Quality of life in Sardinian patients with transfusion-dependent Thalassemia: a cross-sectional study.

PURPOSE: The aim of this study has been to evaluate the physical, psychological, and social well-being in a large group of Sardinian adult patients with transfusion-dependent beta-Thalassemia when compared with a group of healthy subjects of the same age and geographical extraction. METHODS: Male or female patients ≥ 18 years of age with Thalassemia major on regular transfusion at Thalassemia Center in Cagliari (Italy) were requested to complete the World Health Organization Quality of life-BREF (WHOQOL-BREF) questionnaire. The WHOQOL-BREF was also made available online to age- and sex-matched non-thalassemic adult subjects living in Sardinia. RESULTS: Two hundred and seven subjects with Thalassemia were invited to participate in the study. The questionnaire was also completed by 211 age- and sex-matched non-thalassemic subjects living in Sardinia. Scores suggestive of a good quality of life were obtained in all the areas investigated. Thalassemia patients had scores at least as good as those of non-thalassemic subjects in all items and the percentage of those with a score ≥ 60 was higher among patients. The analysis of demographic actually highlights that the disease has a little effect on their personal and social lives. There was a positive association between subjective well-being and effective clinical conditions. Moreover, the association between health perception and adherence to treatment suggests that compliance with treatment contributes to the well-being of the patient, both physically and psychologically. CONCLUSIONS: Adult subjects with Thalassemia who live in Western countries have a good quality of life in accordance with the advances in the management of the disease.

The role of FTO genotype on eating behavior in obese Sardinian children and adolescents.

AIM: We aimed to study the influence of the fat mass and obesity-associated (FTO) gene on eating behavior in 412 obese Sardinian children and adolescents. Genome-wide association studies (GWAS) have identified several susceptibility loci for obesity. Among these, the polymorphisms in the intron 1 of the FTO gene has been found associated to weight gain and obesity in various populations. METHODS: All obese patients were genotyped for the FTO single nucleotide polimorphysm (SNP) rs9939609. In all subjects we evaluated eating behavior using the Child Eating Behaviour Questionnaire (CEBQ). RESULTS: We found no differences in eating behavior according to the genotype, either in the entire cohort, or when subjects were subdivided into four different age groups. CONCLUSIONS: FTO genotype is associated with body mass index but does not influence eating behavior in a selected cohort of obese children from the isolated genetic population of Sardinia.

rs9939609 in the FTO gene is associated with obesity but not with several biochemical parameters in Sardinian obese children.

Several studies have reported an association of the intronic single nucleotide polymorphism (SNP) rs9939609 of the fat mass and obesity-associated (FTO) gene with obesity and with a number of obesity-related features. We studied the association of rs9939609 with obesity in 912 obese children and adolescents (426 males and 486 females, mean ± SD age 10.5 ± 3.3 years) and in 543 normal weight subjects. A number of biochemical and clinical parameters was also evaluated in 700 of these patients. In the obese group, mean body mass index standard deviation score (BMI-SDS) was similar between the three genotypes. The A allele was present in 55% of the patients' and in 43% of controls' chromosomes. The distribution of heterozygotes was similar between patients and controls (47%), while the distribution of AA homozygotes was significantly higher in patients (31% vs. 20%). Logistic regression analysis on the genotypes yielded a χ(2) of 35.5 with an odds ratio of 1.6 (CI = 1.3-1.8), P < 1 × 10(-5) . None of the clinical and metabolic parameters tested was associated with the genotype. In conclusion, we have confirmed the strong association between FTO and obesity, and shown that only AA homozygotes are predisposed to develop obesity while TT homozygotes might be protected. Finally, we found no association between rs9939609 and a number of obesity-related abnormalities.

Effect of body mass index on the growth hormone response to clonidine stimulation testing in children with short stature.

OBJECTIVES: An inverse relationship has been shown between body mass index (BMI) and the peak growth hormone (GH) response to stimulation in adults and in children with short stature. This relation is observed even within a normal range of BMI. The aim of this study was to investigate the effect of BMI on the GH response to clonidine in a large number of children with short stature. DESIGN: We conducted a retrospective study on the GH response to clonidine in a single centre. METHODS: We studied 202 children with short stature (135 M and 67 F) who underwent clonidine testing from 2007 to 2009. RESULTS: One hundred and twenty-eight patients had a GH peak >10 µg/l. In univariate regression analysis, the peak GH after clonidine was negatively correlated with BMI-standard deviation score (BMI-SDS) and positively correlated with height velocity-SDS and IGF-I-SDS. Only the relationship between peak GH and BMI-SDS remained significant in children with a BMI-SDS from -2 to +2. In the multivariate stepwise regression analysis, BMI-SDS and IGF-I-SDS were the only significant variables in the entire cohort, explaining 19·5% of the variance in peak GH. When only subjects with BMI-SDS between -2·0 and +2·0 were included in the analysis (n = 173), BMI-SDS alone explained 21·4% of the variability in peak GH. The number of patients who failed the clonidine test increased with increasing BMI-SDS. CONCLUSIONS: BMI affects the GH response to clonidine in children with short stature and should be considered when interpreting the results to the stimulation test.

An INSIG2 polymorphism affects glucose homeostasis in Sardinian obese children and adolescents.

Allelic variants of a single nucleotide polymorphism (SNP), rs7566605, located approximately 10 kb upstream of the INSIG2 gene have been found in association with body weight and with other clinical features related to obesity in some populations but not in others. Our objective was to test the association of this SNP in obese children and adolescents from the genetically isolated population of Sardinia. We tested the association of rs7566605 with body mass index (BMI) and with serum glucose and insulin concentrations and a surrogate measure of insulin resistance (HOMA-IR) in a cohort of 747 Sardinian obese children and adolescents. A case control analysis was performed using 548 ethnically-matched healthy controls. Allelic frequencies of the SNP were similar between patients and controls. Mean glucose and insulin concentration and mean HOMA-IR values were significantly higher in patients carrying the CC genotype than in the CG and GG carriers. In the patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), allele C was significantly more frequent than in controls. Although INSIG2 polymorphisms do not consistently associate with BMI, the observation of an association with glucose concentration would support a role for this gene in the metabolic complications of obesity.

Impact of the direct-acting antiviral agents (DAAs) on chronic hepatitis C in Sardinian patients with transfusion-dependent Thalassemia major.

BACKGROUND AND AIMS: Direct antiviral agents (DAAs) have revolutionised the standard of care for the treatment of hepatitis even in patients with hemoglobinopathies. The aim of this study is to show how, thanks to DAAs, HCV infection has been substantially eradicated in one of the biggest Centres for the management of Thalassemia in Europe. METHODS: Thalassemia major patients regularly transfused and iron chelated in Cagliari (Italy) who were HCV-RNA positive were evaluated for the potential prescription of antiviral therapy. RESULTS: A total of 99 patients, 26 of whom had been diagnosed with cirrhosis, were treated with at least one dose of DAAs, which proved to be safe and well tolerated. Two of the patients died during the treatment after becoming HCV-RNA negative while another voluntarily interrupted the therapy. The final SVR in the patients who completed the treatment was 100%, while measuring 97% (96/99) in the Intention-to-Treat analysis. After DAAs, no new cases of hepatocellular carcinoma have been reported. CONCLUSIONS: The use of DAAs in patients suffering from beta-Thalassemia major with chronic hepatitis C or cirrhosis can be considered safe and effective. Close monitoring for hepatocellular carcinoma development is, in any case, recommended indefinitely post-SVR.

Turner syndrome mosaicism: an unusual case with a de novo large dicentric marker chromosome: mos 45,X/46,X, ter rea(X;X)(p22.3;p22.3).

X/X translocations are quite rare in humans. The effect of this anomaly on the phenotype is variable and depends on the amount of deleted material and whether the chromosomes are joined by their long or short arms. We report an unusual case of Turner syndrome mosaicism in a 16-year-old girl, who was referred to our Institute for primary amenorrhoea associated with short stature. Endocrine evaluation revealed hypergonadotropic hypogonadism, which required a study of the karyotype. Cytogenetic analysis, performed on peripheral blood leucocytes, showed a mos 45,X/46,X,ter rea (X;X)(p22.3;p22.3) de novo karyotype. The prevalent cell line was 45,X (90% cells). A second cell line (10% cells) showed a very large marker chromosome, similar to a large metacentric chromosome. FISH (fluorescent in situ hybridisation) and molecular analysis revealed that the marker chromosome was dicentric and totally derived from the paternal X chromosome.

Thyroid function in obese children and adolescents.

OBJECTIVE: Obesity is frequently associated with modifications of thyroid size and function. We evaluated the prevalence of thyroid function abnormalities and the effects of puberty and weight loss in obese children and adolescents. METHODS: We examined 468 obese children (255 girls and 213 boys aged 3.7-17.9 years) and 52 normal-weight age-matched children as controls. TSH, fT3, fT4, fasting serum insulin and glucose were measured at baseline. fT3, fT4 and TSH were also measured after 6 months of lifestyle intervention in a subset of 43 patients. RESULTS: 109 obese children showed abnormal circulating thyroid hormone concentrations (84 had elevated fT3 levels, 15 elevated TSH, 6 elevated fT4, 3 elevated fT3 and TSH, and 1 elevated fT3, fT4 and TSH levels). Serum TSH and fT3 concentrations were positively correlated with BMI-SDS. The prevalence of patients with abnormal thyroid hormone concentrations was similar between sexes and between prepubertal and pubertal subjects. After 6 months of lifestyle intervention, thyroid hormone concentrations normalized in 27 of the patients with decreased BMI-SDS, and in 2 patients in whom BMI-SDS increased. CONCLUSIONS: In obese children, an increased fT3 concentration is the most frequent thyroid function abnormality. Serum fT3 and TSH correlate with BMI. Moderate weight loss frequently restores these abnormalities.

The glucagon test in the diagnosis of growth hormone deficiency in children with short stature younger than 6 years.

CONTEXT: Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). OBJECTIVE: The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. DESIGN AND SETTING: This study was conducted in two pediatric endocrinology centers. PATIENTS AND METHODS: Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. RESULTS: Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P < 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P < 0.0001). CONCLUSIONS: This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.

Results of early reevaluation of growth hormone secretion in short children with apparent growth hormone deficiency.

OBJECTIVE: To test the hypothesis that normalization of the growth hormone (GH) response to stimulation in patients with GH deficiency (GHD) and normal magnetic resonance imaging (MRI) of the hypothalamic-pituitary area might occur earlier than at attainment of final height. STUDY DESIGN: Prepubertal children with short stature (21 boys and 12 girls; age, 5.2-10 years), in whom a diagnosis of GHD was based on a GH response <10 microg/L after 2 pharmacologic tests (clonidine, arginine, or insulin hypoglycemia), and normal MRI of the hypothalamic-pituitary area were studied. After 1 to 6 months, all children underwent reevaluation of GH secretion by means of one of the provocative tests previously used. During that time, none of the children received GH therapy or entered puberty. RESULTS: A GH response > or =10 microg/L after retesting was found in 28 patients, and a GH response <10 microg/L was found in 5. In 9 patients, the peak GH response at diagnosis was <7 microg/L to both tests used. In 8, the GH response at retesting was > or =10 microg/L and was 9.0 microg/L in the remaining child. CONCLUSIONS: We suggest that patients with pathologic GH responses to provocative tests but normal MRI should be reevaluated and followed up before a diagnosis of GHD is firmly established.