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The prevalence of celiac disease (CD) in patients with chronic autoimmune thyroiditis (CAIT) is estimated to be between 2 and 7.8%. A gluten-free diet (GFD) in patients with CD is suggested to have a beneficial effect on CAIT. Thus, the present systematic review was undertaken to achieve more robust evidence about the change in thyroid stimulating hormone (TSH) and thyroid-specific antibodies (T-Ab) levels obtained in CD patients following a GFD. A specific search strategy was planned. The last search was performed on March 2022. The following data were mainly searched for in order to be extracted: sample size, mean and/or median with standard deviation (SD), and error (SE), individually, of thyroid hormones and T-Ab at baseline and after GFD, and the duration of the study. The initial search retrieved 297 records and 6 articles met the inclusion criteria. In total, 50 patients with both CD and CAIT and 45 controls were reported. The effects of a GFD on the thyroid hormonal and immunological profile could be extracted only in a part of the studies. Two studies were case reports. A low risk of bias was observed. These findings advise further studies, ideally randomized, in order to better investigate the potential relationship between GFD and thyroid homeostasis. The level of evidence is not still sufficient to recommend GFD to patients with CAIT.

Background: Obesity is known to promote mild hyperthyrotropinaemia by unknown metabolic mechanisms. This investigation aimed to explore the association between thyroid function and metabolic phenotype in euthyroid obese individuals. Retrospective, cross-sectional study. Tertiary care center., Methods: 952 euthyroid obese individuals referred to our Institution for obesity. Serum levels of TSH, FT4, glucose, insulin and HbA1c levels, lipid profile, liver function and proinflammatory indices were measured. Resting energy expenditure was assessed by indirect calorimetry and body composition by bioimpedance analysis., Results: On admission, 306 patients had previously diagnosed diabetes mellitus on treatment with metformin, while 113 patients were diagnosed with incident diabetes mellitus. Serum TSH levels were similar between metformin-treated diabetic subjects and metformin-untreated subjects, while FT4 was slightly but significantly higher in the former. Analysis stratified by TSH categories found no effect of metformin-treated diabetes mellitus on TSH levels. Interestingly, obese patients with incident diabetes showed lower TSH levels than normoglycaemic ones. In correlation studies on the whole dataset, an association related TSH to BMI and total cholesterol levels, which was lost upon adjustment for individual confounders. FT4 levels were found to be inversely related to BMI, insulin resistance and triglycerides, while being directly associated with HDL-cholesterol levels. These correlations remained unaltered after controlling for individual confounders. In multivariate linear regression analysis, TSH was associated with FT4, total cholesterol and BMI values. Significant predictors of FT4 were constituted by previously diagnosed diabetes mellitus, BMI, TSH and age., Conclusions: In euthyroid obese subjects, FT4 seems more closely related than TSH levels to parameters of cardiometabolic risk. TSH levels did not differ between metformin-treated and untreated subjects, while they were lower in patients with incident diabetes mellitus compared to normoglycaemic ones.

High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m(2)), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R(2) = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity.

Context: The last decades have provided insights into vitamin D physiology linked to glucose homeostasis. Uncertainties remain in obesity due to its intrinsic effects on vitamin D and glucose tolerance., Objectives: To assess the relationship between vitamin D and glucose abnormalities in severely obese individuals previously unknown to suffer from abnormal glucose metabolism., Setting: Tertiary care centre., Patients: 524 obese patients (50.3 ± 14.9 yrs; BMI, 47.7 ± 7.3 kg/m2) screened by OGTT, HbA1c and the lipid profile. Vitamin D status was assessed by 25(OH)D3, PTH and electrolyte levels. 25(OH)D3 deficiency/insufficiency were set at 20 and 30 ng/ml, respectively. All comparative and regression analyses were controlled for age, BMI and gender., Results: The prevalence of vitamin D deficiency/insufficiency and secondary hyperparathyroidism were 95% and 50.8%, respectively. Normal glucose tolerance (NGT), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) were found in 37.8%, 40.5% and 21.7% of cases, respectively. Large variations in metabolic parameters were seen across categories of vitamin D status, but the only significant differences were found for C-peptide, tryglicerides, LDL- and HDL-cholesterol levels (p < 0.05 for all). The prevalence of vitamin D deficiency was documented to be slightly but significantly more frequent in glucose-intolerant patients (IFG + IGT + T2DM) compared to the -normotolerant counterpart (87% vs. 80%, p < 0.05). In partial correlation analyses, there was no association between vitamin D levels and glucose-related markers but for HbA1c (r = -0.091, p < 0.05), and both basal and OGTT-stimulated insulin levels (r = 0.097 and r = 0.099; p < 0.05 for all). Vitamin D levels were also correlated to HDL-cholesterol (r = 0.13, p = 0.002). Multivariate regression analysis inclusive of vitamin D, age, BMI, gender and fat mass as independent variables, showed that vitamin D was capable of predicting HbA1c levels (β = -0.101, p < 0.05)., Conclusions: Given the inherent effect of obesity on vitamin D and glucose homeostasis, current data suggest a potential independent role for vitamin D in the regulation of glucose metabolism in a setting of obese patients previously unknown to harbour glucose metabolism abnormalities.

Obesity is a cause of sleep breathing disorders that result in excessive daytime sleepiness. We describe the adaptive strategy used by an obese person who started to snort cocaine to remedy incoercible drowsiness affecting his working financial skills. Clinical workup documented severe sleep apnea, which was treated by noninvasive ventilation and resulted in withdrawing cocaine abuse. Undiagnosed sleep disorders may trigger surreptitious psychostimulant abuse in vulnerable individuals.

Objectives: Obesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD)., Study Design: This cross-sectional study was performed in a tertiary care center., Methods: Free thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects. Results were plotted against variables related to body composition, leptin levels, glucose homeostasis, energy expenditure, and pattern of weight accrual., Results: Compared with controls, obese patients had lower free T3 levels and free T4 levels (P<0.01), greater prevalence of hypothyroidism (P<0.05), and higher commonness of antithyroid antibodies (P<0.05). As a marker of AITD, thyroid peroxidase antibodies were more frequent in the obese group (P<0.01). Correlation analysis showed that leptin levels were associated with AITD (P<0.01) independent of bioanthropometric variables. Multiple logistic regression analysis in pooled groups identified female sex and leptin as significant predictors of AITD., Conclusions: Obesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.

Abdominal visceral tissue (VAT) and subcutaneous adipose tissue (SAT), comprised of superficial-SAT (sSAT) and deep-SAT (dSAT), are metabolically distinct. The antidiabetic agents thiazolidinediones (TZDs), in addition to their insulin-sensitizing effects, redistribute SAT suggesting that TZD action involves adipose tissue depot-specific regulation. We investigated the expression of proteins key to adipocyte metabolism on differentiated first passage (P1) preadipocytes treated with rosiglitazone, to establish a role for the diverse depots of abdominal adipose tissue in the insulin-sensitizing effects of TZDs. Adipocytes and preadipocytes were isolated from sSAT, dSAT, and VAT samples obtained from eight normal subjects. Preadipocytes (P1) left untreated (U) or treated with a classic differentiation cocktail (DI) including rosiglitazone (DIR) for 9 days were evaluated for strata-specific differences in differentiation including peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and lipoprotein lipase (LPL) expression, insulin sensitivity via adiponectin and glucose transport-4 (GLUT4), glucocorticoid metabolism with 11 beta-hydroxysteroid dehydrogenase type-1 (11 beta HSD1), and alterations in the adipokine leptin. While depot-specific differences were absent with the classic differentiation cocktail, with rosiglitazone sSAT had the most potent response followed by dSAT, whereas VAT was resistant to differentiation. With rosiglitazone, universal strata effects were observed for PPAR-gamma, LPL, and leptin, with VAT in all cases expressing significantly lower basal expression levels. Clear dSAT-specific changes were observed with decreased intracellular GLUT4. Specific sSAT alterations included decreased 11 beta HSD1 whereas secreted adiponectin was potently upregulated in sSAT with respect to dSAT and VAT. Overall, the subcompartments of SAT, sSAT, and dSAT, appear to participate in the metabolic changes that arise with rosiglitazone administration.

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.

Objective: The worldwide increase in the prevalence of childhood obesity is reaching epidemic proportions and is associated with a dramatic rise in cases of type 2 diabetes. The prevalence of glucose intolerance and its determinants and the relation of cardiovascular risk factors with levels of glycemia and degree of obesity were studied in grossly obese children of European origin., Research Design and Methods: A total of 710 grossly obese Italian children (SD score [SDS] of BMI 3.8 +/- 0.7) aged 6-18 years, including 345 male subjects, underwent an oral glucose tolerance test. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment for insulin resistance and the insulinogenic index, respectively. Fibrinogen, C-reactive protein, lipids, and uric acid were measured. The 2-h postload glucose and degree of obesity, calculated as the SDS of weight/height(2), were used as dependent variables., Results: The prevalence of glucose intolerance was 4.5%. Insulin resistance (P < 0.0001), impaired insulin secretion (P < 0.0001), and diastolic blood pressure (BP) (P < 0.05) were significantly and independently related to 2-h postload glucose values. The degree of obesity did not relate to insulin resistance but was independently correlated with inflammatory proteins, uric acid, and systolic BP, variables that were often abnormal in this population., Conclusions: In these grossly obese children, both insulin resistance and impaired insulin secretion contribute to the elevation of glycemia, and the degree of obesity is related to cardiovascular risk factors independently of insulin resistance.

Several methods have been developed to assess insulin resistance (IR), insulin secretion, and sensitivity: some of them, such as the homeostasis model assessment (HOMA) for IR (HOMA IR) and for insulin secretion (HOMA beta cell) and the quantitative insulin sensitivity check index (QUICKI) are based on fasting levels of glucose (fasting G) and insulin (fasting I); others, such as the pancreatic insulin response to glucose (IRG) and the insulin sensitivity index (ISI) are derived from the glycemic and insulinemic responses to the oral glucose tolerance test (OGTT). The aim of the study was to compare these indexes in a large group of prepubertal and pubertal obese subjects and verify whether the data from fasting samples were enough for evaluating IR and insulin secretion or if OGTT was mandatory. A total of 405 obese subjects (221 boys and 184 girls) was studied. Ninty-three were prepubertal (Tanner stage I), 98 early pubertal (stage II to III) and 214 late pubertal (stage IV to V). In each subject, a 120-minute OGTT was performed, and the glycemic (mean blood glucose [MBG]) and insulinemic (mean serum insulin [MSI]) responses, expressed as AUC/120, as well as IRG and ISI were calculated. The fasting I/fasting G ratio (FIGR), HOMA IR, HOMA beta cell, and QUICKI were then measured. FIGR and HOMA IR increased in both sexes during puberty, but in girls, the increase was already evident from stage I to stage II to III, while in boys, it was evident only from stage II to III to stage IV to V. QUICKI decreased in girls at the onset of puberty and was lower than in boys in stage II to III; on the other hand, HOMA beta cell did not show any variation. IRG increased throughout puberty, although it was higher in boys than in girls in stages II to III and IV to V, while ISI decreased at the onset of puberty in boys; HOMA IR correlated with MSI and IRG, and HOMA beta cell with MSI in pubertal subjects only. In conclusion, the indexes deriving from fasting samples, such as FIGR and HOMA IR, proved to be enough for evaluating IR in prepubertal and pubertal obese subjects, as did QUICKI for insulin sensitivity, However, OGTT is still useful for assessing insulin secretion, because IRG is more sensitive in depicting the pubertal variations of IR than HOMA beta cell., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background: Prader-Willi syndrome (PWS) is the most common genetic obesity. Excessive weight gain follows failure-to-thrive in early infancy; in adolescents and young adults, excess body weight can exceed 100%. The hyperphagia associated with PWS is responsible for the early mortality. Dietary restriction, alone or combined with anorexic drugs, are ineffective to induce a permanent weight loss. Thus, surgical treatment of morbid obesity in PWS has been attempted, but gastric restrictive operations are unable to produce stable weight loss. In a small number of patients, favorable results have been reported with biliopancreatic diversion (BPD)., Case Report: A 24-year-old woman with PWS, Pickwickian, at age 21 weighed 80 kg (BMI= 50) and underwent BPD., Results: 3 years after the BPD she regained 21 of the 26 kg lost; somnolence and respiratory difficulties were the same as before surgery. The patient now presents severe reduction of bone mass density, hypochromic anemia, hypoproteinemia, and diarrhea associated with eating., Conclusion: The regain of weight following BPD suggests that this procedure alone is not adequate for long-term control of obesity in PWS.

Background: Hexarelin (HEX), a synthetic hexapeptide with a strong GH-stimulating activity, has been suggested as a stimulus for evaluating GH secretion. However, in childhood it has never been compared with other stimuli capable to reduce the effect of the somatostatinergic tone and of the low production of gonadal steroids., Methods: We evaluated GH response (expressed as the maximum value after stimulus [Cmax] and as area under the curve [AUC], mean +/- SD) to HEX at a dose of 2 micrograms/kg i.v., in comparison with those obtained after GHRH (1 microgram/kg i.v.) + pyridostigmine (PD, 60 mg p.o.) and arginine + ethynylestradiol (E2, 1 mg/day p.o. for 3 days before the test), in 5 subjects with familial short stature (FSS), 11 with constitutional growth delay (CGD), prepubertal (Tanner's stage I) and early pubertal (stage II), and in 8 healthy children age-matched as controls., Results: HEX induced a Cmax of 31.9 +/- 18.4 micrograms/l and an AUC of 1511 +/- 923 micrograms/min x l in stage I, of 36.7 +/- 12.3 micrograms/l and 1938 +/- 903 micrograms/min x l in stage II (ns). GHRH + PD induced a Cmax of 33.8 +/- 14.6 micrograms/l and an AUC of 2072 +/- 1233 micrograms/min x l in stage I, of 29.6 +/- 15.6 micrograms/l and 1901 +/- 1252 micrograms/min x l in stage II (ns). ARG + E2 induced a Cmax of 17.8 +/- 7 micrograms/l and an AUC of 1157 +/- 505 micrograms/min x l in stage I, of 15.6 +/- 11.6 micrograms/l and 649 +/- 452 micrograms/min x l in stage II (ns). The Cmax of HEX was higher than that of ARG + E2 in both stages I and II (p < 0.05); AUC of HEX, was higher than that of ARG + E2 only in stage II (p < 0.01); the Cmax and the AUC of GHRH + PD were higher than those of ARG + E2 both in stage I (p < 0.01 and p < 0.05, respectively) and in stage II (p < 0.05). No difference, neither in the extent of GH response to HEX and GHRH + PD nor in that to stimuli between subjects and controls, was found. HEX has given 32% false positives in stage I and 17% in stage II, GHRH + PD 12% and 15%, while ARG + E2 provided 20% in stage I and 32% in stage II. On the whole, specificity was 76% for HEX and ARG + E2 and 89% for GHRH + PD., Conclusions: HEX induced greater GH response than that of ARG + E2 but similar to that of GHRH + PD and its specificity was not different to that of ARG + E2 and lower than that of GHRH + PD: then its use does not show a diagnostic advantage in respect to the other two stimuli in peripubertal age.

Background and Aim: Correlations between serum leptin (LEP) and BMI and the percentage of fat mass (FM), as well as differences between male and female serum levels and their behaviour during weight loss have already been extensively described in adult obesity, whereas few cases have been examined in child and adolescent obesity. There are also few studies of the alterations in NPY in peripheral blood in obese subjects during weight loss., Methods: This study aimed to evaluate the correlations between LEP and BMI, FM% and NPY in 72 obese subjects, with BMI > 35 (29 males and 43 females) aged between 9.6 and 19.8 years old, during weight loss together with any differences between the sexes., Results: LEP was positively correlated in both sexes with BMI and FM%, whereas no correlation emerged with NPY; LEP levels decreased gradually during weight loss, whereas no changes were observed in NPY except during the first phases of weight loss in males when the decrease was significant. LEP concentrations were significantly higher in females, who also showed a higher FM% with equal BMI. No difference was observed between NPY levels in both sexes., Conclusions: The authors conclude that: 1) the behaviour of LEP in child-adolescent obesity is broadly comparable to that described in adult obesity; 2) the highest LEP concentrations with equal BMI in females appear to reflect the different body composition of the two sexes given that females have a higher FM%; 3) the control exerted by LEP on hypothalamic NPY cannot be seen in peripheral blood and no differences emerged between the two sexes.

Background: Knemometer is a non invasive device for measuring the leg length and evaluating statural variations otherwise not disclosed by means of Harpenden stadiometer. In several clinical conditions of short stature, knemometer allows to evaluate the short-term effect of growth promoting agents, as well as the role of infections on growth dynamics., Methods: The short-term (37-56 days) variability of the leg length in subjects with isolated growth hormone deficiency (1 case), Turner syndrome (2 cases) and Silver-Russel syndrome (1 case) treated with rhGH have been evaluated. The measurements were performed weekly by the same operator, at the same weekday and daytime., Results and Conclusions: The results show a correlation between intercurrent illnesses and growth failure, as well as a growth resumption at the end of the former, despite the etiology of short stature. Growth hormone treatment seems to exert an influence on growth only in the subject with GH deficiency, whereas a similar short term effect is not found in the cases of Turner syndrome and Silver Russel syndrome. This fact suggests that, also by knemometry, a most prolonged follow-up is required to evaluate the effect of GH on short term growth.

Background: The aim of this study was to investigate the potential of dexfenfluramine (dF) for reducing cardiovascular risk factors and improving compliance towards diet in a group of young patients hospitalized for essential obesity of high degree (BMI > or = 35)., Methods: 103 adolescents (mean age 15.4 +/- 0.2) participated in a nine-week randomized double-blind study of dF (15 mg bid) versus placebo. All patients received a VLCD (2,512 kJ/day = 600 kcal/day) for two months. In basal conditions, and after 30 and 60 days of treatment, anthropometric variables (height, weight, BMI, and W/H) and cardiovascular risk factors (blood glucose concentration, total cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressure) were monitored. Modifications in hunger and satiety were also assessed., Results: During the treatment period, both the dF group and the placebo group presented a similar pattern of weight loss (BMI = dF: 36.7 +/- 0.5 vs 32.5 +/- 0.4 vs 30.1 +/- 0.4; placebo: 37.0 +/- 0.6 vs 33.1 +/- 0.5 vs 30.8 +/- 0.5). No important side-effects were recorded in either group. Blood pressure and metabolic markers decreased significantly in both groups. Earlier reductions in total cholesterol and diastolic blood pressure in dF-treated subjects were the only significant differences observed as compared to the patients receiving placebo (day 30 = total cholesterol: 120 +/- 2 (dF) vs 132 +/- 3 (placebo) mg/dI; p < 0.005; diastolic blood pressure: 73 +/- 1 (dF) vs 77 +/- 1 (placebo) mmHg; p < 0.01). However, after 60 days, these values were similar in the two groups. As far as non-parametric data are concerned, dF determined a reduction in hunger and an increase in satiety in a significantly higher number of subjects than did the placebo, not only after 30 days of treatment (92.8% vs 55.3% and 92.8% vs 45.5%, respectively; p < 0.0001), but also after two months of treatment (97.8% vs 67.4% and 97.8% vs 45.8%, respectively; p < 0.0001)., Conclusions: These findings demonstrate that dF represents a useful support in the treatment of juvenile obesity and might ensure a better individual compliance towards restrictive diets, particularly in the initial "critical" stages, in the absence of important side-effects.

Growth hormone response to galanin (GAL) and growth hormone releasing hormone have been demonstrated to be higher in females than in males, and moreover the cholinergic system appears to be able to enhance them. On the basis of this presumption, we evaluated the GH response (expressed as area under the curve: AUC-GH) to galanin (GAL, 10 mg/kg i.v.) or GHRH (1 mg/kg i.v.) either alone or associated together and with pyridostigmine (PD, 60 mg p.o.), and to saline infusion as a control, in 5 males and 5 females, in puberty, aged 16 +/- 0.4 years old (mean +/- SD). In females tests were performed during the follicular phase of the menstrual cycle. GAL alone cannot provoke a response from GH unless associated with GHRH. The contemporary administration of PD does not increase the extent of the response. The latter did not differ between sexes. The GHRH-GAL association induced a higher response in GH compared to GAL alone and GAL-PD, without any differences between the sexes. Lastly, the combination GHRH-GAL-PD induced responses that were comparable to GHRH and GAL alone. Therefore GAL does not act alone but enhances the effect of GHRH and the cholinergic system appears to be involved as a modulator. Moreover, the effect of GAL is comparable in both sexes.

It has been observed that the pineal gland seems to modulate diencephalic neuroendocrine activity through its principal hormone, melatonin. In animals, melatonin inhibits the secretion and release of hypophyseal gonadotropins, probably by inhibiting hypothalamic releasing factors; in man, on the contrary, the administration of LHRH seems to have a stimulating effect on melatonin serum levels. In the light of this, in pathologies characterised by an imbalance in the hypothalamus-hypophyseal-gonad axis, it is possible to hypothesise variations in the secretion of melatonin and/or in its circadian fluctuations. In order to clarify further the relationship between the epiphysis and the hypothalamus-hypophyseal axis, the present study evaluated the pattern of melatonin secretion in a group of 16 patients with Klinefelter's syndrome. The circadian rhythm of melatonin secretion was determined from venous blood samples taken at 9 am, 1 pm, 5 pm, 9 pm, 1 am and 5 am; the same protocol was also followed in two control groups of respectively prepuberal and puberal healthy subjects. During the night samples were taken as rapidly as possible, using a red light source in order to not interfere with melatonin secretion. All of the examinations were performed during the winter period. Serum levels of melatonin were determined, after extractions with diethylether, by means of a double antibody RIA using commercially available kits (Bioscience Product--The Netherlands). Intra- and inter-assay coefficients of variation were respectively 3% and 8%. The data are reported as mean values +/- SD; the results were analysed by means of Student's test for unpaired data and analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the present study was to evaluate social integration in adulthood in a group of 48 subjects with Turner's syndrome. This was done by asking subjects to fill in a multi-choice questionnaire concerning their personal, social and working situation. The mean age (+/- SD) of the group was 24.8 +/- 1 and the reported stature was 142.2 +/- 1.4. The results obtained were compared with those formulated by ISTAT in 1990 for the entire Italian population. As far as regards education it was seen that 100% of subjects had completed primary school, 52% had attended secondary school, 29% had been to high school and 6% had attended university. It was therefore concluded that educational status, at least in this group, was higher than that of the Italian population in general. The cultural level of these subjects meant that most had found appropriate employment and only 6% were unemployed. 90% of the subjects were unmarried and only 5 were married (10%); the majority of those unmarried lived with their parents (83%). This underlines a prolonged dependence on the family nucleus and probable disorders regarding the subjects' own sexual identity and affective capacities. Among the parameters examined no substantial differences were found between subjects with a 45,X karyotype and those with chromosomic mosaicism. In the light of these findings it is apparent that efficacious medical and psychological strategies should be developed to enable a greater realization of interpersonal relations in the familial and social field.

It has been demonstrated that the direct and/or indirect stimulation of hematopoiesis is one of the effects of the growth hormone (GH) in vitro. In order to study the effect of GH on erythropoiesis in vivo, the variation of hemochrome in a group of 8 subjects with GH deficiency (GHD) were monitored during a substitutive therapy with biosynthetic GH (rhGH) at dose of 0.4 U/kg/week. Hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), number of red blood cells (RBC) were analysed in all subjects at the beginning and after 9 months of treatment. The effectiveness of therapy was demonstrated by statistically significant variations in height, height SDS, growth velocity, serum levels of IGF-I. After 9 months of rhGH therapy, a significant increase was observed in all values considered with exception of MCV. In conclusion Gh would appear to stimulate erythropoiesis, directly or indirectly, and these results would appear to indicate an in vivo confirmation.

In order to evaluate the functionality of the hypothalamic-hypophyseal-thyroid axis in Turner's syndrome (TS), 27 subjects, aged between 5.1 and 16.1 years old, were studied, 14 of whom were karyotype 45,XO and 13 affected by mosaicism. The TRH test (200 mcg i.v.) was performed in all subjects using a single bolus. TRH titers were assayed in serum samples collected at 0, 15, 30, 60 and 90 minutes, and anti-microsome and anti-thyroglobulin, T4 and T3, were assayed in the basal sample; the latter were also assayed in the blood sample collected at 120 minutes. These results were compared with those obtained using the same test in a group of age- and sex-matched controls. Anti-thyroid antibodies and basal levels of T3 and T4 were within the norm in 26 subjects; a high basal value of TSH was only found in one patient with chromosomic mosaicism with an elevated response to TRH and a high titer of anti-microsomic antibodies. Apart from this no statistically significant differences were found in patients compared to control subjects in relation to TSH values at all stages of the test and between the two groups of TS; no significant results were found in the comparison between the areas below the curves (AUC). On the basis of these results the Authors conclude that it is not possible to reveal alterations in thyroid function attributable to hypothalamic and hypophyseal anomalies in this group of patients either with karyotype 45,XO and mosaicism.

The well know fact that high blood pressure and impaired glucose tolerance are frequently associated with obesity has suggested that hyperinsulinemia could represent one of the possible pathogenetic connections between obesity and systodiastolic hypertension. With the aim of verifying this hypothesis 67 obese subjects (36 hypertensive and 31 normotensive), males, were admitted to our study. All of the subjects underwent standard OGTT in order to measure their glycemic and insulinemic levels. No differences were found between two groups, as regard age and the degree of obesity; blood pressure values were significantly different (p less than 0.01). No significative differences were detected for glycemic and insulinemic levels between normotensive and hypertensive subjects; basal hyperinsulinemia was detected in a similar percentage (16.6 vs 19.3%) in the two groups. Under these circumstances it is not possible to confirm that hyperinsulinemia is the prominent link between obesity and high blood pressure, as previously observed by others.

The incidence of impaired glucose tolerance (IGT) in obese juvenile has not yet been well defined. Glycemic and insulin responses to OGTT were evaluated in 398 obese juveniles (and 70 healthy control subjects) to investigate possible correlations with age, body mass index (BMI) and obesity duration. Subjects were subdivided into two groups according to OGTT results: obese with normal glucose tolerance (OB-NGT) and obese with impaired glucose tolerance (OB-IGT). IGT was found in 11% of subjects but no correlations were observed in relation to age, BMI and obesity duration. There was no difference in the glycemic response to OGTT in terms of the biological parameters examined. Insulin plasma levels were twice as high in OB-NGT in comparison to control subjects and OB-NGT. Basal insulinemia increased with BMI in OB-IGT but not in OB-NGT.

The study aimed to assess the effect of juvenile simple adiposity on growth. The height (measured using a Hapenden stadiometer) of 1443 subjects (799 boys and 644 girls) aged from 6 to 16 was measured. The Quetelet index (QI) of adiposity was used; all subjects examined exceeded the 95th centile of the standard Cronk and Roche scale. Heights are expressed as standard deviation scores (SDS) and are compared to the British Standard. Adipose boys are taller than British boys up to the age of 12, then the difference lessens and the average heights of 15-year-old adipose boys are below the 50th centile of British growth charts. Female subjects showed a higher SDS from 6 to 8 years, after which the difference lessens gradually, and after 13 years the average height is below the 50th centile of British standards. Adipose boys are taller than normal boys during childhood; in prepuberty and puberty this difference lessens and during puberty they are shorter than British boys. This growth model is probably due to advanced skeletal maturity in adipose subjects with the result that at puberty growth lessens because it is exhausted. The wide epidemiological cross-sectional study confirms that growth is favourable in juvenile adiposity but does not alter adult height.

Lipid plasma levels were measured in a group of 519 obese subjects, aged 7-66 years, divided according to age, sex and BMI. Lipidemia and total cholesterolemia increased both with age and BMI, irrespective of sex; LDL and VLDL increased in relation to age and, with less evident differences, to BMI. Triglycerides increased in the age bracket from adolescent to adult, especially in males, whereas their increase in relation to BMI showed no difference between the sexes. Chylomicron plasma levels remained steady both in relation to age and BMI.

Essential adiposity positively influences growth during childhood, but little is known about its effects on final height. A study was performed in 39 subjects (20 males and 19 females, mean age 10.7 for males, and 8.2 years for females) affected by essential adiposity to assess height during and at the end of the developmental age. During childhood the height of adipose subjects included in the study exceeded the mean values for matched chronological ages from the British reference sample (0.716 SDS for males, 0.587 for females). In adulthood, this advantage was completely reversed: the height of males in the study was in line with mean values (0.069 SDS), whereas the females were slightly under the mean height of the reference group (0.165 SDS). Since height is known to be heavily influenced by genetic factors, the results have been corrected for genetic bias. Improved results are obtained following correction for genetic influence: males (0.890 SDS), females (0.584 SDS). In conclusion, childhood adiposity has a positive influence on growth during the developmental age, and also appears to have a positive influence on genetic potential, as may be deduced from the height of the parents, thus improving final height.

High blood pressure and impaired glucose tolerance are frequently associated with obesity: it has been suggested that hyperinsulinemia could represent one of the possible pathogenetic connections between obesity and systodiastolic hypertension. In order to verify this hypothesis we examined fasting and post-load insulin and glucose levels in a group of 102 obese females, 58 hypertensive and 44 normotensive. All of the subjects underwent standard OGTT in order to measure their glycemic and insulinemic levels. No differences were found between two groups, as regard age and degree of obesity; blood pressure values were significantly different (p less than 0.01). No significative differences were detected for glycemic and insulinemic levels between hypertensive and normotensive subjects. These results indicate that hyperinsulinemia is not the prominent link between obesity and arterial hypertension; the relationship between these two conditions may be indirect.

We investigated the beta-pancreatic function in response to a standard oral glucose tolerance test (OGTT) and a tolbutamide test in a group of GH-deficient adult subjects and in a group of control subjects. Fasting plasma glucose levels were normal in all subjects; the insulin levels, basal (0.19 +/- 0.02 vs 0.99 +/- 0.08) and, as n-AUC, after OGTT (195.2 +/- 23 vs 520.5 +/- 69) and tolbutamide test (33.6 +/- 4.4 vs 177.7 +/- 12.1) (means +/- ES), were significantly lower (p less than 0.001) in the GH-deficient subjects compared to controls. These data indicate a reduced beta-cell activity, secondary to absence of trophic effect of GH on pancreatic beta-cells, in GH-deficient adults.

Lipid plasma levels were measured in a group of 251 adipose juveniles. Triglycerides were elevated in relation to age but not to weight excess. Cholesterol and LDL levels had a same behaviour, through childhood toward adolescence, with significantly higher values in males than in females. VLDL levels prove a significative increase in reference to BML rise, but not so much increasing age. In short, the juvenile adiposity doesn't seem to produce considerable alterations of lipidaemia incides, even if we can foresee a possible evolution toward an acclaimed dislipidaemic pattern in adulthood.