Amnon Zung

Breast Development in the First 2 Years of Life: An Association With Soy-based Infant Formulas

Objective: To evaluate the estrogenic effect of soy-based formulas in female infants. These formulas contain significant amounts of phytoestrogens, compounds with structural similarity to estradiol. Patients and Methods: A cross-sectional study consisting of 694 female infants ages 3 to 24 months that consecutively attended 10 general pediatric clinics, none of them having been referred for breast development. The presence of breast buds served as a marker for the endocrine effect of soy-derived phytoestrogens. Results: Of the participants, 92 had consumed soy formulas for more than 3 months. Breast tissue was more prevalent in the second year of life in infants fed soy-based formula vs those that were breast-fed and those fed dairy-based formula (22.0% vs 10.3%; P = 0.02) with an odds ratio of 2.45 (95% confidence interval 1.11–5.39). No differences in breast bud prevalence were observed during the first year of life. Unlike infants on dairy-based formulas and breast-feeding, infants fed a soy-based formula did not demonstrate a decline in the prevalence of breast during the second year of life. Conclusions: We suggest that phytoestrogens impose a preserving effect on breast tissue that is evolved in early infancy, leading eventually to a slower waning of infantile breast tissue.

Familial Mediterranean fever and growth: effect of disease severity and colchicine treatment.

OBJECTIVE To evaluate the effect of disease severity and colchicine treatment on height and weight parameters in children with familial Mediterranean fever (FMF). METHODS Thirty prepubertal children (19 M, 11 F) were studied retrospectively. Z-score values of height, growth velocity, weight and body mass index were obtained over 1.84 +/- 1.14 years before and 2.58 +/- 1.55 years during colchicine therapy. Disease severity was evaluated by a specific score for FMF. RESULTS By comparison to growth before treatment, during colchicine therapy height SDS increased from -1.00 +/- 1.17 to -0.54 +/- 0.96 (p < 0.001) and weight SDS increased from -0.74 +/- 1.09 to -0.47 +/- 1.06 (p = 0.008). An effect of disease severity on growth pattern could not be detected. Height SDS during therapy was negatively correlated with age at colchicine initiation. CONCLUSIONS Colchicine therapy has a positive effect on both height and weight parameters in children with FMF. Early initiation of treatment is beneficial for height gain.

The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels.

Nephropathy is a major complication of diabetes mellitus and is associated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increase in the levels of extractable renal IGF-I. This study examined the possibility that this difference is GH dependent, and that very early changes in plasma GH and/or IGF-I in the adult animal are associated with an early accumulation of renal IGF-I. Silastic jugular catheters were placed in adult (13–14 week) male Sprague-Dawley (S-D) rats for blood collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 μg/kg, IV) rats from 1–6 h, 9–15 h, and 24–30 h post-injection, and plasma GH profiles were determined by RIA. Renal IGF-I content was assessed following acid extraction. Following STZ, there was an immediate, step-wise reduction in peak GH levels (saline controls, 54±7 ng/mlvs 30±5 (1–6 h); 23±10 (9–15 h); and 13±3 ng/ml (24–30 h post-STZ);P<0.05 for all STZ groupsvs control). The same significant step-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing factor antagonist (GRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic GRF-AN administration reduced plasma IGF-I levels significantly to 63% of control values (P<0.01). However, despite the reduction in plasma IGF-I, renal IGF-I remained significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467±49 ng IGF-I/g KW in control salinevs 778±100 in saline/STZ and 705±87 ng IGF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclusion, following STZ administration in the adult rat, there is an immediate reduction in GH levels, indicating the renal IGF-I accumulation occurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF-I content remains elevated. These data suggest that early diabetic renal growth is not associated with elevated circulating GH levels, and that high basal plasma IGF-I levels are not necessary for IGF-I accumulation.

Soy-derived Isoflavones Treatment in Children with Hypercholesterolemia: A Pilot Study

AIMS To evaluate for the first time in children the effect of soy-derived isoflavones on lipid profile and insulin resistance. METHODS Twelve hypercholesterolemic children (8 females) aged 5.3 to 11.2 years have completed a prospective, controlled pilot study. After a low-fat diet for 12 weeks, children who maintained high cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels were randomly assigned to three intervention periods of either placebo or low and high dose isoflavone (16 or 48 mg) consumption, each period lasting 8 weeks. RESULTS The diet significantly reduced LDL-C and apolipoprotein B (Apo B) levels. However, isoflavones had no effect on cholesterol, LDL-C, high-density lipoprotein-cholesterol (HDL-C), triglycerides, lipoprotein (a), Apo B, or insulin resistance, at either low or high doses. Isoflavones had no effect on sex hormones, gonadotropins, sex-hormone binding globulin and thyroid hormones. CONCLUSIONS The results of this pilot study do not suggest a beneficial role of an isoflavone-enriched diet in children with hypercholesterolemia.

Effect of age on the response to parathyroid hormone

Serum phosphate (PO4) levels and the tubular threshold for PO4 corrected for glomerular filtration (TP/GF) are age-dependent, being higher in children than in adults. We evaluated the effect of age on the response to infusion of parathyroid hormone(1-34) (PTH) in healthy children (n = 8) and adults (n = 12). In addition, six patients with pseudohypoparathyroidism (PHP) and two with PTH deficiency (hypoparathyroidism [HP]) were also studied. At baseline, TP/GF in normal subjects was inversely correlated with urinary cyclic adenosine monophosphate corrected for glomerular filtration (UcAMP/GF) (P < .0359). After PTH administration in the controls, UcAMP/GF was inversely correlated with TP/GF (P < .0007) and directly correlated with maximal fractional extraction of PO4 (FEP) (P < .0002). The slope of the regression of TP/GF (P < .0076) and FEP (P < .0034) with UcAMP/GF was steeper in children than in adults. Two HP patients had high PTH-stimulated UcAMP/GF levels, but stimulated TP/GF and FEP were not changed commensurate with levels that would expected from the normative data. In six patients with PHP, PTH-stimulated TP/GF was also correlated with peak UcAMP/GF (r = .96, P < .002). PHP patients could be distinguished from normal controls based on the combination of low peak FEP or high TP/GF together with low peak UcAMP/GF. Thus, in normal subjects, the phosphaturic response to PTH is correlated with the increase in urinary cAMP and is age-dependent, with a greater decrease of TP/GF in children than in adults.

GROWTH HORMONE DEFICIENCY IN AUTOIMMUNE POLYGLANDULAR SYNDROME

We describe a boy with autoimmune adrenal failure and compensated hypothyroidism, associated with isolated growth hormone deficiency (GHD). We suggest an autoimmune mechanism as the underlying etiology for the GHD in this case.

Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods.

Abstract Aim: The objective of this study was to validate basal, post-gonadotropin-releasing hormone analogue (post-GnRHa) and first-voided urinary LH (ULH) as alternatives to an LHRH stimulation test in monitoring treatment efficacy in central precocious puberty (CPP). Methods: Seventeen girls with CPP were followed over 22.5±9.1 months during GnRHa (triptorelin) treatment. ULH and post-GnRHa LH levels were obtained every 4 months before and 24 h after GnRHa administration, respectively, along with clinical and bone age (BA) evaluation. LHRH stimulation tests were performed annually. Results: A total of 36 LHRH stimulation tests demonstrated adequate suppression with a peak LH of 0.57±0.33 IU/L. The corresponding basal LH was 0.27±0.16 IU/L. Ninety post-GnRHa LH measurements were similar to LHRH-stimulated LH levels (0.56±0.31 IU/L), whereas 8% of ULH levels were above prepubertal threshold. Fourteen episodes of growth acceleration and ten episodes of BA advancement resolved without treatment modification. Conclusion: Suppressed basal and post-GnRHa LH levels indicate adequate suppression of puberty. Clinical breakthroughs during treatment are transient and resolved spontaneously.

Lack of association between seroconversion and catch-up growth in children with celiac disease.

Abstract Objective: To assess the association between seroconversion and catch-up growth during the first year of a gluten-free diet (GFD) program in children with celiac disease (CD). Methods: All prepubertal and biopsy-proven children diagnosed with CD between January 1999 and August 2009 were included in a retrospective study (n=55). Growth parameters and celiac antibodies were documented before and after 6 (period 1) and 12 months (period 2) of GFD, respectively. Results: Mean height velocity-standard deviation score (SDS) was significantly higher in period 1 compared with that in period 2 (2.90±3.20 vs. 0.20±2.08, p<0.001) irrespective of the serology status, with marginal difference in mean weight-SDS gain (p=0.074). Mean levels of height velocity-SDS and the weight-SDS gain were similar in the seropositive and seronegative groups in both periods of the study. Mean height-SDS and weight-SDS levels after 6 months were higher than those in baseline levels, both in seropositive (–0.47±0.91 vs. –0.82±0.82, p<0.001 and –0.59±1.17 vs. –1.11±1.33, p<0.001, respectively) and seronegative patients (–1.02±1.14 vs. –1.50±1.12, p<0.001 and –1.19±1.27 vs. –1.45±1.40, p=0.048, respectively). These growth parameters were higher at the end compared with the beginning of period 2, but only in seropositive patients. Conclusions: The most remarkable catch-up growth in children with CD can be expected during the first 6 months of GFD, irrespective of the serology status.

β-Adrenergic Hyperresponsiveness in Compensated Hypothyroidism Associated with Down Syndrome

Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonadal failure is another DS-associated endocrinopathy, we hypothesized that an impaired signal-transduction pathway shared by several organs may provide a unifying explanation for both endocrinopathies. We assessed two possible transduction-pathway components associated with CH in DS: the G-protein adenylate-cyclase (AC) system and β-adrenergic responsiveness, previously reported to be enhanced in DS fibroblasts. Twenty-one DS patients and 14 control subjects were studied. Peripheral mononuclear cells (PMCs) were incubated with G-protein modulators [prostaglandin E1 (PGE1) and cholera toxin (CTx)], an AC stimulator (forskolin), and a β-adrenergic agonist (isoproterenol), and cAMP levels were determined. All participants had normal plasma thyroid hormone levels, but 11 of the DS patients had elevated TSH levels (hTSH), whereas in the 10 others, they were normal (nTSH). cAMP levels in response to forskolin, PGE1, and CTx were similar in all groups, whereas isoproterenol-stimulated cAMP levels were significantly higher in the hTSH group than in the nTSH group and control subjects (45 ± 30 versus 22 ± 9 and 21 ± 9 pmol · 106 cells−1 · 10 min−1, respectively; p = 0.02). Four patients in the DS hTSH subgroup had impaired sexual development. We found hyperresponsiveness of PMCs to a β-adrenergic agonist in a subgroup of DS patients with CH. If this observation is applicable to the thyroid gland, then it may reflect a mechanism in which negative effects on cell growth or responsiveness to TSH lead to CH.

PHOSPHATE (P) EXCRETION IN RESPONSE TO PARATHYROID HORMONE (PTH) IS DEPENDENT ON URINARY c-AMP (UcAMP/GF) AND AGE. † 594

PHOSPHATE (P) EXCRETION IN RESPONSE TO PARATHYROID HORMONE (PTH) IS DEPENDENT ON URINARY c-AMP (UcAMP/GF) AND AGE. † 594