Growth hormone treatment and the short child: to treat or not to treat?
Explore the source record for details and available documents.
Body Height↗
Biomedical subjects
B B Bercu
Publications and source records attributed to B B Bercu.
Maturational arrest: an experiment in nature.
Explore the source record for details and available documents.
Adult↗
Evaluation of growth hormone secretion: provocative testing vs endogenous 24-hour growth hormone profile.
A total of 55 children underwent hGH provocative testing with two or more provocative agents, and measurement of endogenous 24-hour hGH secretion. Patients were divided into groups according to their peak hGH secretory response to provocative testing and their mean 24-hour hGH concentration. Peak hGH response to provocative testing was significantly greater in control children and in children with hGH neurosecretory dysfunction (GHND) than in the classical hGH deficient group. Mean 24-hour hGH concentration was significantly greater in the control group than in either the classical hGH deficient or GHND groups. Responses to provocative stimuli were intermediate for the GHND group compared to the classical hGH deficient and the control groups. The mean peak hGH secretory response to insulin-induced hypoglycaemia in the GHND group was poor compared to controls and was greatest following clonidine. The mean peak hGH response to an intravenous bolus of growth hormone releasing hormone was intermediate for the GHND group compared to hGH deficient and control groups. Highest nocturnal peak, first hGH pulse after sleep, mean peak hGH pulse and total number of pulses were also intermediate for the GHND group compared to the other groups. The control group had significantly more pulses greater than 5 ng/ml than did the other groups. Night-time and daytime hGH pools were lower in the classical hGH deficient and GHND groups compared to controls; however, there was overlap between groups. Six of seven children in the GHND group have responded to exogenous hGH therapy with increased linear growth velocity. Measurements of endogenous 24-hour hGH secretion may identify a subgroup of hGH deficient children who are not detected by provocative testing yet who may respond to exogenous hGH therapy with improved linear growth.
Adolescent↗
Developmental outcome in children exposed to chloride-deficient formula.
The developmental outcome of 2- and 4-year-old children who had been exposed as infants to chloride-deficient formula was studied. A negative dose-response relationship was demonstrated between use of the formula without additional nutritional supplementation and cognitive outcome as measured by the Bayley Scales of Infant Development (Pearson r = -.55, P = .01) at 2 years of age. A similar negative relationship was demonstrated between this exclusive use of the defective formula and perceptual (Pearson r = -.51, P less than .05), motor (Pearson r = -.52, P less than .05), and fine motor (Pearson r = -.75, P less than .002) ability as measured by the McCarthy Scales of Children's Abilities at 4 years of age. When other know predictors of developmental outcome were taken into account by means of multiple linear regression analyses, exclusive formula use emerged as an important predictor of the children's cognitive functioning at 2 years (model R2 = .59, P less than .005) and of quantitative (model R2 = .58, P less than .006), perceptual (model R2 = .63, P less than .009), and fine motor ability (model R2 = .74, P less than .003) at 4 years of age. These data raise concern about the developmental outcome of the children exposed to chloride-deficient formula.
Child, Preschool↗
Regulation of growth hormone secretion. Relevance to the pediatrician.
The regulation of human growth hormone secretion is complex involving both a hypothalamic stimulating and inhibiting hormone. These neurohormones are further regulated by neurotransmitters. Abnormalities in growth hormone secretion may occur in neurologic, psychiatric and metabolic disorders not related to short stature. In addition, the diagnosis of deficiency states of growth hormone secretion can often be very difficult. Guidelines for the work-up of short children are given.
Female↗
Hypothalamic-pituitary dysfunction in primary empty sella syndrome in childhood.
In a series of 37 consecutive CT scans performed in children referred to our pediatric endocrine unit, an empty (eight) or partially empty (one) sella turcica was found in nine (24%) patients with short stature or delay in sexual maturation, precocious puberty, or hypoparathyroidism. The size and contour of the sella were abnormal in only three patients. Five of the nine children had evidence of decreased growth hormone secretion as determined by subnormal GH secretory responses to provocative tests (peak GH concentration less than 7 ng/ml) or assessment of endogenous 24-hour GH secretion (mean 24-hour GH concentration less than 3 ng/ml). Two children had multiple pituitary hormone deficiencies. Although primary empty sella syndrome was often associated with hypothalamic-pituitary dysfunction in this series, the prevalence of an empty sella in normal children is unknown. Further identification and evaluation of children with empty sella may provide new information regarding the cause of pituitary dysfunction in childhood.
Adolescent↗
Growth hormone neurosecretory dysfunction.
The basis for understanding clinical disorders in the neuroregulation of GH secretion is derived from the complexity of the CNS-hypothalamic-pituitary axis. Studies in animals and humans demonstrate an anatomic, physiological and pharmacological evidence for neurosecretory control over GH secretion including neurohormones (GRH, somatostatin), neurotransmitters (dopaminergic, adrenergic, cholinergic, serotonergic, histaminergic, GABAergic), and neuropeptides (gut hormones, opioids, CRH, TRH, etc). The observation of a defect in the neuroregulatory control of GH secretion in CNS-irradiated humans and animals led to the hypothesis of a disorder in neurosecretion, GHND, as a cause for short stature. We speculate that in this heterogeneous group of children a disruption in the neurotransmitter-neurohormonal functional pathway could modify secretion ultimately expressed as poor growth velocity and short stature.
Amino Acid Sequence↗
Growth hormone (GH) provocative testing frequently does not reflect endogenous GH secretion.
GH secretion was studied in 73 children with classical GH deficiency or GH neurosecretory dysfunction (GHND), intrinsic short stature, or normal stature. The GH-deficient group was defined by a peak GH secretory response below 10 ng/ml to all provocative tests (arginine, L-dopa, insulin hypoglycemia, and clonidine). GHND was defined by a mean serum 24-h GH concentration below 3 ng/ml, with a normal response (greater than or equal to 10 ng/ml) to provocative testing. Twenty-one GH-deficient children, 21 children with GHND, and 18 short control children underwent provocative GH testing and a 24-h study with GH sampling every 20 min. A group of 13 normal stature control children also underwent 24-h GH sampling. The mean stimulated peak serum GH level [4.7 +/- 0.6 (+/- SEM) ng/ml] in the GH-deficient group was significantly below that in the GHND (19.5 +/- 1.7 ng/ml) and short control groups (24.0 +/- 3.5 ng/ml; P less than 0.01). The mean 24-h serum GH concentration was reduced in GH-deficient (1.5 +/- 0.2 ng/ml) and GHND (2.0 +/- 0.1 ng/ml) children compared to those in short (5.6 +/- 0.5 ng/ml) and normal stature (5.8 +/- 0.8 ng/ml) control children (P less than 0.01). Peak GH concentrations after provocative testing correlated poorly with 24-h mean concentrations in GH-deficient, GHND, and short control children (r = 0.38, 0.23, and 0.41, respectively; P = NS for all groups). Mean serum GH concentrations from blood sampling intervals of 12 h (day/night; 0800-2000/2000-0800 h, respectively) or even 6 h (day; 0900-1500 h) were statistically different in GHND or GH-deficient groups compared to those in control children; however, there was significantly more overlap for individual children using the 6- and 12-h daytime intervals than for the 24-h data. Plasma somatomedin-C/insulin-like growth factor I correlated with mean 24-h GH concentration endogenous secretion (r = 0.7; P less than 0.001). These data suggest that provocative GH testing frequently does not correlate with endogenous GH secretion.
Adolescent↗
Preservation of dopaminergic and alpha-adrenergic function in children with growth hormone neurosecretory dysfunction.
The integrity of dopaminergic and alpha-adrenergic neurotransmitter regulation of GH secretion was examined in children with decreased GH secretion. Children with GH neurosecretory dysfunction (GHND; n = 16) those with classical GH deficiency (n = 9), and short but otherwise normal children (n = 12) underwent 24 h GH studies (blood sampling every 20 min for 24 h) and provocative tests using arginine, insulin hypoglycemia, L-dopa (dopaminergic) and clonidine (alpha-adrenergic), and GH-releasing hormone (GHRH). GHND was defined as children with height in the first percentile or below, growth velocity of 4 cm/yr or less, low plasma somatomedin-C for age, delayed skeletal age by 2 or more yr, peak serum GH responses to any one (or more) provocative test of 10 ng/ml or more, and mean 24-h GH concentration below 3 ng/ml. GHND and GH-deficient children had reduced endogenous GH secretion, expressed as mean serum 24-h GH concentration [1.6 +/- 0.1 (+/- SEM) and 2.1 +/- 0.1 vs. 6.1 +/- 0.5 ng/ml (GH-deficient and GHND vs. normal, respectively); P less than 0.01]. the mean peak serum GH levels after arginine [8.2 +/- 2.0 vs. 20.8 +/- 6.6 ng/ml (GHND vs. normal); P less than 0.05] and insulin [9.3 +/- 1.0 vs. 16.2 +/- 1.7 ng/ml (GHND vs. normal); P less than 0.01) were lower in GHND children. The mean peak responses after L-dopa [13.4 +/- 3.4 vs. 14.6 +/- 4.7 ng/ml (GHND vs. normal); P = NS] and clonidine [19.0 +/- 2.2 vs. 23.3 +/- 3.8 ng/ml (GHND vs. normal); P = NS] were preserved in GHND children. In GH-deficient children, mean peak serum GH concentrations after all four provocative tests were low (arginine, 2.7 +/- 0.8; insulin, 2.6 +/- 0.8; L-dopa, 3.0 +/- 0.9; clonidine, 3.4 +/- 1.0 ng/ml; all P less than 0.01 vs. normal). The mean peak serum GH concentration after GHRH was blunted in GH-deficient children (9.1 +/- 1.7 ng/ml) compared to those in GHND (32.9 +/- 8.5 ng/ml) and normal (43.2 +/- 6.4 ng/ml) children (P less than 0.01). The area under the GH curve after GHRH stimulation was greater for normal than GHND children (P less than 0.05). These data demonstrate preservation of dopaminergic and alpha-adrenergic neurotransmitter pathways in GHND children. They further suggest a defect in the release of pituitary GH secondary to an abnormality in alternative neurotransmitter pathways resulting in decreased GHRH and/or increased somatostatin secretion.
Adolescent↗
A determinant of stature: regulation of growth hormone secretion.
Explore the source record for details and available documents.
Adolescent↗
Blunted prolactin response to thyrotropin-releasing hormone stimulation in cystinotic children receiving cysteamine.
We investigated whether long term cysteamine therapy in cystinotic children altered their basal and stimulated serum PRL levels. Five subjects who had normal plasma PRL responses to TRH stimulation before cysteamine treatment each had a lower basal PRL level and a blunted PRL response during long term (19-59 months) cysteamine therapy. A blunted PRL response was not found in 12 cystinotic subjects of the same age and stage of disease who had not received cysteamine. The effect on PRL release was not found in 2 subjects who received short term (1-2 weeks) treatment with full-dose cysteamine (50 mg/kg . day). The TSH response to TRH stimulation was not blunted during long term cysteamine therapy. These findings suggest that cysteamine alters PRL secretion in humans.
Administration, Oral↗
Effect of a potent gonadotropin releasing hormone antagonist on pulsatile testosterone and gonadotropin secretion in the male nonhuman primate.
A potent gonadotropin releasing hormone (GnRH) antagonist [Ac-delta 3Pro1, pFDPhe2, DTrp3,6]-GnRH was given to adult male monkeys to determine the acute effect on pulsatile testosterone and gonadotropin secretion. Blood was drawn at 30 min intervals over 54 h without anesthesia using a mobile vest and tether assembly to support an indwelling catheter. After a 6 h control period, 0.1, 1.0, 2.0, 4.0 mg GnRH antagonist/kg bw in 1 ml corn oil sc, was given to intact adult male monkeys. The highest dose of GnRH antagonist decreased circulating testosterone within 6 h and for approximately 24-36 h duration. These data demonstrate that this GnRH antagonist can reduce serum testosterone both acutely and for intervals greater than 24 h and that the effective dose in intact animals is several-fold (up to 20 times) greater than in castrate animals.
Animals↗
Growth hormone neurosecretory dysfunction. A treatable cause of short stature.
Pulsatile growth hormone (GH) secretion was assessed in a subgroup of short children to determine whether they had GH secretory abnormalities, and these results were compared with those of normal and GH-deficient children. This subgroup of children was defined as having GH neurosecretory dysfunction and met the following criteria: height, less than first percentile; growth velocity, 4 cm/yr or less; bone age, two or more years behind chronological age, normal findings from provocative GH tests (peak, greater than or equal to 10 ng/mL), low somatomedin-C level, and abnormal 24-hour GH secretory patterns. When compared with controls, both children with GH neurosecretory dysfunction and GH-deficient patients had a significant decrease in parameters relating to the total GH secretion during the 24-hour period. As with GH-deficient children, the group with GH neurosecretory dysfunction more than doubled their growth velocity after replacement therapy with exogenous human GH during the first year of treatment. As a result of these detailed studies on pulsatile GH secretion, we suggest that there is a spectrum of GH secretory abnormalities from absolute deficiency to an intermittent irregularity in GH secretion.
Adolescent↗
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.
Adolescent↗
Resistance of the male gonad to a high galactose diet.
Rats were fed a 50% galactose diet during pregnancy and nursing, and the testes were later examined and hormone levels determined in male offspring. Exposure to galactose for various periods during pregnancy, throughout the entire gestation, or postnatally to nursing mother until pups were 5 wk of age produced no significant differences from control testicular weight, seminiferous tubular diameter, or microscopic appearance of the testis when the offspring became adult (66 or 127 d). Serum luteinizing hormone, follicle stimulating hormone, and testosterone levels were determined 127 d postnatally and no significant differences from controls were observed in any of the treatment groups. Blood galactose-1-phosphate levels in animals receiving the 50% galactose diet were comparable to levels observed in human galactosemia. The resistance of the rat testis to a high galactose diet is consistent with the infrequency of testicular insufficiency in human galactosemia, and contrasts with the prenatal female gonadal sensitivity to galactose previously demonstrated in the rat and the high frequency of ovarian failure in human galactosemia.
Animals↗
Pituitary secretion of alpha and beta subunits of thyroid-stimulating hormone (TSH) in nephropathic cystinosis.
In 13 children with nephropathic cystinosis but without clinical features of hyperthyroidism or hypothyroidism, mean circulating thyroid-stimulating hormone (TSH) levels were high, while concentrations of thyroid hormones were either increased or in the high-normal range compared with those in age-matched, healthy control subjects. Serum TSHalpha was significantly elevated and was above the normal range in 7 of 12 patients; in contrast, only 2 of 13 patients had minimally increased TSHbeta levels. Patients with cystinosis appear to have pituitary resistance to thyroid hormones, and the increase in serum TSH is often associated with high levels of TSHalpha .
Child↗
Circulating somatomedin-C levels in nephropathic cystinosis.
Explore the source record for details and available documents.
Child↗
Male sexual development in the nonhuman primate. III. Sertoli cell culture and age-related differences.
Homogenous preparations of primary Sertoli cell cultures were obtained from the testes of the macaque of different ages. The characteristics of Sertoli cells were confirmed by electron microscopy. Sertoli cell cultures were segregated into three developmental age groups: prepubertal, pubertal, and adult. The highest response to follicle-stimulating hormone [FSH (NIH-FSH-S13) as measured by cAMP and testosterone to estradiol conversion occurred in Sertoli cells from pubertal animals, whereas the responses were diminished in cells from both younger and older animals. Specific binding of 125I-human FSH was also increased in Sertoli cells prepared from pubertal animals when compared to cells from the other two age groups. These data demonstrate: 1) the utility of primate Sertoli cells as an in vitro model, and 2) the age-related differences in monkey Sertoli cell response to FSH and to specific FSH receptor binding.
Age Factors↗