Biomedical subjects

C G Brook

Publications and source records attributed to C G Brook.

At least 181 records · Page 10Linked to original sources

PubMed1988

Changes in serum insulin concentration during puberty and their relationship to growth hormone.

In 40 tall and short children we have demonstrated using oral glucose tolerance tests that there is an increase in serum insulin concentration during puberty with no change in blood glucose concentration. Fasting serum insulin concentration rose from a pre-pubertal value between 4.0 and 5.7 mU/l to values between 11.0 and 14.6 mU/l during puberty. This rise in both fasting serum insulin concentration and the incremental area under the insulin curve is probably due to changes in circulating GH concentrations. In 16 tall girls a rise in serum GH concentration was observed during pubertal growth and the rise was accompanied by a two- to three-fold increase in fasting serum insulin concentration. In 13 children in whom 24 h growth hormone profiles were recorded higher insulin concentrations were seen in those who secreted the most growth hormone. These data suggest that during pubertal growth in diabetic children the standard dosage of insulin administered (0.9 units/kg per day) should be doubled or possibly tripled to maintain good metabolic control and maximize pubertal growth.

Adolescent↗

PubMed1988

Abnormal pubertal development in primary hypothyroidism.

We have studied three patients (1M, 2F), age range 10.9 to 15.5 years, who had abnormal sexual maturation secondary to primary hypothyroidism. The boy had inappropriately large testes for his stage of puberty, the girls had isolated breast development and there was absence of pubertal growth acceleration. FSH, LH, TSH and GH secretion, pituitary imaging and ovarian ultrasound morphology were studied before and during thyroxine treatment. In the hypothyroid state, FSH levels were elevated with abnormal pulsatility and LH:FSH concentrations were reversed.

Adolescent↗

PubMed1988

Continuous subcutaneous growth hormone releasing factor analogue augments growth hormone secretion in normal male subjects with no desensitization of the somatotroph.

The effects of 8 day continuous subcutaneous (s.c.) infusions of growth hormone releasing hormone analogue (NLE27GRF(1-29)NH2 (GHRH.A)) on growth hormone (GH) secretion were studied in 14 normal adult male volunteers. GHRH.A was administered in doses which ranged from 7.5 to 120 ng/kg/min in doubling steps. Baseline GH profiles obtained during a 24 h infusion of normal saline in each subject were compared with profiles performed on days 1 and 8 of the infusion. Doses above 30 ng/kg/min augmented GH pulse amplitude and frequency. Doses of 60 ng/kg/min and 120 ng/kg/min appeared more satisfactory as these represented doses on the upwards slope of the dose response curve. However, at a dose of 120 ng/kg/min the GH secretion did not return to baseline for 12 of the 24 h. There was no evidence of desensitization or of depletion of the releasable GH pool with any dose. The possibility of treatment of short children with depot preparations of GHRH.A appears promising.

Adult↗

PubMed1988

The relationship between the response to growth hormone therapy and pre-treatment growth hormone secretory status.

In 35 children (22 M, 13 F) aged between 5.3 years and 10.3 years who received Somatrem therapy for 1 year there was a curvi-linear relationship between pretreatment GH sensory status (x) and response (y) (change in height velocity standard deviation score (SDS)) to therapy described by the equation y = A + B (e-Cx). A, B and C are constants. Dose of GH administered was found to be an important additional factor in determining response to therapy. This was confirmed by stepwise multiple regression which resulted in a correlation coefficient of 0.74. These data suggest that in the assessment of response to GH therapy, pretreatment height velocity and/or GH secretory status as well as dose and frequency of GH administration need to be taken into account.

Body Height↗

PubMed1988

Growth, growth hormone and sex steroid secretion in girls with central precocious puberty treated with a gonadotrophin releasing hormone (GnRH) analogue.

We have treated 14 girls with central precocious puberty for a mean period of 2.3 years (range, 0.5-3.9) with intranasal (D-Ser6) GnRH analogue administered in a mean dose of 28 micrograms/kg/day (range, 15-56). With the onset of treatment there was an initial increase in sitting height compared to subischial leg length, but overall there was no significant change in height standard deviation score for bone age. In this respect our results were indistinguishable from untreated children with central precocious puberty. There was a decrease in physiological GH secretion, associated with decreased sex steroid secretion, which probably accounts for the growth deceleration which has been described during GnRH analogue therapy. The effect of this growth deceleration combined with slowing of the rate of epiphyseal maturation may explain the absence of alteration in height prognosis.

Administration, Intranasal↗

PubMed1988

Auxological and biochemical assessment of short stature.

Measurements of height and calculation of height velocity are highly accurate and sensitive to changes in a child's health. Definition of normality must be based on height velocity, and it is not acceptable to label a child as short and normal purely on the basis of a biochemical test unless this is substantiated with the demonstration of a normal height velocity. Response to therapy is dependent on the child's pretreatment growth rate and also on the amount of GH administered and the frequency of administration.

Body Height↗

PubMed1988

Somatostatin analogue in short term management of hyperinsulinism.

Five infants with hypoglycaemia due to hyperinsulinism were treated for between three and 11 days with a somatostatin analogue, which raised the mean blood glucose concentration and lowered the glucose requirements in all. Somatostatin analogue appears to be useful in the short term management of these patients.

Dose-Response Relationship, Drug↗

PubMed1988

Contribution of dose and frequency of administration to the therapeutic effect of growth hormone.

Forty two prepubertal children who were growth hormone insufficient were treated for the first time with 12 IU of biosynthetic methionyl growth hormone a week in three subcutaneous regimens for one year after one year of pretreatment observation. Thirteen received 4 IU growth hormone three days a week (group 1), 21 received 2 IU six days a week (group 2), and eight received 1 IU twice daily six days a week (group 3). The mean (SD) changes in height velocity standard deviation score (SDS) were +3.8 (1.7) in group 1, +5.3 (2.6) in group 2, and +5.9 (2.7) in group 3. There was a highly significant relation between the change in height velocity SDS and pretreatment height velocity SDS with a significant difference between the response of subjects receiving less than 15 IU/m2/week or greater than 15 IU/m2/week growth hormone. Age, bone age, height SDS, and height for bone age SDS did not contribute to the prediction of response during the first year of treatment. We recommend that growth hormone should be given in a dose of at least 15 IU/m2/week by equally divided daily subcutaneous injections.

Body Height↗

PubMed1988

Gonadal dysfunction after treatment of intracranial tumours.

Ninety three children (51 boys, 42 girls) who had been treated for brain tumours not affecting the hypothalamopituitary axis, were studied for evidence of gonadal dysfunction. All had received cranial irradiation, 59 spinal irradiation, and 28 adjuvant chemotherapy. Mean age at treatment was 6.3 years (range 1.5-15). Mean follow up after completion of radiotherapy was 8.5 years (range 1-27). Primary ovarian damage occurred in seven out of 11 (64%) girls treated with craniospinal irradiation alone and in nine out of 14 (64%) of those treated with craniospinal irradiation and chemotherapy. The association with spinal irradiation was significant. Primary gonadal damage also occurred in three out of four children treated with chemotherapy combined with cranial irradiation and in three out of nine boys treated with chemotherapy and craniospinal irradiation but in no boy given craniospinal irradiation alone. The only common chemotherapeutic agent was a nitrosourea. Hypogonadotrophic hypogonadism was found in seven boys, 5.8% of children of pubertal age.

Adolescent↗

PubMed1988

Growth hormone releasing hormone or growth hormone treatment in growth hormone insufficiency?

Sixteen prepubertal children who were insufficient for growth hormone were treated with growth hormone releasing hormone (GHRH) 1-40 and GHRH 1-29 for a mean time of nine months (range 6-12 months) with each peptide. Eleven children received GHRH 1-40 in four subcutaneous nocturnal pulses (dose 4-8 micrograms/kg/day) and eight (three of whom were also treated with GHRH 1-40) received GHRH 1-29 twice daily (dose 8-16 micrograms/kg/day). Altogether 73% of the children receiving GHRH 1-40 and 63% receiving GHRH 1-29 showed a growth response. Double the daily dose of GHRH 1-29 was required to obtain equivalent growth response to pulsatile GHRH 1-40. A significant linear correlation was shown between growth hormone secretion and height velocity on GHRH 1-40 but not on GHRH 1-29 and there was a significant correlation between plasma GHRH and serum growth hormone concentrations during GHRH 1-40 administration. Response to conventional growth hormone treatment in a matched group of children was significantly better than the response after GHRH. A significant improvement in height velocity was observed in the children transferred to growth hormone replacement. Growth hormone remains the treatment of choice in growth hormone insufficiency. GHRH treatment may be of benefit in children with less severe growth hormone insufficiency in the presence of pulsatile endogenous growth hormone secretion.

Child↗

PubMed1988

Relation between height velocity and fasting insulin concentrations.

A linear relation between fasting serum insulin concentration and height velocity was found in 47 normal children. This suggests that doubling of growth velocity at puberty is accompanied by a two to threefold rise in insulin. This implies that insulin dosage should be increased by a similar magnitude in pubertal diabetic children during their growth spurt.

Adolescent↗

PubMed1988

Body segments and growth hormone.

The effects of human growth hormone treatment for five years on sitting height and subischial leg length of 35 prepubertal children with isolated growth hormone deficiency were investigated. Body segments reacted equally to treatment with human growth hormone; this is important when comparing the effect of growth hormone on the growth of children with skeletal dysplasias or after spinal irradiation.

Anthropometry↗

PubMed1988

The 24-hour growth hormone secretion in a boy with giantism.

The endocrinological and radiological findings in a 7.5-year-old boy with giantism are reported and compared with an age and sex matched normal tall boy. A 24-h GH profile demonstrated a persistently elevated GH concentration (mean GH concentration: giant 19.3 mU/l; tall boy 5.4 mU/l) with loss of the dominant GH periodicity of 3 h seen in the boy with tall stature and substitution with one of 8 h. These data support the view that giantism and acromegaly are similar diseases occurring prior to and following epiphyseal fusion, respectively.

Child↗

PubMed1988

An evaluation of hormonal changes at puberty in man.

The pulsatile nature of the secretion of gonadotrophins, sex steroids and growth hormone are important in both the onset and maintenance of sexual maturation. The night-time is intimately related to the endocrine events which result in puberty, such that hormone measurements during the daytime have little meaning. This relationship between the night-time and gonadal function is not restricted to puberty but continues in adult life; the onset of the preovulatory LH surge occurs in the early hours of the morning. Girls seem more sensitive to small changes in GnRH concentrations than boys, which is why the physical signs of puberty appear slightly earlier in them. Low levels of oestradiol appear to assist growth hormone secretion, whereas higher levels of testosterone are required for the same effect. This probably explains the sex differences in the timing of the pubertal growth spurts.

Adolescent↗

PubMed1988

Growth and growth hormone secretion.

Growth hormone pulse amplitude is intimately connected with growth in childhood. Its effects are most clear in middle childhood, although the influence of adrenal androgens is probably also important. In infancy, nutrition plays an important part and, in the adolescent growth spurt, the synergism with sex steroids is important. Detailed attention needs now to be focussed on the mechanisms by which growth hormone is secreted and has its action; these include the effects of GHRH, somatostatin, insulin and IGF-I.

Adolescent↗

PubMed1988

New concepts of the growth spurt of puberty.

The timing of the growth spurt of normal children does not affect their final height attainment. Growth rate during the growth acceleration of puberty correlates with changes in GH, and not sex steroid, secretion. GH secretion during puberty is pulse amplitude, and not frequency, modulated. In both central precocious puberty and normal puberty suppressed with a GnRH analogue, the rate of epiphyseal maturation is decreased as are GH pulse amplitude and growth, but with no influence on final height.

Adolescent↗

PubMed1988

Evolution of polycystic ovaries in a girl with delayed menarche. A case report.

A 17-year-old girl had delayed growth secondary to low birth weight. Although she entered puberty at 12.5 years, she had delayed menarche. She underwent serial ovarian ultrasound scans, and a change in ovarian morphology was observed, from a normal multicystic appearance to one typical of polycystic ovaries (PCOs). We hypothesize that normal ovarian morphology may change to PCOs during the peripubertal period because of a change in the endocrine milieu.

Adolescent↗

PubMed1987

Induction of puberty by pulsatile gonadotropin releasing hormone.

15 girls and 17 boys with delayed or arrested puberty were treated with gonadotropin releasing hormone (GnRH) for a mean of 1.04 years. GnRH was administered subcutaneously in a pulsatile fashion at 90 min intervals, and the dose was increased as required to maintain progression of puberty, initially only at night and subsequently over 24 h. Initial GnRH dose was 1-2 micrograms per pulse in the girls and 2-4 micrograms per pulse in the boys. The effect of treatment was monitored by serial overnight gonadotropin profiles in all patients and with pelvic ultrasound in the girls. The clinical features, growth acceleration, endocrinology, and ovarian ultrasound morphology of puberty were those seen in normal children. Measurement of spontaneous gonadotropin pulsatility after treatment had been discontinued allowed the distinction between 20 patients with hypogonadotropic hypogonadism and 12 who had constitutional delay of growth and puberty. 2 girls and 6 boys did not respond to the treatment regimen. These findings indicate that normal puberty is GnRH dependent.

Adolescent↗