The Journal of pediatric endocrinology最新文献

Cranial radiation for childhood cancer can cause growth hormone deficiency (GHD), usually due to hypothalamic rather than pituitary dysfunction. To investigate whether this hypothalamic dysfunction is secondary to altered neurotransmitter input from other brain centers, we used neurotransmitter-excitatory substances to study the GH secretory response in 17 children who had received 12 to 60 Grey (Gy) to the cranium and 40 short children with normal endocrine function. As expected, the irradiated children had decreased mean GH secretion in response to insulin-induced hypoglycemia and arginine infusion, and decreased mean 24 hour GH concentrations, compared to the control group. In contrast, the two groups had similar GH secretory responses to GHRH stimulation and somatostatin suppression. Assessment of neurotransmitter pathways in the irradiated children revealed significantly lower mean peak GH concentrations in response to 5 of the 6 substances tested compared to control children: alpha-adrenergic stimulation (clonidine), beta-adrenergic blockade (propranolol), cholinergic stimulation, dopaminergic stimulation (L-dopa), and GABA-ergic stimulation (valproic acid). Results of serotonergic stimulation (L-tryptophan) were not statistically significant. Eleven patients who had abnormal GH secretion underwent 4 or more tests with neurotransmitter-stimulatory agents; 3 patients had peak GH concentrations of < 2.5 micrograms/l to all tests, whereas 4 patients had a peak GH concentration of > or = 7 micrograms/l to one or more tests but < 5 micrograms/l to one or more other tests. These observations suggest that radiation damage may sometimes spare growth hormone-releasing hormone (GHRH) and somatostatin secretion while affecting neurotransmitter pathways. We postulate that the hierarchy of sensitivity to radiation damage may be hypothalamic and extra-hypothalamic neurotransmitters > hypothalamic GHRH and/or somatostatin secretion > pituitary GH secretion.

After a brief history of the development of neonatal hypoglycemia, this review emphasizes the current approach to the anticipation, diagnosis, and management of the neonate with a low plasma glucose concentration. Both transient and recurrent or persistent hypoglycemia are discussed. Current techniques for studying the neurophysiologic and endocrine-metabolic effects of significant hypoglycemia provide new approaches for establishing relevant definitions of significant hypoglycemia, its prognosis, and pathogenesis. The inadequacy of glucose oxidase strips for screening, the definition of high risk infants, new definitions for low plasma glucose concentrations and their treatment are discussed. New data concerning the hereditary aspects of hyperinsulinemia, the role of glucose transporters, and the ability of the neonate to respond to significantly low glucose values are presented as well.

Microalbuminuria is considered to be an early indicator of diabetic nephropathy. In this report, we developed an enzyme-linked immunosorbent assay (ELISA) for the measurement of urinary albumin (UA) and examined UA in 38 patients with insulin-dependent diabetes mellitus (IDDM). The assay range of ELISA for albumin was 5-1,000 ng/ml, and the albumin levels determined by ELISA were well correlated with those by immunoagglutination methods. The UA values of daytime single-void specimens in control subjects, which correlated significantly with UA excretion rates (micrograms/minute) in 24-hour urine, were 10.9 +/- 8.2 micrograms/mg creatinine. In 38 IDDM patients, there were four cases with microalbuminuria and one case with overt nephropathy. Their disease duration was longer than 8 years, and the diabetic control was fair to poor. On SDS-PAGE analysis. the urinary protein of the cases with microalbuminuria consisted mainly of albumin, and in the case of nephropathy, an IgG band was also detected. The measurements of UA in single-void specimens by ELISA is a satisfactory approach to detect impending nephropathy in IDDM patients.

In 116 short children (height < -1.6 SDs), the authors examined GH secretion over 24 hours, by taking blood samples every 20 min and performing an electroencephalographic sleep control. The following GH parameters were evaluated: 24-h mean GH concentration (MGHC); maximum GH peak during the initial cycle of sleep (iMGHP), the nocturnal 12 h (nMGHP) or diurnal 12 h (dMGHP), the number of GH pulses over 24 h (NP), or nocturnal 12 h (nNP) or diurnal 12 h (dNP), the mean pulse amplitude over 24 h (MPA), or nocturnal 12 h (nMPA) or diurnal 12 h (dMPA). The subjects were divided into 3 groups: group 1, 12 subjects with low responses to provocative tests and MGHC < 3 ng/ml; group 2, 36 subjects with normal responses to provocative tests and MGHC < 3 ng/ml; group 3, 68 subjects with MGHC > 3 ng/ml. MGHC was highly correlated (p < 0.001) with iMGHP (r = 0.80), nMGHP (r = 0.82), dMGHP (r = 0.59), MPA (r = 0.85), nMPA (r = 0.86), dMPA (r = 0.56), NP (r = 0.70), nNP (r = 0.68), dNP (r = 0.46). By the analysis of the regression equations, the values corresponding to 3 ng/ml for MGHC were 11.08 ng/ml for iMGHP, 11.66 ng/ml for nMGHP, 5.21 ng/ml for dMGHP, 7.29 ng/ml for MPA, 8.40 ng/ml for nMPA, 4.25 ng/ml for dMPA, 3.2 for NP, 2.41 for nNP and 0.78 for dNP. By using these values as cut-off points, the diagnostic accuracy yielded 83.6% for iMGHP, 84.5% for nMGHP, 69.8% for dMGHP, 92.2% for MPA, 90.5% for nMPA, 81.9% for dMPA, 80.2% for NP, 77.6% for nNP, 71.5% for dNP. In conclusion, we found a strong correlation between mean GH secretion over 24 h and the number or amplitude of pulses: particularly, nocturnal pulsatile GH parameters show a higher correlation in comparison with diurnal pulsatile GH parameters, so that the examination of GH values during nocturnal hours may be considered a reliable index of GH secretory status.

Study objective: To assess the effect of endogenous estrogen secretion on the final heights of patients with 45,X Turner's syndrome.

Design: European and American reports of patients with 45,X Turner's syndrome and spontaneous sexual maturation in which final heights were available were analyzed and compared with existing norms for untreated patients with Turner's syndrome. Subgroups of patients were compared as a means of distinguishing low from normal endogenous estrogen exposure, and the effect of the age of menarche was assessed.

Patients: Twenty-three cases were collected, including eight who became pregnant. One had full somatic maturation but did not menstruate. RESULTS OF ANALYSES: Mean height of all 23 patients was 140.8 cm +/- 8.07 (s.d.) vs 143.1 cm +/- 6.0 (p = 0.035) for literature norms for Turner's syndrome. Mean height of those who achieved pregnancy was 138.6 cm +/- 8.21 (p = 0.035 vs literature norm); of those with normal gonadotropins 137.5 cm +/- 6.03; and of those with high gonadotropins 139.2 cm +/- 1.44 (p = 0.374). Age of menarche was available in 21 and showed no correlation with final height.

Conclusions: Physiological and subphysiological endogenous secretion of estrogen in Turner's syndrome does not increase final height, suggesting that even low-dose exogenous estrogen would not increase ultimate stature in these patients.

Genetic and immunological markers in children with Type I diabetes have not been studied previously in Venezuela. We evaluated 91 newly diagnosed IDDM children mean age 7.8 +/- 4.5 (range 0.8-20.8 years), 51 females and 40 males. Eleven percent of first degree relatives had a family history of Type I IDDM; 56.7% had had upper respiratory infection prior to diagnosis and 12.7% had had either mumps or varicella. Peak incidence of disease was found in February and March and August to October. Eighty seven percent had HLA-DR3 and/or DR4 vs 36% of the Venezuelan general population; 81.6% were HLA-DQW2 and/or HLA-DQW8. We found 55.9% to have positive islet cell antibodies (ICA) with 4 of these having a positive complement fixation test. Three patients (7.9%) were found to have positive insulin autoantibodies. Only 3 out of 11 HLA-identical siblings had positive ICAs, while none had positive insulin autoantibodies. One of them also had a positive complement fixation test; this subject developed IDDM. No positive serotypes for enterovirus (Coxsackie-B) were found in our patients, but we detected 11 cases with elevated titers for cytomegalovirus antibodies and positive antibodies for measles, mumps, herpes and varicella were found in some children. These data confirm that most of our Type I diabetics carry HLA-DR3 or DR4 and that the heterozygous DR3/DR4 phenotype is markedly increased in this population; they also indicate that DR3QW2 and DR4QW8 are associated with increased risk in our population.

We studied an 8 year-old girl whose height was 129 cm (25-50th percentile), weight 30 kg (75th percentile), blood pressure 115/75 mm Hg (75th percentile) and had a calcified mass lesion in the left posterior mediastinum. In the histopathological investigation of this mass lesion, symptoms of complicated atherosclerosis, such as mural thrombus and diffused calcification, were observed. Lipid investigations were performed in this patient whose total cholesterol and triglyceride levels were in the normal ranges. HDL-cholesterol, apoprotein A-I and alpha band were low without any other lipid and lipoprotein abnormalities. During one year, in her monthly lipid analysis the mean levels of HDL-cholesterol, apoprotein A-I and alpha band were found to be 0.73 +/- 0.11 mmol/l, 90 +/- 20 mg/dl and 23 +/- 5% respectively. Studies of her family revealed low levels of HDL-cholesterol, apoprotein A-I and alpha band in her mother and sister. We describe our investigation of this rare case of familial hypoalphalipoproteinemia.

The clinical features of Cushing's disease in childhood are usually abnormal fat distribution, moon face, growth failure and hirsutism. Laboratory studies include evidence of cortisol and ACTH hypersecretion. This report concerns a boy who presented only with arrested puberty and growth failure as physical evidence of Cushing's syndrome and showed rapid progression of puberty once pituitary adenomas were removed.

We studied height velocity (HV), bone age progression (delta BA/delta CA), urinary pregnanetriol (PT) and plasma 17-hydroxyprogesterone (17-OH-P) during the first years of life in 12 patients with 21-hydroxylase deficiency, treated by cortisone acetate. In the well-controlled phases normal growth rate (SDS between -1 and +1), satisfactory bone age progression (delta BA/delta CA < or = 1) and no clinical sign of poor treatment were found; in the undertreatment phases enhanced growth rate, rapid bone age progression and, in some instances, signs of virilization were found; in the overtreatment phases, reduced growth rate was the only sign of poor treatment. Hormonal values were only weakly correlated to therapeutic control. Therefore, growth rate evaluation can represent the best method of monitoring treatment in very young patients with 21-hydroxylase deficiency.

The cause of the growth retardation present in patients with hypophosphatemic rickets has not been totally elucidated. There has been a previous report of a growth hormone deficit in a group of these patients. To verify this abnormality we studied two groups of patients with hypophosphatemic rickets, one with (n = 6) and the other without (n = 7) treatment with calcitriol and oral phosphates. All patients in both groups showed a normal growth hormone response (> 10 micrograms/l) to standard stimulatory tests and normal IGF-I plasma levels. Mean IGF-I plasma levels were not significantly different (untreated 1.46 +/- 0.80 U/ml, treated 1.25 +/- 0.69 U/ml) and the mean logarithmic deviation of IGF-I plasma levels from both groups did not differ from normal. In summary, we found no abnormalities of the growth hormone-IGF-I axis in our patients with hypophosphatemic rickets.