The Journal of pediatric endocrinology最新文献

Skeletal dysplasia or osteochondrodysplasia is the designation of more than 200 different disorders, that are characterized by abnormalities of the skeleton, disproportional short stature, and a variety of other problems. The underlying biochemical defect is unknown in the vast majority of skeletal dysplasias, and the diagnosis is based on radiological findings and anthropometric measurements. Despite this fact, the information on body proportions in even the more common forms of skeletal dysplasia is scarce. Patients with achondroplasia are often diagnosed shortly after birth. Linear growth is severely compromised with relatively short extremities. Head circumference is above normal and final height ranges from 115 to 145 cm in males and 112 to 137 cm in females. Individuals with hypochondroplasia may go unnoticed until puberty, at which time the growth problem becomes obvious. Sitting height to height ratio is increased, but the body disproportion may not be apparent until puberty. Final height has been reported between 118 and 165 cm. Spondyloepiphyseal and spondylometaepiphyseal dysplasias are characterized by severe impairment of growth both in trunk and extremities, and therefore the sitting height to height ratio may be normal. Final height is severely reduced and ranges from 94 to 132 cm. It is concluded that anthropometric studies of patients with skeletal dysplasia are needed. More quantitative information on body proportions may assist in the diagnostic procedure and ensure that growth promoting therapy, e.g. growth hormone, does not worsen the disproportion.

Chronic renal failure (CRF) is characterized by a series of compensatory adaptations in the surviving nephrons of the diseased kidney aimed at maintaining glomerular filtration rate and tubular resorptive functions. Several lines of evidence indicate that in normal kidney growth hormone (GH) and insulin-like growth factors (IGFs) modulate the nephron, both in respect to function and size. Virtually all members of the GH/IGF axis are present in the kidney, comprising: 1) GH-receptors; 2) IGF-1 and IGF-2 mRNA; 3) distinct receptors for IGFs: the IGF-1 receptor and the IGF-2/mannose-6-phosphate receptor, and 4) specific binding proteins (IGFBPs), indicating that GH and IGFs may affect the kidney in both an endocrine and autocrine/paracrine fashion. GH and IGFs modulate renal metabolism and the kidney plays an important role in the metabolism and degradation of circulating GH and IGFs. The action of GH to enhance kidney function and size is mediated through IGF-1, and IGF-1 infusion in animals and man stimulates renal function and volume. In addition, renal growth following various pathophysiological conditions (e.g. reduction in renal mass, diabetes mellitus) is preceded by an increase in endogenous renal IGF-1. In CRF circulating levels of GH are elevated, serum IGF-1 is normal and circulating IGFBP-1, -2, and -3 are elevated. Given the ability of GH and IGF-1 to stimulate various functions of the kidney, the potential use of GH or IGF-1 in the setting of CRF has been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of the somatotropic axis is altered in chronic renal failure (CRF) resulting in a secondary syndrome of growth hormone (GH) insensitivity. Secretion of growth hormone estimated by deconvolution analysis is low normal in prepubertal patients and reduced in late pubertal children with CRF. Basal and integrated GH serum concentration measured by RIA is increased due to reduced renal metabolic clearance, whereas the fractional urinary excretion is increased due to damage of renal tubular cells. GH receptor mRNA is decreased (rat) and the serum concentration of GH binding protein (BP) activity is low (man). Insulin-like growth factor (IGF)-1 production rate is reduced, whereas serum concentrations of IGFBPs are increased secondary to reduced renal metabolic clearance. This results in a reduction of free, active IGF-1. Treatment with GH induces a rise in serum IGF-1 concentration and normalizes IGF bioactivity. Clinical studies in prepubertal children demonstrated a dramatic rise in height velocity during the first treatment year and to a lesser extent during the following years. In children on conservative treatment prior to dialysis, mean height SDS improved by 1.5 within two years and by 2.0 within four years. Patients with renal allografts responded in a similar way. Age and pretreatment height velocity SDS are confounding variables for the response to GH. Renal function seems not be altered by recombinant human (rh) GH in patients with CRF, and the number of renal allograft rejection crises seems not to be substantially increased under rhGH treatment in allograft recipients.

We report a thirteen year-old girl with symptomatic hypocalcemia secondary to celiac disease. Serum vitamin D levels [25OH-VitD3 and 24,25(OH)2-VitD3] were low, whereas 1,25(OH)2D3 and PTH levels were higher than normal. Shortly after introducing a gluten-free diet, the patient became asymptomatic, regaining normal growth and pubertal development and serum calcium levels returned to normal.

11 males, aged 2.5-16.3 years (6.8 +/- 4.1) with growth retardation (Standard Deviation Score--SDS > -2.00) consequent to chronic renal failure (CRF) received recombinant human growth hormone (rhGH) for 18 to 60 mo (40.9 +/- 15.4). Growth velocity (GV) increased from 5.4 +/- 2.2 for the year prior to rhGH to 8.9 +/- 1.6 (p = 0.00001), 7.4 +/- 1.7 (p < 0.03), 7.6 +/- 1.6 (p < 0.006), 6.5 +/- 1.0 (p < 0.05) and 7.5 +/- 1.3 (p = NS) cm/yr following 12, 24, 36, 48 and 60 mo respectively of treatment. The mean SDS for height decreased from -3.21 at baseline to -0.85 at 60 mo (p = 0.0004); 7 of 8 pts treated for > 36 mo had a SDS more positive than -2.00; 3 reached the 50th percentile on the growth curve. In 2 patients the dosage was doubled to achieve the increase in GV; in one patient it took 5 yrs to reach a SDS more positive than -2.00. A significant increase in weight gain and mid-arm muscle circumference over baseline values were indicative of the anabolic effect of rhGH. The mean increase in bone age was similar to the increase in chronologic age; the delta bone age-delta height age was not significant indicating no loss of growth potential following rhGH. Although 3 patients required the initiation of dialysis following rhGH treatment, the mean calculated creatinine clearance did not decrease significantly. No significant adverse effects were noted. These data indicate that long-term rhGH treatment is effective in improving the GV of children with CRF and facilitating catch-up growth without loss of growth potential.

Diabetic nephropathy is an uncommon finding in the pediatric age group. Previous reports have demonstrated that persistent proteinuria does not occur during the first five years following the diagnosis of insulin dependent diabetes mellitus. We report a prepubertal female child with less than five years duration of diabetes who developed persistent proteinuria and histologic changes diagnostic of diabetic nephropathy. The earlier than expected diabetic nephropathy noted in our patient raises the question regarding the need for earlier surveillance for diabetic nephropathy in children with a family history of chronic diabetic complications.

A 14.8 year old boy was evaluated for galactorrhea of two months duration and growth deceleration for greater than three years. He was 3.7 standard deviations (SD) below the mean for age in height and euthyroid with uncompromised vision, bilateral galactorrhea, and pubertal arrest. MRI demonstrated a 10 x 8 mm left pituitary mass. Bone age was 11.5 years. Serum prolactin (PRL) decreased by more than 85% after 5 weeks of treatment with bromocriptine (Br). After five months, the prolactinoma (PRLoma) measured 5 x 4 mm. Hypothalamic-pituitary function indicated growth hormone (GH) deficiency and hypogonadotropic hypogonadism as assessed by ITT-TRH-GnRH-clonidine. After nine months of Br, despite return of adequate gonadotropin and GH secretion as assessed by repeat ITT-TRH-GnRH-clonidine, pooled 12 hour nocturnal spontaneous GH secretion, and clinical progression of puberty, there was no linear "catch-up growth" (growth rate = 4.4 cm/yr and height 4.2 SD below the mean for age). Growth rate increased following supplemental GH administration without untoward effect. We conclude that there may be discordance/lag between reduction in secretion and size of PRLomas and growth despite resolution of other anterior pituitary dysfunction. Other possibilities are discussed.

Over a three-and-a-half year period, 26 children with precocious pubarche or other forms of sexual precocity were studied. All had plasma steroid patterns analyzed, in most cases both before and after stimulation with ACTH. 17 of the children had elevation of the delta 5-steroids dehydroepiandrosterone and 17-OH-pregnenolone and their individual results are presented. Five of these children were diagnosed with probable late-onset 3 beta-HSD deficiency. The difficulties in differentiating this entity from idiopathic premature adrenarche are emphasized.

Two cases of transient neonatal diabetes mellitus associated with anemia, macroglossia and umbilical hernia were studied in relation to the possible etiologies that have been postulated to be responsible for this syndrome. Both patients required insulin therapy for the control of their hyperglycemia but case number two needed to be treated for 14 months before glucose normalization occurred. This patient developed classical insulin dependent diabetes mellitus during our follow-up; the HLA typing showed DR4 allele.

The aim of our study was to determine whether first-phase insulin response to intravenous (i.v.) glucose could be used as a simple and rapid test to identify cystic fibrosis (CF) patients at risk to develop diabetes mellitus. Forty consecutive CF patients with normal fasting blood glucose values but with different degrees of glucose tolerance on the standard oral glucose tolerance test (22 with normal glucose tolerance, 16 with impaired glucose tolerance, 2 with diabetes mellitus) and 12 normal subjects, matched for age and body mass index, underwent an i.v. glucose bolus to evaluate early phase insulin release. When compared to the normal subjects, CF patients had significantly reduced basal (76 +/- 50 vs 108 +/- 30 pM/l, 2 p < 0.02) and glucose stimulated insulin levels (1 + 3 min insulin = 456 +/- 275 vs 951 +/- 170 pM/l, 2 p < 0.01). Early phase insulin release, however, did not differentiate between CF patients with normal and impaired glucose tolerance; also in the two diabetic patients insulin levels did not clearly differ from those observed in the other groups of CF subjects. In conclusion, first-phase insulin response may identify an impairment of B-cell function in CF subjects; however, it does not discriminate between different degrees of glucose tolerance, as determined by the oral glucose tolerance test and, therefore, it does not reliably identify those patients who will eventually develop overt diabetes mellitus.