Effects Of Growth Hormone Treatment Research Articles

The Effect of Growth Hormone Treatment on Albumin Requirements in Burned Children: Clinical Implications

The Effect of Growth Hormone Treatment on Albumin Requirements in Burned Children: Clinical Implications

Renal and hemodynamic effects of growth hormone treatment in experimental heart failure

Renal and hemodynamic effects of growth hormone treatment in experimental heart failure

A Risk-Benefit Assessment of Growth Hormone Use in Children

Growth hormone prepared by recombinant DNA technology (somatropin) has been commercially available for over 11 years. More than 38,000 children have been treated with different growth hormone products. While the best response to treatment occurs in children with severe growth hormone deficiency, therapy with growth hormone will increase the rate of statural growth in children with short stature of many different aetiologies. There are few studies of the effect of growth hormone treatment of final adult height, and the magnitude of this effect is harder to gauge, particularly in children with idiopathic short stature. Other benefits of growth hormone treatment in children include improvement in psychosocial functioning and physiological parameters, such as bone mineral density. Adverse effects associated with growth hormone treatment have been relatively uncommon. Most of the safety data on growth hormone have come from large postmarketing databases maintained by 2 pharmaceutical companies. The adverse event profile reported in children treated with growth hormone is different from that found in adults. Peripheral oedema and carpal tunnel syndrome, which are common in adults treated with growth hormone and frequently result in treatment discontinuation, are rare in children. Intracranial hypertension is rare, but can occur in children with growth hormone deficiency, Ullrich-Turner syndrome or renal insufficiency during the first 8 to 12 weeks after the start of growth hormone treatment; it has seldom been reported in adults with growth hormone deficiency. Children with growth hormone deficiency, Ullrich-Turner syndrome or renal insufficiency are prone to develop slipped capital femoral epiphyses both before and during growth hormone treatment. Therefore, limping and complaints of hip or knee pain should be carefully investigated.

Growth hormone regulates ternary complex factors and serum response factor associated with the c-fos serum response element.

For insight into the mechanisms of gene regulation by growth hormone (GH), the regulation of transcription factors associated with the serum response element (SRE) located upstream of c-fos was examined. The SRE can mediate induction of reporter expression in response to GH. For insight into the mechanism by which GH regulates transcription factors, regulation of SRE-associated proteins by GH was examined. In nuclear extracts from 3T3-F442A fibroblasts, several SRE-binding complexes were identified by electrophoretic mobility shift assay. GH treatment for 2-10 min transiently increased binding of two complexes; binding returned to control values within 30 min. The two GH-stimulated complexes were supershifted by antibodies against the serum response factor (SRF), indicating that they contained SRF or an antigenically related protein. One of the GH-stimulated complexes was supershifted by antibody against Elk-1, suggesting that it contains a ternary complex factor (TCF) such as Elk-1 in addition to SRF. Induction of binding by GH was lost when the SRF binding site in the SRE was mutated, and mutation of either the SRF or TCF binding site altered the pattern of protein binding to the SRE. Mutation of the SRF or TCF binding site in SRE-luciferase plasmids inhibited the ability of GH to stimulate reporter expression, supporting a role for both SRF and TCF in GH-induced transcription of c-fos via the SRE. The TCF family member Elk-1 is capable of mediating GH-stimulated transcription, since GH-stimulated reporter expression was mediated by the transcriptional activation domain of Elk-1. Consistent with this stimulation, GH rapidly and transiently stimulated the serine phosphorylation of Elk-1. The increase was evident within 10 min and subsided after 30 min. Taken together, these data indicate that SRF and TCF contribute to GH-promoted transcription of c-fos via the SRE and are consistent with GH-promoted phosphorylation of Elk-1 contributing to GH-promoted transcriptional activation via the SRE.

Lack of effect of growth hormone therapy on the count and density of melanocytic naevi in children.

An observation of accelerated growth of acquired melanocytic naevi (AMN) during treatment with human growth hormone (GH) raised concerns about the potential risk of melanoma in treated patients. An increased number of AMN, rather than growth rate, is associated with a higher risk for melanoma. It is unknown whether treatment with GH causes an increase in numbers of AMN. We evaluated the effect of GH treatment on the number of AMN in a cross-sectional study of 90 children with GH deficiency. AMN counts and densities in these children were compared with those found in a control group of 100 children. Factors potentially related to increased numbers of AMN, such as age, sex, skin colour, number of episodes of sunburn and duration of GH therapy were determined. Among the various factors, only the age and colour of unexposed skin area were predictive for the total number and density of AMN. No correlation was found between the AMN counts or density and the duration of GH therapy. There was no difference in AMN counts or density between the GH-deficient patient group and the control groups. We conclude that GH therapy in children is not associated with increased AMN count and density and is unlikely to potentiate the risk for melanoma in these children.

Effects of growth hormone treatment in children with cystic fibrosis: The National Cooperative Growth Study experience

Poor longitudinal growth and low body weight affect many persons with cystic fibrosis (CF). The Cystic Fibrosis Foundation reports that 28% of all persons with CF are below the 10th percentile for height and that 34% are below the 10th percentile for weight. Intensive nutritional supplementation has not resulted in sustained improvement in the poor linear growth and low weight in CF. Because of the significant impact of nutrition in CF, the anabolic effects of growth hormone (GH) may make the agent useful as adjunctive treatment for malnutrition and poor linear growth. To date, 24 patients with CF (16 boys; 87% Tanner stage 1) have been enrolled in the National Cooperative Growth Study. The average age at enrollment was 10.3 years, and there was significant delay in height in all patients (mean height age, 7.1 years). Bone age was also significantly delayed (mean delay, 3.0 years). The mean maximum stimulated GH level was 12.3 μ g/L and the mean GH dose given was 0.291 ± 0.038 mg/kg per week. After 1 and 2 years of treatment with GH the growth rate increased in all patients with available growth rate data. The growth rates in these children were slightly lower than in children who were treated with GH for idiopathic GH deficiency. The weight-for-height standard deviation scores improved significantly after 2 years of GH treatment. There were adverse reactions (glucose intolerance) to GH in only two patients; treatment was suspended in one of these patients but was continued in the other. National Cooperative Growth Study data indicate that treatment with GH increases linear growth and weight in prepubertal patients with CF. These data suggest that GH may be useful for treating malnutrition in CF. (J Pediatr 1997;131:S65-9)

Growth Hormone (GH)-Binding Protein in Prepubertal Short Children Born Small for Gestational Age: Effects of Growth Hormone Treatment

Growth Hormone (GH)-Binding Protein in Prepubertal Short Children Born Small for Gestational Age: Effects of Growth Hormone Treatment

Effects of growth hormone treatment on oxygen consumption and sea water adaptability in Atlantic salmon parr and pre-smolts

Atlantic salmon parr and pre-smolts, reared under natural conditions in fresh water (FW) were implanted with an intraperitoneal cholesterol pellet containing either ovine growth hormone (oGH, 7 μg/g for pre-smolts and 18 μg/g for parr), or no hormone for control fish, 12 or 3 months respectively before natural completion of their parr-smolt transformation. Twelve days after treatment, fish were directly transferred into full salinity sea water (SW, 35 ppt). In FW, both parr and pre-smolts had normal daily rhythms of oxygen consumption (MO 2). Treatment with oGH caused a greater increase in mean MO 2 in pre-smolts (+30%) than in parr (+16%), which was illustrated by an upward shift of the curves representing daily variation of oxygen demand. In addition, gill (Na +-K +)ATPase activity increased by +50% in parr and +184% in pre-smolts treated with oGH. In parr, the increased salinity caused a reduction in MO 2. This effect, together with the disappearance of the rhythm of oxygen consumption in control parr, could be regarded as the consequence of the profound physiological disturbance caused by the abrupt transfer to SW suggesting that these fish were not totally adapted to SW. The attenuated decrease in MO 2 in treated SW-transferred parr (−27% compared with −50% in controls) and the increase in MO 2, in treated SW-transferred pre-smolts (+13% compared with +5% controls), underline the positive effect of oGH on SW adaptability in parr and especially pre-smolts. This interpretation is supported by the improved ionic regulation in all treated fish. Moreover, changes in the plasma ion concentrations in parr may indicate a metabolic acidosis which, at least partly, may explain the marked fall of MO 2 observed after SW transfer.

Effect of growth hormone treatment in children with craniopharyngioma with reference to the KIGS (Kabi International Growth Study) database.

In children with craniopharyngioma, poor growth commonly precedes diagnosis, but is observed less frequently than neurological or visual symptoms. A deficiency of growth hormone (GH) is common before, and almost universal after, treatment of the tumour, and is usually treated with GH. However, a minority of these children with GH deficiency (GHD) grow well without GH replacement therapy but exhibit other metabolic effects of GHD that are correctable by GH treatment. This article provides a review of studies in 422 children with craniopharyngioma whose details have been entered into the database of KIGS, the Kabi International Growth Study. The response to GH during the first year of therapy was similar to that seen in children with idiopathic GHD (IGHD). Leg length was relatively greater than sitting height and this disproportion was maintained during treatment. Adiposity increased in some children receiving GH treatment. At the end of GH treatment in 82 patients, there was a median gain in height SD score of 1.51, with evidence of residual growth potential still remaining in the majority. Tumour recurrence occurred in 13.5% of the total group of patients with craniopharyngioma within KIGS, at a median of 3.9 years from diagnosis and 2.3 years from the start of GH therapy. Tumour recurrence was not associated with an impairment in height achieved, but there was a tendency towards greater adiposity in patients in whom recurrence occurred. Adverse events during GH treatment were more frequent in children with craniopharyngioma than in those with IGHD, and headache was commonly reported. The results of these studies suggest that GH treatment is recommended for the treatment of children with craniopharyngioma on the grounds of improved growth velocity, adult height and other GH-dependent metabolic functions, and of the good safety profile of GH in these patients.

Urinary pyridinium collagen cross-links predict growth performance in children with idiopathic short stature and with growth hormone (GH) deficiency treated with GH. Skeletal metabolism during GH treatment.

GH is able to promote longitudinal growth in children with GH-deficiency (GHD) and in some children with idiopathic short stature (ISS). The objectives of this study were to evaluate the predictive value of bone and collagen markers on the growth response to GH therapy in children with ISS and with GHD, and to characterize the effects of GH treatment on bone and collagen turnover in children with ISS and with GHD. Twenty prepubertal short, slowly growing, children treated with GH, 15 IU/m2 per week, were studied; of them 13 (10 males) had ISS and 7 (5 males) had GHD. An overnight 12-h urinary collection and a fasting morning blood sample were obtained at baseline, 1, 3, 6, and 12 months of treatment. Urinary levels of collagen cross-links, pyridinoline (Pyd) and deoxypyridinoline (Dpd), and circulating levels of osteocalcin, intact PTH, calcitonin, procollagen type III aminoterminal propeptide (PIIINP), insulin-like growth factor-I, and alkaline phosphatase were determined. Urinary collection was also obtained from 127 healthy children (51 males) aged 6-13 yr. In children with ISS, the changes in Dpd over 1 month of GH therapy were related to the changes in height velocity (HV) over 1 yr of therapy (r = 0.67; P < 0.05); the changes in Pyd after 1 month of GH treatment were related to the changes in HV at 6 months of GH treatment (r = 0.57; P < 0.05). All the other markers evaluated were not related to the HV changes in children with ISS. In children with GHD, the changes in Pyd and in Dpd after 1 month of GH treatment were positively related to the changes in HV after 12 months of therapy (r = 0.82; P < 0.05, and r = 0.82; P < 0.05, respectively). The changes in Pyd after 1 month were also related to the HV changes after 6 months of GH (r = 0.77; P < 0.05). Positive relationships between the HV after 6 months of GH and the increases of PIIINP (r = 0.80; P < 0.05) and osteocalcin (r = 0.77; P < 0.05) after 3 months of GH therapy were observed. All patients showed urinary Dpd and Pyd excretions in the normal range. In patients with ISS, Pyd (P < 0.05), Dpd (P < 0.05), osteocalcin (P < 0.01), PIIINP (P < 0.01), and alkaline phosphatase (P < 0.01) increased longitudinally during the GH treatment and the increments reached a maximum after 3-6 months of therapy. Patients with GHD showed an increase of the same markers but the increases occurred earlier, after 1 month of GH therapy. The collagen cross-links, Pyd and Dpd, could be helpful early markers in predicting the responsiveness to GH therapy in children with ISS and with GHD. GH treatment stimulates bone and collagen metabolism.

Safety of human growth hormone therapy: Current topics

Current data on patients treated with human growth hormone (GH) were analyzed for the following safety topics. New leukemia . Thirteen of 46 new cases of leukemia were in non-Japanese patients without risk factors for leukemia (compared with at least 13 new cases expected). A possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors. Nonleukemic extracranial neoplasms. The number of cases reported (10) does not differ significantly from the number expected. Acute pancreatitis . In five of the seven cases reported risk factors (renal failure, valproic acid use, insulin-dependent diabetes mellitus) were present. The available data do not indicate a clear cause-and-effect relation between GH therapy and pancreatitis. Prepubertal gynecomastia . Of 15 possible cases, two were pubertal, eight resolved or improved with continued GH therapy, and two resolved with the cessation of GH therapy. An effect of GH treatment on prepubertal gynecomastia remains unknown. Scoliosis . Scoliosis is reported in fewer than 1% of the patients in the National Cooperative Growth Study (general-population prevalence, 1.5% to 3%). Curvature progression can occur during growth acceleration, and a causal association with GH treatment is not substantiated. Pigmented nevi . Nevi growth may be increased with GH treatment. Biopsies have detected no neoplasia or premalignant nevi transformations. (J P EDIATR 1996;128:S8-13)

The effect of growth hormone treatment on the insulin-like growth factor axis in a child with nonislet cell tumor hypoglycemia

The effect of growth hormone treatment on the insulin-like growth factor axis in a child with nonislet cell tumor hypoglycemia

Growth hormone and its receptors in the central nervous system--location and functional significance.

During the past few years, there has been increasing interest in functions that growth hormone (GH) may play in the central nervous system. Accumulating evidence that the hormone may pass the blood-brain barrier and the psychological improvements seen in adults following GH therapy have received particular attention. This paper will review our recent studies on GH receptors in the human and rat brain. A recent study on the effects of GH treatment in adult growth hormone-deficient patients on quality of life and cerebrospinal fluid levels of various hormones and neurotransmitters is also included.

Role of growth hormone and sex steroids in achieving and maintaining normal bone mass.

It is now established that adults with growth hormone (GH) deficiency, of childhood or adult onset, have reduced bone mass. GH deficiency is believed to interfere with acquisition of bone mass, although an alternative mechanism is required to explain the reduction in bone mass present in adults who acquire GH deficiency after peak bone mass has been achieved. GH replacement increases bone turnover and may increase bone mass in the longer term, although short-term studies show a decrease in bone mass which can be explained by an increase in bone resorption before new bone formation occurs. Abnormalities of GH secretion have also been implicated in the development of osteoporosis, but the effect of GH treatment on bone mass in such patients is disappointing. Sex steroids have an important role to play in the acquisition of bone mass, and reduced sex steroid levels during adolescence have a deleterious effect on bone mass. The importance of sex steroids in the maintenance of bone mass is illustrated by the development of osteopenia in men and women with hypogonadism, and by the preservation of bone mass by restoration of normal endogenous sex steroid levels, or by treatment with exogenous sex steroid. Sex steroids also influence circulating levels of GH and insulin-like growth factor-1, and the inter-action between these hormones is likely to be important in the acquisition and maintenance of normal bone mass.

Collagen structural organization of healing colonic anastomoses and the effect of growth hormone treatment.

This experimental study was designed to investigate the collagen fibrils of colonic anastomoses in rats and to compare normal healing with rats treated with biosynthetic growth hormone (bGH). The healing zone of left colonic anastomoses was studied at days 2, 4, and 6 after surgery by means of scanning electron microscopy. After four days of healing a normal anastomosis was filled with loosely packed and unorganized collagen fibrils, which were organized into collagen fibers after six days. Compared with normal anastomoses, rats treated with bGH showed a more organized healing, characterized by a dense structure of a new-formed collagen framework of fibrils and immature collagen fibers after six days. Healing colonic anastomoses are characterized by new-formed collagen fibrils at postoperative day 4, and bGH seems to stimulate structural organization of the anastomotic collagen fibrils into fibers.

Acute and chronic effects of subcutaneous growth hormone (GH) injections on plasma levels of GH binding protein in short children.

A ligand-mediated immunofunctional assay was used to measure levels of GH binding protein (GHBP) in plasma from children on GH treatment. Blood was drawn at the time of sc injection of GH and thereafter every 2 h for 16 or 24 h in the acute group. The samples were analyzed for GHBP and GH. To study changes in GHBP levels after onset of GH treatment, samples were taken at the start and after 10, 30, and 90 days of treatment (short-term group) and at the start and after 1 and 2 yr of treatment (long-term group). All children in the short-term and long-term groups were prepubertal throughout the study. For the study of short-term and long-term effects of GH treatment, the children were divided into two groups according to the maximal GH response (GHmax) in an arginine-insulin tolerance test and, if available, the maximum peak on 24-h secretion. Children with a GHmax below 20 mU/L(10 micrograms/L) were classified as GH deficient (GHD), and children with a GHmax above 20 mU/L were classified as children of short stature (SS). In the acute group, GH was injected either at 1800 h (n = 73) or at 1000 h (n = 12). In the group given GH at 1800 h there was a decrease in GHBP levels, with the lowest values occurring after 8-10 h, i.e. between 0200 and 0400 h. We have previously reported that there was no correlation between endogenous GH peaks and changes in GHBP levels, but there was a small but significant diurnal variation in GHBP levels (coefficient of variation of about 10%), with a nadir between 0000 and 0400 h. In the group given GH at 1000 h, GHBP levels decreased to a minimum at 10 h after injection (at 2000 h, P < 0.01), with a further decrease at 16 h after injection (P < 0.05), corresponding to the nadir seen in normal children. The mean GHBP levels fell to 71.2% of the baseline value after 90 days in children with GHD (P = 0.004), but was unchanged in children with SS (P = 0.92). In children with GHD, the GHBP levels were unchanged at 1 yr (100.5% +/- 10.7) and 2 yr (97.1% +/- 6.6) after start of treatment. In children with SS, there was no significant increase after 1 yr (125.6% +/- 10.9, P = 0.16) and 2 yr (120.3% +/- 6.4, P = 0.17).(ABSTRACT TRUNCATED AT 400 WORDS)

Long-Term Effects of Growth Hormone Treatment on Height in Turner Syndrome: Results of a 6-Year Multicentre Study in Japan

Patients with Turner syndrome have many somatic characteristics, including short stature. We report the results of a 6-year multicentre clinical trial of recombinant human growth hormone (GH) therapy in 63 patients with Turner syndrome. Twenty-six patients received GH at a dose of 0.5 IU/kg/week, while 37 received GH, 1.0 IU/kg/week, by daily subcutaneous injection. At the start of GH treatment, there was no significant difference between the two groups in chronological age, bone age, height or growth rate. Both treatment groups showed a significant growth increase during treatment. The current mean height of the 12 patients over the age of 16 treated with GH, 0.5 IU/kg/week, is 145.1 +/- 4.7 cm, and in the 16 patients treated with GH, 1.0 IU/kg/week, is 144.0 +/- 2.2 cm. In conclusion, treatment with GH does increase final height in patients with Turner syndrome. However, further studies are needed to determine the optimum age for the initiation of GH therapy, the best dose regimen and the optimal time and manner of sex and anabolic steroid use.

Endocrine Aspects of Growth Deficiency in OI

Growth deficiency is the most common secondary feature of osteogenesis imperfecta. It is unrelated to fracture history and appears to be due to the growth failure of the defective bony matrix. There are characteristic growth curves for different types of OI. We have been investigating the endocrine features of this disorder, in which the skeletal target tissue synthesizes defective matrix. We review the results of our evaluation of the growth hormone axis in 28 children with short stature and OI and of our pilot study to stimulate OI bone to increased growth rates. Our current focus is on the effect of growth hormone treatment on linear growth, bony mineral and bony matrix in OI.

Effect of growth hormone treatment on quality of life of short-stature children.

While enhanced growth velocity is a well-established benefit following the initiation of growth hormone treatment (GHT), the potential benefit of GHT on quality of life (QOL) of short-stature children has not yet been documented. We compare QOL of two groups of short-stature children who attended the Endocrine Unit (EU) and were 2 SD or more below the average for age and gender. The first group included 96 patients of whom 65 were without any underlying disease, 15 had classical GH deficiency and 16 had Turner syndrome or renal disease. These patients were on GHT for at least 2 years. The other group included 33 patients. Owing to lack of resources to include these 33 patients in a clinical trial, they did not get GHT. They were normal variant of short stature, and their height was similar to the height of the 65 children included in the first group. QOL was assessed using self-administered questionnaires, which were filled out by the patients on their regular visit to the EU. QOL was defined in terms of school achievements, leisure activities, emotional and physical self-esteem, relationships with peers and family members. No significant differences were found between the two groups. The mean scores for the different domains of QOL ranged between 2.6 and 3.8 on a scale ranging from 1 (very pessimistic view) to 4 (very optimistic view).

Effect of Growth Hormone Treatment with Noonan Syndrome: Experience from Kabi International Growth Study (KIGS/ICGS)

55 children, 34 males, 21 females, with Noonan syndrome (NS) included in the Kabi Pharmacia International Growth Study were treated with growth hormone (GH) in a median dose of 0.6 IU/kg/week. Median age at start of treatment was 10.6 years and median height standard deviation score (SDS) was-3.1. Pretreatment height velocity was 4.3 cm/year and during the first, second and third years it increased to 7.0, 6.0 and 4.8 cm/year respectively. Projected adult height with Noonan specific standard increased from -0.4 SDS to 0.3 SDS at the end of three years' treatment. No adverse reactions were reported.