Sitting height and subischial leg length centile curves for boys and girls from Southeast England.

PRIMARY OBJECTIVES: The only reference centile curves currently available for body proportions of children in the UK were constructed more than 20 years ago by Tanner and Whitehouse. The current study was designed to produce up-to-date sitting height and subischial leg length centile curves for boys and girls in Southeast England. RESEARCH DESIGN AND METHODS: A convenience sample of 1424 boys and 1208 girls aged under 25 years from Southeast England was measured by a single observer in 1995-1996. Using Cole's LMS method, centile curves were constructed for sitting height and subischial leg length, and the medians by age and sex were then scaled to sum to the corresponding median height of the British 1990 reference. RESULTS: The new centile curves for boys and girls are presented. They differ significantly from those of Tanner and Whitehouse in leg length (boys p < 0.001; girls p < 0.01), but not in sitting height. CONCLUSIONS: The Tanner and Whitehouse reference curves for body segment length are not suitable for contemporary British children, whose legs are longer than they were a generation ago. It is proposed that the curves presented here be adopted provisionally as the new British reference.

Growth reference charts for use in the United Kingdom.

Since the introduction of new growth charts in the mid 1990s, there has been confusion about which charts should be used, with many districts using more than one version. Because of this uncertainty, an expert working party, the Growth Reference Review Group, was convened by the Royal College of Paediatrics and Child Health to provide guidance on the validity and comparability of the different charts currently in use. This paper describes the technical background to the construction and evaluation of growth charts and outlines the group's findings on the validity of each growth reference in relation to contemporary British children. The group concluded that for most clinical purposes the UK90 reference is superior and for many measures is the only usable reference that can be recommended, while the original Tanner-Whitehouse and the Gairdner-Pearson charts are no longer reliable for use at any age. After the age of 2 the revised Buckler-Tanner references are still suitable for assessing height. There are presently no reliable head circumference reference charts for use beyond infancy. The group propose that apart from refinements of chart design and layout, the new UK90 reference should now be "frozen", with any future revisions only undertaken after careful planning and widespread consultation.

United Kingdom community growth screening 1994: a survey of current practice. "Screening for Growth Towards 2000" Scientific Organising Committee.

OBJECTIVE: To determine current policies, resources, and attitudes to community growth screening in the United Kingdom. METHODS: A postal survey of community paediatricians and paediatric endocrinologists. RESULTS: 164 replies were received-most from senior clinical medical officers or community paediatricians-covering between 68 and 78% of the United Kingdom population. One hundred and thirty three (81%) trusts or districts had a written growth policy. Preschool and school age height screening took place in 75% and 81% of districts respectively, but most children were only measured once before school or at school. Policies for the age at which measurements were made and their frequency varied enormously. Seventy three per cent used standard equipment, the most popular being the Minimetre. A wide variety of charts were used, of which 23% were decimal age charts. A large number of referral criteria were used, including height, height velocity, and weight. Most children were referred to hospital outpatient clinics rather than specialist growth clinics. CONCLUSIONS: Over 90% of respondents felt that growth screening was either extremely valuable or useful depending on resources. The survey showed a widespread lack of standardisation of equipment, charts, and policies. Referral criteria and objectives need to be clarified by research and audit, and growth monitoring integrated into a systematic programme of child health surveillance.

Referral criteria for growth screening.

Population height screening studies performed over the past 20 years have shown that between 17 and 21% of children with heights below the third centile have organic disease, of whom about 20% will be new diagnoses. The likelihood of organic disease increases to 50% for children with heights below -3 SDs. The age of screening will also influence the outcome as both acquired disease and disorders with progressive growth slowing, such as Turner's syndrome, are more likely to be detected by screening at an older age. Height velocity as a screening tool has evoked interest for many years as, despite technical problems, slowly growing children are thought more likely to have disease. Inclusion of height or height/weight relations may further improve screening sensitivity. It may assist in the early detection of coeliac disease or eating disorders in older children. A minimum of three measurements is required to define an individual's growth pattern and, preferably, five or six measurements spread over the preschool and primary school years. The value of extension of growth screening to the secondary school age group remains uncertain. Children should be screened for both height and weight and referred when there are major discrepancies between these two measurements (more than three centile bands). A two level system of referral with a community assessment for some children and a direct referral to a growth clinic for children with more severe growth disturbance may be the best use of resources.

Congenital hypothyroidism: physiological and psychological factors in early development.

Children diagnosed as congenitally hypothyroid and treated from a very early age were followed up at 1 and 3 years. At 1 year they seemed to be developing normally, unless they were undertreated or had an additional disorder. There were no significant correlations between biochemical or social factors and psychological outcome at 1 year. At 3 years, however, those children whose T4 and/or T3 had been very low initially had significantly lower IQ scores than both other hypothyroid children and matched controls. Children with only moderately low initial T4 and/or T3, however, were doing just as well as their matched controls. Initial levels of TSH, the number of symptoms at first clinical interview and the age at the start of treatment were not good indicators of ability at 3 years. Undertreatment was rare but did appear to affect ability. Psychological outcome at 3 years was also correlated with social class (for both cases and controls). Multiple regression analyses indicated that both low initial T4 (less than 20 nmol/l) and social class contributed significantly to outcome.

Ectopic thyroid: residual function after withdrawal of treatment in infancy and later childhood.

Plasma thyroxine (T4) and thyrotrophin (TSH) were estimated in 34 children identified by neonatal hypothyroid screening and subsequently found to have ectopic thyroid tissue on isotope scan. Before treatment plasma T4 ranged from 8-143 nmol/l and TSH from 39-1,230 mU/l. After one week off treatment during their second year, repeat T4 in 26 of these cases showed a significant correlation with the pre-treatment values (r = 0.57). However, only 3 of the 5 children with pre-treatment T4 levels over 100 nmol/l at diagnosis had normal T4 values when retested. Similarly, when 10 children with pre-treatment T4 values over 65 nmol/l were retested off treatment at the ages of 5.8-8.2 years, only 4 had plasma T4 levels in the normal range. These results illustrate the wide range of thyroid function which can occur in children with ectopic thyroid tissue and indicate that some continue to have near-normal thyroid function for considerable periods. However, pre-treatment T4 results do not allow accurate identification of these latter cases.

Evaluation of hypothalamic dysfunction in growth hormone (GH)-deficient patients using single versus multiple doses of GH-releasing hormone (GHRH-44) and evidence for diurnal variation in somatotroph responsiveness to GHRH in GH-deficient patients.

To examine the efficacy of multiple doses of GHRH-44 to enhance GH secretion and to determine the number of GHRH-44 doses required to exclude hypothalamic dysfunction, 12 doses of GHRH-44 were administered iv every 2 h to 4 GH-deficient patients beginning in the morning (group A) and to 4 GH-deficient patients beginning in the evening (group B). Five additional GH-deficient patients (group C) were given 4-18 GHRH-44 doses. The first and last doses were 5 micrograms/kg; all others were 1 microgram/kg. Higher GH responses were attained by 9 of the 13 patients after multiple GHRH-44 doses than after the initial GHRH-44 dose. After the first GHRH-44 dose, the peak plasma GH concentrations were less than 7 micrograms/L in 9 patients; 4 of 9 achieved GH concentrations above 7 micrograms/L after 5-7 GHRH-44 doses; 2 had measurable levels below 7 micrograms/L. GH concentrations remained undetectable in 3 older patients in group C. In the patients who had detectable GH levels after GHRH-44 treatment, serum somatomedin-C concentrations increased from 0.67 +/- 0.14 (+/- SEM) to 0.79 +/- 0.14 U/mL after 6 GHRH-44 doses (P less than 0.01; n = 10) then to 1.00 +/- 0.14 (+/- SEM) U/mL after an additional 4-6 GHRH-44 doses (P less than 0.05; n = 9). After 6 GHRH-44 doses in groups A and B, the integrated GH concentrations between 2000 and 0800 h were greater than the integrated GH concentrations between 0800 and 2000 h (P less than 0.02). These findings indicate that a hypothalamic defect cannot be excluded on the basis of an impaired response to a single dose of GHRH-44, that the number of GHRH doses required to stimulate GH release in GH-deficient patients is variable, and that in addition to the possibility of genetically determined GHRH insensitivity some non-responding patients have developed severe acquired resistance to GHRH. Evidence for diurnal variation in the responsiveness of somatotropes to GHRH-44 in GH-deficient patients was also found.

The effect of pulsatile administration, continuous infusion, and diurnal variation on the growth hormone (GH) response to GH-releasing hormone in normal men.

To examine the relative effectiveness of GH-releasing hormone (GHRH) given either as multiple iv pulses or as a continuous iv infusion, we studied the GH response to a nearly equivalent total dose of GHRH-44 administered by both routes in a group of normal men. Further, in view of the pulsatile nature of GH secretion and its augmentation with sleep, we investigated whether a diurnal difference in GH release was present during chronic pulsatile administration of GHRH during day and night. Seven men received six GHRH pulses (1 microgram/kg, iv) at 2-h intervals during both day (0900-2100 h) and night (2100-0900 h), and four underwent nighttime placebo pulsing. Eight men received a daytime continuous GHRH infusion (0.15 microgram/kg X h for 5 h, followed by 0.75 microgram/kg X h for 5 h) and a separate 10-h placebo infusion. The GH response to a bolus dose of GHRH (1 microgram/kg, iv) was determined after both continuous GHRH and placebo infusions. No significant difference was found in the GH area response (mean +/- SEM) during total day and night GHRH pulsing periods (6095 +/- 1192 vs. 6506 +/- 1483 ng/min X ml; P = NS). GH secretion was blunted after the initial daytime GHRH pulse (P = 0.02), and only two of seven men had a GH increase after the second pulse; responsiveness was restored after the fourth pulse. In contrast, all subjects responded to the second nighttime GHRH pulse. During continuous GHRH infusions, GH secretion was unsustained and pulsatile. The incremental GH response to a single GHRH bolus dose was decreased after GHRH infusion compared to that after placebo (4.4 +/- 1.8 vs. 10.3 +/- 3.4 ng/ml; P less than 0.05). No difference was found in the total GH area response to a nearly equivalent dose of GHRH administered as either multiple pulses or continuous infusion followed by a single GHRH bolus dose. The apparent pulsatile nature of GH secretion during continuous GHRH infusion and the lack of a significant difference in the GH response to a nearly equivalent dose of GHRH administered as either multiple pulses or a continuous infusion suggest that GHRH need not be administered in a pulsatile manner to be an effective therapeutic agent for the stimulation of GH secretion in children with hypothalamic GHRH deficiency.

Early treated hypothyroidism: development at 3 years.

Eighty children from the North West and North East Thames Regional Health Authorities who had been identified as having congenital hypothyroidism either by neonatal screening (76 cases) or by clinical symptoms (four) were seen for psychological assessments at 1 (60 cases), 3 (58), and/or 5 (20) years of age. Almost all the children's scores were in the normal range, and comparisons with matched controls suggested that they were doing only slightly less well than normal children in overall development. They were significantly slower, however, on a motor skills task. Moreover, a low initial serum thyroxine and triiodothyronine value, considerable delay in initial bone age, and an absence of thyroid tissue on isotope scan seemed to be associated with a somewhat poorer prognosis.

Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.

Previous studies from this laboratory and by others in rats, monkeys, and humans support the concept that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism. With the availability of human growth hormone-releasing factor (GRF), the possible existence of such a mechanism was reexplored by examining the effect of exogenous GH on the GH response induced by GRF-44-NH2 in six normal men (mean age, 32.4 yr). In all subjects the plasma GH response evoked by GRF-44-NH2 (1 microgram/kg i.v. bolus) was studied before and after 5 d of placebo (1 ml normal saline i.m. every 12 h), and then before and 12 h after 5 d of biosynthetic methionyl human GH (5 U i.m. every 12 h). The GH response to GRF (maximal increment over time 0 value) was significantly inhibited after GH treatment (0-1.3 vs. 2.3-11.2 ng/ml before treatment, P = 0.05), but was not significantly affected by placebo. This impaired pituitary response to GRF persisted for at least 24 h following exogenous GH treatment in two subjects who underwent further study. Serum somatomedin-C concentrations were significantly increased after 5 d of GH treatment (2.66-5.00 vs. 0.92-1.91 U/ml before treatment, P = less than 0.01). The impaired pituitary response to GRF may be mediated indirectly through somatomedin, somatostatin, by a direct effect of GH on the pituitary somatotropes, or by all of these mechanisms. These data suggest that after GH treatment, the blunted GH response to synthetic GRF is not solely a consequence of the inhibition of hypothalamic GRF secretion.

Human erythrocyte carbonic anhydrase I concentrations in dried blood spots from normal and hypothyroid neonates and children.

The ELISA technique was used to assay carbonic anhydrase I (HCAI) in hemolysates prepared by the elution of dried blood samples from Guthrie cards. The ratio HCAI (mg)/hemoglobin (g) measured in blood samples eluted from Guthrie cards was not significantly different from that determined in aliquots of the same blood samples after storage as erythrocyte (RBC) lysates at -20 degrees C, provided that the dried blood was eluted within three weeks of collection. The normal neonatal mean (SD) RBC HCAI concentrations were 2.05 (1.01) and 1.82 (0.86) mg HCAI/g hemoglobin for females and males respectively. Erythrocyte HCAI concentrations gradually rose with age, approaching normal adult levels by 16 years. Blood from hypothyroid neonates and hypothyroid infants on treatment gave normal HCAI/hemoglobin ratios.

Outcome for congenital hypothyroidism.

In a study designed to provide retrospective control data for a neonatal thyroid screening programme, the problems of 141 hypothyroid children were examined. The mean IQ (Weschler intelligence scale) was 79.5 for children with congenital hypothyroidism but was normal in 6 children diagnosed before age 6 weeks. Diagnostic delay was associated with a steady decline in mean IQ but there was an improvement in some late diagnosed cases. A strong association was found between IQ and parental social class. Twenty five percent of the children were mentally retarded and 29% were at special schools; 54% of children at normal schools and 43% at special schools showed deviant behaviour. Other problems included clumsiness (26.2%) and squints (26.2%), and these were more common in children with a lower IQ. Congenital hypothyroidism is associated with persistent morbidity in many aspects of cerebral function. The adverse effects of prenatal hypothyroidism are largely reversible if treated before age 6 weeks.

Growth, development, and reassessment of hypothyroid infants diagnosed by screening.

Thirty]six neonates in whom hypothyroidism was diagnosed after thyroid stimulating hormone screening were reassessed at 1 year. All had grown satisfactorily and the mental development scores were normal in all except two. Treatment was withdrawn in 32 and persistent hypothyroidism was confirmed in 31 cases. Thyroid stimulating hormone concentrations were raised in one-third of cases before the withdrawal of treatment and this was associated with generally lower concentrations of serum thyroxine (T4) and smaller doses of L-thyroxine than in those cases with normal concentrations of thyroid stimulating hormone. In treating congenital hypothyroidism, serum T4 concentrations should be monitored regularly and the dose of thyroxine adjusted to maintain serum T4 in the upper part of the reference range.

Two children with cerebral gigantism and congenital primary hypothyroidism.

Two children are described in whom congenital primary hypothyroidism was associated with excessive growth during early childhood and who had typical morphological features of cerebral gigantism. One child was completely athyreotic. This association has been described previously in only one other child.

Programming and running radioimmunoassay in the h-TSH screening procedure using dried blood spots and the NE1600 gamma counter on line to the HP9815S calculator.

Screening for hypothyroidism has been achieved by seeking raised concentrations of thyroid stimulating hormone (h-TSH) in dried blood samples collected on absorbent paper from some 1700 newborn babies each week using double antibody radioimmunoassay and 125I-label counting on a NE1600 gamma counter linked to a HP9815S desk top calculator. Specificity, accuracy, and quality control of the assay have been investigated. The calculator programme stores all count, time, and calculated data and uses log-log function formation and third-power homoscedastic polynomial fit to the calibration data followed, if necessary, by elimination of outliers set at P = 0.5%. Branching in the calculation procedure provides the ability to process sample data in subgroups, completely to reprocess data (including presentation in a form suitable for making a histogram plot), and to reset without loss of data in case of instrument or main power failure. Variance analysis was used to select the minimum duration of count (50 s), and it was demonstrated that homoscedasticity pertains in the regression calculation.