Poly I:C induces development of diabetes mellitus in BB rat.

Polyinosinic polycytidilic acid (poly I:C), an inducer of alpha-interferon, accelerates the development of diabetes in diabetes-prone (DP) BioBreeding (BB) rats. This study investigates the effect of administering poly I:C to a diabetes-resistant (DR) strain of BB rats. We compared the incidence of diabetes, the degree of insulitis, the number of NK cells, helper-inducer cells, cytotoxic-suppressor cells, Ia+ T cells, RT6.1+ T cells, and NK cell bioactivity in DR rats treated with saline and with a 5 micrograms/g body wt (poly-5) dose and a 10 micrograms/g body wt (poly-10) dose of poly I:C. The incidence of diabetes was also compared with that of DP rats receiving poly-5. We found that both doses of poly I:C significantly induce the development of diabetes in the DR BB rat. However, treatment of DR rats with the higher dose induces a greater rate of development of diabetes and earlier onset of diabetes than the lower poly-5 dose. The rate of diabetes development and the mean age of onset were similar in poly-10-treated DR and poly-5-treated DP rats. A significant degree of insulitis occurred in all the poly I:C-treated DR rats, even those not developing diabetes. Peripheral blood NK cell number was greater in poly I:C than in saline-treated rats, after 2 wk of treatment and when killed. The percentage of OX19+ peripheral blood mononuclear cells expressing RT6.1 allotype or Ia antigen were similar in poly I:C- and saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Poly I:C induction of alpha-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships.

Although the administration of a fixed dose of the alpha-interferon (alpha-IFN) inducer, polyinosinic polycytidilic acid (poly I:C), accelerates the development of diabetes in DP-BB rats, no reports have characterized the dose-response relationship of poly I:C with serum alpha-IFN levels and the development of diabetes. This study examines the dose-response relationships of poly I:C with the induction of serum alpha-IFN and the development of diabetes in DP-BB and normal Wistar rats. Also tested in this study is the hypothesis that the lack of development of diabetes in poly I:C-treated normal Wistar rats is attributable to a deficient alpha-IFN response. Using poly I:C doses of 0.5, 1.5, 5, and 10 micrograms/g body weight, a direct dose-response relationship was observed in DP-BB rats with the serum alpha-IFN response. Moreover, all doses of poly I:C accelerated the onset of diabetes in BB rats. Serum alpha-IFN levels inversely correlated with time of onset of diabetes (P < 0.01). Also, BB rats with higher levels of serum alpha-IFN were associated with earlier onset of diabetes (P < 0.001). Poly I:C-induced serum alpha-IFN levels were significantly lower in diabetic than in nondiabetic BB rats. In normal Wistar rats, although all doses of poly I:C significantly increased serum alpha-IFN levels, diabetes was not induced. The results of this study indicate that poly I:C administration elevates serum alpha-IFN and accelerates the development of diabetes in BB rats at even very low doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of fructosamine test in diabetic children.

OBJECTIVE: The goal of this study was to assess the effect of glucose and the contribution of the aldimine component on the measurement of fructosamine, the relationship of serum fructosamine with glycosylated plasma proteins, as measured by a new high-performance liquid chromatography methodology (Glyc PP-HPLC) and by an affinity chromatography (Glyc PP), and the ability of serum fructosamine to assess acute, short-term (1-2 wk), and long-term (2-3 mo) glycemic control. RESEARCH DESIGN AND METHODS: The measurement of fructosamine was unaltered by the addition of up to 27.5 mM glucose or by the elimination of the aldimine component of serum specimens by dialysis. Fructosamine was generated in vitro by incubating serum aliquots. This generation was dependent on time, glucose concentration, and temperature. RESULTS: Fructosamine (n = 27) correlated well with Glyc PP (r = 0.76, P less than 0.01) and significantly less with Glyc PP-HPLC (r = 0.46, P less than 0.01). Although oral glucose ingestion increased serum glucose acutely by 200%, fructosamine was unchanged at each time interval. Improving glycemic control decreased the mean serum fructosamine concentration from 3.68 (baseline) to 3.28 mM (P less than 0.01) at 1 wk and to 3.13 mM (P less than 0.01) at 2 wk. HbA1c correlated with fructosamine (r = 0.59) and Glyc PP-HPLC (r = 0.47) but correlated best with Glyc PP (r = 0.83). CONCLUSIONS: These results indicate the fructosamine assay is unaltered by serum glucose, solely measures the ketoamine component, correlates well with glycosylated plasma proteins measured by aminophenylboronic acid column chromatography, is unaffected by acute changes of serum glucose, and may be used to monitor changes in glycemic control over a 1-wk interval.

Growth and normal puberty.

We reviewed the growth characteristics of American boys and girls from published studies, including age at takeoff, age at peak height velocity, peak height velocity, duration of puberty, and the magnitude of the pubertal contribution to adult height. Age at takeoff is highly variable and sex-dependent. The mean takeoff age in children growing at an average rate is approximately 11 years in boys and 9 years in girls, and peak height velocity occurs at a mean age of 13.5 years and 11.5 years, respectively, in these children. Whole-year peak height velocity is 9.5 cm/y in boys and 8.3 cm/y in girls, with slight variations in the different studies. The contribution of pubertal growth to final height is approximately 30 to 31 cm in boys, accounting for 17% to 18% of the final height, and 27.5 to 29 cm in girls, accounting for 17% of the final height. The magnitude of pubertal growth has a negative correlation with age at takeoff, but no correlation with final height. Age at takeoff, however, correlates highly with pubertal stage, but correlates negatively with duration of puberty.

Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia.

The nature of hypothyroxinemia in sick very low-birth-weight (VLBW) infants was evaluated by assessment of the hypothalamic-pituitary axis and by the clinical response to thyroxine (T4) therapy. Twenty-three very low-birth-weight infants of gestational age 26 to 28 weeks, whose serum T4 concentrations were 4 micrograms/dL on two occasions, and thyrotropin less than 20 microU/mL, were included in a double-blind study. Following a thyrotropin-releasing hormone stimulation test, babies were given either T4 or placebo. Nine babies were thyrotropin-releasing hormone tested prior to therapy; four babies, two from each group, were tested 1 to 2 weeks after therapy. In 11 untreated babies, mean base line serum thyrotropin of 7.0 +/- 1.4 rose to 23.7 +/- 4.1 microU/mL in 30 minutes. This response was not significantly greater than the observed response in full-term babies, 23.7 +/- 4.1 v 16.6 +/- 0.97 microU/mL, respectively, P greater than .05. In two babies treated with T4 the thyrotropin response to thyrotropin-releasing hormone was completely suppressed. Serial serum T4 determinations showed normalization in both groups after a similar time interval. There was no beneficial effect of T4 therapy on growth of head circumference, length, or weight. Developmental data revealed no significant differences in the mental, motor, or gross neurologic outcome in the treated and nontreated infants after 1 year of follow-up. These observations imply that hypothyroxinemia in sick preterm infants is not a direct consequence of hypothyroidism. Despite the lack of demonstrable short-term beneficial effects of T4 therapy, follow-up studies are necessary to resolve the question of long-term benefits.

Thyroglossal duct cyst: an infrequently considered diagnosis in pediatric patients with anterior neck masses.

OBJECTIVE: To describe a pediatric patient with an anterior neck mass and discuss the evaluation and treatment. METHODS: We present a case report and a discussion of the differential diagnosis of anterior cervical masses. The workup and therapy for an anterior neck mass, which was a thyroglossal duct cyst, are reviewed. RESULTS: A thyroglossal duct cyst in pediatric patients is an uncommon finding. For establishing a correct diagnosis, surgical confirmation is necessary. Identification is important because of the high incidence of misdiagnosis, recurrent infections, inadequate treatment, and possible neoplastic change. CONCLUSION: A thyroglossal duct cyst should be included in the differential diagnosis of an anterior neck mass. Recommended treatment consists of surgical removal of the cyst, the entire thyroglossal duct tract, and the central portion of the hyoid bone.

Clinical recognition of juvenile hypothyroidism in the early stage.

The clinical manifestations of biochemically-confirmed acquired hypothyroidism in nineteen children and adolescents were reviewed to evaluate the symptoms and signs in the early stage of the disease. The group consisted of 14 girls and 5 boys ranging in age from 4 to 15 years. In 13 of the 19 patients with profound biochemical hypothyroidism, classical symptoms were often absent and clinical signs limited. In these patients, hypothyroidism was presumed to have been short in duration and consequence of chronic lymphocytic thyroiditis. In the remaining 6 patients, hypothyroidism was long-standing and clinical presentation classical, including disproportionate weight gain, fatigue, cold intolerance, myxedematous feature, growth retardation and constipation. Goiter was the most consistent finding in both groups and was present in all instances of spontaneously acquired primary hypothyroidism. These observations emphasize the importance of routine examination of the thyroid gland, particularly in preadolescent and adolescent girls. The finding of goiter may be the only detectable sign of hypothyroidism in the early stage of the disease. Biochemical evaluation should not be deferred because of a clinically euthyroid presentation. Replacement therapy must be instituted when findings indicate a hypothyroid state. Failure to recognize and treat hypothyroidism in these pubertal patients may compromise the adult height, since skeletal maturation will proceed under the influence of sex hormones despite the presence of hypothyroidism.

Benign elevation of serum alkaline phosphatase, transient and persistent variety.

Markedly increased serum concentration of alkaline phosphatase (AP) was discovered in seven children. Investigation showed the finding to be benign in each case. Family survey and follow-up studies revealed a familial pattern in four children and a transient, idiopathic origin in the other three. Awareness of these benign forms of hyperphosphatasemia will aid the physician in the interpretation of elevated AP.

Evaluation of sodium L-thyroxine (T4) requirement in replacement therapy of hypothyroidism.

Sodium-L-thyroxine (T4) was utilized in the treatment of 15 pediatric patients with hypothyroidism. Adequacy of replacement therapy was confirmed by clinical evaluation in conjunction with determination of serum thyroxine, tri-odothyronine, and thyrotropin concentrations. Daily dose of thyroxine capable of including clinical and biochemical euthyroidism ranged from 2.5 to 5 mug/kg of body weight with a mean of 3.5 +/- 0.3 mug in the 4- to 17-year-old age group. Two infants with congenital hypothyroidism diagnosese observations imply that physiologic requirements of thyroxine are distinctly lower than previously recommended dosages. Further studies to establish more precise therapeutic guidelines are needed.

Postnatal triiodothyronine concentrations in healthy preterm infants and in infants with respiratory distress syndrome.

Postnatal changes in triiodotyronine (T3) concentration were investigated in 12 preterm infants of 26-34 weeks of gestational age. Blood for measurement of T3 was obtained from the cord at delivery and from infants at 1 day of age and at weekly intervals for 4 weeks. Seven of the babies suffered from respiratory distress syndrome (RDS) and five were considred healthy. Gestational ages and body weight were comparable in both groups. In preterm infants with RDS, cord blood T3 concentration was significantly lower than that in cord blood of babies without RDS (22 +/- 2.6 versus 36 +/- 5 ng/dl, P less than 0.05). There was no significant rise in T3 concentration of RDS babies at 24 hr of age (22 +/- 2.6 versus 34.0 +/- 8 ng/dl, P greater than 0.05), and hypotriiodothyroninemia persisted for 3 weeks. At 4 weeks of age, T3 concentration in babies with RDS, although within the normal range (80-190 ng/dl), was significantly lower than that in the healthy preterm infants (110 +/- 10 versus 165 +/- 11 ng/dl, P less than 0.05). Postnatal T3 changes in healthy preterm infants wre characterized by the absence of the initial hypertriiodothyroninemia and by a gradual rise within the first month of life. The noted difference in the pattern of postnatal T3 changes in healthy preterm infants compared to full term infants may reflect thyroid immaturity. The machanism and the significance of the neonatal hypotriiodothyroninemia in RDS and its long term effects on the development of these babies remain to be investigated.

Triiodothyronine (T3) concentration and therapy in autistic children.

The clinical and biochemical status of thyroid function of patients with an autistic syndrome was investigated. The study consisted of 13 patients between the ages of 7 and 21 years. There was no clinical evidence for hypothyroidism in any patient, and T3, T4, and TSH concentrations were within the normal range. Two patients who had retarded bone ages were treated with triiodothyronine for 6 months. Hyperthyroidism developed when T3 levels exceeded physiologic concentrations in these patients. The concept that the clinical response to triiodothyronine in autistic patients results from correction of thyroid dysfunction is not supported by these findings.

Humoral and cell-mediated immunity in growth hormone-deficient children: effect of therapy with human growth hormone.

To delineate the role of growth hormone (GH) in the development and function of the immune system, immunological parameters including quantitative immunoglobulins, T and B lymphocytes, phytohemagglutinin lymphoproliferative response and delayed hypersensitivity skin tests were studied in nine GH-deficient children prior to GH therapy and at 2 months and 9 to 12 months following therapy. The phytohemagglutinin response (74.1 +/- 37.6, mean +/- SD), and the T rosette (58.3% +/- 9.4), B rosette (21.1% +/- 6.1), IgG (810 +/- 241 mg/dl), (IgA 140 +/- 85), and IgM (176 +/- 70) levels in GH-deficient children were comparable to age adjusted values in normal children. Following GH therapy the phytohemagglutinin response increased significantly at 9 to 12 months post-therapy, 123.2 +/- 51.9 versus 74.1 +/- 37.6, p less than 0.05. T and B rosettes, immunoglobulin concentrations, and hypersensitivity skin tests were not affected by GH therapy. Although an effect of GH was not demonstrable by these studies, a positive role of GH cannot be entirely excluded since total GH deficiency did not exist in all children.

Female pseudohermaphroditism in a neonate born to a mother with polycystic ovarian disease.

A newborn with female pseudohermaphroditism (profound masculinization of the external genitalia and preservation of the internal female genitalia) is presented. During pregnancy progressive hirsutism was noted in the mother, and polycystic ovaries were found at cesarean section. The serum testosterone level in the cord blood was elevated markedly (1,232 ng./dl). After birth the serum testosterone levels of the mother and newborn decreased dramatically. Over-all it appears that the polycystic ovaries were the source of the excessive androgen secretion that caused maternal and fetal masculinization during the pregnancy.

Prenatal thyroid function abnormalities in infants with idiopathic respiratory distress syndrome.

Thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were measured on cord sera of 21 preterm infants with idiopathic respiratory distress syndrome (IRDS) and were compared to the values obtained from 15 healthy preterm infants. When log T3, log T4, and log TSH were considered as the dependent variables in the multivariate test Hotelling-Lawley-Trace, there was an overall difference between the two groups: F = 3.94, p = 0.03. When log T3 and log T4 were considered separately in an analysis of covariance, there was a significant difference between the two groups for log T3 after adjusting for birth weight and gestational age (F = 7.98, p = 0.008). However, for log T4 and TSH, there was no difference between the IRDS and control infants. These findings exclude the possibility of antenatal thyroid dysfunction in babies with IRDS. An explanation for reduced cord blood T3 concentration in infants with IRDS is lacking at present. Extrathyroidal factors that predispose to IRDS may also affect peripheral T3 generation. Alternatively, one might postulate that there is relative immaturity of both peripheral T3 generating pathway and lung development in infants who develop IRDS.