Robert M. Ehrlich

The effect of hypoglycemic seizures on cognitive function in children with diabetes : A 7-year prospective study

Sixteen children with insulin-dependent diabetes mellitus were evaluated at diagnosis and after 1, 3, and 7 years. They showed significant declines in verbal but not visuospatial abilities, particularly if they had any seizures from hypoglycemia. At the 7-year assessment those with hypoglycemic seizures showed deficits on perceptual, motor, memory, and attention tasks.

Intellectual outcome in children with fetal hypothyroidism

Eighty children with congenital hypothyroidism detected by newborn screening were grouped for presence of fetal hypothyroidism using skeletal maturity at the time of diagnosis as the index. Forty-five children with bone age less than 36 weeks were assigned to the delayed group; 35 with bone age 37 weeks to term were assigned to the nondelayed group. Although most children with athyrosis were found in the delayed group, the groups did not differ in birth weight, hormone levels, or family background. Assessments of intellectual and behavioral characteristics at 1, 2, 3, 4, and 5 years of age revealed that, although children in the delayed group performed within the normal range, their scores were significantly lower than those of the nondelayed group from age 2 years on. Perceptual-motor, visuospatial, and language areas were most affected. There were no differences in behavior or temperamental characteristics.

Intellectual Deficits Associated With Early Onset of Insulin-Dependent Diabetes Mellitus in Children

Twenty-seven children with early-onset (< 4 yr) diabetes (EOD), 24 children with late-onset (> 4 yr) diabetes (LOD), and 30 sibling controls were compared in their performance on tests of intellectual functioning and school achievement. The results indicated that children with EOD, particularly girls, scored lower than the other groups of diabetic children and siblings on tests of visuospatial (P < .05) but not verbal ability. Many of the girls with EOD were also having difficulty at school, and several were receiving special education. Children with EOD had more hypoglycemic convulsions than those with LOD. Both convulsions and age of onset were associated with poorer performance on spatial tasks. Girls with EOD had lower spatial test scores regardless of convulsion history, whereas boys with EOD scored lower only if they had had a convulsion.

Long-term effects of L-thyroxine therapy for congenital hypothyroidism

OBJECTIVE To study the effects of initial and concurrent dose levels of L-thyroxine on ability and behavior in children with congenital hypothyroidism. METHODS An existing database, involving a large cohort of children with congenital hypothyroidism detected by neonatal screening, was analyzed retrospectively. There were 94 children: 89 were assessed at age 7 years for intelligence and selective cognitive abilities, and 87 at age 8 years for behavior, achievement, and selective abilities. RESULTS Subjects were stratified by median split into low and high starting dose groups. The high-dose group performed better on indexes of intelligence, verbal ability, and memory but had more behavior problems reflecting increased anxiety, social withdrawal, and poorer concentration. The dose of L-thyroxine at age 8 years was negatively correlated with memory task performance. CONCLUSION A higher starting dose of L-thyroxine is beneficial for subsequent intellectual outcome in children with congenital hypothyroidism but may be associated with internalizing behavior problems.

Psychoeducational outcome in children with early-treated congenital hypothyroidism

Objectives. To describe the psychoeducational characteristics of children with congenital hypothyroidism (CH) identified through newborn screening and to study changes over time. Method. Examined were 83 children with early-treated CH, who were long-time participants in a prospective study of outcome after newborn screening, and 120 control children who were classmates (n = 80) or siblings (n = 42). Children were tested during the third (53 children with CH and 46 control children) or the sixth (51 children with CH and 76 control children) grades at school with 21 children with CH being seen in both grades. Test instruments included multiple measures of achievement and cognitive abilities as well as behavior rating scales completed by parents and teachers. Results. CH was associated with a slightly increased risk of learning disabilities in grade 3 but not grade 6. Third grade CH children scored lower than control children on tests of reading comprehension and arithmetic but did not differ on word recognition, writing, or spelling. Sixth grade CH children performed similar to controls on basic achievement tests but were reported to be doing poorer in several subject areas. For children with CH in grade 3, delayed skeletal maturity at diagnosis was associated with poorer word recognition ability and a longer period for normalizing thyroid hormone in infancy was correlated with weaker skill in learning sound–symbol correspondences. Conclusion. Early-treated CH is associated with mild delays in several basic achievement areas (reading comprehension and arithmetic) at the third grade level, with catch up by the sixth grade. However, as other findings indicate cognitive problems do persist into adolescence in memory, attention, and visuospatial processing areas, the implications of these deficits for other educational accomplishments needs additional follow-up. congenital hypothyroidism, thyroid hormone, newborn screening, achievement, behavior, attention.

Factors affecting and patterns of residual insulin secretion during the first year of type 1 (insulin-dependent) diabetes mellitus in children.

SummaryWe measured serum C-peptide, glucose, pH, islet antibodies and insulin antibody binding at diagnosis in 84 children with Type 1 (insulin-dependent) diabetes. In a subgroup of 33 children, residual insulin secretion (basal and peak C-peptide response to Sustacal), insulin antibody binding and HbA1c were measured at 10 days, 1, 3, 6 and 12 months. At presentation C-peptide correlated positively with age at onset and negatively with the blood glucose concentration. Median C-peptide concentration at diagnosis was low, rose significantly (p<0.05) at 10 days, reached a maximum at 1–3 months and declined gradually to 1 year. C-peptide concentration both at diagnosis and at 10 days correlated with that at 3 and 6 months. Of the factors investigated, only age (p<0.005) and sex (higher in females, p<0.01) were found to have a significant influence on basal/peak C-peptide levels throughout the first year. In particular there was no relationship between C-peptide, HbA1c and insulin dose during this period. A peak C-peptide response at 3–6 months>/<0.32 nmol/l was used to divide the group into two: 16 had a peak response <0.32 nmol/l (low secretors) while in 17, the peak C-peptide was >0.32 nmol/l (high secretors). While the low secretors had significantly (p<0.05) lower C-peptide levels during the first year, there were no differences between low and high secretors in HbA1c or insulin dose. These data suggest that there are two patterns of residual insulin secretion during the first 12 months after diagnosis of Type 1 diabetes. One pattern shows good amplitude and duration of residual insulin secretion, while both these features are significantly (p<0.05) reduced in the other. The C-peptide concentration both at diagnosis and at 10 days, as well as age at onset and sex are important predictors of the pattern to be followed. Our data suggest further that the magnitude of residual insulin secretion does not play a decisive role in metabolic control during this period.

Long-term sequelae of hearing impairment in congenital hypothyroidism☆☆☆★★★

Hearing loss and its functional consequences were evaluated retrospectively in children with congenital hypothyroidism. From a cohort of 101 children followed longitudinally to evaluate newborn screening, 75 with previous hearing tests were studied. Fifteen (20%) were found to have hearing problems. Of these, nine had unilateral or sensorineural loss mostly at high frequencies, five had a conductive loss, and one had both problems. Hearing impaired children differed from children with normal hearing in age of treatment onset (22 vs 14 days) but not disease severity or duration. A comparison of language and auditory processing skills at ages 3, 5, and 7 years revealed that early speech was delayed in hearing impaired children, whereas deficits persisted in later receptive language and auditory discrimination skills. Comparing hearing impaired children and children with normal hearing with matched control subjects at grade 3 showed that hearing impaired children were poorer readers because of less adequate phonologic processing skills.

Severe hypoglycemia in children with insulin-dependent diabetes mellitus: Frequency and predisposing factors

We surveyed 311 children with insulin-dependent diabetes mellitus to evaluate the frequency and characteristics of those children experiencing severe hypoglycemia (defined by an episode of coma, convulsion, or both). The children and their parents completed a questionnaire, and we reviewed the hospital records to confirm reported episodes. Ninety-seven (31%) reported severe hypoglycemia, and a further 50 (16%) reported moderate hypoglycemia requiring the assistance of another person but not resulting in coma or convulsion. In 164 children (53%) there was no history of either moderate or severe hypoglycemia. Sixty-nine (22%) reported the occurrence of more than one severe hypoglycemic episode (range 2 to 20); 52 (16%) reported such an event in a single year. A total of 285 episodes were reported, 39% during sleep and 61% while awake. Children reporting such events tended to have diabetes of longer duration and be younger at the time of the first episode. Hemoglobin A1c concentration at the time closest to the severe episode was significantly lower than in children reporting no hypoglycemia. All families had been taught to use glucagon to reverse severe hypoglycemia at home, but it was available in only 80 of the 97 homes and used in only 30. These data suggest that severe hypoglycemia is common in children with insulin-dependent diabetes mellitus who are treated conventionally. Greater vigilance and education are required both to prevent and to treat severe hypoglycemia in children with insulin-dependent diabetes mellitus.

The Endocrine Outcome after Surgical Removal of Craniopharyngiomas

The postoperative course of children undergoing surgery for craniopharyngioma was reviewed. Typically they were below height at presentation. All had an attempt at radical surgical resection of the tumor. Most developed diabetes insipidus in the postoperative period, which was permanent in all but 1 child. 94% required thyroid replacement therapy, and sex steroids were administered in 100% when they reached the age of puberty. 91% required maintenance corticosteroids. 54% required growth hormone replacement, but some children showed continued growth despite apparent growth hormone deficiency. Postoperative obesity develops in one half of patients, and may be improved with administration of growth hormone; a controlled trial is underway.

Growth in children with congenital hypothyroidism detected by neonatal screening

A prospective analysis of physical growth in 56 children with congenital hypothyroidism compared the childrens height, weight, and head circumference with population percentiles. Two measures of skeletal maturation and predictions of adult height were also compared with population standards. The mean percentiles for the childrens height and head circumference were higher than population means. Although mean bone age scores were slightly higher, predictions of adult height did not differ significantly from midparental height (arithmetic mean of sum of parental heights) and population means. The duration of intrauterine hypothyroidism as measured by gestational bone age and the duration of postnatal hypothyroidism were inversely correlated with heights attained up to 9 years. This association suggests a possible long-term influence of early hypothyroidism on growth. In children with congenital hypothyroidism, maintenance of serum thyroxine levels in the upper half of the normal range results in normal growth patterns.