficiency and GH therapy.

Abstract IGF-1 measurement is used for screening of GH deficiency and monitoring of GH therapy in children. However, several commercial immunoassays are currently used and reference values provided by manufacturers are very different. The aim of this study was to compare commercial IGF-I assays 1) in terms of absolute values and 2) in terms of clinical interpretation of results based on IGF-I reference values in serum samples from children with GH therapy, with untreated GH deficiency and with obesity. Serum samples of 9 patients were sent frozen to 5 university hospitals using 5 different IGF-I assays. The inter-laboratory coefficient of variation (CV) was calculated for the 9 samples. For clinical interpretation, results were expressed as SD scores based on reference values provided by manufacturers (and used in these laboratories). The mean inter-laboratory CV (range) for the 9 serum samples was 25.8% (16.7-35.9%). Major variability was noted in the SD-scores between IGF-I assays for 3 tested serum samples from GH-treated patients with a difference between the lowest and highest SD score of 2.6 up to 3.2. In conclusion, there is a large variability among commercial IGF-I immunoassays, not only in terms of absolute values, but also in terms of clinical interpretation in pediatric serum samples. There is a need for IGF-I immunoassay harmonization and for the establishment of adequate reference values.

Cognitive, emotional and psychosocial functioning of girls treated with pharmacological puberty blockage for idiopathic central precocious puberty

Central precocious puberty (CPP) develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa) leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well-researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls. Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate—Decapeptyl SR® 11.25) and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the childrens parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohens d = 1.04) on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohens d = 1.03); lower heart rate was associated with longer treatment duration (r = −0.582, p = 0.037). The results suggest that GnRHa treated CPP girls do not differ in their cognitive or psychosocial functioning from age matched controls. However, they might process emotional stimuli differently. The unexpected finding of lower heart rate that was associated with longer duration of the treatment should be further explored by methods appropriate for assessment of cardiac health.

Circulating anti-prolactin auto-antibodies must be considered in the differential diagnosis of hyperprolactinaemia in adolescents

Abstract. In four adolescents (two girls and two boys), who were investigated for galactorrhoea or short stature, we found moderately elevated serum prolactin (PRL) levels, but without a decreased gonadotropin and sex hormone production. Serum PRL levels were not responding to the intravenous injection of thyrotropin releasing hormone. Magnetic resonance imaging of the hypothalamic-pituitary region revealed no abnormality. Initial diagnoses were idiopathic and drug-induced hyperprolactinaemia. The presence of anti-prolactin auto-antibodies was suspected because of low recovery of PRL after precipitation with polyethylene glycol and confirmed by immunoprecipitation with anti-human IgG-agarose. Conclusion: anti-prolactin auto-antibodies causing high prolactin values in some immunoassays can cause hyperprolactinaemia in adolescents without other signs of hormonal disturbances or auto-immune disease.

Forearm bone mineralization in recently diagnosed female adolescents with a premenarchal onset of anorexia nervosa

OBJECTIVE Data available on bone mineralization by peripheral quantitative computed tomography (pQCT) in adolescents with an early onset anorexia nervosa (AN) is limited. We investigated whether a disturbed bone mineralization can be observed at the distal radius in recently diagnosed female adolescents with AN and a premenarchal onset of this disease. METHOD Twenty-four premenarchal patients with AN and 22 healthy females which were age and height matched, were selected from our reference database; both groups underwent a pQCT bone assessment at the distal radius of the nondominant arm. RESULTS The patients age ranged between 13.3 and 18.4 years. Their percent weight loss ranged between 5 and 36% (median 23%) and occurred within the preceding 3 to 44 months. Trabecular volumetric bone mineral density of the patient group was significantly lower than the comparison group (185.6 ± 30.2 vs.209.3 ± 34.0 mm(2) ; p = 0.02). Bone cross-sectional area, bone mineral content, total volumetric bone mineral density and periosteal circumference were also lower, albeit not significantly. The bone parameters were unrelated to the under nutrition severity and duration. DISCUSSION In premenarchal patients with AN the trabecular bone mineralization of the forearm is significantly reduced, this might be an early indicator of altered bone mineral accrual.

Albumin and pre-albumin levels do not reflect the nutritional status of female adolescents with restrictive eating disorders

Albumin and pre‐albumin are frequently used as nutritional markers in clinical practice. We examined whether serum albumin and pre‐albumin were predicted by body mass index (BMI), hydration and/or inflammation in female adolescents with a recently diagnosed restrictive eating disorder (RED).

QUANTITATIVE BONE ULTRASOUND AT THE DISTAL RADIUS IN ADULTS WITH CYSTIC FIBROSIS

It is of clinical importance to identify bone disease related to cystic fibrosis (CF) early in its course to allow therapeutic interventions that optimize bone health. To test the technical (precision) and clinical (percentage of abnormal results, correlation with clinical parameters) performance of a commercial quantitative ultrasound apparatus for radial measurements, speed of sound (SOS) was measured at the distal third of the left radius with the Omnisense 7000p apparatus (Sunlight Medical, Tel-Aviv, Israel) in a group of young adult CF patients with regular follow-up at the Brussels and Ghent University Hospital. Sixty-three (37 males) CF patients at a median (range) age of 23.5 y (18.1-39.9) were included. SOS, SOS z-score and SOS t-score were respectively 4017 ± 97 m/s, -0.31 ± 0.74 and -0.60 ± 0.78 in males and 4086 ± 97 m/s, -0.19 ± 0.75 and -0.51 ± 0.95 in females. Mean SOS t-score was significantly lower compared with the manufacturers reference data for males (p < 0.0001) and females (p = 0.01). SOS z- and t-scores correlated with weight z-score and body mass index z-score in females. No significant correlation was found between SOS and forced expiratory volume in 1 s (%). Neither diabetes mellitus nor liver disease was found to influence SOS. Radial quantitative ultrasound has a precision of 0.55%. The SOS is in the low normal range in 14% of CF patients and is influenced by weight in female patients, but not by the severity of the lung disease.

260 Are Type 1 Diabetes Children and Adolescents at Risk for An Impaired Bone Mineralization|[quest]|

Aim: Diabetic adolescents, particularly girls, often show poor metabolic control. The aim of this study is to investigate whether glycemic control (GC) during puberty has an influence on radial trabecular bone mineral density (BMD) at the final growth. Methods: We studied 52 adolescent type 1 diabetes mellitus (DM1) (24 females) at the end of puberty. Median (range) age was 18.4 (17.2-24.8). Duration of diabetes ranged between 1.4-19.9 years (median 9.1). Trabecular BMD of the distal radius was investigated using peripheral quantitative computed tomography (XCT-2000, Stratec, Germany). Mean glycosylated hemoglobin (HbA1c) in the last 4 years (13.8±3.9 measurements per patient) was calculated as GC parameter. We recruited 44 healthy controls (C) (32 females; similar age range). Results: In males DM1 and C subjects had similar height, weight, body mass index (BMI), trabecular BMD and age-adjusted trabecular BMD values (Z-score). Female DM1 patients had a significant higher BMI Z-score (0.51±0.84 vs. -0.11±0.95; p=0.01) and a significant lower trabecular BMD (175.7±30.6 vs. 195.2±32.7mg/cm2; p=0.03) and Z-score (-0.55±0.87 vs. 0.03±0.92; p=0.02). Only 2 DM1 females and none of the males had a trabecular BMD Z-score < -2. Mean HbA1c was significantly higher in female patients (8.68±1.19 vs. 7.83±1.24%; p=0.02). HbA1c ranged between 6.0-10.8% and was negatively correlated with trabecular BMD Z-score (r=-0.15; p=0.3), but correlation was not significant. Conclusions: Whereas diabetes type 1 females, compared to healthy controls, have a lower trabecular bone mineralization at the end of puberty, the majority of adolescent DM1 patients have a trabecular BMD within normal range.Hospitalized infants are exposed to numerous devices containing the plasticizer di-(2-ethylhexyl) phthalate. Urinary levels of the phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are markedly elevated in premature infants. Phthalates inactivate peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear transcription factor that mediates the resolution of inflammation, a process impaired in neonates. We speculate that this increases their susceptibility to MEHP, and this was analyzed. MEHP inhibited neutrophil apoptosis; neonatal cells were more sensitive than adult cells. In neonatal, but not in adult neutrophils, MEHP also inhibited chemotaxis, stimulated oxidative metabolism, and up-regulated expression of NADPH oxidase-1. In both adult and neonatal neutrophils, MEHP stimulated IL-1beta and VEGF production, whereas IL-8 production was stimulated only in adult cells. In contrast, MEHP-inhibited production of MIP-1beta by adult cells, and Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) by neonatal neutrophils. The effects of MEHP on apoptosis and oxidative metabolism in neonatal cells were reversed by the PPAR-gamma agonist, troglitazone. Whereas troglitazone had no effect on MEHP-induced alterations in inflammatory protein or chemokine production, constitutive IL-8 and MIP-1beta production was reduced in adult neutrophils, and RANTES and MIP-1beta in neonatal cells. These findings suggest that neonatal neutrophils are more sensitive to phthalate-mediated inhibition of PPAR-gamma, which may be related to decreased anti-inflammatory signaling.