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Biomedical subjects

P Hindmarsh

Publications and source records attributed to P Hindmarsh.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1991

Management of growth hormone deficiency through puberty.

As a model of the growth hormone (GH) dependence of growth in prepuberty and puberty, the growth of 182 children (93 boys, 89 girls) who survived in first remission for treatment of acute lymphoblastic leukaemia was examined. Chemotherapy regimens, including intrathecal methotrexate, were similar in all patients, but CNS treatment differed, in that one group received 2400 cGy cranial irradiation, while the other received 1800 cGy. There was a significant decrease in height SDS during prepuberty, which was equivalent in both sexes, whereas there was a much greater decrease in pubertal growth in girls than in boys. Girls treated with the lower dose regimen of cranial irradiation had their onset of pubertal maturation significantly advanced, to a mean of 9.9 years (p less than 0.001). Previous studies have indicated that the duration of puberty is shortened by GH treatment in patients with idiopathic multiple pituitary hormone deficiency or isolated GH deficiency (GHD). To determine whether an increase in the dose of GH administered during the adolescent growth spurt would improve final height, a prospective randomized trial was performed in 32 children (25 boys, 7 girls) with isolated GHD treated with a GH dose regimen of 15 IU/m2/week as daily s.c. injections. At the onset of the pubertal growth spurt, the patients were randomized either to an unchanged dose or to 30 IU/m2/week. There was no significant change in height velocity with the doubled dose of GH, but there was a trend in the advancement of pubertal maturation which was considered to be dose related. It is suggested that these findings are of relevance to the treatment of GHD in puberty, especially in girls with early or precocious puberty occurring as a consequence of low-dose cranial irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Growth velocity, growth hormone therapy, and serum concentrations of the amino-terminal propeptide of type III procollagen.

The relationship between serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and growth was assessed in 307 healthy subjects and 82 children with disorders of growth (41 with insufficient growth hormone, 23 with short stature and normal endocrinologic studies, 18 with tall stature) by means of a recently developed, simplified PIIINP radioimmunoassay. The PIIINP value appeared to be related to height velocity; in healthy children of each sex, the pattern of change with age mirrored the shape of the standard height velocity curve; in children with disorders of growth, there was a statistical correlation (p less than 0.001) between PIIINP concentration and height velocity. However, measurement of serum PIIINP alone had no diagnostic value because there was considerable overlap of PIIINP values in children with growth hormone insufficiency, short stature, normal stature, and tall stature. The most appropriate application of PIIINP may be in the monitoring of prepubertal children receiving exogenous growth hormone therapy; in these patients, increases in height velocity were reflected by increases in PIIINP, and early increases in PIIINP may have predictive value.

Body Height↗
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↗
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

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

High resolution CT scanning of the pituitary gland in growth disorders.

We have performed 217 GEC 8800 CT scans of the hypothalamus and pituitary glands of 202 children with disorders of growth and development. Pituitary morphological abnormalities were common. Intrapituitary low density lesions were found in 17% of the whole series and in 58% of children with tall stature. Seventy-seven children with idiopathic growth hormone deficiency could be divided on the basis of pituitary morphology seen on CT scan into pituitary aplasia (n = 11) and pituitary hypoplasia (n = 53). Patients with pituitary aplasia had an absent adenohypophysis which probably dated from early intrauterine life and therefore could not be related to birth trauma. We have found a high incidence of evolving endocrinopathy in children with pituitary insufficiency: thus, if a short child is investigated the initial endocrine findings need to be repeated as the pattern of pituitary insufficiency changes with time. An evolving endocrinopathy starting in later childhood is suggestive of the presence of a cerebral tumour. Children with subnormal growth velocities and a normal growth hormone response to pharmacological tests have a wide spectrum of pituitary morphological abnormalities which may be associated with growth hormone neurosecretory dysfunction.

Adolescent↗
PubMed1986

Dysgenesis of the corpus callosum and hypopituitarism.

A high resolution CT scan demonstrated the unexpected finding of dysgenesis of the corpus callosum in addition to the expected finding of pituitary hypoplasia in three children who presented with growth failure secondary to hypopituitarism. Several of the clinical features reported in association with dysgenesis of the corpus callosum may be ascribed to hypothalamo-pituitary dysfunction. These children emphasize the need to assess the endocrine function of patients with midline structural defects. It should not be assumed that the clinical manifestations are related solely to the anatomical abnormality.

Agenesis of Corpus Callosum↗