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Scarpa R.,University of Padua | Alaggio R.,University of Padua | Norberto L.,Surgical Endoscopy Unit | Furmaniak J.,FIRS Laboratories | And 15 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Background: Autoantibodies to tryptophan hydroxylase (TPHAbs) directed against serotonin-producing enterochromaffin cells (EC) have been reported in autoimmune-polyendocrine-syndrome type 1 (APS-1) patients with gastrointestinal dysfunction (GID). Serotonin plays a critical role in enteric function and its peripheral blood levels reflect serotonin release from the gastrointestinal tract. Aims: We test the hypothesis that TPHAbs mark a distinct autoimmune component of APS-1 characterized by an autoimmune attack toward EC, which results in clinical GID. Methods: TPHAbs were measured in 64 APS-1 patients. Endoscopy with gastric (antrum/body) and duodenal biopsy was carried in 16 TPHAbs+ patients (8 with and 8 without GID) and in 2 TPHAbs- patients (without GID). Immunohistochemistry of biopsy specimens was carried out using antibodies to serotonin, chromogranin-A, CD3, CD4, CD8, and CD20. Serotonin serum levels were measured in TPHAbs+ and TPHAbs- patients who had endoscopy. Results: Thirty-seven of 64 patients were TPHAbs+ (11/12 with GID and 26/52 without GID; P < .001). Gastric and duodenal biopsies in all 8 TPHAb+ patients with GID showed lymphocytic infiltration with increased CD3+CD8+ intraepithelial lymphocytes and absence of EC. Furthermore, mean serotonin serum levels were below the normal range in TPHAb- patients with GID (P < .01). In 8 TPHAb+ patients without GID gastric and duodenal biopsies showed different grades of inflammatory infiltration and reduced number of EC. Mean serotonin serum levels were near the lower limit of the normal range. In all TPHAbs+ patients the biopsies showed a reduced number of chromogranin-A positive cells consistent with enteroendocrine cells depletion. TPHAbs- patients without GID showed normal gastrointestinal mucosa and serotonin serum levels. Conclusions: TPHAbs appear to be markers of a distinct autoimmune component of APS-1. Progressive involvement of the gastrointestinal EC leads to the transition from preclinical to clinical disease, characterized by GID and reduced serotonin serum levels. Copyright © 2013 by The Endocrine Society. Source

Iughetti L.,University of Modena and Reggio Emilia | Capone L.,Regional Hospital of Bolzano | Maggio M.C.,Associazione Cante of Montevecchio | Predieri B.,University of Modena and Reggio Emilia
Hormone Research in Paediatrics | Year: 2012

Background/Aims: Mutations of the short stature homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency. Patients and Design: We studied 16 patients (10 females; 9.7 ± 2.9 years old; height-2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 ± 0.053 mg/kg/week). Results: Impaired GH secretion was present in 37.5% of the studied subjects. Comparing baseline data with those at the last visit, we found that rhGH treatment improved growth velocity SDS (from-1.03 ± 1.44 to 2.77 ± 1.95; p = 0.001), height SDS (from-2.41 ± 0.71 to-1.81 ± 0.87; p < 0.001), and IGF-1 values (from-0.57 ± 1.23 to 0.63 ± 1.63 SDS, p = 0.010) without affecting body mass index SDS. Height SDS measured at the last visit was significantly correlated with chronological age (r =-0.618, p = 0.032), bone age (r =-0.582, p = 0.047) and height SDS (r = 0.938, p < 0.001) at the beginning of treatment. No adverse events were reported on rhGH therapy which was never discontinued. Conclusion: These data showed that impaired GH secretion is not uncommon in SHOX deficiency subjects, and that rhGH therapy may be effective in increasing height in most of these patients independent of their GH secretory status, without causing any adverse events of concern. Copyright © 2012 S. Karger AG, Basel. Source

Ruys T.E.P.,Erasmus Medical Center | Roos-Hesselink J.W.,Erasmus Medical Center | Hall R.,Norwich University | Subirana-Domelnech M.T.,Hospital de Sant Pau | And 8 more authors.
Heart | Year: 2014

Objective Heart failure (HF) is one of the most important complications in pregnant women with heart disease, causing maternal and fetal mortality and morbidity. Methods This is an international observational registry of patients with structural heart disease during pregnancy. Sixty hospitals in 28 countries enrolled 1321 women between 2007 and 2011. Pregnant women with valvular heart disease, congenital heart disease, ischaemic heart disease, or cardiomyopathy could be included. Main outcome measures were onset and predictors of HF and maternal and fetal death. Results In total, 173 (13.1%) of the 1321 patients developed HF, making HF the most common major cardiovascular complication during pregnancy. Baseline parameters associated with HF were New York Heart Association class ≥3, signs of HF, WHO category ≥3, cardiomyopathy or pulmonary hypertension. HF occurred at a median time of 31 weeks gestation (IQR 23-40) with the highest incidence at the end of the second trimester (34%) or peripartum (31%). Maternal mortality was higher in patients with HF (4.8% in patients with HF and 0.5% in those without HF p<0.001). Pre-eclampsia was strongly related to HF (OR 7.1, 95% CI 3.9 to 13.2, p<0.001). Fetal death and the incidence of preterm birth were higher in women with HF compared to women without HF (4.6% vs 1.2%, p=0.001; and 30% vs 13%, p=0.001). Conclusions HF was the most common complication during pregnancy, and occurred typically at the end of the second trimester, or after birth. It was most common in women with cardiomyopathy or pulmonary hypertension and was strongly associated with pre-eclampsia and an adverse maternal and perinatal outcome. Source

Crepaz R.,Regional Hospital of Bolzano | Romeo C.,Regional Hospital of Bolzano | Montanaro D.,Regional Hospital of Bolzano | De Santis S.,Actelion Pharmaceuticals
BMC Cardiovascular Disorders | Year: 2013

Background: Patients with Down's syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down's syndrome. However, data on the efficacy of PAH-specific therapy in patients with Down's syndrome are limited. The aim of this retrospective analysis was to determine the long-term efficacy of the dual endothelin receptor antagonist, bosentan, in Eisenmenger's syndrome (ES) patients with Down's syndrome.Methods: In this observational study adults with Down's syndrome with a confirmed diagnosis of ES (World Health Organization functional class III) and receiving bosentan therapy and were followed up long term. Clinical evaluation at baseline and follow-up visits included resting transcutaneous arterial oxygen saturation and laboratory assessments. Exercise capacity was evaluated using a 6-minute walk test where transcutaneous arterial oxygen saturation at peak exercise (SpO2), 6-minute walk distance (6MWD) and Borg dyspnoea index were assessed. A full echocardiographic assessment was conducted at baseline and follow-up visits.Results: Overall, seven adults (mean age 29.6 ± 11.2 years; 57% male) received bosentan at a starting dose of 62.5 mg twice daily. This was increased to the target dose of 125 mg twice daily 4 weeks later. All patients remained on bosentan until the end of the study. After a mean (± standard deviation) duration of 52.2 ± 3.9 months (range: 46.0-55.5 months), 6MWD had increased from 199.6 ± 69.1 metres to 303.7 ± 99.9 metres (P < 0.05) and SpO2 at the end of the 6-minute walk test had increased from 61.6 ± 7.6% to 74.7 ± 6.2% (P < 0.05). Echocardiography demonstrated a significant change in acceleration time from 62.9 ± 11.6 m/s to 83.0 ± 9.6 m/s (P = 0.0156), and acceleration time/ejection time ratio from the pulmonary flow from 0.24 ± 0.04 at baseline to 0.30 ± 0.02 (P = 0.0156) at final follow-up.Conclusions: Long-term treatment with bosentan significantly improved exercise capacity and oxygen saturation following exercise in adult ES patients with Down's syndrome. These data confirm that the presence of Down's syndrome does not affect the response to oral bosentan therapy. © 2013 Crepaz et al.; licensee BioMed Central Ltd. Source

Radetti G.,Regional Hospital of Bolzano | Maselli M.,Regional Hospital of Bolzano | Buzi F.,Regional Hospital of Brescia | Corrias A.,Regina Margherita Children Hospital | And 8 more authors.
Clinical Endocrinology | Year: 2012

Objective The natural history of Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors. Design This is retrospective cross-sectional study. Patients Three hundred and twenty-three patients with HT (88 boys and 235 girls) and 59 with IH (30 boys and 29 girls), mean age 9·9 ± 3·8 years were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but <100% of the upper limit (G1). All IH subjects had elevated TSH. Potential risk factors for thyroid failure were evaluated after 3 years and included the presence or familiarity for endocrine/autoimmune diseases, premature birth, signs and symptoms of hypothyroidism, TSH levels, antithyroid antibodies and thyroid volume. Results HT: Of those with HT, 170 G0 patients remained stable, 31 moved to G1 and 35 to G2 (hypothyroidism). Thirty-six G1 children moved to G0, 17 remained stable and 34 moved to G2. Of patients with IH: 23 normalized, 28 remained stable and eight became overtly hypothyroid. In patients with HT, the presence of coeliac disease, elevated TSH and thyroid peroxidase antibodies (TPOAb) increased the risk of developing hypothyroidism by 4·0-, 3·4- and 3·5-fold, respectively. The increase in TSH levels during follow-up was strongly predictive of the development of hypothyroidism. In patients with IH, no predictive factor could be identified. Conclusions Coeliac disease, elevated TSH and TPOAb at presentation and a progressive increase in TSH are predictive factors for thyroid failure in HT patients. © 2012 Blackwell Publishing Ltd. Source

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