David T. Wyatt

Hypoglycemia in Children Taking Propranolol for the Treatment of Infantile Hemangioma

BACKGROUND Propranolol hydrochloride has been prescribed for decades in the pediatric population for a variety of disorders, but its effectiveness in the treatment of infantile hemangiomas (IHs) was only recently discovered. Since then, the use of propranolol for IHs has exploded because it is viewed as a safer alternative to traditional therapy. OBSERVATIONS We report the cases of 3 patients who developed symptomatic hypoglycemia during treatment with propranolol for their IHs and review the literature to identify other reports of propranolol-associated hypoglycemia in children to highlight this rare adverse effect. CONCLUSIONS Although propranolol has a long history of safe and effective use in infants and children, understanding and recognition of deleterious adverse effects is critical for physicians and caregivers. This is especially important when new medical indications evolve as physicians who may not be as familiar with propranolol and its adverse effects begin to recommend it as therapy.

The prevalence and clinical characteristics of celiac disease in juvenile diabetes in Wisconsin.

Background The relationship between celiac disease and juvenile diabetes has long been known. Only a single study in the United States, from Buffalo, New York, has reported the prevalence of celiac disease in a pediatric diabetic population. This study was conducted to determine the prevalence and clinical presentation of celiac disease in children and adolescents with juvenile diabetes in Wisconsin, U.S.A., using serum antiendomysial antibody as a screening test. Methods Two hundred eighteen patients with diabetes (113 males; age range, 4–21 years) and 117 age-and gender-matched control participants were tested for immunoglobulin A endomysial antibody. Patients with positive results were offered a small bowel biopsy. A questionnaire regarding abdominal pain, diarrhea, and growth failure was completed by the parents. Results Seventeen of 218 diabetic patients (7.7%) had positive endomysial antibody. All control participants had negative results for the endomysial antibody. Small bowel biopsy was performed in 14 patients. Ten patients had villous atrophy. In one patient without villous atrophy, a repeat biopsy 2 years later showed villous atrophy, and two patients had increased intraepithelial lymphocytes without villous atrophy. Seventy percent of the patients with celiac disease were asymptomatic. The reported symptoms were abdominal pain and diarrhea (n = 1) and growth failure (n = 2). Two patients with celiac disease had Down syndrome. Conclusions The prevalence of celiac disease in children with juvenile diabetes in Wisconsin is at least 4.6%, which is comparable with European and Canadian studies. Because patients without villous atrophy may have latent celiac disease, the prevalence may be even higher. All children with juvenile diabetes should be screened for celiac disease.

Screening girls with turner syndrome: the national cooperative growth study experience

The National Cooperative Growth Study (NCGS) database was examined to determine whether the availability of expert guidelines affected the clinical management of 955 patients with Turner syndrome (TS). Although cardiac and renal evaluations increased in frequency after guideline publication, hearing screenings declined. Although girls with TS show significant cardiac, renal, and hearing problems, screening for these disorders remains inadequate.

Lack of effect of growth hormone therapy on the count and density of melanocytic naevi in children

An observation of accelerated growth of acquired melanocytic naevi (AMN) during treatment with human growth hormone (GH) raised concerns about the potential risk of melanoma in treated patients. An increased number of AMN, rather than growth rate, is associated with a higher risk for melanoma. It is unknown whether treatment with GH causes an increase in numbers of AMN. We evaluated the effect of GH treatment on the number of AMN in a cross‐sectional study of 90 children with GH deficiency. AMN counts and densities in these children were compared with those found in a control group of 100 children. Factors potentially related to increased numbers of AMN, such as age, sex, skin colour, number of episodes of sunburn and duration of GH therapy were determined. Among the various factors, only the age and colour of unexposed skin area were predictive for the total number and density of AMN. No correlation was found between the AMN counts or density and the duration of GH therapy. There was no difference in the AMN counts or density between the GH‐deficient patient group and the control groups. We conclude that GH therapy in children is not associated with increased AMN count and density and is unlikely to potentiate the risk for melanoma in these children.

Thiamine status in Urban adolescents: Effects of race

To evaluate thiamine status in an urban adolescent population, we performed two investigations. In Study I, we compared whole blood thiamine levels in 101 healthy adolescents from varied racial backgrounds with those that had been obtained previously in 146 healthy white adults from a different geographic locale. Blood thiamine values were significantly lower in the adolescents as a group, but the differences were entirely due to the lower levels in the black adolescents. To explore further these differences (Study II), we compared thiamine status in 34 adolescents with that of their parents using measures of both whole blood thiamine content and of erythrocyte transketolase activity. White adolescents had significantly higher total whole blood thiamine values than black adolescents, and white parents had significantly higher thiamine values than black parents by both total whole blood assay and level of transketolase activity. There were no differences in thiamine status between adolescents and parents of the same race. Racial composition is an important variable to consider in population surveys of thiamine status.

Cyanogen bromide-based assay of thiamin.

Publisher Summary This chapter describes the thiochrome method used to develop a low-cost thiamin assay sufficiently sensitive for pediatric application in both whole blood and cerebral spinal fluid, and the normative ranges for those biological fluids. It presents reagents used and procedure employed for sample preparation. For whole blood, the within-run coefficients of variations (CVs) are 3.6% (total) and 4.6% (nonphosphorylated). The long-term between-run CVs (control blood over 40 weekly assays) are 6.0% (total) and 15.5% (nonphosphorylated). The total and nonphosphorylated thiamin values are moderately higher in blood samples from heparinized vs EDTA tubes. There is a strong negative correlation for both total and phosphorylated thiamin with age. The greatest decline occurs in the first three months of age, with a smaller additional decrease from 3–12 months. Thereafter, thiamin levels are comparable to adults. The decline occurs relatively independently of the changes in hematocrit characteristically seen in infancy. There are no differences by sex at any age or by race if less than 10 years of age.

Human Growth Hormone (hGH) May Influence Chromosome Aberrations and Fragility 487

The influence of hGH treatment on spontaneous chromosome aberrations and chromosome fragility was tested in 23 naive patients aged 4 to 16 years. The breaking action of ionizing radiation was used as an indicator of chromosome fragility. 17 patients had growth hormone deficiency, 1 Turner syndrome, and 5 neurosecretory growth hormone dysfunction. Blood samples were taken at baseline and following 6 months of hGH treatment (0.3 mg/Kg/week). Lymphocyte cultures and cytogenetic preparations were established using standard cytogenetic techniques. Half of the cultures were irradiated with 3 Gy of gamma rays. All mitotic preparations were coded to ensure “blind” enumeration of aberrations. A one-way ANOVA was performed on log transformed data for analysis of aberrations per cell. There were no significant differences between pre-treatment (9,500 cells) and post-treatment (8,000 cells) cells for spontaneous chromosome-type aberrations (mean ± SEM) 4.2 × 10-3 ± 1.2 × 10-3 vs 7.9 × 10-3 ± 2.9 × 10-3 (p=0.08); for chromatid-type aberrations 9.2 × 10-3 ± 2.8 × 10-3 vs 1.1× 10-2 ± 4.0 × 10-3 (p=0.42); and for total aberrations (chromosome + chromatid) 1.3 × 10-2 ± 3.0× 10-3 vs 1.9 × 10-2 ± 7.0 × 10-3 (p=0.10). There were also no significant differences for radiation-induced aberrations (4,550 pretreatment cells and 4,850 post-treatment cells) for chromosome aberrations 1.12 ± 3.0 × 10-2 vs 1.05 ± 5.0 × 10-2 (p=0.18); for chromatid aberrations 2.6 × 10-2 ± 5.0 × 10-3 vs 2.0× 10-2 ± 3.0 × 10-3 (p=0.60); and for total aberrations 1.15 ± 3.0 × 10-2 vs 1.07 ± 5.0 × 10-2 (p=0.17). However, when the data were analyzed on a per chromosome basis (i.e. number of aberrant chromosomes ÷ total number of chromosomes scored) with binomial probability being applied to the raw data, small but significant differences were seen. Total spontaneous aberrations per cell (mean with 95% confidence limits) were: pre-treatment 2.65 × 10-4 (2.18 × 10-4 to 3.13 × 10-4) vs post-treatment 3.42 × 10-4 (2.83 × 10-4 to 4.02× 10-4) p<0.05), and for total radiation-induced aberrations 2.51 × 10-2 (2.44 × 10-2 to 2.57 × 10-2) vs 2.40 × 10-2 (2.34 × 10-2 to 2.47× 10-2) (p<0.05). This analysis suggests that 6 months of hGH treatment may lead to a significant increase in spontaneous chromosome aberrations and significant decrease in chromosome fragility. The disparity between the chromosome aberration and fragility data is unexplained and requires further investigation.

Delayed Involution of the Fetal Adrenal Cortex in Two Infants Simulating Non-Salt-Losing Congenital Adrenal Hyperplasia Due to a Deficiency of 3ß-Hydroxysteroid Dehydrogenase

We report two infants who had elevated blood levels of the Δ adrenal steroids 17-hydroxypregnenolone and DHEA suggestive of congenital adrenal hyperplasia due to non-salt-losing 3/3-hydroxysteroid dehydrogenase deficiency. One of the infants was a male with perineal hypospadias and the other a female with an increased level of 17-hydroxyprogesterone on a neonatal screen for congenital adrenal hyperplasia. Retesting some months later demonstrated a normal response of precursor adrenal steroids to ACTH stimulation. We suggest that delayed involution of the fetal adrenal cortex was the cause of the abnormal test results in these two patients.