Growth Hormone Secretion In Children Research Articles

Cholinergic muscarinic blockade produces short-term suppression of growth hormone secretion in children with tall stature.

We have studied the effects of oral pirenzepine (50 mg twice daily) on growth and growth hormone (GH) secretion in 10 children with tall stature (9F, 1M). Suppression of GH secretion was observed in all children for 2-3 h after drug administration but was followed by rebound secretion of GH after 4-6 h. Consequently there was little overall change in GH secretion. In the dose regimen used the disruption of normal pulsatile GH secretion was not sufficiently significant to change final or predicted heights.

Enhancement of cholinergic tone by pyridostigmine promotes both basal and growth hormone (GH)-releasing hormone-induced GH secretion in children of short stature.

Increased cholinergic tone induced by pyridostigmine (PD) increases basal plasma GH levels and potentiates the GH response to GHRH in normal adults. In this study the effects of PD (60 mg, orally) on both basal and GHRH (1 microgram/kg)-induced GH secretion in seven children with familial short stature (FSS), six with GH deficiency (GHD) and 10 with constitutional growth delay (CGD) were studied and compared with results obtained by stimulation with insulin-induced hypoglycemia (IH) and GHRH alone. The mean peak plasma GH levels were variable, but individual values were frequently low in all groups after both IH [FSS, 9.7 +/- 1.3 (+/- SEM) ng/mL; GHD, 1.6 +/- 0.4 ng/mL; CGD, 7.0 +/- 0.8 ng/mL] and GHRH (FSS, 23.8 +/- 6.6 ng/mL; GHD, 11.1 +/- 5.8 ng/mL; CGD, 15.1 +/- 4.5 ng/mL) administration. PD induced GH responses (FSS, 14.5 +/- 1.6 ng/mL; GHD, 3.8 +/- 0.8 ng/mL; CGD, 18.3 +/- 3.2 ng/mL) that in many children in the FSS and CGD groups were higher than those after IH and GHRH treatment. PD clearly increased the GH response to GHRH in all children [FSS, 69.5 +/- 9.4 ng/mL (P less than 0.01 vs. other stimuli); GHD, 18.0 +/- 7.5 ng/mL; CGD, 50.0 +/- 8.5 ng/mL (P less than 0.01 vs. other stimuli)]. We conclude that in children with short stature, as in adults, enhancement of cholinergic tone increases both basal and GHRH-induced GH secretion, and that PD plus GHRH is the best provocative stimulus for evaluating the somatotroph response.

Arginine‐Induced Insulin and Growth Hormone Secretion in Children with Nutritional Rickets

SummaryWe evaluated arginine‐induced insulin and growth hormone (GH) secretion in ten children with vitamin D deficiency rickets and compared these values with those of eight age‐matched control children. All ra‐chitic children had biochemical (increased serum alkaline phosphatase activity and decreased calcium ± phosphate product) and clinical evidence for rickets. After an intravenous infusion of arginine‐HCl (10% solution, 0.5 g/kg), blood samples were obtained for the measurement of serum insulin and GH concentrations. The mean insulin level 30 min after the start of the infusion was 22.2 ± 17.1 μU/ml for the rachitic children. This value is significantly below that for the normal children, 63.4 ± 38.7 μU/ml (p = 0.004). Neither the fasting insulin level nor any others after the arginine infusion differed significantly from those for the control children. There were no significant differences in the fasting or the arginine‐stimulated GH levels between the rachitic and control children. The concentrations of insulin‐like growth factors did not differ between the two groups.

Arginine-induced insulin and growth hormone secretion in children with nutritional rickets.

We evaluated arginine-induced insulin and growth hormone (GH) secretion in ten children with vitamin D deficiency rickets and compared these values with those of eight age-matched control children. All rachitic children had biochemical (increased serum alkaline phosphatase activity and decreased calcium x phosphate product) and clinical evidence for rickets. After an intravenous infusion of arginine-HCl (10% solution, 0.5 g/kg), blood samples were obtained for the measurement of serum insulin and GH concentrations. The mean insulin level 30 min after the start of the infusion was 22.2 +/- 17.1 microU/ml for the rachitic children. This value is significantly below that for the normal children, 63.4 +/- 38.7 microU/ml (p = 0.004). Neither the fasting insulin level nor any others after the arginine infusion differed significantly from those for the control children. There were no significant differences in the fasting or the arginine-stimulated GH levels between the rachitic and control children. The concentrations of insulin-like growth factors did not differ between the two groups.

The effects of intranasal insufflation of growth hormone releasing factor analogie GRF1 – 29 NH2 on growth hormone secretion in children with short stature

The effects of intranasal insufflation of the synthetic growth hormone releasing factor GRF 1-29-NH2 on serum growth hormone (GH) were investigated in five healthy prepubertal children with short stature. 100 micrograms/kg/body weight of synthetic GRF 1-29-NH2, 500 micrograms in 100 microliters water, were insufflated intranasally after careful cleaning of the nose. GRF 1-29-NH2 induced a prompt rise of serum GH levels with peak values at 15 minutes in all children investigated. Peak serum GH values were 28.3 +/- 12.0 ng/ml (mean +/- SD), range 17.1 - 47.6 ng/ml; delta GH was 27.0 +/- 12.2 ng/ml (mean +/- SD). Serum GH levels were still significantly raised 120 minutes after the insufflation of GRF 1-29-NH2 (p less than 0.05). No side effects, except for burning of the nasal mucosa in one patient, were observed. The results of this study demonstrate that intranasal insufflation of synthetic GRF 1-29-NH2 induces a prompt release of GH in otherwise normal children with short stature. Pulsatile intranasal insufflation of GRF 1-29-NH2 probably could be used for the treatment of some children with GH deficiency due to a defect at a suprapituitary level.

Effect of overnight constant infusion of human growth hormone (GH)-releasing hormone-(1-44) on 24-hour GH secretion in children with partial GH deficiency.

A continuous infusion (0.5 or 1 microgram/kg X h) of GH-releasing factor-(1-44) [GHRH-(1-44)] was administered from 2000-0800 h to 16 children with GH deficiency, defined as a maximum peak plasma GH less than 11 ng/ml in response to 2 provocative tests [first test; mean, 7.4 +/- 2.6 (+/- SD) ng/ml; second test; mean, 8.4 +/- 2.4 ng/ml]. Eight were boys and 8 girls; their average age was 10 yr, 5 months; and growth was retarded in all [mean, -3 +/- 0.6 (+/- SD)]. Polygraphic monitoring was carried out during the night, and blood samples for plasma GH measurements were drawn every 20 min during the night and the following day. A control study had been carried out in the preceding months with the same children. During GHRH infusion, a significant increase in nocturnal GH secretion occurred; the mean maximum peak increased from 17.5 +/- 3.4 (+/- SD) to 38.7 +/- 3.2 ng/ml, the mean area under the curve from 2243 +/- 459 to 5348 +/- 710 ng/ml, the mean integrated concentration from 4.2 +/- 0.8 to 9.9 +/- 1.3 ng/ml X min, and the mean number of peaks above 5 ng/ml from 2.7 +/- 0.3 to 4.7 +/- 0.4. During GHRH infusion, the 16 children had 2 peaks during the first 4 h of sleep and a third peak at the end of the night. Plasma GH levels the day after the infusions were not significantly increased. We conclude that continuous nocturnal GHRH infusion increases pulsatile sleep GH secretion throughout the night in children with partial GH deficiency.

Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia

Basal growth hormone levels were measured every 20 minutes over 24 hours in eight long-term survivors of acute lymphoblastic leukemia and in 13 age- and pubertal stage-matched normal children. Among the patients, the median total basal growth hormone output (AUC) was 43 units, compared with 341 units in the normal control group (P less than 0.001). In the patients, mean pulse amplitude (6.9 ng/ml) and frequency (4.6) over 24 hours also were reduced, compared with the control values (32 ng/ml and 8.5, P less than 0.001 and P less than 0.05, respectively). In addition, normal children secreted more GH at night (median AUC 280) than during the day (113, P less than 0.001). However, this diurnal pattern was absent in three of the patients studied. These data suggest that perturbations of spontaneous pulsatile GH secretion are common after standard therapy for ALL and may be a sensitive means of detecting therapy-related neuroendocrine damage. Blunting of spontaneous pulsatile GH secretion may contribute to the abnormalities in growth seen in children with ALL.

Height, weight, and growth hormone secretion in children treated for acute leukemia

Growth, weight gain, and human growth hormone secretion were studied for 3 to 7 years in 27 children with acute leukemia in complete continuous remission. Growth and weight gain were matched for sex and age by calculating the standard deviation score. The mean SD score for height velocity was subnormal during the three years of therapy. A catch up in growth and weight gain occurred during the first year after the cessation of therapy. The loss of final attained height was small. HGH secretion was studied at the end of therapy and at yearly intervals thereafter by two provocative tests; glucagon and sleep. No significant difference in secretion was seen between the group studied and a control group of children. Acute leukemia, children, growth, growth hormone, irradiation, weight gain.

The Effect of Single-Dose Radiation on Cell Survival and Growth Hormone Secretion by Rat Anterior Pituitary Cells

Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100-1500 rad: Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0-300 rad, followed by a decline between 300-750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad.

Normal growth despite abnormalities of growthhormone secretion in children treated for acute leukemia

We have studied the relationship between abnormalities of the growth hormone-somatomedin axis and growth in 26 children previously treated for acute lymphatic leukemia. Each child had previously received cranial irradiation, was in complete clinical and hematologic remission, and off all drugs. The mean standing height SDS of the 26 children was significantly less than normal. There was no significant difference between the mean standing height SDS, height velocity SDS, somatomedin activities, and degree of bone age retardation between the 17 children who received the higher dose of cranial irradiation (Group 1) and the nine who had the lower dose of cranial irradiation (Group II). Furthermore, there was no significant reduction in mean height velocity SDS, somatomedin activity, or bone age in either group when compared to normal age-matched controls. The peak GH responses to both insulin hypoglycemia and an arginine test were significantly lowered in Groups I and II when compared to a control group of children. We conclude that only a minority of children, who previously received cranial irradiation for ALL were clinically GH deficient and, therefore, likely to benefit from GH therapy despite the finding that the majority of these children had reduced GH responses to pharmacologic stimuli.

Irradiation of the head. Immediate effect on growth hormone secretion in children.

Plasma growth hormone (GH) was determined in samples obtained hourly from 1000 h to 0700 h before, and after a 3 week course of "prophylactic" cranial irradiation, in ten leukemic children who had no clinical or laboratory evidence of central nervous system involvement. The mean per hour value of GH prior to irradiation (4.1 +/- 2.4 ng/ml) was similar to that of 7 endocrinologically normal children (4.09 +/- 2.4 ng/ml), a finding strongly suggesting normal pituitary function prior to irradiation. Following irradiation GH levels at each hour were, in general, lower than before. The difference is statistically significant at 0100 h. The peak GH responses were lower following than preceeding irradiation (p less than 0.02). The findings suggest an immediate suppressive effect of irradiadiation on the apparently normal hypothalamic pituitary axis in children.

THE EFFECT OF THE STIMULANT DRUGS DEXTROAMPHETAMINE AND METHYLPHENDIATE ON GROWTH HORMONE SECRETION IN HYPERACTIVE CHILDREN

Recent reports that prolonged use of the stimulant drugs dextroamphetamine and methylphendiate (Ritalin) in high doses can suppress growth in hyperactive children and that rebound growth occurred after cessation of therapy, prompted us to test whether these two drugs could provoke growth hormone (GH) secretion. The effect of L-dopa (l25–500 mg) and 15 mg of amphetamine on GH secretion was studied in 10 hyperactive children. Each of the children had both tests performed on alternate days, and serum GH was determined at 0, 30, 60, 90, 120 and 180 min. Individuals with a peak serum GH level of less than 6 ug/ml were considered “non-responders”. There were two non-responders to each drug, and one child did not respond to either test. Peak GH response occured at 60 min in both tests with a mean peak CH level of 11.7 ug/ml after L-dopa and 9.8 ug/ml after amphetamine. There were no significant differencesbetween the mean values at any time of sampling. Preliminary data indicate that methylphendiate also can provoke GH secretion to similar extent as amphetamine. We are now in progress to retest the effect of these drugs on GH secretion in children who have been on methylphendiate treatment for 6 months or more.

Growth hormone secretion in children during corticosteroid treatment. Responses to arginine.

Growth hormone response was studied during long term corticosteroid treatment in 13 children. Arginine infusion was used as the stimulus of growth hormone release. The growth hormone levels were significantly higher in the steroid treated group than in normal controls. There was no correlation between the dose of the drug or the duration of the treatment and growth hormone concentration.

Abnormalities of insulin and growth hormone secreton in children with coeliac disease.

The effect of intravenous tolbutamide on plasma levels of glucose, cortisol, growth hormone, and insulin, and the effect of oral Bovril on plasma growth hormone have been studied in 10 children with coeliac disease and 6 children who, though small, had normal jejunal morphology (`controls9). The growth hormone and insulin responses to tolbutamide in the children with coeliac disease were significantly smaller than in the controls. Growth hormone response to Bovril was normal in most of the children but 3 of them with coeliac disease failed to achieve a satisfactory response in growth hormone levels after both tolbutamide and Bovril. These results cannot be explained by malnutrition or by inadequate hypoglycaemia during tolbutamide stimulation, and a convincing hypothesis to explain them has not been formulated. Clinically, though tests of other conventional stimuli of growth hormone and insulin production require study, the diagnosis of coeliac disease should actively be considered in any child with low levels of insulin and growth hormone. These observations may partly explain the association of coeliac disease and diabetes mellitus.

Studies of Growth Hormone Secretion in Children: Normal, Hypopituitary and Constitutionally Delayed

Plasma growth hormone levels in normal children, in children with pituitary or hypothalamic disorders, in children with idiopathic growth hormone deficiency and in children with a constitutional delay in growth were examined in the fasting state and following stimulation with insulin hypoglycemia, arginine and bacterial pyrogen (Piromen). Normal children exhibited a marked fluctuation in fasting growth hormone levels. The highest plasma growth hormone levels were observed after insulin, but the mean maximal levels in response to each of the stimuli were not statistically different from one another because of a marked variation in response. Four children with a constitutional delay in growth had plasma growth hormone values indistinguishable from those of normal children. Seven children with idiopathic growth hormone deficiency had fasting and post-stimulatory plasma growth hormone levels significantly lower than normal children. In subjects with known pituitary or hypothalamic disorders virtually no elevations in plasma growth hormone levels occurred following stimulation. The levels in these subjects were lower than in some of the children with idiopathic growth hormone deficiency. The results suggest that 1) constitutional delay in growth is not associated with abnormalities in growth hormone responses to the stimuli used, 2) children with idiopathic growth hormone deficiency have significantly lower pre- and poststimulatory growth hormone levels than do normals, and 3) the lack of response to stimulation occasionally seen in normal children is often associated with high resting levels of growth hormone.