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Biomedical subjects

R Stanhope

Publications and source records attributed to R Stanhope.

At least 91 records · Page 5Linked to original sources

Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. Cooperative Study Group of Pubertal development in Chronic Renal Failure.

To elucidate the endocrine mechanisms underlying the pubertal growth failure observed in patients with chronic renal failure (CRF), we used deconvolution analysis to estimate the rates of GH secretion and elimination in nighttime plasma GH profiles of peripubertal boys with CRF and after renal transplantation (Tx). Forty-three boys with advanced CRF (conservative treatment with glomerular filtration rate < 25 mL/min.1.73 m2 or dialysis; CT/D group), 38 boys after Tx, and 40 healthy control boys were studied. The estimated plasma GH half-life (mean +/- SEM) was significantly higher (P < 0.05) in CRF (25 +/- 1.8 min) than in Tx patients (21 +/- 1.6 min) and controls (20 +/- 0.5 min). In the pre- and early pubertal CT/D boys, the calculated GH secretion rate was low normal or reduced when expressed in absolute numbers or normalized per unit distribution volume or body surface. In late puberty, whereas body surface-corrected GH secretion was double the prepubertal value in normal boys (389 +/- 56 vs. 868 +/- 113 micrograms/m2.11 h; P < 0.01), it did not differ significantly from the prepubertal rate in CT/D boys (281 +/- 59 vs. 389 +/- 56 micrograms/m2.11 h). GH hyposecretion resulted from a decrease in the mass of GH released within each burst, whereas burst frequency was unchanged. In the Tx group, GH secretion rates were significantly reduced in the prepubertal (221 +/- 39 micrograms/m2.11 h; P < 0.05) and late pubertal period (266 +/- 64 micrograms/m2.11 h; P < 0.01). The mass of hormone secreted per burst was significantly reduced at each pubertal stage, whereas GH secretory burst frequency tended to be increased (significant in prepubertal group, P < 0.05). The GH secretion rate was positively correlated with plasma testosterone levels (r = 0.58; P < 0.0001) in controls, but not in CT/D or Tx patients. GH secretion rates were lower than expected at each level of plasma testosterone in both patient groups except CT/D boys with plasma testosterone below 0.9 nmol/L. In the Tx group, GH secretion rate was positively correlated with relative height (r = 0.31; P < 0.05). The dosage of corticosteroids administered for immunosuppression was negatively correlated with GH burst mass (r = -0.42; P < 0.01) and GH secretion rate (r = -0.29; P = 0.08) and positively correlated with GH burst frequency (r = 0.49; P < 0.01). We conclude that in peripubertal boys with CRF, a state of GH hyposecretion is associated with an increase in the apparent plasma half-life of GH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Treatment of growth delay in boys with isolated growth hormone deficiency.

We report our experience in treating growth delay in boys with isolated growth hormone deficiency (IGHD) receiving biosynthetic human growth hormone. The study was performed in 15 boys with IGHD receiving GH. At the chronological age of 13.1 (1.1) years (SD), 13 were prepubertal, two were in early puberty and there was a mean bone age delay of 2.5 (1.4) years. A growth spurt was induced by either depot testosterone or oxandrolone. There was an increase in growth rate from 5.7 (1.6) cm/year, occurring the year before anabolic or sex steroid therapy, to 8.1 (1.2) cm/year during treatment (p < 0.05), followed by 7.3 (1.9) cm/year the year after the cessation of treatment (p < 0.05). There was no significant change in height SD score for bone age, which was -0.69 (0.97) at the commencement of anabolic or sex steroid therapy and -0.53 (0.84) at the end of treatment. Before the induced growth spurt, there was equal body proportion between sitting height and subischial leg length, which had no significant change following androgen treatment. Spontaneous progress in pubertal development was achieved by all patients with an increase in testicular volume from a mean of 2.9 (2-8) to 6.1 (4-10) ml. The pattern of growth presented by patients treated with oxandrolone or those with testosterone was similar. Our data suggest that growth delay and delayed puberty, in patients with IGHD during concomitant growth hormone therapy, can be treated without deterioration in height prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hypomelanosis of Ito and precocious puberty.

We describe two girls with hypomelanosis of Ito, one of whom was demonstrated to have diploid-triploid mixoploidy in skin fibroblasts. Both had precocious puberty which was probably gonadotrophin-independent. The association of precocious puberty and hypomelanosis of Ito has not been previously reported. We have speculated on the possible mechanism of gonadotrophin-independent precocious puberty.

Child↗

Does constitutional delayed puberty cause segmental disproportion and short stature?

We have reviewed the growth of 98 boys and 34 girls with constitutional delay of growth and puberty followed until final height. At presentation chronological age was 14.1 (1.3) years (SD) in the boys and 13.0 (1.3) years in the girls. At presentation all patients were either prepubertal or in early pubertal maturation (4 ml testicular volume in the boys and breast stage II in the girls). Twenty-nine boys (30%) and 2 girls (6%) were treated with either sex or anabolic steroids. Mean height SDS in the boys at presentation was -2.7 (0.7) which rose to -1.9 (0.9) at final height attainment. This was significantly lower than the predicted final height SDS of -1.4 (0.8) and mid-parental height SDS of -0.5 (0.7). Similar results were obtained for the girls with a height SDS at presentation of -3.2 (0.8) which increased to -2.3 (0.7) at final height which was significantly lower than predicted final height SDS of -1.7 (0.6) and mid-parental height SDS of -0.8 (0.8). Both sexes had a relatively short sitting height at presentation; sitting height SDS -3.4 (1.0) and subischial leg length SDS -2.2 (1.0) in the boys and sitting height SDS -3.6 (1.1) and subischial leg length SDS -2.5 (0.7) in the girls. The relative disproportion between the segments had no significant change at final height. We are unable to explain the failure to achieve final height potential and the relatively disproportionate stature. Our data suggest that the late timing of the onset of puberty may be deleterious to spinal growth and consequently final height.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Growth following single fraction and fractionated total body irradiation for bone marrow transplantation.

Total body irradiation (TBI) is used as preparative regimen prior to bone marrow transplantation (BMT). Since there are more long-term survivors, follow up studies are important. We have performed a retrospective analysis of growth for 49 children, who had undergone treatment with cyclophosphamide and TBI before BMT. Of these patients 26 received single fraction (SF) TBI as a dose of 900-1000 cGy, whereas 23 received fractionated (FF) TBI as a total dose of either 1200 cGy divided in six fractions or 1440 cGy divided in eight fractions over 3 days. Half of the patients in the SF-TBI group, and 9 in the FF-TBI group had received low-dose cranial irradiation prior to TBI. In all groups a decrease in height SDS was observed. By evaluating the major factors leading to growth impairment the influence of cranial irradiation, which was demonstrable in the 1st year after TBI, could not be shown after 3 years. At this time growth was significantly more impaired in the SF group with a mean height SDS of -0.9 (+/- SD 0.9) compared to a mean height SDS -0.22 (1.02) in the FF group (P < 0.05). Measurement of segmental proportions showed a significant difference in SDS for sitting height in comparison to SDS for subischial leg length, irrespective of the TBI regimen. This was already evident 1 year after TBI and decreased during the following years. Twenty four of the patients (17 in the single fraction and 7 in the fractionated TBI group) were treated with growth hormone, but demonstrated an inappropriate response with absent catch-up growth in their legs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Long-term treatment with growth hormone in Noonan's syndrome.

Five children (four boys, one girl) with Noonan's syndrome were treated with growth hormone for a mean of 2.9 (range 1.8 to 4.6) years. Treatment was commenced at a mean age of 3.9 (range 2.5 to 6.0) years. After one year of treatment, height velocity SDS increased from a mean of -2.1 (range -4.1 to -0.3) to a mean of +3.1 (range +2.0 to +3.5). Subsequently, height SDS increased significantly from -3.3 (range -4.2 to -2.2) to -2.4 (range -3.3 to -1.6). Although in all patients a marked decrease in height velocity was observed in the following years of treatment, compared to the first year, height SDS continued to improve in comparison to pretreatment (mean height SDS in the third year for four patients was -2.1) (range -3.1 to -1.4). In the four patients who had completed their second year of treatment, height SDS for bone age had increased from -1.8 (range -2.8 to -0.9) to -1.2 (range -1.6 to -0.6).

Child↗

Growth and metabolic data following growth hormone treatment of children with intrauterine growth retardation.

Twenty-five short children (6F, 19M) with intrauterine growth retardation were treated with daily subcutaneous injections of biosynthetic human growth hormone for 4 years. The treatment was commenced at a chronological age of 6.3 years (range 2.1-9.8). Eighteen of the patients had major dysmorphic signs of Russell-Silver syndrome. During the first year they were randomised into two groups treated with either 15 or 30 IU of growth hormone/m2/week. The higher dose was administered to all the children after the first year of the trial. After the initial increase in growth velocity SDS (greater in those treated with the higher dose regimen), there was a progressive decrease although with values significantly higher than pretreatment levels (p < 0.02) in both groups. However there was no improvement in height SDS for bone age after 4 years. The triceps and skinfold thickness showed a decrease during the first years followed by a gradual increase. The body mass index improved during the 4 years although showing no difference between the two treatment groups. There was no alteration in thyroid function or metabolic indices (glucose or lipid homeostasis) during the study.

Blood Glucose↗

Gonadotropin releasing hormone analogue and growth hormone therapy in precocious and premature puberty following cranial irradiation for acute lymphoblastic leukaemia.

Ten girls with early puberty secondary to cranial irradiation as a part of the treatment for acute lymphoblastic leukaemia (ALL) were treated with either gonadotropin-releasing hormone analogue (GnRHa) and human growth hormone (GH) (8 girls) or with GnRHa alone (2 girls). After 4 years of treatment, height SDS for bone age was improved in the group who received combined treatment (from -0.97 to +0.07, p < 0.001), in contrast to the 2 patients who received GnRHa alone in whom height standard deviation scores for bone age decreased (from -1.10 to -1.33). Sitting height in all patients was relatively shorter than leg length, and there was no significant alteration during the 4 years of treatment.

Age Determination by Skeleton↗

Endocrine function following single fraction and fractionated total body irradiation for bone marrow transplantation in childhood.

Forty-nine children who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation were investigated for impaired endocrine function. Twenty-six patients received single fraction total body irradiation as a dose of 9-10 Gy, whereas 23 patients received fractionated total body irradiation as a total dose of either 12 Gy divided into six fractions or 14.4 Gy divided into eight fractions, administered over 3 or 4 days. Half of the patients in the single fraction group and nine in the fractionated group had received cranial irradiation prior to total body irradiation. Pathological changes in thyroid function were observed in 19 patients (73%) of the single fraction group (elevated thyrotrophin (58%) and decreased thyroxine levels (15%)), whereas in the fractionated group only six patients (25%) developed transient raised thyrotrophin levels: the mean observation period was 3.2 years in the single fraction group and 2.7 years in the fractionated group. The stimulated growth hormone peak concentration was influenced significantly by previous cranial irradiation and was independent of the type of total body irradiation administered. In the patients who had received cranial irradiation, the mean growth hormone peak levels were 8.4 mU/l (single fraction group) and 13.9 mU/l (fractionated group), whereas in those who received only total body irradiation they were 24.9 mU/l(single fraction group) and 28.1 mU/l (fractionated group). The basal gonadotrophin concentration in children older than 9 years showed elevated levels in nine patients (50%) of the single fraction group and in only three patients (30%) of the fractionated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Delayed puberty.

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Child↗

Is testosterone therapy for boys with constitutional delay of growth and puberty associated with impaired final height and suppression of the hypothalamo-pituitary-gonadal axis?

We report the treatment of 44 boys with constitutional delay of growth and puberty (CDGP) at a mean chronological age of 14.3 years (range, 12.4-17.1) and bone age of 12.1 years (range, 9.1-15.0). All were below the 3rd height percentile for chronological age. They received monthly intramuscular injections of depot testosterone esters (50 mg) for a mean period of 0.35 years (range, 0.25-0.5). Means (SD) height velocity was 4.5 (1.5) cm/year during a pretreatment period of 0.5 years. During a period of 0.9 years which included the period of treatment with depot testosterone, mean growth velocity increased to 8.8 (1.9) cm/year (P less than 0.001). In the initial 1.8 years following the cessation of treatment growth velocity was sustained at 7.0 (1.7) cm/year. Pretreatment height standard deviation score (SDS) for bone age was -0.89 and this gradually reduced over the next 1.5 years to a minimum of -1.48. Thereafter, height SDS for bone age gradually increased to attain a value of -1.2, 3 years after the commencement of therapy (P less than 0.02). The same pattern of an initial decrease, followed by an increase, in height prediction was also observed when TW2 height prediction was analysed. Sexual maturation progressed during treatment, with mean testicular volume increasing both during and after treatment, confirming the diagnosis of CDGP. The time interval for progress through puberty was shorter in boys with testosterone therapy than in the normal population. The mean duration of puberty was 2.2 years compared to 3.3 years in normal boys. We conclude that low-dose depot testosterone treatment is safe and effective for boys with CDGP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Growth hormone deficiency throughout puberty.

Growth during puberty does not appear to be the major determinate of final height in isolated GH deficient patients. Early diagnosis and commencement of therapy are probably the most important factors, as reflected by the correlation between final height and height at the onset of puberty. The cost effectiveness of increasing the dose of GH during puberty does not appear to represent any advantage from the data presently available. Indeed, such an approach may have a deleterious effect on final height by shortening the duration of pubertal maturation. Further prospective studies are required to demonstrate the effectiveness of manipulating the onset and duration of puberty using gonadotrophin releasing hormone analogues on final height in isolated GH deficiency.

Adolescent↗

Optimum method for administration of biosynthetic human growth hormone: a randomised crossover trial of an Auto Injector and a pen injection system.

The use of optimum conventional growth hormone administration, using a growth hormone vial combined with an Auto Injector, was compared with a pen injection system using a cartridge of growth hormone. In both methods of administration the concentration of growth hormone was 16 IU/ml. Thirty patients (22 boys, eight girls) who had all previously been treated with growth hormone (4 IU/ml) administered using needles and syringes (without an Auto Injector) were randomised into receiving one of either treatment for three months and then crossed over for a further three months. Fourteen patients (10 boys, four girls) initially received KabiVial 16 IU/ml combined with an Auto Injector while 16 patients (12 boys, four girls) were treated with KabiPen 16 IU/ml. Mean age in both groups was 9.6 years. The majority of patients in both groups were treated with a regimen of either 15 or 20 units/m2/week as a daily subcutaneous injection. Of the 30 patients who started in this trial, two who commenced using an Auto Injector refused to change to a pen system and were excluded from further analysis. When scored on a scale of -5 to +5 general convenience when changing from an Auto Injector to the KabiPen decreased from +4.7 to +1.0. When assessed for pain, the Auto Injector group scored +4.7, which decreased to -0.2 (more painful) for the pen. At the end of the trial 23 patients (82%) chose to continue with the KabiVial/Auto Injector combination as they found this less painful and the child did not see the needle or need to insert the needle manually. Five patients (18%) continued with the KabiPen as they considered the device smaller and easier to use. The accuracy of dosing using KabiVial was 100% compared with the range of 88% to 111% using KabiPen as the latter was available only in 0.5 unit increments. No growth hormone was wasted using KabiVial, although a mean of 0.6 units was wasted with every 16 IU cartridge in the KabiPen system. It is concluded that patients should be able to contribute to the choice of growth hormone delivery systems and that newer methods need careful assessment.

Adolescent↗

The effects of growth hormone therapy on spontaneous sexual development.

We have carried out a prospective randomised study in 52 (46 male, 6 female) children with isolated growth hormone (GH) deficiency treated with a GH regimen of 15 IU/m2/week administered as a daily subcutaneous injection. At the onset of the pubertal growth spurt, the patients were randomised to receive either an unaltered regimen (26 males, 1 female) or 30 IU/m2/week (20 males, 5 females). There was no change in the frequency of GH administration. The number of females in this study was too small to give a meaningful result. In contrast, the boys treated with either dose regimen showed no significant alteration in growth rate, but there was a faster than normal progression in pubertal maturation. It is concluded that the optimum final height of children with isolated GH deficiency may not be achieved in patients without the therapeutic manipulation of the onset and/or duration of puberty. 16 short normal children (9 males, 7 females) were treated with GH in a regimen of 25 IU/m2/week (range: 20-30) as a daily subcutaneous injection. The mean age for the onset of GH treatment was 11.5 and 11.0 years in the boys and girls, respectively. Our data suggest that both boys and girls had a more rapid rate of pubertal maturation than normal. It may be that in terms of final height prognosis, the events of puberty related to GH treatment counterbalance the improvement in growth prognosis during prepuberty.

Adolescent↗