Bone loss determined by quantitative ultrasonometry correlates inversely with disease activity in patients with endogenous glucocorticoid excess due to adrenal mass.

OBJECTIVE: Glucocorticoid excess is widely recognized as one of the most important causes of bone loss. The mechanism of glucocorticoid-induced osteoporosis is presumably multifactorial, and consists of the loss of organic and non-organic compounds. Efforts have been made to develop simple physical methods for the assessment of bone tissue for the screening of subjects at high risk of osteoporosis, without the use of radioactive sources or ionizing radiation. Quantitative ultrasonometry (QUS) has been suggested as a useful method for monitoring patients undergoing glucocorticoid therapy, which is the most common cause of glucocorticoid excess. QUS appears to detect more structural bone changes than the traditional methods and allows assessment of bone density and elasticity, both characteristics influenced by organic and non-organic bone compounds. However, the use of QUS has not yet been extensively investigated in subjects with endogenous cortisol excess. The aim of this study was to evaluate the usefulness and predictive power of QUS in assessing bone loss in subjects with differing degrees of endogenous cortisol excess due to adrenal mass. DESIGN: Thirty-four patients (20 women and 14 men) aged between 21 and 59 years were evaluated; fifteen (9 women and 6 men; median age, 42 years) were affected by overt Cushing's syndrome (CS) and nineteen (11 women and 8 men; median age, 44 years) by subclinical CS, defined as lacking clinical signs of hormone excess despite the presence of at least two abnormalities in hypothalamic-pituitary-adrenal axis function, as assessed by routine endocrine tests. All women included were eumenorrhoic. METHODS: QUS measurement of amplitude-dependent speed of sound was performed on the 2nd to 5th proximal phalanges of the non-dominant hand using a DBM Sonic 1200R bone profiler (Igea S.r.l, Italy). The results were compared with bone density assessed on lumbar vertebrae (L1-L4) and femoral neck sites by dual-energy X-ray absorptiometry (DEXA). RESULTS: A strongly significant bone loss was detected by finger QUS measurement when the patients were considered either all together or as two subgroups (P<0.001, all). The bone density decrease in the fingers was similar to that found at the lumbar spine and femoral neck by the DEXA technique. Lumbar and finger Z-scores correlated inversely with 24 h urinary free cortisol (UFF) excretion (P<0.01, both). Finger Z-scores also correlated inversely with the estimated duration of subclinical CS (P<0.05). Concerning disease activity, only UFF was confirmed by multivariate analysis to be an independent factor influencing bone loss (P<0.05). A positive correlation between the results of the two techniques was found in controls (P<0.05) but not in patients. The lack of correlation between the two techniques in patients can probably be attributed to the different parameters of bone alteration measured by the techniques. CONCLUSIONS: The detection of bone loss in subclinical CS similar to that in overt CS suggests that all subjects with endogenous cortisol excess should be evaluated for bone mass. QUS measurement appears to be a reliable, radiation-free, simple and fast tool for the identification of bone alteration in subjects with endogenous cortisol excess.

Increased urinary excretion of collagen crosslinks in type 1 diabetic children in the first 5 years of disease.

To analyze possible early abnormalities in bone resorption in type 1 diabetes mellitus the urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline was evaluated by immunoassay in 26 prepubertal diabetic patients (mean age 7.8 +/- 1.6 years, mean duration 3.0 +/- 1.1 years) and 46 healthy children (age 8.3 +/- 1.3 years). Relationships with growth parameters (height-standard deviation score, body mass index and height velocity during the year preceding the study) and metabolic control were sought. Longitudinal and ponderal growth was normal in diabetic children. Urinary collagen crosslink excretion was 88.4 +/- 25 nmol/mmol creatinine (median 86, range 44-146) in diabetic patients and 65.6 +/- 19 nmol/mmol creatinine (median 61, range 32-108) in controls (p = 0. 0002). It was positively influenced by diabetic status (beta = 20.5) and negatively by age (beta = -6.41), controlling by sex and BMI (p = 0.0001). A positive correlation was found between collagen crosslinks and blood glucose (r = 0.48, p = 0.01) or HbA1c levels (r = 0.44, p = 0.02) evaluated at the time of the study, while no significant correlation was found with the mean HbA1c values assessed in the last year or throughout the whole duration of diabetes. Collagen crosslink excretion was significantly increased in patients who presented worsening of their metabolic control in the last 3 months. No relationship was found with the duration of disease or growth parameters. In conclusion, the elevated urinary excretion of collagen crosslinks in diabetic children indicates that bone resorption may be disturbed. Poor metabolic control influences the increased rate of bone resorption and may expose growing diabetic patients to a risk of bone loss.

[Urinary calcium excretion in a population of children living in Southern Italy]. / Escrezione urinaria di calcio in una popolazione infantile del sud Italia.

BACKGROUND: Very few studies have evaluated the role of urinary calcium excretion as marker of bone metabolism in children. Normative data are lacking in these age groups. METHODS: In a group of 122 children (66 females e 56 males), mean age 108.13 +/- 18.73 months, attending a primary school in Nocera Superiore (Southern Italy) the following parameters were evaluated: sex, age, weight, height, BMI (weight/height2), urinary calcium excretion which was measured as the urinary calcium/creatinine concentration ratio (Uca/cr) in extemporaneous sample of the second urine in the morning. The Uca/cr ratio was not normally distributed in this childhood population. Natural logarithmic transformation was used to analyze the data. RESULTS: The mean value of Uca/cr was 0.125 +/- 0.102 mg/mg. A significant correlation was found between the Uca/cr ratio and sex. The Uca/cr ratio values were higher in girls than in boys. Mean Uca/cr was 0.144 +/- 0.113 mg/mg in females while it was 0.102 +/- 0.083 mg/mg in males ("t"-test: p < 0.05). No correlation was found between the Uca/cr ratio and other variables such as age, height, weight and BMI either in the simple or in the multiple linear regression analysis correcting both for the sex and the age. Data by age-group and sex were reported as percentile tables. CONCLUSIONS: The discussed variations of the Uca/cr in children from different areas and sex confirm the need for reference standards calculated in the different population groups.

Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy.

Osteoporosis is a well-known complication of thyrotoxicosis. Prolonged subclinical hyperthyroidism due to L-thyroxine treatment has been associated with reduced bone mass and thus with the potential risk of premature development of osteoporosis. The aim of this study was to assess the effect of a chronic L-thyroxine suppressive treatment on bone mineral density (BMD) in a group of premenopausal women. Forty consecutive patients (mean age +/- SE = 40.95 +/- 1.56 years) affected by non-toxic goiter underwent bone mineral densitometry (dual energy X-ray absorptiometry; DEXA) of the lumbar spine (L1-L4) and right femoral neck. At the time of the study the patients had been under thyroid stimulating hormone (TSH) suppressive therapy for 74.95 +/- 10.34 months (range 17-168 months). Baseline levels of free thyroxine (fT4), free triiodothyronine (fT3), TSH, calcium and phosphorus were measured and correlated with BMD. The age of starting, duration of treatment, main daily dose, cumulative dose of treatment and body mass index (BMI) were also correlated with BMD. Statistical analysis was performed by multiple linear regression. BMD among female patients was not significantly different from that of the general population matched for age and sex. With the use of the regression model, no significant correlation was found between BMD and the variables considered. In conclusion, our data suggest that L-thyroxine suppressive therapy, if carefully carried out and monitored, has no significant effect on bone mass.

Peripheral body fat has a protective role on bone mineral density in elderly women.

OBJECTIVES: To determine whether bone mineral density is lower in women living in homes for the elderly as compared to free dwelling control subjects, and to investigate factors affecting possible differences. This is the first study with this objective as the primary aim. DESIGN: Case-control study. SUBJECTS AND METHODS: Institutionalised independent elderly women (n = 22, mean age = 75.1 y+/-6.43 s.d.) randomly selected in a home for the elderly and 22 age-matched control women randomly selected from a sample representative of the independent non institutionalised local population who underwent dual energy X-ray absorptiometry (DXA) at the lumbar spine and right femoral neck; anthropometric measurements (height, weight, subscapular and triceps skinfold thickness); general questionnaire. RESULTS: Mean bone mineral density at the femoral neck was 0.618 g/cm2 (+/-0.130s.d.) in institutionalised women and 0.709 g/cm2 (+/-0.106 s.d.) in controls (P = 0.02, t-test). Controlling for confounding factors in the analysis of covariance, triceps skinfold thickness and living in a home for the elderly turned out to be significant determinants of bone mineral density. CONCLUSION: When compared to free dwelling control subjects, institutionalised women show lower bone density, that is the main risk factor for fracture. Reduced peripheral body fat was significantly associated with the low bone mineral density observed. Health programs aimed at decreasing the incidence of fractures among institutionalised subjects will also have to consider the effect of nutritional or life style factors that reduce peripheral body fat.

Fasting respiratory quotient as a predictor of weight changes in non-obese women.

OBJECTIVE: To detect predictive variables of weight changes in non-obese women. DESIGN: Three year follow-up study. SUBJECTS: Fifty-eight women (age 40.0+/-12.8 y, height 159+/-7 cm, weight 62.5+/-9.6 kg and body mass index ((BMI) 24.7+/-3.7 kg/m2). MEASUREMENTS: At baseline, basal metabolic rate (BMR) and respiratory quotient (RQ) by indirect calorimetry. Weight and BMI at baseline and after 3 y. RESULTS: In both univariate and multivariate analyses, age and RQ at baseline were significant predictors (P<0.05) of subsequent changes in weight and BMI. CONCLUSION: In non-obese women, RQ and age are independent predictors of subsequent weight changes.

Onset of obesity in children through the recall of parents: relationship to parental obesity and life events.

Obesity is a multifactorial disease due to the influence of both genetic and environmental factors. Parents of 886 obese patients (427 boys and 459 girls, aged 1-18 years) were investigated by means of a questionnaire in order to study the factors associated with the onset of obesity in children and the relationship to genetic background. At presentation obese patients had a very high mean ideal body weight percent (IBW%) (154 +/- 19%, median 152%, range 120-246). A significantly higher mean IBW% was found in children of obese parents (one obese parent: 158 +/- 21%, median 156%, range 120-246; two obese parents 160 +/- 18%, median 158%, range 123-226) in comparison to children of normal weight parents (150 +/- 18%; median 147%, range 120-235; p = 0.0001 for children of one or two obese parents versus children of normal weight parents). Parents of 414 subjects (46.7%) (Group A) answered that obesity had always been present. The remaining 472 parents (53.3%) (Group B) stated that obesity had had a beginning at a mean age of 5.3 +/- 2.6 years (median 5.0 years, range 1.0-17.0). No difference was found in age at presentation, sex distribution, birth weight and number of obese parents between the two groups. Parents in Group B recalled an event associated with obesity onset in 197 cases (health event: 119 answers, psycho-social event: 78 answers). Genetic background did not influence this pattern of feedback. In conclusion, parents of obese subjects seek medical advice when obesity is severe. Pediatricians should exert strict surveillance on weight from a very young age. The recall in 22% patients of health or psychosocial events at the onset of obesity emphasizes that medical counselling is important when the occurrence of particular events in life may cause erroneous eating habits.

High prevalence of overweight in a children population living in Naples (Italy).

OBJECTIVE: The present study estimates the prevalence of obesity among ten-year old children living in Southern Italy and compares it with the prevalence of obesity among children living in other western countries. METHODS: 110 children attending the 4th grade of a randomly selected primary school in Naples were studies in the 1992. Eighty-eight per cent of the total school population was examined: 52 girls, 58 boys: mean age = 9.6 years (SEM = +/- 0.10). Each child underwent medical examination and anthropometric assessment. The percentile values for Body Mass Index (BMI = weight/height 2) and triceps skinfolds thickness (mm) were calculated and compared to that of children of the same age and sex living in other countries, chosen from comparable studies available in the literature. RESULTS: Percentile values for triceps skinfolds thickness in Neapolitan children are similar to those reported in the other populations considered for comparison, however BMI values were different. Children in Naples have the highest BMI values at the 50th, 75th, 90th and 95th percentile. The prevalence of obesity among Neapolitan children was estimated using as a cut-off, the BMI value at the 90th percentile of each population considered for the comparison and calculating the rate ratio with 95% confidence interval (95% CI). The prevalence of obesity in Naples among girls, was 5.2 times (3.8-6.6 95% CI) as high as in France, 3.3 times (2.2-4.4) as high as in Holland, 1.7 times (0.9-2.5) as high as in USA, 2.5 times (1.7-3.4) as high as in Milan (Northern Italy); among boys it was 4.3 times (3.0-5.6) as high as in France, 4.0 times (2.7-5.2) as high as in Holland, 2.1 times (1.2-3.0) as high as in the USA, 2.5 times (1.7-3.4) as high as in Milan.

Glycemic response to stress is altered in euglycemic Pima Indians.

The aim of this work was to study the effects of a computer-driven mental arithmetic task on blood glucose in a group of four male and four female euglycemic Caucasians and a group of seven male and six female euglycemic Pima Indians. Approximately 60% of euglycemic Pima Indian Native Americans eventually develop type 2 diabetes, while only 5% of Caucasians develop the disease. All subjects had normal glucose tolerance. Subjects were given a standard breakfast; 2 h later, they were given a computerized mental arithmetic stress test for 10 min. Before, during and after the test, several variables were analyzed, including serum concentrations of glucose, insulin, glucagon and plasma cortisol and catecholamines. Heart rate, systolic and diastolic blood pressure and all the stress hormones increased during stress and decreased during recovery in all subjects. Blood glucose consistently declined one hour after the meal in all subjects. However, while it continued to decline following stress in seven out of eight Caucasian subjects, it consistently increased during and following stress in 10 out of 13 Pima Indians. Fasting serum glucose in Pima Indians and Caucasians was respectively 5.07 + 0.08 mM and 5.04 + 0.09 mM. Two-hour post-prandial values were 5.63 + 0.22 mM and 5.48 + 0.19 mM respectively, whereas post-stress values were 6.15 + 0.19 mM for Pima Indians and 5.22 + 0.20 mM for Caucasians. Both serum glucose means following stress (t = 3.1, P < 0.005) and the direction of change in serum glucose in response to mental arithmetic (chi 2 = 8.2, P < 0.01) clearly differentiated Pimas from Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial and environmental influences on body composition and body fat distribution in childhood in southern Italy.

The aim of this paper was to evaluate the factors affecting body fat excess and distribution in prepubertal age. A cross-sectional survey was carried out on children attending the 4th grade of a primary school in Naples. Eighty-eight per cent of the total sample was examined: 52 girls, 58 boys; mean age = 9.6 yrs (s.e. +/- 0.10). Each child underwent a medical examination, anthropometric measurements and bio-impedance analysis of body composition. The parents were asked to fill in a questionnaire that included demographic data, family history, parent's weight and height, child's perinatal history and his or her involvement in sports activities. Data were analyzed by multiple linear regression. The results showed a direct correlation between parental BMI and children's anthropometric measurements: the children's BMI correlated with the fathers' (P = 0.02) and mothers' BMI (P = 0.027); the children's waist/hip ratio correlated with the fathers' BMI (P = 0.07); the children's subscapular skinfolds correlated with the father's (P = 0.07) and mothers' BMI (P = 0.02); the children's triceps skinfolds correlated with the fathers' BMI (P = 0.004). Among congenital factors, sex was shown to be correlated with the children's waist/hip ratio (P = 0.05) with a lower ratio in the female, indicating a sex influence on body fat distribution even in prepubertal age. The children's BMI correlated with their waist/hip ratio (P = 0.001). Children's systolic blood pressure showed a positive correlation with triceps (P = 0.04) and subscapular (P = 0.05) skinfolds thickness % FAT-PLI (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Hand deformities in extrapyramidal disorders.

Hand deformities cause severe discomfort and functional limitations to patients with Parkinson disease (PD) and related disorders. In clinical practice the problem is often overlooked or misdiagnosed. This paper reports on four cases whose characteristics are discussed.

[Determinants of body fat in prepubertal age]. / Determinanti della massa corporea lipidica in età prepuberale.

In order to evaluate the factors affecting body fat excess and distribution, we have studied children attending the 4th grade of a primary school randomly selected in Naples. 52 girls, 58 boys; mean age = 9.6 years (SE +/- 0.1) were examined. Among the familial factors assessed, a correlation between parental BMI and child's anthropometry was found. Among congenital factors, sex correlates with the children's waist/hip ratio ("t" = -2.07; p = 0.05). Moreover the girl's percent body fat was higher. These two findings suggest the expression of sexual characters in prepubertal age. Systolic blood pressure showed a positive correlation with children's percent body fat ("t" = 2.43; p = 0.016) and subscapular skinfold thickness ("t" = 1.19; p = 0.05), suggesting an influence of these factors on blood pressure level since this age. No correlation was found between children's BMI and weight at birth, family history of diabetes, hypertension or hyperlipidemia. Among environmental factors, only the mothers weight gain during pregnancy ("t" = -2.21; p = 0.03) and breast feeding ("t" = -2.07; p = 0.05) correlated with the children's BMI. The correlation between children's BMI and waist/hip ratio ("t" = 4.64; p = 0.0001), was not confirmed in children who exercise, suggesting a beneficial action of physical activity on body fat distribution. The identification in different populations of factors associated with childhood obesity is important for prevention planning.

Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ.

Reduced oxidation of fat leading to a positive fat balance could be a factor in the development of obesity. Twenty-four-hour respiratory quotient (RQ) was measured in 152 nondiabetic Pima Indians fed a weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean +/- SD); 93.9 +/- 22.9 kg; 32 +/- 9% fat]. Twenty-four-hour RQ varied from 0.799 to 0.903. Prior change in body weight, 24-h energy balance, sex, and percent body fat explained 18% of the variance in 24-h RQ (P less than 0.001). In a subgroup of 66 siblings from 28 families, family membership explained 28% of the remaining variance in 24-h RQ (P less than 0.05). In 111 subjects for whom follow-up data (25 +/- 11 mo) were available, 24-h RQ was correlated with subsequent changes in body weight and fat mass (r = 0.27, P less than 0.01 and r = 0.19, P less than 0.05, respectively). Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile). We conclude that in Pima Indians fed a standard diet 1) family membership is the principal determinant of the ratio of fat to carbohydrate oxidation, and 2) a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity.

Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle.

Insulin-stimulated glycogen synthase activity in human skeletal muscle correlates with insulin-mediated glucose disposal rate (M) and is reduced in insulin-resistant subjects. We have previously reported reduced insulin-stimulated glycogen synthase activity associated with reduced fasting glycogen synthase phosphatase activity in skeletal muscle of insulin-resistant Pima Indians. In this study we investigated the time course for insulin stimulation of glycogen synthase and synthase phosphatase during a 2-h high-dose insulin infusion (600 mU/min per m2) in six insulin-sensitive caucasians (group S) and in five insulin-resistant Pima Indians (group R). Percutaneous muscle biopsies were obtained from the quadriceps femoris muscle after insulin infusion for 0, 10, 20, 40, and 120 min. In group S, insulin-stimulated glycogen synthase activity increased with time and was significantly higher than in group R. In group S, synthase phosphatase activity increased significantly by 25% at 10 min and then decreased gradually. No significant change in synthase phosphatase was seen in group R and activity was lower than group S at 0 to 20 min. These data suggest that a low basal synthase phosphatase activity and a defect in its response to insulin explain, at least in part, reduced insulin stimulation of skeletal muscle glycogen synthase associated with insulin resistance.

Distribution of in vivo insulin action in Pima Indians as mixture of three normal distributions.

If a single gene produced insulin resistance, with environmental effects creating some additional variance, insulin action might be distributed as a mixture of two normal distributions if the gene is dominant or recessive or as a mixture of three normal distributions if the gene is codominant. To estimate maximal insulin-stimulated glucose uptake rates (MaxMs), hyperinsulinemic-euglycemic clamps were performed on 245 nondiabetic Pima Indians (126 men, 119 women). Five models (for 1, 2, 3, 4, or 5 components each, normally distributed with a common variance) were fitted to the frequency distribution of MaxM by iterative maximum-likelihood estimation. The three-component model fit the data significantly better than a single normal distribution (chi 2 = 14.3 with 4 df P less than .01) or a mixture of two normal distributions (chi 2 = 9.9 with 2 df, P less than .01). Mixtures of four or five normal distributions did not fit the data significantly better than a mixture of three normal distributions. The first component of the distribution comprised 23%, the second 48%, and the third 29% of the total distribution. Similarly, the frequency distributions of fasting plasma insulin concentrations and a principal component score derived from MaxM and fasting insulin were best fitted by a mixture of three normal distributions. These results are consistent with the hypothesis that among Pimas, insulin resistance is determined by a single gene with a codominant mode of inheritance. Segregation analyses of studies performed in pedigrees are indicated to prove or disprove this genetic hypothesis.