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Biomedical subjects

C G Brook

Publications and source records attributed to C G Brook.

At least 199 records · Page 11Linked to original sources
PubMed1987

Effect of growth hormone on short normal children.

The growth of 26 short normal prepubertal children (mean age 8.4, height velocity standard deviation score for chronological age between +0.4 and -0.8) was studied for two years. Sixteen children were treated with somatrem (methionyl growth hormone) during the second year, and the remaining 10 children served as controls. During one year of treatment the height velocity standard deviation score for chronological age increased from the pretreatment mean of -0.44 (SD 0.33) to +2.20 (1.03). These values represented a change in height velocity from a pretreatment mean of 5.3 cm/year (range 4.6-6.9) to 7.4 cm/year (range 5.7-9.9). In the control group the height velocity standard deviation score was unchanged. Bone age advanced by 0.75 (0.33) years in the treated group compared with 0.70 (0.18) years in the control group. There was a significant increase in the height standard deviation score for bone age (0.63 (0.55] in the treated group. Multiple regression analysis of predictive factors contributing to the change in height velocity standard deviation score over the first year of treatment showed that the dose of growth hormone and pretreatment height velocity standard deviation score were important, together yielding a regression correlation coefficient of 0.80. The only metabolic side effect of treatment was an increase in fasting insulin concentration, which may be an important mediator of the anabolic effects of growth hormone. Treatment had no effect on thyroid function, blood pressure, or glucose tolerance. At the end of the treatment year seven of the 16 treated children had developed antibodies to growth hormone, but they were present in low titre with low binding capacity and in no child was growth attenuated. Biosynthetic growth hormone improved the height velocity of children growing along or parallel to the third height centile, but the effects on height prognosis need to be assessed over a longer period.

Antibodies↗
PubMed1987

The evolution of polycystic ovaries in a girl with hypogonadotropic hypogonadism before puberty and during puberty induced with pulsatile gonadotropin-releasing hormone.

We describe a girl of 12.7 years who had GnRH deficiency after surgery and radiotherapy for a craniopharyngioma at age 5 years. She had large cystic ovaries with a small uterus in the absence of spontaneous gonadotropin pulsatility. Puberty was induced by low-dose pulsatile GnRH treatment over a 1.5-year period. In the perimenarcheal period, ovarian morphology became typical of PCO with abnormal diurnal pulsatile gonadotropin secretion. These data suggest that PCO is primarily a disorder of the ovary and that the observed gonadotropin abnormalities are secondary to the ovarian lesion.

Child↗
PubMed1987

The place of intravenous GHRH 1-40 studies in the therapy of growth hormone-deficient children with GHRH.

We studied GH responses to i.v. GH releasing hormone (GHRH) (1 microgram/kg) before and during the treatment of 11 GH deficient children with s.c. nocturnal pulsatile GHRH 1-40; seven for 9 months and four for 6 months. Each subject demonstrated GH stimulation at each i.v. study. There was a wide variation of response between subjects and in each subject on different occasions. Significant growth acceleration following s.c. GHRH was demonstrated in eight of 11 patients (73%). The sensitivity or true positive rate of the index GHRH study to predict a clinical response to s.c. treatment, regardless of the GH response achieved, was also 73%. When an index GH 'cut-off' response of less than 10 mU/l was employed, the probability of an increase in growth rate to s.c. GHRH fell to 0.50 (sensitivity 80%). The GHRH study was unhelpful, and in fact misleading, when assessed as a method of monitoring clinical progress and the outcome of pulsatile s.c. GHRH treatment. The growth response of a child to s.c. GHRH therapy is of far greater importance than the GH response following an i.v. bolus of GHRH. The index study gave no useful indication of either the potential GH pituitary reserve or which subjects would respond to treatment. Pretreatment and repeated GHRH studies are of limited value and should be interpreted with caution.

Child↗
PubMed1987

Plasma immunoreactive GHRH and serum GH concentrations following pulsatile GHRH 1-40 administration in GH deficient children.

We have studied the clearance from plasma of immunoreactive growth hormone releasing hormone 1-40 (IR-GHRH) following intravenous (i.v.) and subcutaneous (s.c.) administration and the relationship between exogenous plasma IR-GHRH concentrations and GH secretion in five GH insufficient children receiving long term nocturnal pulsatile GHRH 1-40. The i.v. studies with GHRH 1-40 1 micrograms/kg demonstrated a distribution half life (t1/2) of 3.9 (SD 0.9) min and an elimination t1/2 of 53.1 (SD 3.2) min. In the s.c. studies the elimination phase was similar to the i.v. results but the transit time to the GHRH peak was slower than the i.v. distribution t1/2 9.9 (SD 3.6) min. These characteristics were maintained during successive pulses of subcutaneous GHRH. The mean IR-GHRH peaks following s.c. GHRH 1-40 administration of 1 microgram/kg and 2 micrograms/kg were 37- and 18-fold lower respectively than the mean IR-GHRH peak observed after the i.v. 1 microgram/kg bolus study. A significant correlation was shown between peak plasma IR-GHRH and serum GH concentrations during the s.c. (r = 0.75) but not the i.v. studies. Pulsatile GHRH administration has been shown to stimulate GH secretion and growth acceleration in GH insufficient children. Knowledge of the relationship between GHRH 1-40 absorption from the subcutaneous site and GH secretion is important for the development of an optimal GHRH treatment regimen in GH insufficient children.

Child↗
PubMed1987

The relationship between height velocity and growth hormone secretion in short prepubertal children.

We have performed 24 h growth hormone (GH) profiles in 50 short prepubertal children aged between 5.2 and 12.9 years, growing with height velocity standard deviation scores (SDS) between 0.4 and -3.9. There was an asymptotic relationship between height velocity and spontaneous GH secretion described by the equation: height velocity SDS = A-B(e-cx), where A, B and C are constants and x is a measure of spontaneous GH secretion. We considered GH pulse amplitude to be the better description of spontaneous GH secretion as duration of the GH pulse (the time component of area under the curve) contributed little to the relationship between height velocity and area under the pulse. The distribution of GH secretion was continuous and there was no dividing point between GH insufficiency and sufficiency. Similar overlap was observed when the results of GH responses to insulin induced hypoglycaemia were considered; 14% of slowly growing children (height velocity SDS less than -0.8), had a response greater than 15 mU/l. Likewise serum IGF-I concentrations could not clearly separate slowly growing children from normal individuals. We conclude that height velocity, which ultimately determines height achieved, is controlled predominantly by GH pulse amplitude. The findings suggest that short normal children growing along or parallel to the third height centile could be made to grow faster by the administration of exogenous GH.

Body Height↗
PubMed1987

Is growth hormone deficiency a useful diagnosis?

Evidence is presented that there is a continuum in endogenous hGH secretion ranging from those children with poor growth velocities who secrete very little, formerly called hGH deficient, to those with normal growth velocities who secrete a much greater amount. The relationship between growth velocity and hGH secretion in short children is described by an asymptotic regression. Further, the relationship between growth and hGH is modulated by hGH pulse amplitude. The therapeutic implications of this relationship are that any short child given hGH will grow more rapidly, and that those children growing most slowly with the least endogenous hGH secretion will have the greatest increment in height velocity for a standard dose of exogenous hGH.

Body Height↗
PubMed1987

Incidence of overt and covert neurological damage in children with sickle cell disease.

We studied 25 patients with sickle cell disease (15 with HbSS; 8 with HbSC and 2 with HbS beta degree) using neurological examination as a marker of overt and computed tomographic (CT) scan as a marker of covert neurological damage. Of the 25 patients, 5 (20%) had evidence of cerebral infarcts on CT scan, but only 4 of these 5 patients had neurological signs. Neurological problems were only seen in patients with HbSS. We could not identify any haematological risk factors, but in this small group of HbSS patients a crisis rate greater than 1 per year of follow up was associated with a significant risk of neurological damage.

Adolescent↗
PubMed1987

Changes of skinfold thickness during puberty induced by pulsatile gonadotrophin-releasing hormone therapy.

We have analysed the changes in triceps and subscapular skinfold thickness ratios of 66 (46 male, 20 female) children with constitutional delay of growth and puberty who progressed through puberty spontaneously and 16 (7 male, 9 female) children with delayed puberty who were treated with pulsatile gonadotrophin-releasing hormone (GnRH). The pattern of change in skinfold thickness in both groups were identical and indistinguishable from standards of normal children when later chronological ages of the patients were allowed for. We observed a decrease in skinfold ratio just prior to the onset of puberty in boys, and such an assessment may be a useful early predictor of the onset of puberty. Our data provided further evidence that all aspects of human puberty are entirely GnRH-dependent.

Adolescent↗
PubMed1987

Oxandrolone induces a sustained rise in physiological growth hormone secretion in boys with constitutional delay of growth and puberty.

We describe the treatment of 3 boys, mean age 14.9 years (range 13.8-16.1 years) with constitutional delay of growth and puberty using oxandrolone in two dose regimens, 2.5 or 1.25 mg/day for 3 months. Treatment induced an increase in mean height velocity from 5.1 to 8.5 cm/year; this was sustained at 8.8 cm/year in the period following treatment. Growth hormone (GH), luteinising hormone and testosterone secretion were assessed by overnight or 24-hour venous sampling at 15-min intervals before, during treatment and after cessation of treatment. A computer programme was used to analyse GH secretory dynamics. The 3 boys had a mean sustained increase in total GH secretion of 190%. The increase in GH secretion was associated with an increase in amplitude of GH pulses rather than an alteration in pulse frequency.

Adolescent↗
PubMed1986

Studies of gonadotrophin pulsatility and pelvic ultrasound examinations distinguish between isolated premature thelarche and central precocious puberty.

We have studied the pulsatile secretion of gonadotrophins at night and made ovarian ultrasound examinations in three girls with central precocious puberty and three with isolated premature thelarche. The three girls with precocious puberty had well-defined pulsatile secretion of LH and FSH with LH predominating, as would be expected in normal puberty. Pulsatile secretion of gonadotrophins was also seen in girls with premature thelarche but the pattern was reversed. In girls with precocious puberty, large "multicystic" ovaries and large uteri were seen on ultrasound examination, whereas girls with isolated premature thelarche had small uteri and ovaries with less than four "cysts" up to 15 mm in diameter. These data provide the key to understanding the aetiology of isolated premature thelarche.

Breast↗
PubMed1986

Tall stature: a clinical, endocrinological and radiological study.

We have studied GH secretory dynamics in 38 (25 F, 13 M) children referred for investigation and treatment of tall stature (Height SD score (SDS) greater than 1.8). Five children had elevated basal GH levels (mean 20.4 mU/l) and a further four had abnormal GH responses to exogenous TRH. Two other children had paradoxical GH responses to oral glucose loading. Although one of these was receiving high dose testosterone to limit final height. All these children were pubertal and did not show concordance between peak GH concentration observed after insulin-induced hypoglycaemia and during stage IV sleep. Twenty-four hour GH profiles revealed increased GH pulse amplitude and area under the pulse during puberty. Morning GH secretion was also regularly observed and it is possible that the paradoxical responses seen by us and reported by others reflect this increased physiological secretion. Pituitary radiology revealed morphological abnormalities suggestive of microadenomata in 17 patients but these were all in late puberty and these changes may be related more to the effects of sex hormones than to somatotroph pathology. 'Abnormal' endocrinology and radiology are seen in tall children in puberty and must be interpreted with caution.

Body Height↗