Diet and physical activity "defeated" Tuberil® in treatment of childhood obesity.

AIM: Childhood obesity is remarkably spreading worldwide, involving both industrialized and low-income countries. Its prevalence, outcome and socioeconomic impact call for the attention of medical community. We conducted a monocentric, open, two-arm, parallel-group study to evaluate the efficacy at reducing appetite and increasing dietary compliance of obese children of Tuberil®, a weight-loss supplement derived from potato and devoid of side effects. METHODS: We recruited participants, children with BMI ≥ 85th, through direct referrals in pediatrician's surgeries. Children were randomized to receive Tuberil® (group A) or nothing (group B), following a chronological order (A-B-A-B). Every child received a nutritionally balanced diet and had to record their appetite and to describe their meals in a diary. RESULTS: Even if we found a significant reduction in BMI, weight and waist circumference in both groups, no statistically significant differences between groups were noted. We did not found any significant differences in appetite between group A and B. CONCLUSION: Our data show that Tuberil® has no efficacy neither in reducing appetite in children nor in increasing dietary compliance. We believe that only a nutritionally balanced diet and our attention in verifying their compliance led to the reduction in BMI, weight and waist circumferences noted in our series.

Oestrogenic mycotoxin exposures and precocious pubertal development.

Since the 1970s, there has been a worldwide scientific discussion on the potential health consequences of human exposure to endocrine disrupters: many environmentally persistent compounds are oestrogen agonists and/or androgen antagonists. Thus, they can dysregulate the hypothalamic-pituitary-gonadal axis potentially affecting human puberty timing. Zearalenone (ZEA) is a non-steroidal mycotoxin produced by Fusarium species on several grains. Despite its low acute toxicity and carcinogenicity, ZEA exhibits oestrogenic and anabolic properties in several animal species. ZEA food contamination is caused either by direct contamination of grains, fruits and their based-products or by 'carry-over' of mycotoxins in animal tissues, milk and eggs after intake of contaminated feedstuff. In addition, zeranol (alpha-ZAL), a resorcyl lactone derived from ZEA, has been widely used in the USA as a growth promoter to improve fattening rates in cattle. From 1978 to 1984, a great epidemic of premature thelarche and precocious puberty occurred in Puerto Rico. To explain this condition, it was suggested that dairy and meat products could be contaminated with anabolic oestrogens such as ZEA or alpha-ZAL. Subsequently, worldwide other groups have also reported causative associations between oestrogenic mycotoxins and development of early thelarche and/or precocious puberty in exposed children. In addition to animal data, epidemiological studies strongly support the hypothesis that human pubertal development may be induced by foetal/early or prepubertal exposure to oestrogenic compounds. Indeed, ZEA and its metabolites are able to adopt molecular conformation, which sufficiently resembles 17beta-oestradiol to allow it to bind to oestrogen receptors (ERs) in target cells exerting oestrogenic (agonist) actions. In this view, oestrogenic mycotoxins are suspected as triggering factor for precocious pubertal development at least in prepubertal exposed girls.

Association between X-linked hypophosphatemic rickets and Klinefelter's syndrome: effects on growth and body proportion.

Growth failure with disproportionate short stature is the major clinical feature of patients with X-linked hypophosphatemic rickets (HYP). We studied the pattern of linear growth and body proportion in an untreated normally growing HYP child also affected by Klinefelter's syndrome. Auxologic data were compared with those of a HYP half-brother who showed growth failure despite long-term treatment either with vitamin D or with vitamin-D-analog plus phosphate salt supplementation. The degree of body disproportion changed from negative values to positive values in the proband, whereas it was reduced in the half-brother. We conclude that, in the proband, the normal pattern of growth and the lack of the typical body disproportion as seen in HYP patients are attributable to the concomitant presence of Klinefelter's syndrome.

Effects of growth hormone on phosphocalcium homeostasis and bone metabolism.

In this review the effects of growth hormone (GH) on phosphocalcium homeostasis and bone metabolism are reported. Some in vitro effects of GH on chondrocytes and osteoblasts are discussed too. The main GH effects on phosphocalcium homeostasis are the permissive action on renal 1 alpha-hydroxylase activity by the hypophosphatemic stimulus and the antiphosphaturic effect by the stimulation of the maximum rate of renal tubular reabsorption of phosphate. On bone, GH is able to stimulate bone turnover and to increase bone mass. In addition, GH stimulates type I and type III collagen metabolism. In vitro, GH increases the proliferation of chondrocytes from the human growing cartilage together with the levels of interleukin-6 in the supernatant. The hormone increases also the proliferation of the human osteosarcoma-derived osteoblast-like cells and augments the osteocalcin levels in the supernatant. Thus, GH markedly influences phosphocalcium homeostasis and bone metabolism in childhood and adolescence. In addition, it is possible that GH continues to play a role in bone physiology during adulthood when final height is reached.

Nutritional aspects of calcium and vitamin D from infancy to adolescence.

Calcium is an essential nutrient for normal growth and development. Growing individuals must be in positive calcium balance to satisfy their calcium needs. Calcium requirements are higher during infancy and adolescence than childhood and adulthood. The achievement of a higher calcium balance in infancy and adolescence is likely due to the increased serum 1,25-dihydroxyvitamin D concentration occurring during these periods. The main determinants of calcium balance in infancy are dietary calcium intake and vitamin D. In normal circumstances, breast milk and formulas supply sufficient amounts of calcium. In the post-natal life, the major sources of vitamin D are sunlight exposure and supplemented formulas; in fact, the amount of vitamin D in breast milk, cow's milk, and common foods is poor. Although sunlight exposure should be able to maintain adequate vitamin D stores, a supplement with 400 IU/day of vitamin D from birth to the second year of life is recommended to assure the prophylaxis of rickets in all breast-fed infants. A dose of 400 IU/day of vitamin D is safe and appropriate. During childhood and adolescence, currently recommended dietary allowances (RDA) for calcium might be augmented, as suggested by calcium balance studies. The higher amount of calcium intake may lead to achieve maximal peak bone mass. The main source of vitamin D in children and adolescents is the casual sunlight exposure; therefore, a sistematical vitamin D supplementation is not usually needed. The major sources of calcium are milk and dairy products. However, if calcium intake is reduced, an additional calcium intake to reach the RDA may be provided by calcium supplements.

Ketoconazole decreases the serum ionized calcium and 1,25-dihydroxyvitamin D levels in tuberculosis-associated hypercalcemia.

OBJECTIVE: To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia. DESIGN: Case study. SETTING: Endocrine Unit, Pediatric Clinic, University of Pisa (Italy). PARTICIPANTS: Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia. MEASUREMENTS/MAIN RESULTS: At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [-72.4%] in one boy and from 321.6 to 115.2 pmol/L [-64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [-13.0%] in one boy and from 1.55 to 1.26 mmol/L [-17.0%] in the other). CONCLUSIONS: Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis.

[Vitamin D prophylaxis in childhood]. / Profilassi con vitamina D in età pediatrica.

The past 10 years have seen a return of rickets. Clinical and/or biochemical signs of vitamin D deficiency are still found in some children and adolescents, mainly during the winter. Sunlight exposure is able to prevent vitamin D deficiency and rickets but the dramatic influence of changes in solar ultraviolet-B radiation on cutaneous vitamin D3 synthesis, related to latitude and season effects, suggest that a vitamin D supplementation may be advisable. Moreover, human milk and common foods contain low quantities of vitamin D. So, we recommend routinely 400 IU of supplementary vitamin D per day in all infants. The vitamin D requirements in low-birth-weight infants are higher than at term infants; it is recommended the use of 1000-1600 IU per day in the first months of life. Intermittent high-dose of vitamin D and vitamin D metabolites are not advisable for prophylaxis of rickets.

Intact parathyroid hormone levels during pregnancy, in healthy term neonates and in hypocalcemic preterm infants.

We measured parathyroid hormone levels in pregnant and nonpregnant women and at 1, 2 and 5 days of life in healthy term neonates and in hypocalcemic preterm infants using a new immunoradiometric assay which measures only biologically active intact parathyroid hormone and by a mid-molecule parathyroid hormone radioimmunoassay. During pregnancy intact and mid-molecule parathyroid hormone levels did not show any modification and were not different from parathyroid hormone levels of nonpregnant age-matched controls. Serum calcium and phosphorus levels did not vary during each trimester of pregnancy. In cord serum intact and mid-molecule parathyroid hormone values were low in both term and preterm infants. In term neonates intact and mid-molecule parathyroid hormone levels peaked on day 1; in preterm infants intact parathyroid hormone levels peaked on day 1 while mid-molecule parathyroid hormone values peaked on day 2. Intact parathyroid hormone levels showed a more marked increase in preterm (19-fold) than in term neonates (7.5-fold) on day 1. Our data do not confirm the previously reported "physiologic" hyperparathyroidism in pregnancy. Moreover we found a normal parathyroid gland responsiveness to decreasing serum calcium levels in the first days of life in term and preterm infants. Our results suggest that measurement of intact parathyroid hormone 1-84 by immunoradiometric assay in the first days of life is a more sensitive index of parathyroid gland secretory function than the measurement of middle or carboxyl-terminal parathyroid hormone fragments allowing the detection of the dynamic changes of parathyroid hormone which occur in hypocalcemic preterm infants.

GHRH-test in short children with "non classic" GH deficiency. A comparison with "classic" GH deficiency and short normal stature.

In this study GHRH-test has been performed (2 micrograms/Kg of an iv bolus of GHRH 1-44) sampling for GH measurement every 15 min over 2 hours in three groups of short children. Group 1 consisted of 10 subjects with classic GH deficiency (CGHD): GH response less than 10 ng/ml to two conventional tests and 24-h mean GH concentration (MGHC) less than 3 ng/ml; group 2 consisted of 16 subjects with non-classic GH deficiency (NCGHD): response greater than 10 ng/ml to at least one conventional test and MGHC less than 3 ng/ml; group 3 consisted of 18 subjects with short normal stature: GH response greater than 10 ng/ml to at least one conventional test and MGHC greater than 3 ng/ml. GH peak and area under the curve (AUC) values were significantly lower in group 1 than groups 2 and 3 and in group 2 than group 3. GH peak and AUC values statistically correlated with height, height velocity, bone age/chronological age ratio and MGHC. Six children in group 1, 14 children in group 2 and all 18 children in group 3 showed after GHRH a GH peak greater than 10 ng/ml and were considered as 'responders'. Considering only the responders, GH peak and AUC values were significantly lower in group 1 than groups 2 and 3 and in group 2 than group 3. In conclusion, our data have shown that 87% of children with NCGHD responded to a single bolus of GHRH with an increase in GH levels greater than 10 ng/ml and that their responses were intermediate compared to those of CGHD and short normal subjects.