Sonographic measurements of the neonatal thyroid gland.

The purpose of this study was to establish the normal dimensions of the thyroid gland in euthyroid neonates. Ultrasonographic evaluation of the thyroid gland was performed in the first week of life in 68 term neonates whose gestational ages at birth were 37 to 41 weeks and whose birth weights ranged from 2570 to 4790 g. Measurements of the thyroid lobes were done in transverse, anteroposterior, and longitudinal planes. All neonates had age-appropriate thyroid stimulating hormone levels at birth. Mean +/- 2 standard deviations for thyroid volume were 472 mm3 and 1430 mm3. The mean measurements for the sum of both lobes for transverse, anteroposterior, and longitudinal dimensions were 13.9 mm, 15.1 mm, and 34.6 mm, respectively. No significant correlation of these measurements was found for gestational age, birth weight, or thyroid-stimulating hormone levels. The correlation coefficient between these measurements and total volume was 0.64 or less. Term euthyroid neonates were found to have a thyroid gland volume ranging between 472 mm3 and 1430 mm3. In term neonates sonographic measurements of thyroid lobes should be obtained in all three planes for reliable assessment of thyroid volume.

Neurologic anomalies of Perrault syndrome.

We report on an 18-year-old man with neurosensory hearing loss and his sister with neurosensory hearing loss, ovarian dysgenesis, mental retardation, generalized ataxia of the trunk and limbs, and saccadic dysmetria. A CT scan showed cerebellar hypoplasia. The cardinal manifestations of Perrault syndrome in females are neurosensory hearing loss and ovarian dysgenesis. Other anomalies, including neurologic and skeletal, have been reported in other individuals with Perrault syndrome. We review the neurologic anomalies in previous patients with Perrault syndrome. Neurologic data are available on 14 of 21 girls; 7 of 14 had neurologic abnormalities. The high incidence of neurologic anomalies suggest that ataxia or mental retardation may not be just coincidental findings, but pleiotropic manifestations of Perrault syndrome.

The emergency management of hyperglycemic-hyperosmolar nonketotic coma in the pediatric patient.

We recommend consideration of HHNK in comatose pediatric patients and advocate the prompt institution of fluid therapy. Insulin is not required during the initial course of treatment and potentially can have adverse effects. Compared to adults, pediatric patients appear to be at a greater risk of developing potentially fatal cerebral during the course of treatment. In order to prevent complications associated with the rapid decrease in serum tonicity the initial management should consist of fluid therapy directed toward repleting the intravascular volume, correcting electrolyte abnormalities, and slowly returning serum tonicity to normal.

Testing for thyroid function recovery in children and adolescents with Hashimoto thyroiditis.

Thyroid function in children and adolescents with primary hypothyroidism owing to Hashimoto thyroiditis was studied to evaluate criteria for the discontinuation of thyroxine therapy. A cohort of 29 children and adolescents was prospectively studied for one year. A thyrotropin-releasing hormone stimulation test with measurements of basal and stimulated thyrotropin and thyroxine was performed at the beginning of the study and 6 and 12 months later. In 59 percent of patients, persistent biochemical evidence of hypothyroidism was observed. Interindividual variations and variations among measurements in individual patients were much greater than those reported for healthy individuals. In one patient, all measured values were consistently normal, and the therapy was successfully discontinued. No single measurement or test could predict the natural course of disease. In summary, children and adolescents with hypothyroidism owing to Hashimoto thyroiditis can not have discontinued replacement thyroxine therapy on the basis of any single evaluation of thyroid function, as proposed for adults. If the decision to discontinue the therapy in this age group is made on the basis of previous follow-up, a substantial possibility of relapse remains and continuous follow up is necessary.

Transient central hypothyroidism as a cause of failure to thrive in newborns and infants.

The course of two neonates and one 4-month-old infant with laboratory and clinical evidence of central hypothyroidism is described. All three presented with failure to thrive and improved after L-T4 therapy. Early recognition and treatment of newborns and infants with central hypothyroidism is important to maximize the potential for growth and development. Two of the three infants have been documented to have transient central hypothyroidism of hypothalamic origin, not previously reported.

Plasma endotoxin concentration after an intraperitoneal injection of endotoxin in fed and fasted suckling rats.

In the adult host response to endotoxin (lipopolysaccharide (LPS)) is dose-related. An intraperitoneal injection is commonly used for LPS administration in small animals. However, plasma endotoxin concentration following an intraperitoneal bolus injection of LPS is not well known. This study was performed to evaluate plasma endotoxin concentration following a bolus intraperitoneal injection of LPS in both fed and 24 h fasted 10 day old rats. Plasma endotoxin concentration increased in a dose-dependent manner after LPS injection (.03 or .1 mg/kg Salmonella enteritidis LPS) in both fed and fasted rats. Plasma endotoxin concentrations were higher (p < .05) in fed than fasted rats. A high dose of LPS (.1 mg/kg) induced 95 and 40% mortality in fed and fasted rats, respectively. A low dose of LPS (.03 mg/kg) induced 26.7% mortality in fed rats but no mortality in fasted rats. The hematocrit was significantly lower in fed than fasted rats. Plasma endotoxin inactivation was similar in fed and fasted rats. Host response appears to be related to plasma endotoxin concentration.

Glucose transporters (GLUT1, 2, & 4) in fat, muscle and liver in a rat model of endotoxic shock.

To explore the mechanisms for hypoglycemia in our rat model of septic shock, we examined whether changes occur in glucose transporter isoform protein level. Total membrane protein fractions were collected from tissues 6 to 8 hours after endotoxin injection at which time animals exhibited hypoglycemia (7.2 +/- 0.5 vs. 2.6 +/- 1.2mM) and lactacidemia (1.0 +/- 1.0 vs. 5.1 +/- 1.8mM/L) as compared to saline-treated controls. The protein level of glucose transporter isoforms GLUT1 and 4 in fat did not significantly change in septic shock when compared to control animals (126 +/- 22% and 114 +/- 79%, respectively). Likewise, no change was seen in GLUT1 or 4 in muscle (124 +/- 52% and 101 +/- 28%, respectively). The protein abundance of isoforms GLUT1 and 2 in liver were not significantly altered (123 +/- 35% and 101 +/- 23%, respectively). Septic shock induced hypoglycemia cannot be directly explained by changes in total glucose transporter protein levels.

Macrophage treatment in suckling rat endotoxic shock.

Gram-negative sepsis/septic shock in the human newborn continues to be a severe medical problem because of significant mortality and morbidity. Since macrophages detoxify endotoxin, a decreased number of macrophages may contribute to the newborn's sensitivity to endotoxin. In this study, peritoneal macrophages were used for the treatment of endotoxic shock in 10-day-old rats, and 24-hr mortality, plasma glucose, and lactate concentrations were monitored. Peritoneal macrophages were harvested from adult or 10-day-old rats. Caseinate-stimulated macrophages from adult and 10-day-old rats significantly decreased the mortality of 10-day-old rat endotoxic shock from 90% to 37.5% and 44.4%, respectively. Resident macrophages from adult and 10-day-old rats also decreased the mortality from 90% to 12.5% and 45.4%, respectively. Peritoneal macrophages from adult rats significantly ameliorated hypoglycemia during endotoxic shock in a dose-dependent manner. Macrophage treatment decreased plasma endotoxin concentration (P < 0.05). Macrophage treatment was important for host defense.

J5 prevents endotoxin shock in suckling rats.

A sublethal dose of endotoxin (lipopolysaccharide: LPS) can induce endotoxin tolerance. It is not well known whether LPS feeding causes endotoxemia and endotoxin tolerance in the newborn. Since Rc mutant Escherichia coli LPS (J5) does not have toxic or lethal effects, J5 is used to induce endotoxin tolerance in this study. This study showed that both an intraperitoneal (ip) injection and feeding of Rc mutant Escherichia coli LPS (J5) induced endotoxin tolerance in suckling rats.

Permanent diabetes without serological evidence of autoimmunity after transient neonatal diabetes.

OBJECTIVE: To describe a probable association between TNDM and subsequent permanent IDDM. RESEARCH DESIGN AND METHODS: A longitudinal follow-up of a single case from birth to 12 yr of age was conducted analyzing sequential OGTTs, ICAs, AIAs, anti-GAD antibodies, and other organ-specific and nonspecific antibodies. RESULTS: A small-for-gestational-age infant developed hyperglycemia at 20 h of age and required insulin therapy for the 1st 14 wk of life (TNDM). Transient hyperglycemia and ketonuria were noted again at age 2 yr 10 mo during an intercurrent illness, but OGTT was normal; and ICA, AIA, anti-GAD65 and anti-GAD67 antibodies, antithyroid microsomal, anti-gastric parietal cell, antiadrenal, antisteroidal, and antinuclear antibodies were negative 3 wk later. At age 9 yr, hyperglycemia returned and persisted in the setting of hypoinsulinemia; ICA, AIA, anti-GAD65 and anti-GAD67 antibodies, and other organ-specific and nonspecific antibodies were again negative. Insulin therapy was initiated and has been maintained over 3 yr of follow-up. CONCLUSIONS: Our case is the fifth reported with permanent diabetes occurring after resolution of TNDM. The etiology of permanent diabetes in this setting is unknown but, unlike classical IDDM, appears unrelated to autoimmunity in our patient. The true frequency of this association remains unknown.

Early endotoxin tolerance in suckling rats.

Early endotoxin tolerance has not been well investigated in the newborn. This study demonstrated that a sublethal dose of Salmonella enteritidis lipopolysaccharide (S. ent-LPS) or rough mutant Salmonella minnesota LPS (Re-LPS) induced early endotoxin tolerance in suckling rats, showing blunted hypoglycemia and decreased mortality. The mortality of endotoxic shock was lower in S. ent-LPS pretreated group than Re-LPS pretreated group. A sublethal dose of S. ent-LPS caused lactacidemia but Re-LPS did not. Therefore, early endotoxin tolerance appeared to be related to physiologic responses to the initial LPS exposure.

Altered glucose transporter mRNA abundance in a rat model of endotoxic shock.

To better understand molecular mechanisms of glucose transport in shock, we studied glucose transporter isoform mRNA abundance after injection of S. enteritidis endotoxin (40 mg/kg) or saline. Six to 8 hours after injection, endotoxin-treated animals compared to controls became hypoglycemic (44 +/- 6 vs. 111 +/- 4 mg/dl) and lactacidemic (5.9 +/- 0.5 vs. 1.3 +/- 0.1). At such times, tissue RNA was isolated and hybridized to Riboprobes for GLUT1 (erythrocyte), GLUT2 (liver), and GLUT4 (muscle/fat) glucose transporter isoforms and expressed as percent of control. GLUT1 mRNA abundance was increased in fat (660%, p less than .05), soleus muscle (314%, p less than .05), and liver (871%, p less than .001) of endotoxin-treated rats. Soleus muscle GLUT4 mRNA levels were increased (+33%, p less than .02), while liver GLUT2 mRNA levels were markedly decreased (-58%, p less than .01). The overall increase in GLUT1 mRNA abundance accompanied by lowered liver GLUT2 mRNA levels may either cause or reflect profoundly altered glucose transport.