Creutzfeldt-Jakob disease following treatment with human pituitary hormones.
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Adult↗
Biomedical subjects
M A Preece
Publications and source records attributed to M A Preece.
Laron-type dwarfism with apparently normal high affinity serum growth hormone-binding protein.
OBJECTIVE: Normal serum contains a high affinity GH-binding protein, which appears to be identical with the extracellular domain of the GH receptor. It is normally absent from the serum of patients with Laron-type dwarfism. We wished in this study to define the serum GH-binding protein status of a family with Laron-type dwarfism. DESIGN AND PATIENTS: We performed an open case study of an Asian family in which three sisters (aged 3 to 15 years) had the phenotype of Laron-type dwarfism. Sera from a fourth, unrelated girl with Laron-type dwarfism and subjects without endocrine disorders were used as control samples. MEASUREMENTS: Laron-type dwarfism was confirmed by demonstration of elevated serum GH levels and low serum IGF-I levels on immunoassay, with serum IGF-I levels failing to rise during treatment with GH. Serum GH-binding proteins were characterized using gel chromatography on Sephacryl S-100HR following incubation of serum with 125I-GH, Scatchard analysis of ligand binding, and by polyacrylamide gel electrophoresis after covalent cross-linking to 125I-GH. RESULTS: All members of the family had high affinity serum GH-binding protein activity similar in size, circulating levels and apparent affinity for GH to that of normal subjects. This contrasted with the very low serum GH-binding protein activity in the unrelated child with Laron-type dwarfism and previous reports of serum GH-binding protein levels in this disorder. CONCLUSIONS: The affected patients may possess a novel biochemical defect which results in GH-resistance and reduced production of IGF-I in the presence of normal serum GH-binding protein levels.
Adolescent↗
Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children.
OBJECTIVE: The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone in normal children at various stages of puberty. DESIGN: Blood samples were taken at 15-minute intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). PATIENTS: Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1-20.9 years). They were of normal height, non-obese, and covered the range of puberty. MEASUREMENTS: Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed in a subgroup of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. RESULTS: Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive luteinizing hormone concentrations were higher than immunoreactive luteinizing hormone levels in all the girls studied (n = 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase in the bioactive: immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4-5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bioactive than immunoreactive luteinizing hormone levels and overall bioactive and immunoreactive luteinizing hormone and testosterone concentrations increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an increase in the bioactive: immunoreactive ratio was observed in the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data in the girls, testosterone secretion always followed luteinizing hormone pulsatility overnight. CONCLUSION: We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than immunoreactive luteinizing hormone in both sexes, but there is very little discordance between immunoreactive and bioactive luteinizing hormone pulsatility. The bioactive: immunoreactive ratio increases with the occurrence of pulsatility overnight in early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion.
Adolescent↗
Does growth hormone treatment improve final height attainment of children with intrauterine growth retardation?
Twenty four children (five girls, 19 boys) who had intrauterine growth retardation were treated with daily subcutaneous biosynthetic human growth hormone, initially in a dose of either 15 or 30 U/m2/week for the first year and in the latter dose for the next two years. Six patients (one girl, five boys) had no dysmorphic signs and 18 (four girls, 14 boys) had signs of Russel-Silver syndrome. All had birth weights below the third centile when adjusted for gestation age and all the children were below the third height centile at the start of treatment. Mean age was 6.3 years (range 2.1-9.7) when growth hormone treatment was started. All had normal growth hormone secretion to either a pharmacological or physiological test. In the first year of treatment, height velocity SD score increased from -0.75 to +3.6 in the group treated with 30 U/m2/week, and from -0.77 to +1.4 in the lower dose group. After three years of treatment, mean height velocity SD score was +1.1, irrespective of which initial treatment dose had been administered during the first year. There was no difference in the growth response of children with or without dysmorphic features. However, despite the sustained increase in growth rate, there was no significant change in height for bone age SD score, pointing to an unaltered final height outcome.
Age Determination by Skeleton↗
Growth prognosis and growth after menarche in primary hypothyroidism.
The long term growth of 20 girls and nine boys with juvenile primary hypothyroidism was studied until they reached final height. At diagnosis the girls had a mean age of 8.8 years (range 3.0-13.0); mean bone age was 5.4 years. The mean age of the boys at diagnosis was 9.5 years (range 3.7-14.2); mean bone age was 6.3 years. The patients were treated with thyroxine 100 micrograms/m2/day and serum thyroxine concentrations were maintained in the normal range. During treatment the rate of skeletal maturation exceeded the change in chronological age. Initial mean height SD score for bone age before treatment in the girls was +0.59 and after 11 years of treatment fell to -0.55 Mean height SD score for bone age in the boys decreased from +1.6 to -0.87 during treatment. In the girls the onset of puberty was 1.2 years later than the normal population but the duration of puberty was reduced. Mean age (SD) of menarche was 13.8 (1.7) years. The pattern of growth in girls with treated hypothyroidism was abnormal as growth continued after menarche, at a time when normal girls have almost stopped growing. During the second year after menarche our patients still had a mean growth velocity of 4.1 cm/year. Our data suggest that juvenile primary hypothyroidism results in a permanent height deficit. In addition, there is a loss of the normal harmony between growth and sexual maturation in girls, despite adequate treatment, in that growth continues for much longer after menarche than in normal girls.
Adolescent↗
Treatment of constitutional growth delay in prepubertal boys with a prolonged course of low dose oxandrolone.
Forty six prepubertal boys who had constitutional growth delay were treated with oxandrolone. Mean age at the onset of treatment was 11.9 years (range 9.0-14.0) and bone age delay was 1.9 'years'. The dose of oxandrolone used was a mean of 0.05 mg/kg (range 0.03-0.18) for a mean of 0.9 years (range 0.2-3.6). Height velocity increased from a mean (SD) before treatment of 4.0 (1.0) to 7.5 (1.2) cm/year with oxandrolone. Growth rate was sustained at 7.6 (2.2) cm/year in the period after treatment. Those boys who attained a testicular volume of 4 ml or greater at the end of the treatment period had the most pronounced sustained growth acceleration. Height for bone age SD score did not alter significantly from a mean of -1.0 before treatment to -1.2 after treatment. Oxandrolone is a safe and effective treatment for prepubertal boys with constitutional growth delay.
Adolescent↗
Evidence for temporal coupling of growth hormone, prolactin, LH and FSH pulsatility overnight during normal puberty.
The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00-08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9.1-20.9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization. The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150-180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30-75 min (r = 0.32; P less than 0.001) and 30 min (r = 0.47; P less than 0.0001) respectively. Generally, LH and prolactin pulses were in phase (r = 0.42; P less than 0.0001) and there was a highly significant correlation (r = 0.64; P less than 0.0001) between FSH and LH pulsatility. Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150-180 min was established and there was remarkable temporal coupling of pulsatility.
Adolescent↗
Oxandrolone for delayed puberty in boys taking long-term steroid therapy for renal disease.
Eleven boys, mean age 15.3 years (range 13.2-17.5), with pubertal delay in association with steroid therapy for steroid-sensitive nephrotic syndrome and following renal transplantation were treated with oxandrolone 2.5 mg daily for a mean of 0.50 years (range 0.34-0.61). Mean growth velocity increased from 3.9 cm/year (range 1.1-6.3) to 6.1 cm/year (range 2.0-14.4) and was maintained at 6.1 cm/year (range 0.4-10.2) (P less than 0.05). However, there was no significant difference in growth between the treated boys and age- and puberty-matched controls. Elevation of blood cyclosporin A and creatinine levels occurred in the transplant patients. Oxandrolone may initiate a pubertal growth spurt in patients taking steroid therapy for renal disease, but should be used with extreme caution because of potential side-effects.
Adolescent↗
Long-term outcome of oxandrolone treatment in boys with constitutional delay of growth and puberty.
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Adolescent↗
Evaluation of the nutritional status of 1st-year school children in Campinas, Brazil.
We present findings from a study of nutritional status amongst 1st year primary school children in Brazil. The study was based on a 10% stratified random sample of children in Campinas, Sao Paulo State. The primary schools in the city were grouped into four socio-economic strata (high, medium, low and very low) based on the type of school maintenance (private or maintained by the local or by the State government) and the socio-economic characteristics of the school's catchment area. The nutritional status of 1942 children was assessed by looking at the distributions of z-scores of weight-for-age, height-for-age and weight-for-height in relation to growth charts of the National Center for Health Statistics reference population. In the overall population, 22% of the children were found to be stunted (z-score of height-for-age less than -1.0), 15% wasted (z-score of weight-for-height less than -1.0), 22% underweight (z-score of weight-for-age less than -1.0) and 5% overweight (z-score of weight-for-height greater than 2.0). These figures represent an excess of 6% of stunted children and also 6% of underweight children in comparison with the expected values in the NCHS reference population, and an excess of 2% overweight. The data were analysed by age, sex, ethnic group and socio-economic level. Both stunting and low weight-for-age were observed in 32% of children from the very low socio-economic level, with the highest percentages amongst the oldest children. A total of 11.6% of children from the high socio-economic stratum were obese. These results emphasize the need for different programmes to deal with nutritional problems in different groups of the population.
Age Factors↗
The growth hormone independent insulin-like growth factor-I binding protein BP-28 is associated with serum insulin-like growth factor-I inhibitory bioactivity in adolescent insulin-dependent diabetics.
The relationship between the growth hormone independent insulin-like growth factor binding protein (BP-28) and serum insulin-like growth factor-I (IGF-I) inhibitory bioactivity observed in diabetic serum was investigated in five poorly controlled adolescent type I diabetics. We have measured the in-vitro effects of purified BP-28 from amniotic fluid on serum IGF-I stimulated and basal cartilage sulphation and compared serum IGF-I bioactivity obtained from 24-h serum profiles from each diabetic subject with serum concentrations of BP-28 and IGF-I measured by specific radioimmunoassays. Purified BP-28 inhibited serum IGF-I stimulated and basal cartilage sulphation in vitro, in a dose-dependent manner. Serum IGF-I bioactivity of diabetic sera showed a change in activity over the 24-h period, with peak inhibitory bioactivity observed in each subject between 0800 and 1000 h. BP-28 concentrations in each individual showed a marked circadian rhythm with maximum peak levels occurring at 0800 h. Long-acting insulin administered in the evening in two of the diabetic subjects blunted the maximum peak level attained compared to the three diabetics who had long-acting insulin administered in the morning. IGF-I concentrations did not change over the 24-h period in each individual. The data shows that BP-28 inhibits serum IGF-bioactivity on cartilage in vitro. The changes in inhibitory bioactivity observed in diabetic serum are associated with similar changes in serum concentrations of BP-28. We propose that BP-28 is one of the IGF-I inhibitors observed in diabetic serum and that it may play a role in retarded growth and delayed puberty often seen in the adolescent diabetic.
Adolescent↗
Growth hormone treatment in non-growth hormone-deficient children: effects of stopping treatment.
Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved GH levels greater than 15 mU/l following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase, demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period, all children received GH according to the same dose regimen; they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating 'catch-down' growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.
Adolescent↗
Dietary management of D-lactic acidosis in short bowel syndrome.
Manipulation of carbohydrate intake was used to treat severe, recurrent D-lactic acidosis in a patient with short bowel syndrome. Dietary carbohydrate composition was determined after assessment of D-lactic acid production from various carbohydrate substrates by faecal flora in vitro. This approach may be preferable to repeated courses of antibiotics.
Acidosis, Lactic↗
Treatment of short stature in renal disease with recombinant human growth hormone.
Six prepubertal children with chronic renal failure (group 1), six prepubertal children with renal transplants (group 2), and six pubertal children with renal transplants (group 3) who were short (mean height SD score, -3.2, range -4.5 to -1.6) and growing poorly (mean (range) growth velocity (cm/year) over the year before treatment: group 1, 4.8 (3.5-5.8), group 2, 2.3 (0.9-4.7), and group 3, 3.2 (0.5-6.5] were treated with recombinant human growth hormone 30 units/m2/week in daily doses for a median of 0.98 years (range 0.25-0.99). Mean (range) growth velocity over the treatment period increased significantly in all groups (group 1, 10.7 (8.8-12.3), group 2, 6.1 (2.7-10.8), and group 3, 6.0 (4.6-6.8]. There was, however, no improvement in height SD score for bone age in any group. The renal function of two children deteriorated after starting treatment with growth hormone, but it was not possible to say whether the growth hormone was responsible for this. The long term effects of treatment and its influence on final height are not yet known.
Adolescent↗
Frequency of administration of growth hormone--an important factor in determining growth response to exogenous growth hormone.
Growth hormone (GH) secretion in man occurs in a pulsatile manner with a dominant periodicity of 200 min. Animal studies and growth hormone-releasing hormone therapeutic studies in man demonstrate the importance of the frequency of GH pulses on the growth response observed. Daily injections of GH produce effective growth. More frequent regimens may be beneficial to prevent waining of the growth spurt induced by GH therapy.
Animals↗
Growth hormone increases rate of pubertal maturation.
We have performed a retrospective analysis of the pubertal parameters of 134 children with isolated GH insufficiency on GH treatment and compared them to the standards of Tanner and to a recent longitudinal study of growth and development in the United Kingdom. The age at onset of puberty (13.0 years in boys, 12.1 years in girls) was found to be significantly delayed (Mann-Whitney p less than 0.001), but duration of puberty (1.5 years in both sexes) was shortened (Kolgomarov-Smirnov p less than 0.01). Skeletal maturity at the onset of puberty was not advanced excluding this as a contributory factor. There was no association between dose of GH administered and the pubertal parameters. The results suggest that GH accelerates the pubertal process.
Adolescent↗
A longitudinal study of total and free thyroid hormones and thyroxine binding globulin during normal puberty.
Thyroid hormones are essential for normal pubertal growth, yet the changes in total and, especially, free thyroid hormones and thyroxine-binding globulin during puberty have not been adequately defined. Serum from 39 normal children (20 girls, 19 boys) between the ages of 10 and 15 years were assayed for total T4, free T4, free T3 and thyroxine-binding globulin at 6-monthly intervals; the free hormone assays were valid, non-analogue methodologies. In the girls, free T4 levels fell from 15.7 +/- 0.6 pmol/l at 10 years to 13.0 +/- 0.6 (p less than 0.001) at 12.5 years before rising to 15.9 +/- 0.7 at 15 years; this nadir occurred at puberty stages 3-4. Changes in total T4 followed a similar pattern with a slight delay in the nadir (13 years, puberty stage 4). In the boys, free T4 fell from 16.3 +/- 0.6 pmol/l at 10 years to 14.3 +/- 0.3 at 13.5 years, then rising to 15.4 +/- 0.5 at 15 years; the nadir again occurred at puberty stages 3-4. The corresponding nadir in total T4 which occurred at puberty stages 4-5 was not apparent by age analysis. Thyroxine-binding globulin concentrations remained unchanged in the girls, but fell slightly in the boys during later puberty. Free T3 concentrations in the girls showed a progressive fall after 12.5 years which was significant by the age of 14 when most had been in puberty stage 5 for more than 1 year. The boys showed no change of free T3 concentration throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
New insights from a large international collaborative growth study. Introduction.
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Adolescent↗