Acute pulmonary exacerbation and lung function decline in patients with cystic fibrosis: high-mobility group box 1 (HMGB1) between inflammation and infection.

Airway inflammation plays a central role in cystic fibrosis (CF) lung disease, and biomarkers of inflammation, such as high-mobility group box 1 (HMGB1) could be used to monitor disease activity. The main aim of this study was to confirm the role of HMGB1 in CF patients, correlating its serum and sputum levels with pulmonary function and inflammation. Serum and sputum HMGB1 were evaluated in a cohort of 31 CF patients and 30 non-smoking healthy subjects (HS group). Acute pulmonary exacerbation events and lung function decline have been also evaluated during a 3-year follow-up period. Serum HMGB1 levels were significantly higher than those measured in HS, such as sputum HMGB1. Kaplan-Meier survival curves revealed that patients with high HMGB1 values experienced a significantly faster evolution to decline of lung function. A multiple Cox regression analysis assessed that an increase of serum HMGB1 was associated with 5% increased risk of pulmonary disease progression, whereas elevated sputum HMGB1 was related to a 10% increased risk of lung function decline. In CF patients, HMGB1 closely reflects the entity of pulmonary impairment and represents a strong and independent risk marker for progression of lung function decline.

[Increasing prevalence of celiac children with negative serum antigliadin antibodies]. / Aumento dei bambini con malattia celiaca e anticorpi antigliadina negativi: studio delle caratteristiche cliniche.

AIM: In the last few years we noted an increasing number of children with celiac disease with negative serum anti-gliadin antibodies (AGA) a useful serologic test to monitor compliance to gluten-free diet. The aim of this study was to verify diagnostic accuracy of AGA and compare clinical characteristics of AGA-negative with AGA-positive celiac children. METHODS: The authors analyzed serum of AGA-negative celiac children with 3 Elisa kits, and compared clinical and anthropometric data of AGA-negative with AGA-positive celiac children. Celiac disease was diagnosed with small bowel biopsy, and total IgA were determined. Children with IgA-deficiency were excluded. RESULTS: When retested with two other commercial kits, serum values of AGA-negative children were confirmed in all but one. In the last 14 years a diagnosis of celiac disease was performed in 166 children, in 56 of them (33.7%) antigliadin antibodies were negative. Preva-lence of AGA-negative celiac children increased significantly in the last years (from 23% before 2002 to 39.8% after 2002, P=0.04). AGA-negative children were significantly older (7.8 years vs. 3.7 years, P=0.0007) they complained more frequently of abdominal pain (55%, vs. 25,4% P=0.04) and less frequently of anaemia (8% vs. 24.5% P=0.012) and were less likely to have a classical celiac triad (5.3 vs. 22%, P=0.004) than AGA-positive children. CONCLUSION: Serum AGA seem no longer useful for monitoring compliance to gluten-free diet. In children where AGA are negative at diagnosis, when the child eats a normal amount of gluten, they are going to remain negative even after poor compliance.

Emerging pathogens in cystic fibrosis: ten years of follow-up in a cohort of patients.

In patients with cystic fibrosis (CF), there is an increasing incidence of some uncommon respiratory pathogens, such as Burkholderia cepacia complex (Bcc), Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. In order to evaluate the prevalence and the clinical impact of these pathogens, we retrospectively studied a total of 109 patients followed in our center from 1996 to 2006 and reviewed the results of 1,550 sputum samples. The isolation of Pseudomonas aeruginosa slightly decreased over the observed decade, whereas Staphylococcus aureus exhibited an irregular trend. Infection with Bcc reached a peak in 1998 and successively decreased to a stable 4%. S. maltophilia and A. xylosoxidans were the real emerging pathogens, since first isolation occurred in 2004; however, the percentage of infected patients remained low (7% and 3.2%, respectively) through the years. In conclusion, in our center for CF, the reduced prevalence of P. aeruginosa over the last decade has been associated with a concurrent reduction of infections by Bcc and, as compared to other centers in Italy, Europe, and the US, with a low incidence of emerging pathogens such as S. maltophilia and A. xylosoxidans.

Heterozygous mutation of HESX1 causing hypopituitarism and multiple anatomical malformations without features of septo-optic dysplasia.

Isolated GH deficiency or combined pituitary hormone deficiencies have been associated with mutations in transcription factors encoding genes that control organogenesis or cell differentiation. Among these factors, Hesx1 is essential for the development of the optic nerve and regulates some of the earliest stages in pituitary development and is intimately involved in orchestrating the expression of other factors involved in pituitary organogenesis. Mutations in HESX1 are reported in patients with hypopituitarism either with typical septo-optic dysplasia (SOD) or with neuromorphological abnormalities not included in classical SOD. The present report describes clinical features, biochemical parameters, and characterization of a missense mutation (Gln6His) in exon1 of HESX1 in a pre-pubertal child who progressively developed multiple hypopituitarism, firstly GH and, afterwards, TSH and ACTH deficiencies, in a pluri-malformative syndrome characterized by short stature and anatomical malformations not associated with a classical SOD phenotype. This finding further supports the necessity to stay alert in evaluating a gene that plays a minor role in the pathogenesis of sporadic hypopituitarism, such as HESX1 gene even when the phenotype does not fit in with a classical SOD syndrome.

Acute ghrelin response to intravenous dexamethasone administration in idiopathic short stature or isolated idiopathic growth hormone-deficient children.

Acylated ghrelin has been originally described for its potent GH-releasing activity mediated by the activation of the GH secretagogue receptor type 1a. More recently, ghrelin has been reported to exert several other GH-independent biological actions, among which in the modulation of metabolic functions. Glucocorticoids are well known to exert important metabolic functions but also to modulate GH secretion, although through mechanisms that have not been fully clarified so far. Interestingly, the existence of a feedback link between glucocorticoids and ghrelin system has already been reported. The aim of our study was to evaluate the acute GH and ghrelin responses to dexamethasone (DEX) administration in children with idiopathic short stature (ISS) or isolated idiopathic GH deficiency (GHD). Eight children with ISS (age: 9.5+/-1.2 yr) and 7 with GHD (12.1+/-1.4 yr) underwent iv DEX administration (0.3 mg/body surface area at 0 min). IGF-I, GH, and ghrelin levels were assayed at baseline and every 30 min from 120 up to 240 min after DEX. Compared to baseline levels DEX decreased ghrelin in ISS at 120 min and 240 min (p<0.04). On the other hand DEX did not modify ghrelin levels in GHD. After DEX, ghrelin was reduced in ISS compared to GHD (p<0.02). DEX increased GH in ISS but not in GHD (peak: 11.1+/-1.2 vs 7.6+/-0.9 microg/l). Basal, as well as after-DEX ghrelin levels negatively correlated with IGF-I in GHD (p<0.03) and with height SD score (HSDS) in ISS (p<0.02). Acute DEX administration is able to decrease ghrelin in ISS, but not in GHD children. Both basal and after-DEX ghrelin levels negatively correlate with IGF-I and HSDS. All these data suggest the existence of a feedback link among ghrelin, glucocorticoids and the GH/IGF-I axis.

[Germinoma: a rare cerebral tumor causing central diabetes insipidus in childhood]. / Il germinoma: un raro tumore cerebrale causa di diabete insipido centrale in età infantile.

Germinoma represents 7.8% of cerebral tumors in pediatric age and 50-65% of germ cell cerebral tumors. Generally it is a definite lesion of the pineal gland or suprasellar region, frequently occurring in the first three decades of life. Clinical presentation depends on tumor localization. Pineal lesions generally determine symptoms due to the compression of cerebral structures, causing Parinaud syndrome, while hypothalamic lesions are often characterized by diabetes insipidus, hypopituitarism and visual defects. In the absence of these classic signs and symptoms, however, the diagnosis of germinoma can be difficult. We presented the case of an 8-year-old boy, referred to our clinic for polyuria and polydipsia. Hormonal evaluations demonstrated central diabetes insipidus (CDI), with normal anterior pituitary function. Magnetic resonance imaging (MRI) showed a lack of posterior pituitary gland and partial pituitary stalk enlargement. The patient started therapy with desmopressin (Minirin) with good hydro-electrolytic balance. During follow-up the pituitary function became insufficient with low growth velocity. A second MRI demonstrated a bifocal lesion with dyshomogeneous and cystic appearance, suggesting the diagnosis of germinoma. On the basis of this case report we would like to point out the importance of an early diagnosis in order to improve the prognosis of the disease and the necessity of a careful follow-up of these patients.

[Polyuria and polydipsia in a 5 year-old child: diagnostic problems]. / Esordio di poliuria e polidipsia in una bambina di 5 anni: le problematiche della diagnosi differenziale.

Polyuria and polydipsia could be present in three groups of diseases; polydipsia psicogena characterized by an excessive water intake, central diabetes insipidus (CDI) with a defect in the production of AVP and nephrogenic diabetes insipidus in which a defect in the renal response to vasopressin is present. In particular, CDI can be caused by lesions like germinoma and craniopharyngioma, Langerhans'cell histiocytosis, inflammatory, autoimmune and vascular diseases, trauma resulting from surgery or an accident; and in rare cases, genetic defects in the synthesis of vasopressin that are inherited as autosomal dominant or X-linked recessive traits. However, 30% to 50% of cases are considered idiopathic. Nevertheless, 30-50% of cases is considered idiopathic. Here we present the case of a 5.5 year-old female patient, referred to our Department of Endocrinology Surgery for polyuria and polydipsia. Hormonal tests demonstrated the presence of CDI with normal anterior pituitary function. Magnetic resonance imaging showed the lack of hyperintensity of posterior pituitary. Pituitary stalk was median and of regular volume. Diagnosis of CDI has been confirmed and therapy has been started with desmopressin (Minirin) 0.2 mg/die. During the follow-up the patient was in good conditions, presented an adequate hydro-electrolytic balance and normal growth velocity. Anterior pituitary function was normal and MR remained stable. This case report highlights problems concerning differential diagnosis and the importance of a careful follow-up which must involve the whole family.

[Iodine status in historically iodine deficiency area]. / Apporto iodico in un'area storicamente iodocarente.

AIM: The median urinary iodine concentration (UIC) for schoolchildren was 90 microg/L in Biella and 136 microg/L in Novara in survey carried out in 1995-1996. Biella resulted as iodine deficiency area and Novara as iodine sufficient area. Aim of our study was to assess goiter prevalence by ultrasonography in Biella and Novara schoolchildren and to evaluate median UIC in Biella schoolchildren. METHODS: A total of 829 Biella schoolchildren and 310 Novara schoolchildren, aged 7-15 years, were submitted to thyroideal ultrasonography. Biella schoolchildren were submitted to morning-spot urine sample's collection for UIC's determination. RESULTS: The ultrasound goiter prevalence as function of age resulted 15.7% in Biella and 14.8% in Novara (P = 0.7, chi 2 test). The ultrasound goiter prevalence as function of body surface area resulted 17.1% in Biella and 7.1% in Novara (P < 0.0001, chi 2 test). UIC (25-75 degrees ) for Biella schoolchildren who attended third and fifth year of primary school was 159 microg/L (107-228 microg/L) while for Biella schoolchildren who attended second year of secondary school was 150 microg/L (92-218 microg/L). CONCLUSIONS: Based on the results of UIC, Biella is considered as iodine sufficient area. Based on the results of goiter prevalence by ultrasonography, both Biella and Novara resulted as iodine deficiency area. UIC and goiter prevalence, however, provide different informations about iodine status: UIC supplies informations about present iodine status while goiter prevalence assesses past iodine status.