The "two bag system" for variable intravenous dextrose and fluid administration: benefits in diabetic ketoacidosis management.

1 case-controlled retrospective analysis compared the "two bag system," based on the euglycemic clamp technique, versus the traditional "one bag" method for intravenous diabetic ketoacidosis management. The two bag system can provide more cost-effective intravenous dextrose and fluid delivery and enhance quality of care by improving the efficiency, timeliness, and flexibility of overall control.

Dual regulation of insulin-like growth factor binding protein-1 levels by insulin and cortisol during fasting.

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) gene transcription is known to be inhibited by insulin in vivo and in vitro. Levels of IGFBP-1 typically rise during fasting but also rise after acute hypoglycemia, including that induced by insulin, through an unknown mechanism that may involve counterregulatory hormones such as cortisol. To study the regulation of IGFBP-1 secretion during fasting, we measured IGFBP-1, insulin, cortisol, GH, and glucose during the course of standardized fasting studies in a total of 21 children. The fasting studies lasted 13-32 h and were terminated for a whole-blood glucose concentration of less than 50 mg/dL (2.8 mmol). Of the children studied, 9 children had no disorder, 8 had ketotic hypoglycemia, 2 had isolated GH deficiency, and 2 had fatty acid oxidation disorders. During fasting, IGFBP-1 rose above the mean baseline levels of 28+/-5 ng/mL to a mean level+/-SEM of 336+/-59 ng/mL at the time of hypoglycemia (P=0.001). IGFBP-1 was strongly associated with serum insulin and cortisol levels over the entire course of fasting (P < 0.0001)). The interaction of the 2 hormones across time was also strongly significant (P < 0.0001). There was no statistically significant association between IGFBP-1 and GH or glucose. At the time of hypoglycemia, insulin levels were suppressed to 1.7 microU/mL or less, and there was no correlation between IGFBP-1 levels at the end of fasting and final insulin level. In contrast, cortisol levels correlated with IGFBP-1 in the final hypoglycemic sample (r=0.56, P < 0.01). Partial correlation analysis revealed that the relationship between IGFBP-1 and cortisol was unchanged when the data was controlled for insulin levels. These data show that insulin and cortisol both regulate IGFBP-1 secretion during fasting; the effects of insulin and cortisol are strong during the course of fasting. Significant hypoglycemia stimulates a further rise in IGFBP-1, which seems to be regulated, in part, by cortisol. The cortisol-induced rise in IGFBP-1 during fasting and during hypoglycemia potentially serves to prevent the hypoglycemic effects of free IGFs.

Pseudopapilledema and congenital disc anomalies in growth hormone deficiency.

Optic nerve hypoplasia is a congenital disc anomaly associated with growth hormone deficiency (GHD). Pseudotumor cerebri is an adverse event associated with growth hormone treatment (hGH) and manifested by increased intracranial pressure and papilledema. Pseudopapilledema is a generic ophthalmologic term encompassing several conditions, including congenital disc anomalies. It is benign and can be distinguished from papilledema by physical examination. The objective of this report is to document that congenital disc abnormalities, which can be confused with papilledema, occur in children with GHD. Three patients with GHD had fundoscopic examinations suggestive of papilledema and possibly pseudotumor cerebri. The abnormal optic nerves were characteristic of pseudo-papilledema, and appear to be a variant of optic nerve hypoplasia. The finding of optic disc abnormality during hGH may reflect pseudo-papilledema and not pseudotumor cerebri. Of equal importance, the reported patients indicate that the finding of pseudopapilledema in short children should suggest the possibility of GHD.

Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.

We describe three families with hypoglycemia caused by familial hyperinsulinism (HI) in whom vertical transmission of the disorder occurred, suggesting autosomal dominant (AD) inheritance. We therefore examined the relationship between the apparent AD disorder and the more common autosomal recessive (AR) form of HI, which has recently been linked to the sulfonylurea receptor on chromosome 11p15.1. The clinical features of the 11 patients with AD HI were milder than those seen in 14 patients with AR HI. Hypoglycemia was readily controlled with either diet alone or with diazoxide in 10 of 11 patients with AD HI but in none of those with the AR form. In one large pedigree, analysis of genomic DNA with polymorphic simple sequence repeat markers excluded linkage of AD HI to the SUR locus in a dominant manner. The possibility of linkage to the SUR locus could not be absolutely excluded in the two smaller pedigrees. None of the published mutations of the SUR gene identified in patients with AR HI were detected in the patients with the AD form. We conclude that the AD form of hyperinsulinism is phenotypically different from the AR variant. The identification of more families with this form of HI may make it possible to locate the responsible gene by the use of linkage analysis.

Insulin-like growth factor binding protein-1 levels in the diagnosis of hypoglycemia caused by hyperinsulinism.

The diagnosis of hypoglycemia caused by hyperinsulinism may be difficult because insulin levels are not uniformly elevated at the time of hypoglycemia. Insulin-like growth factor binding protein-1 (IGFBP-1) is a 28 kd protein whose secretion is acutely inhibited by insulin. We hypothesized that serum levels of IGFBP-1 would be a useful marker of hyperinsulinism. We measured IGFBP-1 levels during the course of standardized fasting studies in hospitalized children; 36 patients became hypoglycemic during the fasting studies, and samples obtained at the point of hypoglycemia were analyzed. On the basis of the currently used diagnostic criteria, 13 children had hyperinsulinism, 16 had ketotic hypoglycemia or no disorder, 3 had hypopituitarism or isolated growth hormone deficiency, 2 had glycogen storage disease type 1 and 2 had fatty acid oxidation disorders. In control subjects (children with ketotic hypoglycemia or no disorder), IGFBP-1 levels rose during fasting to a mean of 343.8 +/- 71.3 ng/ml in the sample drawn at the time of hypoglycemia. Mean IGFBP-1 levels at hypoglycemia for the entire group with hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from levels seen in control subjects (p < 0.0001). In children with moderately controlled hyperinsulinism (fasting tolerance > 4 hours), mean IGFBP-1 levels at the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IGFBP-1 levels in the children with poorly controlled hyperinsulinism (fasting tolerance < 4 hours) failed to rise during fasting, with a mean of 30.1 +/- 10.4 ng/ml in the final sample. IGFBP-1 levels were inversely correlated with serum insulin and C-peptide levels (r = -0.71 and -0.72, respectively; p < 0.0001). Patients with other endocrinologic or metabolic diseases that result in fasting hypoglycemia demonstrated a rise in IGFBP-1 levels similar to that seen in ketotic hypoglycemia. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an additional marker of insulin action that might help to differentiate hyperinsulinism from other hypoglycemic disorders.

Endocrine outcome in long-term survivors of low-grade hypothalamic/chiasmatic glioma.

OBJECTIVE: We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy. DESIGN: Descriptive retrospective study using case note review analysis. PATIENTS: The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow-up was 3.6 years. Thirty-eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment. MEASUREMENTS: Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic-pituitary function. RESULTS: Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). HOwever, 15 children treated with more than 15 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery. CONCLUSIONS: Nearly all studies assessing the patients with different tumour therapy evaluate patients wit different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different form of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.

Arm span as measurement of response to growth hormone (GH) treatment in a group of children with meningomyelocele and GH deficiency.

Children with meningomyelocele (MMC) frequently have impaired linear growth. A number have associated structural brain defects with resultant GH deficiency (GHD). Reproducible measurements of height or length in MMC patients are often hampered by lower limb contractures, spasticity, and scoliosis. Arm span has been proposed as a more reproducible measure of linear growth. Five MMC children documented to have GHD were treated with recombinant human GH (hGH) for 1-3 yr. Their height, arm span, and growth velocity were compared with 32 children with idiopathic GHD treated similarly with hGH. These measures are compared with normal children by being expressed as standard deviation scores. The results of this study indicate that arm span measurements in GHD MMC patients are almost identical to height measurements in idiopathic GHD patients both before and during hGH therapy. The physical condition of children with MMC makes reproducible longitudinal height measurements difficult. Routine determinations of arm span measurements for children with MMC will assist in recognizing growth failure as well as monitoring treatment results.

Non-islet-cell tumor associated with hypoglycemia in a child: successful long-term therapy with growth hormone.

Hypoglycemia occurred in a 2-year-old girl with neuroblastoma. Initially, growth hormone secretion was suppressed, and she had low levels of insulin-like growth factor (IGF)-I and IGF binding protein-3, but elevated levels of large molecular weight IGF-II. We postulated that the pathogenesis of her hypoglycemia involved production of IGF-II by her neuroblastoma, leading to GH suppression and an abnormally elevated ratio of IGF to IGF binding protein. She was successfully treated with growth hormone; treatment was associated with normalization of the growth hormone-dependent growth factor levels and with euglycemia.