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Biomedical subjects

L Iughetti

Publications and source records attributed to L Iughetti.

At least 19 recordsLinked to original sources

High basal serum allopregnanolone levels in overweight girls.

OBJECTIVE: Several studies demonstrated that obese subjects have a hyperactive hypothalamic-pituitary-adrenal axis and that sex steroid hormones have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Allopregnanolone (3alpha-hydroxy-5alpha-pregn-20-one; AP) is a circulating neuroactive steroid hormone involved in the modulation of behavioral functions, stress and neuroendocrine axis. The aim of our study was to evaluate basal serum AP levels in obese children. SUBJECTS AND MEASUREMENTS: We studied 27 normal weight (NW) and 23 overweight (OW) girls. Gonadotropins and steroid hormones were assessed in all patients. RESULTS: Basal AP concentrations in OW girls were significantly higher than in NW controls (P=0.013). There was no difference found between the other gonadal and adrenal hormones. Considering the pubertal stage, we demonstrated that obese pubertal girls presented higher AP concentrations than prepubertal and pubertal NW ones (P=0.020), and higher dehydroepiandrosterone sulfate (DHEAS) levels with respect to prepubertal obese girls, and prepubertal and pubertal NW patients (P=0.025). AP and DHEAS were significantly directly related to weight (r=0.31 and r=0.54, respectively) and body mass index (r=0.29 and r=0.34, respectively). In pubertal OW girls, a significant positive correlation between AP and DHEAS (r=0.60), A (r=0.72) and luteinizing hormone (r=0.64) levels was demonstrated. CONCLUSION: The present study demonstrates that AP is hypersecreted in children and adolescent with OW involving DHEAS concentrations, too. Our data suggest a possible role of AP in the regulation of neuroendocrine axis related to obesity. We can also speculate that in OW girls, who could manifest emotional and behavioral problems, a part of higher levels of this neuroactive steroid might act as gamma-aminobutyric acid agonist producing anxiolytic-sedative effects.

17-alpha-Hydroxyprogesterone↗

Female precocious puberty, obesity and polycystic-like ovaries.

OBJECTIVE: To evaluate the characteristics of obese girls with gonadotropin releasing hormone-dependent precocious puberty with and without polycystic-like ovaries. METHODS: Forty-seven overweight (> 75(th) centile of the Italian reference data) girls with a diagnosis of isosexual precocious puberty underwent auxological analysis, hormonal assay and utero-ovarian sonographic and Doppler evaluation. On the basis of sonography the patients were subdivided into two groups, girls presenting normal ovaries (Group I; n = 31) and those with polycystic-like ovaries (Group II; n = 16). RESULTS: The mean body weight was significantly higher (P = 0.003) in Group II than it was in Group I. In addition, the patients with polycystic-like ovaries fell within our definition of superobese (> or = 97(th) centile of the Italian reference data) in 44% of cases. The uterine and ovarian volumes were significantly greater in Group II compared with Group I patients. The Doppler evaluation showed intraparenchymal ovarian vascularization and low downstream impedance to flow in all patients in Group II. CONCLUSIONS: Girls with precocious puberty and polycystic ovaries, compared with those without polycystic ovaries, have a higher incidence of body weight exceeding the 85(th) centile of the Italian reference data (obesity).

Child↗

Anti-CD38 autoimmunity in children with newly diagnosed type 1 diabetes mellitus.

AIMS: To test for anti-CD38 autoimmunity in children with newly-diagnosed type 1 diabetes mellitus (DM1). METHODS: Serum anti-CD38 autoantibodies were detected by Western blot in 270 children (130 girls, 140 boys, mean age 8 +/- 4 years) with newly-diagnosed DM1 and 179 gender- and age-matched non-diabetic children. In 126 diabetic children, another blood sample was obtained 15 +/- 4 months after the diagnosis. RESULTS: Anti-CD38 autoantibody titers at least 3 SD above the mean value for the control group were found in 4.4% of children with DM1 vs 0.6% of controls (chi2 = 5.8, p <0.016). No statistical differences were observed between anti-CD38 positive and negative patients in terms of phenotype. At follow-up, of six diabetic children who were positive for anti-CD38 antibodies, two were new cases. A positive correlation was found between the antibody titer of diabetic sera at diagnosis and follow up (r = 0.46, p <0.0001). CONCLUSION: An autoimmune reaction against CD38, a protein expressed in human islets, is associated with newly-diagnosed DM1. In children with DM1, CD38 autoimmunity increases with time and persists.

ADP-ribosyl Cyclase 1↗

Bone mass evaluated by calcaneous ultrasound and radial peripheral computed tomography in 726 youngsters.

AIM: To compare the results of ultrasound and computed peripheral tomography in evaluating bone mass in a population of normal children. METHODS: Seven hundred and twenty-six healthy school children (260 males; age 8.3-20.9 y) underwent calcaneous ultrasound and peripheral computed tomography at the ultradistal radius. Broadband ultrasound attenuation (BUA) and areal and volumetric bone mineral density (aBMD and vBMD) were evaluated. The results were compared and correlated among them and with auxological parameters (height, BMI and pubertal stages) using the software package SPSS for Windows. RESULTS: The three variables examined (BUA, aBMD and vBMD) all showed a progressive increase with age and a positive correlation with age, height and BMI. When the population was subdivided according to pubertal stages, all variables showed a progressive increase, the difference being significant when stages 1-2 were compared with stages 4-5. A significant correlation was present among BUA, aBMD and vBMD even if the Pearson correlation coefficient was not high. CONCLUSIONS: The similar pattern of BUA, aBMD and vBMD with respect to age, height and pubertal stages indicates that ultrasound could be a reliable method to screen bone mass abnormalities in children. The low correlation coefficient, however, suggests that the methods employed measure different bone parameters. Moreover, the different skeletal locations could also account for these results.

Adolescent↗

Pelvic ultrasound and color Doppler findings in different isosexual precocities.

OBJECTIVE: To evaluate the role of ultrasound and color Doppler analyses in improving the differential diagnosis of pubertal precocities. METHODS: Sixty-nine girls with premature (<8 years old) breast development and/or pubic hair growth underwent: auxological (height, weight, body mass index, skeletal maturation), hormonal (basal, gonadotropin releasing hormone (GnRH)-test, adrenocorticotropic hormone test), and sonographic (uterine and ovarian volume and endometrial echo) including color Doppler (uterine arteries) evaluations. RESULTS: The uterine size was greater in girls with a pubertal response to the GnRH test (Group II, n = 16; 7.48 +/- 4.18 mL) than in those with a prepubertal response to the GnRH test (Group I, n = 17; 3.02 +/- 1.36 mL; P = 0.006), an isolated pubarche (Group III; n = 20; 2.58 +/- 1.32 mL; P < 0.001) or an isolated thelarche (Group IV, n = 16; 1.82 +/- 1.07 mL; P < 0.001). Endometrial echo was observed in 87.5%, 29.4% and 5% of girls, respectively, in Groups II, I and III. The Doppler analysis of the uterine arteries showed the lowest impedance to be in patients with a pubertal response to the GnRH test (Group II). CONCLUSIONS: Sonographic and color Doppler parameters may improve the diagnosis of GnRH-dependent precocious puberty and may be useful to determine which girls need treatment.

Child↗

Lipoprotein (a) in childhood: correlations with family history of cardiovascular disease.

The association between lipoprotein (a) [Lp(a)] and cardiovascular diseases is well known. Lp(a) is an independent risk factor for the development of atherosclerosis. Little information concerning Lp(a) during childhood is available. The aim of the present investigation was to determine the Lp(a) concentration in a cohort of children aged between 4 and 15 yr and to correlate Lp(a) with: a) overweight status; b) body fat distribution; c) family history of vascular diseases in their parents and grandparents. Six hundred and eighty-nine children (350 males, 339 females), were enrolled in the study. BMI as index of being overweight was calculated; the waist-to-hip ratio (WHR) and the waist-to-thigh ratio (WTR) were calculated to obtain two anthropometric indexes for the pattern of body fat distribution. The areas of visceral (VAT) and subcutaneous adipose tissue (SAT) were evaluated by MRI at the L4-L5 level in only 30 overweight subjects. The serum of Lp(a), total cholesterol (TC), HDL-cholesterol, LDL-cholesterol and triglycerides were evaluated in the whole population. Moreover, the same biochemical study was performed in 70 children's parents randomly chosen. A structured questionnaire was administered to the children's parents to investigate the presence of cardiovascular disease (CVD) in family stories. Our data show no Lp(a) serum differences between children according to sex, age and body composition. The strong correlation between the children's and the parents' Lp(a) concentrations and the occurrence of CVD in their grandparents suggests that Lp(a) represents an important independent early risk factor for the development of CVD in adulthood. Measurements of Lp(a) in childhood may help to evaluate this risk in subjects with family history of cardiovascular diseases.

Adolescent↗

Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases.

Triggering of the Fas receptor induces T cell apoptosis and is involved in shutting-off the immune response. Inherited defects impairing Fas function cause the autoimmune lymphoproliferative syndrome, and may play a role in other autoimmune diseases. The aim of this work was to analyse the Fas function in paediatric patients with thyroid autoimmunities. We found that T cells from 24/28 patients with Graves' disease (GD) and 12/35 patients with Hashimoto's thyroiditis (HT) displayed defective Fas function. In HT, the defect was more frequent in patients requiring replacement therapy (11/20) than in those not requiring (1/15); moreover, in untreated HT the highest defect was displayed by patients with the highest levels of autoantibodies. Fas was always expressed at normal levels and no Fas mutations were detected. Analysis of the healthy parents of seven Fas-resistant patients showed that several of them were Fas-resistant, which suggests a genetic component. Fusion of Fas-resistant T cells with the Fas-sensitive HUT78 T cell line generated Fas-resistant hybrid cells, which suggests the presence of molecules exerting a dominant negative effect on Fas function. Analysis of Fas-induced activation of caspase-8 and -9 showed decreased activity of both caspases in HT, whereas activity of caspase-9 was increased and that of caspase-8 was decreased in GD. These data suggest that heterogeneous inherited defects impairing Fas function favour the development of thyroid autoimmunities.

Adolescent↗

Diagnostic approach and therapy of overgrowth and tall stature in childhood.

Although referral for evaluation of tall stature is much less common than for short stature, early diagnosis in the paediatric age of clinical pictures leading to tall stature is crucial, both in order to detect conditions which can be properly treated and in order to limit excessive final heights; nowadays tall stature may be cause of psychosocial problems. This paper reviews different items related to tall stature in childhood. First of all, our review focuses on the definition of tall stature and the classification of the main clinical conditions associated with either tallness or excessive growth is discussed. Secondly, the clinical picture and the most recent breakthroughs of each of these conditions are reviewed. A diagnostic flow-chart meant to approach a patient presenting with tall stature is designed according to a few simple parameters such as chronological age, height age, bone age and growth velocity. The novel advances in the understanding of constitutional and secondary tall stature are presented and discussed, together with the hormonal treatment of constitutional tall stature and other related outstanding questions.

Child↗

Pelvic sonography and uterine artery color Doppler analysis in the diagnosis of female precocious puberty.

OBJECTIVES: To evaluate the role of ultrasound and color Doppler analyses in the diagnosis of precocious puberty. METHODS: Gray-scale sonographic uterine and ovarian evaluation together with color Doppler analysis of the uterine artery were prospectively performed in 29 girls presenting with premature breast development and pubic hair growth. The values were compared with results obtained from the gonodotrophin releasing hormone stimulation test. Excluded from the study were patients with isolated thelarche or isolated pubarche and those patients with gonodotrophin releasing hormone-independent puberty and with polycystic ovaries. RESULTS: According to the Tanner scale, all the girls presented a breast stage of 2-3 and pubic hair stage 2-3. The uterine size was greater in those girls who presented a pubertal response to the gonodotrophin releasing hormone test (Group II; n = 20) (8.07 +/- 4.47 mL) than in those who did not (Group I; n = 9) (3.07 +/- 1.18 mL; P = 0.001). The ovarian volume and the number of small follicles was not significantly different between the groups. On Doppler analysis, more elevated impedances were observed in Group I (pulsatility index = 3.28 +/- 0.37) than in Group II (pulsatility index = 2.29 +/- 0.19; P = 0.001) girls. The presence of a low pulsatility index (< 2.5) at the level of the uterine arteries had a high diagnostic value for precocious puberty (sensitivity 86%, specificity 100%). CONCLUSIONS: Uterine artery Doppler analysis may assist the diagnosis of gonodotrophin releasing hormone-dependent precocious puberty, may be useful for the selection of those girls needing treatment, and may simplify the follow-up of girls treated for precocities.

Child↗

High serum allopregnanolone levels in girls with precocious puberty.

Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the modulation of behavioral functions, stress, and the neuroendocrine axis. The aim of this study was to evaluate serum allopregnanolone concentrations in girls with central precocious puberty (n = 12), girls with normal pubertal development at the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16). Gonadotropin and steroid hormones (allopregnanolone, cortisol, dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and ACTH stimulation tests were performed in all girls with central precocious puberty and in some pubertal controls. Basal allopregnanolone levels in girls with central precocious puberty were significantly higher than in normal controls (P < 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH stimulation tests (P < 0.05) both in girls with central precocious puberty and in those with normal pubertal development. There was no difference found between the peak values. In conclusion, our study shows that allopregnanolone is hypersecreted in central precocious puberty, confirming a pubertal stage-related increase in its levels during normal pubertal development. The increase in serum allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both adrenal cortex and gonads are sources of this neuroactive steroid.

Adrenocorticotropic Hormone↗

Association of waist circumference and body mass index with fasting blood insulin in severely obese children: a cross-sectional study.

We tested whether body mass index (BMI) and waist circumference (WC) are associated with fasting insulin in severely obese children. A number of 391 (204 female and 187 male) obese children were consecutively enrolled in the study at a Paediatric outpatient clinic. They were aged 10+/-3 yr (mean+/-SD; range: 3-17 yr) and had a relative weight for age of 160+/-27% (mean+/-SD). BMI and WC explained respectively 9 and 13% of the variance of log-transformed (lt) insulin (p<0.0001 for both). After correction for age, however, BMI lost its association with lt-insulin (p=NS) and WC explained only 3% (p<0.001) of lt-insulin variance. Sex and pubertal status did not influence the relationship between WC, BMI and lt-insulin (p=NS, ANCOVA). We conclude that in severely obese children: 1) WC is a marginally better predictor of fasting blood insulin than BMI, 2) age has a substantial influence on the relationship between BMI, WC and insulin and, 3) the contribution of BMI and WC to insulin is of doubtful clinical relevance because it leaves a substantial portion (> or = 87%) of lt-insulin variance unexplained.

Adolescent↗

Increased visceral adipose tissue is associated with increased circulating insulin and decreased sex hormone binding globulin levels in massively obese adolescent girls.

The current study was designed to examine the relationship between body fat distribution, as evaluated by anthropometry and magnetic resonance imaging (MRI), and circulating insulin, sex hormone and SHBG levels in obese adolescent girls. Twenty-nine obese adolescent girls, aged 12.6-16.9 years with a mean BMI of 30.51+/-1.86 participated in this study. All girls had breast stage B4-5 and pubic hair stage P4-5. Percent obesity and BMI as indices of being overweight were calculated; the waist-to-hip ratio (WHR) and the waist-to-thigh ratio (WTR) were calculated to obtain two anthropometric indices for the pattern of body fat distribution. The areas of visceral (VAT) and subcutaneous adipose tissue (SAT) were evaluated by MRI at the L4-L5 level. Serum concentrations of total T, DHEAS, 17beta-estradiol, progesterone and SHBG were measured. Plasma glucose and insulin concentrations were evaluated during an oral glucose tolerance test. WHR was the only anthropometric parameter that was significantly associated with the area of VAT. Insulin level showed correlation with both WHR and the area of VAT; no correlation was found between insulin levels and WTR. Both WHR and VAT were negatively correlated with serum DHEAS level and positively correlated with T level. There were strong negative correlations between serum SHBG level and the area of VAT and WHR. Inverse correlation was found between serum SHBG level and insulin. Serum 17beta-estradiol and progesterone levels showed no significant correlation with all the patterns of body fat distribution. SAT was not significantly correlated with both anthropometric parameters and any of the sex hormones evaluated. We can draw two main conclusions. Firstly, in massively obese adolescent girls, the WHR seems to be a good indicator for the accumulation of VAT, and abdominal obesity, rather than adiposity per se, appears to be related to biochemical complications. Secondly, increased upper body adiposity and, in particular, the intra-abdominal fat area are associated with increased insulin levels in massively obese adolescent girls. The associated reductions in SHBG and DHEAS levels represent an early general risk factor for the development of metabolic and cardiovascular diseases in this population, as previously described for obese adult women.

Adipose Tissue↗

Final height of thalassemic patients who underwent bone marrow transplantation during childhood.

We evaluated the final height achieved by 47 patients who had bone marrow transplantation (BMT) for thalassemia major. Subjects were separated into two groups: patients who received BMT before 7 years of age and patients who received BMT after 7 years of age. Parental height and genetic target height (TH) were calculated. Our data indicated a strict correlation between age at time of transplant and final adult height. The patients whose age at transplant was <7 years had a less impaired growth rate than did patients who were >7 years. Moreover, greatest loss in height was observed in subjects who had higher serum levels of transaminase and ferritin and these biochemical parameters were strictly correlated to the final adult height. Mean final adult height, however, did not differ from the genetic target height in subjects who received BMT before 7 years of age and the final height SDS corrected for TH surpasses even the TH. In contrast, the subjects who received BMT after 7 years of age, failed to achieve their full genetic potential. In conclusion, short stature is present in a significant percentage of transplanted thalassemic children. The data in this study indicate a close effect of the age at time of transplant on subsequent growth rate, but the growth impairment in these subjects remain multifactorial.

Adult↗

Serum activin A levels in males and females during pubertal development.

Activin A is a dimeric protein composed of two beta A-subunits protein of the transforming growth factor-beta (TGF-beta) family. This protein is synthesized by a variety of organs. A sensitive and specific assay for bioactive dimeric activin A has recently been developed, to measure circulating levels in adult women and men, giving a new insights into the possible physiological role of this protein in the reproductive axis and/or in other functions. The aim of the present study was to evaluate serum dimeric activin A levels in boys and girls during pubertal development. The study was performed on a group of children (n = 54) aged between 6 and 18 years at different Tanner stages. Serum levels of activin A were measured using a specific and sensitive two-site ELISA. Serum activin A levels were not significantly different at various Tanner stages (Tanner I, 0.36 +/- 0.02 ng/ml; Tanner II, 0.33 +/- 0.02 ng/ml; Tanner III, 0.35 +/- 0.03 ng/ml; Tanner IV, 0.41 +/- 0.04 ng/ml; Tanner V, 0.35 +/- 0.05 ng/ml; p > 0.01). No difference between male and female children was observed. In conclusion, the lack of significant differences in activin A serum levels according to the Tanner stages or to gender demonstrates that this protein is not involved in the endocrine modifications during pubertal development and that its measurement may not provide a sensitive new tool for determining gonadal maturity at puberty.

Activins↗

Diagnosis of central precocious puberty: endocrine assessment.

The new methods which are currently available have provided substantial help in performing the differential diagnosis of CPP, especially in detecting very early modifications of gonadotropin secretion. Nocturnal sampling is not a practical tool and generates discomfort for patients, and daytime samples do not yet have sufficient sensitivity; thus, determination of LH levels after GnRH stimulation is the most important test. We emphasize that the use of the GnRH agonist test improves the discrimination of the endocrine investigation, making it easier to differentiate CPP from other conditions, such as thelarche. Determination of sex steroids is necessary, but its use in isolation is not recommended.

Brain Diseases↗