Urinary Arginine Vasopressin in Asthma: Consideration of Fluid Therapy

To elucidate the role of antidiuretic hormone (ADH) on water and electrolyte balance in patients with asthmatic attacks, urinary arginine vasopressin (AVP) was assayed in 28 asthmatic patients. In a 3-year-old girl with status asthmaticus who developed a grand mal seizure in association with hyponatremia, urinary AVP levels remained high and fluctuated before convulsion; the cause of the convulsion was considered to be water intoxication due to inappropriate ADH secretion. In 19 of 28 patients with moderately severe asthmatic attacks, increases in urinary AVP levels occurred before treatment (300 ± 80 pg/ml vs. 40 ± 24 pg/ml (normal controls), p < 0.01); elvated AVP levels tended to fall in response to intravenous fluid therapy (appropriate ADH secretion) in 2 of 6 patients, but did not fall (inappropriate ADH secretion) in the remaining patients. It is concluded that inappropriate ADH secretion may occur in asthmatic attacks, and that in such a condition there seems to be a potential risk of water intoxication during fluid therapy, as demonstrated in the present patient.     

Remission of congenital diabetes insipidus after eight years

Septo-optic dysplasia (SOD) (De Morsier's syndrome) is a complex developmental disorder marked by variable and often incomplete formation of cranial midline structures, resulting in absence of the septum pellucidum, optic nerve hypoplasia, and hypothalamic-pituitary dysfunction. We describe a patient with SOD who manifested symptoms in the early neonatal period with severe deficiencies of multiple pituitary hormones including anti-diuretic hormone (ADH). Her congenital diabetic insipidus (DI), consequence of an anatomic defect, can be argued to be of the most severe type. Our patient resolved her severe DI 8 years after her initial presentation, suddenly requiring no further medical treatment for DI following longstanding pharmacological replacement of ADH. This is the first report of a patient with SOD with spontaneous resolution of congenital DI.     

Hypertonic saline test for the investigation of posterior pituitary function.

The hypertonic saline test is a useful technique for distinguishing partial diabetes insipidus from psychogenic polydipsia, and for the diagnosis of complex disorders of osmoreceptor and posterior pituitary function. However, there is little information concerning its use in childhood. The experience of using this test in five children (11 months to 18 years) who presented diagnostic problems is reported. In two patients, in whom water deprivation tests were equivocal or impractical, an inappropriately low antidiuretic hormone (ADH) concentration (< 1 pmol/l) was demonstrated in the presence of an adequate osmotic stimulus (plasma osmolality > 295 mosmol/kg). In two children--one presenting with adipsic hypernatraemia and the other with hyponatraemia complicating desmopressin treatment of partial diabetes insipidus--defects of osmoreceptor function were identified. Confirming a diagnosis of idiopathic syndrome of inappropriate ADH secretion (SIADH) was possible in a patient with no other evidence of pituitary dysfunction. The hypertonic saline test was well tolerated, easy to perform, and diagnostic in all cases.     

Hypertonic saline test for the investigation of posterior pituitary function

The hypertonic saline test is a useful technique for distinguishing partial diabetes insipidus from psychogenic polydipsia, and for the diagnosis of complex disorders of osmoreceptor and posterior pituitary function. However, there is little information concerning its use in childhood. The experience of using this test in five children (11 months to 18 years) who presented diagnostic problems is reported. In two patients, in whom water deprivation tests were equivocal or impractical, an inappropriately low antidiuretic hormone (ADH) concentration (< 1 pmol/l) was demonstrated in the presence of an adequate osmotic stimulus (plasma osmolality > 295 mosmol/kg). In two children--one presenting with adipsic hypernatraemia and the other with hyponatraemia complicating desmopressin treatment of partial diabetes insipidus--defects of osmoreceptor function were identified. Confirming a diagnosis of idiopathic syndrome of inappropriate ADH secretion (SIADH) was possible in a patient with no other evidence of pituitary dysfunction. The hypertonic saline test was well tolerated, easy to perform, and diagnostic in all cases.     

The hormonal and metabolic response to stress in the neonate

Conclusions It is apparent that adult patients demonstrate a catabolic response to the stresses induced by operative or accidental trauma. It seems that the degree of this catabolic response may be quantitatively related to the extent of the trauma or the magnitude of associated complications such as infection. The host response to infection, traumatic injury, or major operative stress is characterized by such events as fever, pituitary and stress hormone elaboration, mineral redistribution, and increased acute-phase protein synthesis [21].The beneficial effects of this stress response consist in providing alternate energy sources to meet metabolic demands and essential building blocks for synthetic activities occuring in the postoperative period. It has been suggested that the hyperglycemic response is essential for supplying the increased glucose requirements of injured tissue [81]. In addition, the proteolytic component of the stress response provides the necessary amino acid elements for reparative protein synthesis and production of acute-phase reactants by the liver. The changes in metabolic patterns induced by the stress response are satisfied in part by increased lipolysis and ketogenesis to provide an alternate source of metabolic fuel for tissues such as the brain and skeletal muscle. Additionally, the observed gluconeogenesis may aid in maintaining the glucose supply for vital organs principally dependent on glucose [52, 160].This metabolic response has also been shown to potentiate many adverse conditions in the postoperative period and to further exacerbate the stress response. Examples include a hypermetabolic state with attendant increased VO₂, increased energy requirements, increased temperature, elevated cardiac output, and altered or impaired inflammatory or immune-responsiveness. Numerous investigators have demonstrated that adult patients exposed to severe degrees of traumatic stress are subjected to greatly increased rates of complications such as cardiac or pulmonary insufficiency, myocardial infarction, impaired hepatic and/or renal function, gastric stress ulcers, and sepsis. Furthermore, evidence exists to suggest that this response may be life-threatening if the induced catabolic activity remains excessive or unchecked for a prolonged period. Moyer et al. were able to identify with a great degree of certainty the patients who were likely to die based on a single analysis of a variety of plasma-borne substrates obtained up to 9 days prior to death [103].It is apparent that modulating or blunting the catabolic response induced by the stress state may have beneficial effects. In studies of postoperative pain management, improved pain control resulted in reduction of postoperative nitrogen loss and shortened periods of convalescence following operation [28, 88].It is evident from this review that human newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin.The catecholamines may be the agents of primary importance in this response, and thus may modulate the remaining components of the hormonal response to stress as well as the metabolic changes, including inhibition of insulin release, marked hyperglycemia, and breakdown of the neonate's stores of nutrients (carbohydrate, protein, and fat). These reactions ultimately result in the release of glucose, NEFA, ketone bodies, and amino acids. Although these metabolic by-products are necessary to meet the body's altered energy needs in a time of increased metabolic demands, it is not difficult to imagine that a severe or prolonged response would be very detrimental to a previously ill neonate with limited reserves of nutrients and already high metabolic demands imposed by rapid growth, organ maturation, and adaptation to the postnatal environment. Preliminary investigations by Anand et al. outlined in this review indicate that alterations in anesthetic technique with the addition of agents such as halothane and fentanyl may be able to significantly blunt this catabolic response. In addition, it appears that modulation of the immune response may also greatly affect the postoperative catabolic response. It is hopeful that future developments and the acquisition of more detailed knowledge o the response will allow us to modify the stress response in neonates in order to further decrease their mortality and morbidity.From the Section of Pediatric Surgery, C. S. Mott Children's Hospital and University of Michigan Medical School Offprint requests to: A. G. Coran     

Water, electrolyte, and endocrine homeostasis in infants with bronchiolitis

Twenty-two of 23 consecutive infants with bronchiolitis, 5.5 +/- 3.5 mo of age, showed a 1.9 +/- 1.4% increase in body weight, increased urinary osmolality of 737 +/- 193 mmol/L with low plasma osmolality of 275 +/- 4 mmol/L, and markedly elevated plasma antidiuretic hormone (ADH) levels of 114 +/- 225 pg/mL. Increased ADH, which usually suppresses plasma renin activity, was associated with increased plasma renin activity of 11-55 ng angiotensin 1/mL/h (normal for age less than 10 ng angiotensin 1/mL/h). Hyperaldosteronism was evident from the low fractional excretion of sodium of 0.27 +/- 0.2% and high fractional excretion of potassium of 21 +/- 15%. Serum sodium concentrations were normal. All of the pathologic findings returned to normal when the bronchiolitis subsided. A control group of 10 infants with nonrespiratory febrile illness did not show any of the above abnormalities. Thus, bronchiolitis of infancy is characterized by both increased ADH secretion and hyperreninemia with secondary hyperaldosteronism, which induce water retention but counterbalance each other with respect to serum sodium. Increased ADH secretion as well as increased plasma renin activity are not "inappropriate," but rather suggest a response to the perception of hypovolemia by intrathoracic receptors. We therefore conclude that the clinical management of bronchiolitis requires close monitoring of body wt and plasma osmolality-urinary osmolality relationship; serum sodium levels may be misleading.     

Increased immunoreactive plasma and urinary growth hormone in growth retardation with defective generation of somatomedin a (Laron's Syndrome).

In a boy 4 years old with clinical hypopituitary dwarfism, high plasma and urinary levels of immunoreactive growth hormone were found. Somatomedin A levels in serum were low and failed to respond after short-term treatment with human growth hormone. The parents were first cousins. In the arginine and insulin tolerance tests the initially high immunoreactive growth hormone levels were later followed by a decrease to high normal values. Insulinopenic response was present during the arginine and glucose tolerance tests. As a growth hormone molecule defect is not found in these patients and no growth or other metabolic response to exogenous HGH can be demonstrated, it is concluded that a defective somatomedin generation may be present, probably in conjunction with a generalized receptor defect and deficient feedback system with abnormal release of HGH. The lack of somatomedin A is responsible for the severe growth retardation and the disturbance in carbohydrate metabolism is probably caused by sustained high growth hormone levels.     

The catecholamine response to hypoglycemia in children with isolated growth hormone deficiency syndromes and multiple pituitary hormone defects

We examined the catecholamine response to insulin-induced hypoglycemia in 46 short children evaluated for growth hormone (GH) deficiency by both pharmacologic stimulation and integrated concentration of GH. Twelve patients had quantitatively normal GH secretion by both pharmacologic stimulation and integrated concentration of GH (GHNORM). Twenty-two patients had normal GH to pharmacologic stimulation but subnormal integrated concentration of GH (GHND). Twelve patients had GH deficiency by both tests (GHD): six had isolated GH deficiency (GHD type 1) and six had multiple hormone deficiencies (GHD type 2). There was no significant difference between the peak epinephrine, norepinephrine, and cortisol responses of GH-NORM, GHND, and GHD type 1 patients. The mean peak epinephrine response of GHD type 2 patients was significantly lower (564 +/- 561 pg/ml, p less than 0.03) compared to the other patient groups. There was no significant difference between the peak norepinephrine levels between GHD type 2 patients and the remaining groups. There was no correlation between decrease in blood glucose and either increase in growth hormone, catecholamine, or cortisol concentrations. There was a significant correlation between log peak epinephrine and peak cortisol response (r = 0.53, p less than 0.0002) of the 46 subjects. Neither the basal nor stimulated catecholamine levels correlated with the integrated concentration of cortisol. We conclude that isolated GH deficiency is not associated with impairment of the catecholamine response to hypoglycemia; impairment of the epinephrine response to hypoglycemia is only associated with multiple pituitary hormone deficiencies; in children, the degree of glucose lowering is not correlated with the magnitude of peak GH, catecholamine, or cortisol responses.     

Hypercalcemia in children: An overview

Hypercalcemia occurs in children of all ages. A serum calcium level over 15 mg/dL can be life-threatening. The association between familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NHPT) has been discussed. FHH is characterized by a high serum calcium concentration, relatively low urine calcium excretion, and an inappropriately normal parathyroid hormone (PTH) concentration. On the other hand, NHPT is a rare disease characterized by markedly increased serum calcium (15 mg/dL) and PTH concentrations, and is fatal without parathyroidectomy early in life. Recently, a complementary DNA encoding an extracellular calcium-sensing receptor has been isolated. Furthermore, three mutations in the receptor gene in FHH and NHPT individuals have been described. Thus, heterozygotes and homozygotes of FHH may have an intermittent hypercalcemia and NHPT, respectively. Vitamin D-related hypercalcemia, and vitamin D intoxication and immobilization are also discussed.     

Carbohydrate and lipid metabolism in Turner syndrome: effect of therapy with growth hormone, oxandrolone, and a combination of both

To evaluate the effects of growth-promoting therapy on carbohydrate metabolism in girls with Turner syndrome, we determined glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) at baseline and after 5 days, 2 months, and 12 months of treatment with growth hormone (GH), oxandrolone, or a combination of GH and oxandrolone, or after the same intervals with no therapy. Before therapy, subjects had a significantly greater glucose response during OGTT than published normal control values. There were no significant changes in mean fasting glucose, cholesterol, or triglyceride concentrations in any of the treatment groups. The integrated glucose concentrations rose significantly over baseline values in the oxandrolone group at 2 and 12 months and in the combination group at 5 days. There were significant increases in the mean integrated insulin concentrations at 2 and 12 months for the group receiving oxandrolone alone and at all three times for the group receiving combination therapy. Thus oxandrolone, alone or in combination with GH, had significant effects on carbohydrate metabolism in subjects with Turner syndrome, whereas GH alone did not.     

Fetal biochemistry in growth retardation.

A substantial proportion of fetuses with severe early onset growth retardation are chromosomally abnormal and in these cases detailed ultrasound scanning will often demonstrate the presence of fetal anatomical defects. Chromosomally normal SGA fetuses with no biochemical abnormalities are likely to be normal small fetuses and seem to develop normally. SGA fetuses with evidence of impaired placental perfusion such as altered fetal cardiovascular dynamics and disturbances in biochemical, haematological, metabolic and endocrine status are at increased of neurodevelopmental delay. Although incomplete, the data collected so far suggest the biochemical changes may be caused by reduced placental transfer of nutrients (e.g. oxygen, glucose and essential amino-acids) and subsequent reduced fetal metabolism leading to high levels of substrates (e.g. triglycerides and non-essential amino-acids) and low levels of tissue products (e.g. thyroid hormone, insulin, platelets and white cells).     

Glucose tolerance in children with renal allografts and effect of growth hormone treatment

We performed oral glucose tolerance tests (oGTTs) on 15 children who had functioning renal allografts received greater than or equal to 18 months previously, had adequate renal function, and had heights greater than 2.5 SD below the mean height for age. Three of the children had impaired glucose tolerance; their mean glucose levels during the last 2 hours of the oGTT were higher (p less than 0.05) than published control values. Integrated glucose concentrations correlated inversely with the prednisone dose on the first day of an alternate-day dosage schedule (R2 = 0.383) and directly with adiposity (partial R2 = 0.322). The integrated insulin concentration correlated directly with the prednisone dose on day 1 of an alternate-day regimen (R2 = 0.355) and with age (partial R2 = 0.163). In 10 children with renal transplants who had been treated with growth hormone for greater than or equal to 6 months, the mean fasting glucose concentration, integrated glucose concentration, and integrated insulin concentration during the oGTTs obtained after 6 months or 12 months of growth hormone treatment were not significantly different (p greater than 0.05) from values measured before the treatment. We conclude that increased integrated concentrations of both glucose and insulin during oGTTs in children with renal allografts correlate with the dose of prednisone administered on the first day of an alternate-day schedule, with age, and with adiposity index. Growth hormone treatment of children with renal allografts who are growing poorly does not significantly affect glucose metabolism as assessed by oGTT.     

THE EFFECT OF L-DOPA ON THE BLOOD CONCENTRATIONS OF GROWTH HORMONE, THYROTROPHIN, GONADOTROPHINS, CORTISOL AND GLUCOSE IN CHILDREN WITH SHORT STATURE

ABSTRACT. Nilsson, K. O. and Thorell, J. I. (Department of Paediatrics, Endocrinology and Nuclear Medicine, University Clinics, Malmö General Hospital, Malmö, Sweden). The effect of L-dopa on the blood concentrations of growth hormone, thyro-trophin, gonadotrophins, cortisol and glucose in children with short stature. Acta Paediatr Scand, 63: 812, 1974.—Studies were performed in nine constitutionally short children to evaluate the diagnostic usefulness of oral L-dopa as compaired to insulin induced hypoglycemia as a provocative agent for the stimulation of growth hormone production. In addition the effect of L-dopa on the blood concentrations of thyro-trophin, gonadotrophins, cortisol and glucose was investigated. The mean growth hormone concentration was 4.8±1.6 (S.E.M.) ng/ml before L-dopa and 2.9±1.0 ng/ml before insulin. The mean peak growth hormone concentration was 20.7±2.6 ng/ml after L-dopa and 17.5±3.1 ng/ml during insulin induced hypoglycemia. AU children showed peak growth hormone concentrations at or above 8 ng/ml both after L-dopa and insulin, although in one patient this level was reached only after priming with testosterone. No significant changes in the blood concentrations of thyrotrophin, gonadotrophins, cortisol or glucose were observed. It is concluded that L-dopa is an effective stimulus for the release of growth hormone in young subjects.     

Hypoglycemia pathogenesis in children with dumping syndrome

Three children with severe hypoglycemic reactions secondary to dumping syndrome were studied to discern the mechanism by which hypoglycemia occurred. Symptoms in patient 1 developed after fundoplication, generalized autonomic dysfunction occurred in patient 2, and dumping syndrome developed in patient 3 after malplacement of a feeding gastrostomy tube. Average blood glucose levels studied during and after two to seven meals in each child were 375 +/- 97 mg/dL (mean +/- SD) 30 minutes postprandially and 35 +/- 10 mg/dL greater than 120 minutes later. Swings in glucose values were proportional to the volume of meals. Insulin and glucagon levels were followed during a single meal challenge test in each patient; the average glucose concentration increased to 356 +/- 59 mg/dL 30 minutes postprandially and decreased to 32 +/- 11 mg/dL at 150 +/- 30 minutes. Hormonal analyses indicated (1) inappropriate early release of glucagon (300 pg/mL at 15 minutes) in patient 1, (2) exuberant early release of insulin (maximum 190 +/- 15 microU/mL) resulting in rapid decrease in glucose concentration in all patients, (3) development and/or persistence of hypoglycemia after the decline in circulating insulin to undetectable levels, and (4) inadequate glucagon response to hypoglycemia resulting in sustained hypoglycemia. These data indicate that gross disturbances of the insulin-glucagon axis attend childhood dumping syndrome.     

INCREASED IMMUNOREACTIVE PLASMA AND URINARY GROWTH HORMONE IN GROWTH RETARDATION WITH DEFECTIVE GENERATION OF SOMATOMEDIN A (LARON'S SYNDROME)

ABSTRACT: Kastrup, K. W., Andersen, H. and Hanssen, K. F. (Childrens Hospital, Fuglebakken, and Steno Memorial Hospital, Copenhagen, Denmark). Increased immunoreac-tive plasma and urinary growth hormone in growth retardation with defective somatomedin A generation (Laron's syndrome). Acta Paediatr Scand 64: 613, 1975.–In a boy 4 years old with clinical hypopituitary dwarfism, high plasma and urinary levels of immunoreactive growth hormone were found. Somatomedin A levels in serum were low and failed to respond after short-term treatment with human growth hormone. The parents were first cousins. In the arginine and insulin tolerance tests the initially high immunoreactive growth hormone levels were later followed by a decrease to high normal values. Insulinopenic response was present during the arginine and glucose tolerance tests. As a growth hormone molecule defect is not found in these patients and no growth or other metabolic response to exogenous HGH can be demonstrated, it is concluded that a defective somatomedin generation may be present, probably in conjunction with a generalized receptor defect and deficient feedback system with abnormal release of HGH. The lack of somatomedin A is responsible for the severe growth retardation and the disturbance in carbohydrate metabolism is probably caused by sustained high growth hormone levels.     

Evidence of hypothalamic-pituitary thyroid abnormalities in children with end-stage renal disease

Patients with end-stage renal disease may have abnormalities of growth and of gonadal and thyroid hormones, so we attempted to determine the mechanisms that may be involved in the altered thyroid function. We evaluated serum thyroid hormone levels, their changes immediately after hemodialysis, the serum thyrotropin (thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone, and the circadian pattern of serum TSH in nine children with end-stage renal disease who were between 7 1/2 years and 17 years 1 month of age. Seven patients had been receiving hemodialysis for a median of 3.3 years; the other two were receiving continuous ambulatory peritoneal dialysis. Four patients had low serum total thyroxine (T4) values, and all nine had low free T4 values. Mean concentrations of total T4, free T4, and total triiodothyronine (T3), which were significantly less than normal before hemodialysis, returned to normal levels immediately after dialysis. Postdialysis thyroid hormone increases did not correlate with the decrease in weight or the increase in hematocrit observed immediately after dialysis. All but one patient had basal TSH levels within the normal range. Three patients had a deficient TSH response to thyrotropin releasing hormone, and the TSH response was prolonged in all of them. The mean (+/- SD) nocturnal TSH surge was 50 +/- 68%. Five of the eight patients studied had a nocturnal TSH surge below the normal range (95% confidence limits 47% to 300%). Serum free T4 values correlated with the TSH nocturnal surge (r, 0.73; p less than 0.05). Our findings support the hypothesis that some patients with end-stage renal disease have central hypothyroidism.     

Clinical phenotype and endocrinological investigations in a patient with a mutation in the MCT8 thyroid hormone transporter

Thyroid hormones are known to be essential for growth, development, and metabolism. Recently, the monocarboxylate transporter 8 (MCT8) was identified as a thyroid hormone transporter, and MCT8 mutations have been associated with Allan-Herndon-Dudley syndrome, an X linked condition characterized by severe mental retardation, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. Here we describe in detail the clinical and biochemical features and the response to thyroid hormone (L-thyroxine (LT4)) administration in a boy with an MCT8 mutation (c.1649delA) that truncates the protein in the twelfth transmembrane domain. It is of note that brain magnetic resonance imaging (MRI) revealed delayed myelination from infancy. Endocrine functions other than thyroid hormone regulation and metabolism were intact, resulting in normal hypothalamic/pituitary function tests. While LT4 administration suppressed thyrotropin (TSH) secretion, no significant changes in thyroid hormone values or clinical symptoms were observed. Conclusion: the characteristic thyroid hormone function tests and brain MRI findings may allow screening of high-risk populations for a better understanding of MCT8 pathophysiology.     

Impaired glucose tolerance and risk factors for progression to type 2 diabetes in youth

Abstract:  Impaired glucose tolerance and impaired fasting glucose represent two potentially reversible prediabetes conditions. Previous reports from various regions across the globe indicate that both conditions may be relatively common in obese children and adolescents. The major factor driving the development of compromised glucose metabolism in obese youth is severe insulin resistance. This severe insulin resistance has been strongly associated with specific patterns of lipid partitioning. Severe obesity along with continued weight gain, specifically in obese youth belonging to ethnic minorities, have been shown to be associated with deterioration of glucose tolerance over short periods of time. As obesity-related insulin resistance in the pediatric age-group is associated with the development of altered glucose metabolism and other elements of the metabolic syndrome, severely obese youth are a high-risk group for the development of type 2 diabetes and may benefit most from preventive interventions such as environmental changes that promote increased physical activity.     

Hypoglycemia in newborn infants: Features associated with adverse outcomes

The purpose of this review article is to document from the literature values of blood/plasma glucose concentration and associated clinical signs and conditions in newborn infants (both term and preterm) that indicate a reasonable clinical probability that hypoglycemia is a proximate cause of acute and/or sustained neurological injury and to review the physiological and pathophysiological responses to hypoglycemia that may influence the ultimate outcome of newborns with low blood glucose. Our overall conclusion is that there is inadequate information in the literature to define any one value of glucose below which irreparable hypoglycemic injury to the central nervous system occurs, at any one time or for any defined period of time, in a population of infants or in any given infant. Clinical signs of prolonged and severe neurological disturbance (coma, seizures), extremely and persistently low plasma/blood glucose concentrations (0 to <1.0 mmol/l [0 to <18-20 mg/dl] for more than 1-2 h), and the absence of other obvious central nervous system (CNS) pathology (hypoxia-ischemia, intracranial hemorrhage, infection, etc.) are important for the diagnosis of injury due to glucose deficiency. Specific conditions, such as persistent hyperinsulinemia with severe hypoglycemic episodes that include seizures, also contribute to the diagnosis of hypoglycemic injury. Such lack of definitive measures of injury specific to glucose deficiency indicates that clinicians should be on the alert for infants at risk of hypoglycemia and for clinical signs and conditions that might herald severe hypoglycemia; they should have a low threshold for investigating and diagnosing 'hypoglycemia' with frequent measurements of plasma/blood glucose concentration; and they should treat low glucose concentrations promptly and maintain them in a safe range. Because there is no conclusive evidence or consensus in the literature that defines an absolute value or duration of 'hypoglycemia' that must occur, with our without related clinical complications, to produce neurological injury, clinicians should consider the information currently available, determine a 'target' plasma or blood glucose concentration that is acceptable, and treat infants with glucose concentrations below this value accordingly. Our intent in this review article is to highlight the studies relevant to this issue and help clinicians formulate a safe and, hopefully, effective strategy for the diagnosis and treatment of hypoglycemia.     

PLASMA CONCENTRATIONS OF VITAMIN D METABOLITES IN A CASE OF RICKETS OF PREMATURITY

ABSTRACT. Rickets was diagnosed in an extremely low-birthweight infant 16 weeks after birth. She had a normal plasma concentration of 25-hydroxyvitamin D, a relatively low level of 24,25-dthy-droxyvitamin D, and a markedly elevated 1,25-dihydroxyvitamin D level compared with adult standards. The plasma concentrations of the vitamin D metabolites were, however, indistin-guishable from those of healthy preterm infants who received a similar diet of human milk and vitamins. The results indicate that rickets was not caused by vitamin D deficiency or by abnormal vitamin D metabolism, but by calcium and/or phosphate deficiency, and that the calcium and phosphorous content of human milk may be inappropriately low for very low-birthweight infants.