The Journal of pediatric endocrinology最新文献

As part of a multicenter study to evaluate the efficacy and safety of one daily subcutaneous dose of 30 micrograms/kg of GHRH, 16 prepubertal GH-deficient children with a mean chronological age of 9.0 +/- 2.3 years were treated for 12 to 24 months. After six months of therapy 11 children (68.7%) were considered good responders in that their growth velocity increased by greater than 2 cm/yr over baseline and were continued on GHRH, while five subjects (31.3%) were regarded as poor responders and switched to recombinant hGH for the following six months. Growth velocity increased significantly in responders from a baseline of 3.4 +/- 0.7 cm/yr (mean +/- SD) to 6.8 +/- 0.1 cm/yr, 6.2 +/- 0.9 cm/yr, 6.6 +/- 1.0 cm/yr and 6.5 +/- 0.7 cm/yr at 6, 12, 18 and 24 months respectively. Bone ages advanced by an amount equivalent to the months of treatment. GHRH antibodies were detected in 4/11 and 6/11 responders at six and 12 months of treatment and in 2/5 non-responders at six months, but seemed not to interfere with growth. No side effects or changes in glucose and lipid levels were noted during therapy. These results suggest that GHRH (1-29) at the dose and schedule used is generally effective in the treatment of GH deficiency.

In an attempt to rest the beta cells of newly diagnosed children with type I diabetes mellitus (IDDM) and thus possibly preserve beta cell function, ten children were given Octreotide, a somatostatin analog, for the first 21 days after diagnosis. Ten age-matched diabetic children served as controls. Although there were no differences in either insulin requirements or in hemoglobin A1 levels, there were significant increases in the glucagon-stimulated C-peptide levels of the experimental group at six and 12 months after diagnosis, compared to control patients.

To investigate the genetic polymorphisms of the HLA region and the molecular defect of the P450c21B gene in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, we studied 89 individuals from 25 families of CAH patients (14 classical forms, 11 non-classical forms). The following immunogenetic and hormonal investigations were performed: HLA-A and B typing, restriction fragment length polymorphism (RFLP) analysis of 21-hydroxylase A and B genes, and serum 17-OH-progesterone values determined basally and 60 min after ACTH stimulation. In the patients affected by the classical form, RFLP analysis revealed 5 deletions and 1 gene conversion in 6 haplotypes and no molecular defect in the others, who probably carry point mutations. In the patients with non-classical form we found P450c21A duplication in 11/18 haplotypes; 9 of the 11 patients shared the HLA-B14 allele. Utilizing both hormonal and genetic data we identified two cryptic forms; hormonal data alone failed to differentiate heterozygous from normal individuals.

LHRH and TRH tests were performed in 16 boys age 14.5-18.5 years with constitutional delayed puberty (CDP); 9 idiopathic hypogonadotropic hypogonadism (IHH) males, age 15.0-22.0 years; and 7 control subjects age 14.5-19.5 years. The responses of FSH and LH to LHRH stimulation overlapped so that it was difficult to differentiate IHH from CDP. Some patients with IHH had normal gonadotropin responses. Basal PRL levels were in the normal range in control, IHH, and CDP patients. We found a 6 to 25 times increment or a response of more than 22 ng/ml (normal response) with respect to basal levels in the control group. In the CDP group, we found 2 to 19 fold increments in basal PRL levels after TRH stimulation and the maximum response was more than 22 ng/ml in all the patients. In the IHH group, the increment in basal PRL levels was 2-9 times more after the TRH test and the maximum PRL response was more than 22 ng/ml in 6 of the 9 patients. Although the mean peak responses of PRL to TRH were significantly lower in the IHH group compared to CDP and controls (p < 0.001), the mean peak individual responses in all groups were in the normal range (minimum 2-fold increment) and the responses were more than 22 ng/ml in all cases except 3 of 9 patients in the IHH group. We conclude that PRL response to TRH may help in differentiating CDP from IHH if a "cut off" response level of 22 ng/ml is used.

We present two siblings with neonatal Hirschsprung's disease in whom isolated familial medullary carcinoma of the thyroid was diagnosed at the age of 16 and 19 years. Rectal biopsy in each patient revealed total absence of ganglion cells in the myenteric plexus and hypertrophied nerve fibers characteristic of Hirschsprung's disease. Both underwent total thyroidectomy and histological examination revealed bilateral and multifocal medullary carcinoma of the thyroid. These two patients belong to a large family in whom another 12 affected members with medullary carcinoma of the thyroid were found. Our description is the first report of an association between Hirschsprung's disease and isolated familial medullary carcinoma of the thyroid. We suggest that familial occurrence of Hirschsprung's disease could be an early presentation of familial medullary carcinoma of the thyroid either as the isolated form or as part of multiple endocrine neoplasia type IIa or IIb.

More than 80% of children with growth hormone deficiency (GHD) respond with a rise in growth hormone levels when given 1 microgram/kg body weight of growth hormone-releasing hormone (GHRH) in an i.v. bolus. We conducted a study to determine whether the failure of the remaining 20% to respond to GHRH is due to a pituitary deficiency or a secondary effect associated with chronically understimulated somatotrophs. We administered GHRH to "prime" 16 short-statured children (> 2 SD) presenting delayed growth (< 4 cm/year), who had not responded initially when given a single dose of GHRH. Priming consisted of administering GHRH (1-29) NH2 (5 micrograms/kg body weight, s.c.) for six consecutive days. Plasma GH response was studied again after an i.v. injection of 1 microgram/kg body weight of GHRH (1-29) NH2 on the seventh morning. On the basis of these results we were able to separate our patients into two groups: a) responders to priming (n = 8), whose GH responses to pharmacological and acute GHRH tests were < 10 ng/ml, with a 12-hour sleep secretion < 3 ng/ml/min. Priming increased the plasma GH response to acute GHRH in all the children in this group (6.0 +/- 2.1 ng/ml to 18.0 +/- 5.4 ng/ml; p < 0.001); b) non-responders to priming (n = 8), whose GH responses to pharmacological and acute GHRH tests were also < 10 ng/ml, with 12-hour sleep secretion < 3 ng/ml/min, but in whom priming with GH did not increase the plasma GH response (5.5 +/- 2.8 ng/ml to 6.2 +/- 2.9 ng/ml; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of placental development directly interferes with fetal growth. Epidermal growth factor (EGF) plays a major role in placental implantation, growth and differentiation. EGF acts on its placental target cells, i.e. the trophoblasts, via a specific receptor (EGFR) which belongs to the tyrosine kinase receptor family. Abundant placental EGF receptors are located in the brush border at the fetomaternal interface. EGFR expression is modulated by trophoblast differentiation and by hormones or toxic substances such as smoke. Interestingly, in microvilli purified from placentae of infants with intrauterine growth retardation (IUGR) a decrease or absence of tyrosine kinase activity is observed. This suggests that an alteration of EGFR biological activity might interfere with the fetoplacental unit development.

We studied a girl with phenylketonuria who demonstrated signs of precocious puberty. At the age of 7.5 years she had premature telarche. Her height age was 7-9/12 years and her bone age was 9 years. Gonadotropin responses to LHRH administration were consistent with central precocious puberty. Elevated serum phenylalanine levels in this patient, due to poor compliance with the phenylalanine restricted diet, may be related to the early onset of puberty.

This study was designed to evaluate a short term metyrapone test using a highly sensitive (HS) IRMA ACTH assay and to evaluate the usefulness of a morning ACTH level as a screening test for partial ACTH deficiency. ACTH, 11-deoxycortisol and cortisol levels were evaluated over four hours in the morning after a single 40 mg/kg oral dose of metyrapone was administered at 0800 hours. 26 control children and 32 possibly pituitary deficient patients were evaluated. Based on 11-deoxycortisol levels alone, 17 of the patients passed the test, 11 patients failed the test and the result was inconclusive in four patients (12.5%). Evaluation of the increase in ACTH levels (delta ACTH) following metyrapone identified three of the above four with partial ACTH deficiency. The delta ACTH was consistent with the 11-deoxycortisol results in the remainder of patients. There was no difference in morning ACTH levels between controls and patients with partial ACTH deficiency. The measurement of ACTH using the HS IRMA assay, increases the sensitivity of the metyrapone test in detecting patients with partial ACTH deficiency. This test may be used safely in pediatric patients on a repetitive basis, especially in those children who may have progressive ACTH failure following hypothalamic-pituitary irradiation.