List of references
Growth Hormone therapy in JIA
(December 2001)

  1. NAKAGAWA R, KAWANO Y, YOSHIMURA E, SUZUYA H, WATANABE T, KANAMARU S, ONISHI T, NAKAYAMA H, NAKAGAWA R, MATSUOKA S, YAMASHITA K, KURODA Y: Intense immunosuppression followed by purified blood CD34SUP+ cell autografting in a patient with refractory juvenile rheumatoid arthritis. Bone Marrow Transplant. 2001, 27:333-336.
    Organism:Dr. R. Nakagawa, Department of Pediatrics, Univ. of Tokushima School of Med., 2-50-1 Kuramoto-cho, Tokushima 770-8503
    Abstract:     A 15-year-old boy with refractory juvenile rheumatoid arthritis (JRA) underwent intense immunosuppressive therapy followed by purified blood CD34SUP+ cell autografting. He had been taking prednisolone (PDN) daily or every other day combined with methotrexate once a week to control the disease for 7 years. He suffered from psychological complications and a very short stature due to the adverse effects of these drugs. CD34SUP+ cells were purified in bulk from G-CSF-mobilized PBSC using an Isolex 300. After the administration of cyclophosphamide (200 mg/kg) and anti-lymphocyte globulin (45 mg/kg), 3.6 x 10SUP6/kg purified CD34SUP+ cells were infused. His post-transplant course was uneventful except for herpes-zoster infection. He is now more than 1 year post transplant and has not taken any immunosuppressive medication. His rate of growth has increased (> 10 cm/year) due to the effects of the cessation of PDN and the administration of recombinant human growth hormone (rGH), in contrast to the gain of 2 cm in the preceding 3 years with rGH treatment. Although the durability of this remission is unknown, intense immunosuppressive therapy followed by purified blood CD34SUP+ cell autografting might be acceptable for adolescent patients with refractory JRA to achieve a drug-free period for physical and psychological maturation

  2. PRIEUR AM, CHEDEVILLE G: Prognostic factors in juvenile idiopathic arthritis. Curr.Rheumatol.Rep. 2001, 3:371-378.
    Organism:Unite d'Immunologie, Hematologie et Rhumatologie Pediatriques, Hopital Necker Enfants Malades, 149 rue de Sevres, 75743 Paris cedex 15, France anne-marieprieur@nckap-hop-parisfr
    Abstract:     Prognostic factors in juvenile arthritis are related to many variables that must be evaluated according to the different subtypes. The International League of Associations of Rheumatologists (ILAR) recently proposed six different categories referred to as the Durban criteria, under the eponym of juvenile idiopathic arthritis (JIA). The aim of this classification was to define homogeneous groups according to their clinical and biologic features. The prognostic factors were classified into the different categories of JIA. A poor outcome in the systemic form correlated with markers of disease activity, such as fever and polyarticular involvement, within the first 6 months. The risk of joint destruction in oligoarthritis correlated with the severity of arthritis within the first 2 years. Polyarthritis with positive rheumatoid factor is associated with marked disability in adulthood. In a group of psoriatic patients, the risk of developing sacroiliitis is higher in male and HLA-B27-positive patients. Patients with enthesitis-related arthritis with lower limb, knee, and tarsal involvement also are at greater risk of developing sacroiliitis. Chronic uveitis is a complication of JIA observed mainly in patients with oligoarthritis associated with positive antinuclear antibodies in serum. Secondary amyloidosis is observed mainly in children with systemic JIA. The long-term outcome must be discussed according to the various therapies. Corticosteroids contribute to growth retardation and osteoporosis, for which the use of human recombinant growth hormone and biphosphonates may be an option. Newer encouraging therapies such as anticytokines have been proposed for children with active disease. Autologous stem cell transplantation is being evaluated in some centers with promising results; however, it has a high rate of mortality. Further discussion regarding which patients should undergo autologous stem cell transplantion is needed, as is further discussion regarding the technical adaptations necessary
    Internet : PM:11564367

  3. AL MUTAIR A, BAHABRI S, AL MAYOUF S, AL ASHWAL A: Efficacy of recombinant human growth hormone in children with juvenile rheumatoid arthritis and growth failure. Journal of Pediatric Endocrinology & Metabolism 2000, 13:899-905.
    Organism:Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, 11211 Saudi Arabia
    Abstract:     Ten patients with juvenile rheumatoid arthritis (JRA) and growth failure were treated with recombinant human growth hormone (GH) for 1 to 3 years at a dosage of 0.57 IU/kg/wk. All the patients had been on prednisone at a mean dosage of 4.12 mg p.o. daily. GH was low in one patient, two patients had a borderline level and seven patients had adequate response to provocative tests or post-sleep measurement. Serum IGF-I was found to be low in five of six patients. Mean growth velocity increased from 2.45 cm/yr to 4.79 cm/yr after 1 year's treatment with GH (P<0.004). Six patients continued on GH treatment for a second year and continued to have a better growth velocity, with a mean of 5.43 cm/yr (P<0.014). Two patients entered puberty during the second year of GH treatment. This study demonstrates the potential beneficial effect of GH treatment in patients with JRA with growth failure of systemic onset or polyarticular onset who are on prednisone. Further study is needed to determine the long-term effect of GH treatment on ultimate height

  4. BUCKWAY CK, ROSENFELD RG: Should we use growth hormone to treat genetic syndromes? Journal of Investigative Medicine 2000, 48:8A
    Organism:Department of Pediatrics, Oregon Health Sciences University, Portland, OR USA

  5. BUCKWAY CK, ROSENFELD RG: Genetic syndromes: Treatment with growth hormone. Pediatric Research 2000, 47:126A
    Organism:Pediatrics, Oregon Health Sciences University, Portland, OR USA

  6. CHIKANZA IC, KUIS W, HEIJNEN CJ: The influence of the hormonal system on pediatric rheumatic diseases. Rheumatic Disease Clinics of North America 2000, 26:911-925.
    Organism:Bone and Joint Research Unit, St Bartholomew and Royal London Hospital School of Medicine and Dentistry New Science Building, Charterhouse Square, London, EC1M 6BQ: i.c.chikanza@mds.qmw.uk UK

  7. ROONEY M, DAVIES UM, REEVE J, PREECE M, ANSELL BM, WOO PM: Bone mineral content and bone mineral metabolism: changes after growth hormone treatment in juvenile chronic arthritis [In Process Citation]. J Rheumatol 2000, 27:1073-1081.
    Organism:Centre for Paediatric and Adolescent Rheumatology, Department of Molecular Pathology, The Windeyer Institute of Medical Sciences, London, UK
    Abstract:     OBJECTIVE: To determine whether growth hormone (rhGH) affects bone mineral metabolism and bone mineral content (BMC, g/cm) in a therapeutic trial of recombinant growth hormone in growth retarded children with juvenile chronic arthritis (JCA) treated with steroid. METHODS: BMC was measured in 20 children (of whom 17 were treated with corticosteroid) before and after one year of rhGH. Children were randomized to receive either low dose (12 IU/m2/week) or high dose (24 IU/m2/week) for one year. Three monthly assessments were made of disease activity and anthropomorphic measurements. Blood and urine samples were also obtained to measure indicators of disease activity, bone remodeling, and vitamin D and parathyroid hormone (PTH) status. RESULTS: BMC increased during the treatment period and correlated with increasing height. Osteocalcin levels, normally indicators of bone formation, increased after rhGH treatment and correlated significantly with height velocity, particularly for the high dose treatment group. In contrast, osteocalcin levels were negatively correlated with C-reactive protein levels, both before and during treatment. Height velocity, vitamin D, PTH, and osteocalcin levels were significantly lower than age matched controls before treatment. CONCLUSION: Steroid treated children with both JCA and severe growth retardation have reduced vitamin D, PTH, and osteocalcin levels. After treatment with rhGH, height velocity increased, as did BMC. Growth hormone might be a useful adjunct in the treatment of severe growth retardation and osteoporosis in children with JCA. The longterm benefits of rhGH in the treatment of osteoporosis remain unclear
    Internet : PM:0010782840

  8. SIMON D, PRIEUR A-M, CZERNICHOW P: Treatment of juvenile rheumatoid arthritis with growth hormone. Horm.Res. 2000, 53:82-86.
    Organism:Prof. P. Czernichow, Svc. d'Endocrinol./Diabetol. Pediat., Hopital Robert-Debre, 48, bd Serurier, F-75019 Paris
    Abstract:     Severe growth retardation and profoundly altered body composition are observed in children with juvenile chronic arthritis receiving glucocorticoids. This study assessed the effects of growth hormone (GH) on height velocity, body composition and bone density. Fourteen patients were treated with GH (1.4 U/kg/week) for 1 year and then studied for a 2nd year off GH. The treatment increased insulin-like growth factor 1 and insulin-like growth factor binding protein 3 plasma levels. All patients showed an increase in height velocity. Lean body mass increased by 12%. After the cessation of GH therapy, height velocity fell to pretreatment values, and weight and fat mass increased markedly. Bone formation and resorption markers significantly increased during treatment and returned to pretreatment values after discontinuation of GH treatment. These results suggest that GH may partially counteract the adverse effects of glucocorticoids on growth and metabolism in patients with chronic inflammatory disease. (C) 2000 S. Karger AG, Basel

  9. TOUATI G, RUIZ JC, PORQUET D, KINDERMANS C, PRIEUR AM, CZERNICHOW P: Effects on bone metabolism of one year recombinant human growth hormone administration to children with juvenile chronic arthritis undergoing chronic steroid therapy [In Process Citation]. J Rheumatol 2000, 27:1287-1293.
    Organism:Centre d'Investigation Clinique et Service Endocrinologie-Diabetologie Pediatrique, INSERM U457, Hopital Robert Debre, Paris, France
    Abstract:     OBJECTIVE: To study the effects on bone metabolism of treatment with recombinant human growth hormone (rhGH) in children with juvenile chronic arthritis (JCA) who are undergoing treatment with glucocorticoids (GC) and have severe bone lesions. METHODS: We assessed the effects of rhGH treatment (1.4 U/kg/week) on bone metabolism markers and bone density measured during a one year treatment course in 14 patients with systemic forms of JCA undergoing longterm GC treatment. RESULT: All patients at inclusion showed severe bone demineralization (mean bone density: -3.7 standard deviation score for chronological age). Compared to pretreatment values, bone formation markers (blood levels of osteocalcin and C-terminal propeptide of type 1 procollagen) and bone resorption markers (urinary hydroxyproline, pyridinoline, and deoxypyridinoline levels) increased significantly during treatment and returned to pretreatment values after discontinuation of rhGH. We observed that plasma level of osteocalcin was the best predictive variable of growth response to rhGH treatment in these patients. CONCLUSION: The results reflect an increase in bone turnover in these patients. Despite these biochemical changes no improvement of bone density was observed during the one year treatment. Treatment of longer duration is necessary to evaluate the curative effects of GH
    Internet : PM:0010813303

  10. CHIKANZA IC: Prolactin and neuroimmunomodulation: in vitro and in vivo observations. Ann N Y Acad Sci 1999, 876:119-130.
    Organism:Department of Rheumatology, St. Bartholomews, London, United Kingdom. i.c.chikanza+AEA-mds.qmw.ac.uk
    Abstract:     Prolactin (PL) is a mammotropic neuropeptide produced by the pituitary and extrapituitary cells existing as several isoforms and belongs to the growth and lactogenic hormone family, which includes growth hormone and placental lactogens. The secretion of pituitary PL is under hypothalamic control. The cytokines IL-1, IL-2, and IL-6 also stimulate production, while IFN-gamma and endothelin-3 are inhibitory. PL exerts its effects via PL receptors (PLr) which exist as three isoforms. PL regulates reproduction, osmoregulation, and behavior and has potent immunomodulatory effects. PL is structurally related to members of the cytokine/hematopoietic family such as erythropoietin, GM-CSF, growth hormone, and IL-2 to IL-7. The PLr is a member of the cytokine/hematopoietic receptor family. Interaction of PL with PLr activates the Jak kinases which phosphorylate latent STAT proteins resulting in the activation of transcription. PL counteracts the effects of corticosteroids by enhancing Th1 cellular responses. Perturbations of PL physiology have significant immunologic effects. Hypoprolactinemia impairs immune function while hyperprolactinemia enhances active systemic lupus erythematosus, Reiter's disease, juvenile and adult rheumatoid arthritis (RA), autoimmune thyroiditis, multiple sclerosis, and cardiac allograft rejection. PL gene polymorphisms have now been shown to be linked to RA. Thus, manipulation of PL may have significant clinical utility. Further study of the relationship of the PL/PLr complex, other hormones, and the immune system will provide further insights into the potential therapeutic utility of this complex in immune diseases
    Type: JOURNAL ARTICLE
    Type: REVIEW
    Type: REVIEW, TUTORIAL
     
  11. CHIKANZA IC: Neuroendocrine immune features of pediatric inflammatory rheumatic diseases. Ann N Y Acad Sci 1999, 876:71-72.
    Organism:Department of Rheumatology, Bone and Joint Research Unit, St. Bartholomews, London, United Kingdom. i.c.chikanza+AEA-mds.qmw.ac.uk
    Abstract:     Juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (JSLE) are the most common autoimmune rheumatic diseases in children associated with high levels of autoantibodies and immune reactivity. JRA and JSLE are more common in girls. Disease activity is worse in the morning, improves during the daytime and worsens at night suggesting that neuroendocrine immune mechanisms are involved in disease pathophysiology. Adult patients with RA and SLE have excessive levels of prolactin (PL) while cortisol (CS) production is down-regulated for the degree of ongoing inflammation. PL has potent proinflammatory properties. Normal to low levels of cortisol have been observed in children with active JRA despite the high serum levels of IL-6, IL-1 beta, and TNF-alpha, which activate the hypothalamic-pituitary-adrenal axis (HPA). The CS levels are in fact subnormal because inflammatory stress activates the HPA. Normal serum PL levels were seen in children with JRA, most of whom were not active with higher levels in those with active ANA JRA complicated by uveitis. A trend toward high PL levels was seen in 33 children with JSLE. High serum PL levels are seen in patients with active juvenile ankylosing spondylitis (JAS) only. Growth retardation is a feature of JRA. Patients with JRA have low to normal levels of growth hormone (GH) and low levels of insulin-like growth factor 1 (IGF-1). IGF-1 mediates the effects of GH. The observation of low IGF-1 in JRA raises the therapeutic possibility with IGF-1. Overall, high levels of follicle stimulating hormone and luteinizing hormone are found in children with JSLE while the levels in JRA tend to be normal. Testosterone levels are low in patients with JRA. No significant differences in estrogen levels have been found between patients with JRA and those with JSLE and matched controls. There is evidence that the autonomic nervous function is defective in patients with JRA
    Type: JOURNAL ARTICLE
    Type: REVIEW
    Type: REVIEW, TUTORIAL
     
  12. HAQUE MA, BARI MA, SAHA GK, ALI MA, HOQUE SA, ABDULLAH ABM, CHOUDHURY AI, ALAM MN: Prospective, nonblind trial of methotrexate on seronegative spondyloarthropathy. Journal of Institute of Postgraduate Medicine and Research 1999, 14:56-63.
    Organism:M.A. Bari, Department of Medicine, BSMMU, Dhaka
    Abstract:     This study was designed to see the efficacy of methotrexate (MTX) in patients with seronegative spondyloarthropathies viz ankylosing spondylitis (AS), juvenile chronic arthritis (JCA) and Reiter's syndrome (ReS) / Reactive arthritis (RA). Thirty two patients were randomly selected and methotrexate was given orally to each patient. 6 (18.7%) and 11 (34.3%) cases showed complete and partial improvement respectively. Individual therapeutic response with MTX were 38.9% in ankylosing spondylitis, 70.0% in JCA and 75% in RS/ReA respectively. The improvement was significant (P<.001)

  13. SIMON D, TOUATI G, PRIEUR AM, RUIZ JC, CZERNICHOW P: Growth hormone treatment of short stature and metabolic dysfunction in juvenile chronic arthritis. Acta Paediatr Suppl 1999, 88:100-105.
    Organism:Paediatric Endocrinology and Diabetology Unit, Hopital Robert Debre, Paris, France.
    Abstract:     Severe growth retardation and profoundly altered body composition are observed in children treated with glucocorticoids for systemic forms of juvenile chronic arthritis. The aim of this study was to assess the effects of 1 year of treatment with growth hormone (GH) on height velocity and body composition, and the potential effects of such treatment on glucose tolerance. Fourteen children receiving steroid therapy for juvenile chronic arthritis were treated with GH, 1.4 IU/kg/week (0.47 mg/kg/week), for 1 year and were then followed up for 1 year after cessation of treatment. Baseline GH secretion and plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were at the lower limit of normal, but increased with GH treatment. During the year of GH treatment, mean height velocity increased from 1.9 to 5.4 cm/year (p < 0.001), mean lean body mass increased by 12% (p < 0.01) and mean fat mass fell by 20% (p < 0.01) compared with baseline. Decreased glucose tolerance and increased glycosylated haemoglobin levels were also observed. This may have been a result of insulin resistance, as indicated by induced hyperinsulinaemia. Following the 1-year GH treatment period, height velocity fell to pretreatment values, and the height SDS at the end of the second year was lower (p < 0.01) than before treatment. Weight and fat mass increased markedly after cessation of GH treatment. These results suggest that GH may partially counteract the adverse effects of glucocorticoids on growth and metabolism in patients with chronic inflammatory disease. Long-term controlled studies are needed to determine the risks and benefits of GH therapy in such patients
    Type: CLINICAL TRIAL
    Type: JOURNAL ARTICLE
     
  14. TSATSOULIS A, SIAMOPOULOU A, PETSOUKIS C, CHALLA A, BAIRAKTARI E, SEFERIADIS K: Study of growth hormone secretion and action in growth-retarded children with juvenile chronic arthritis (JCA). Growth Horm IGF Res 1999, 9:143-149.
    Organism:Endocrine Unit, Department of Medicine, Department of Paediatrics, University of Ioannina, Ioannina, Greece. atsatsou+AEA-cc.uoi.gr
    Abstract:     The stimulated and spontaneous growth hormone (GH) secretion and the response to GH action were assessed in growth-retarded children with juvenile chronic arthritis (JCA), in order to determine the underlying mechanisms of growth retardation in such children. Six children (4 boys and 2 girls aged 10.7-13.8 years) with active JCA of systemic onset were included in the study which involved: (1) anthropometric measurements+ADs- (2) assessment of GH responses to insulin-induced hypoglycaemia and clonidine stimulation+ADs- (3) assessment of the nocturnal pulsatile GH secretion by measuring GH in blood samples obtained every 20 min from 20.00 to 08.00 h+ADs- and (4) the IGF-I generation test. As a control, the latter test was also performed in eight aged-matched children with physiological delay in puberty. Biosynthetic hGH (0.1 IU/kg BW) was administered s. c. for 4 days and blood samples were taken at baseline and the morning after the last GH injection for measurement of IGF-I and IGFBP-3.All six children with JCA were prepubertal and their growth velocity was +ADw-3 cm/year. The GH responses to both stimulation tests were normal (peak GH +AD4-20 mU/l). Analysis of the pulsatile GH secretion during the night revealed three-to-four GH pulses of normal amplitude (+AD4-20 mU/l). IGF-I (26.74.6 nmol/l, meanSD) and IGFBP-3 (2.10.2 mg/l) levels were lower in the patients compared with the controls (43.03.7 nmol/l and 2.80.2 mg/l, respectively, P+ADw-0.01). Following stimulation with exogenous hGH, there was a significant increase in IGF-I and IGFBP-3 levels in the control group (85 and 73+ACU-, respectively), but only a small increase in the patients (31 and 14+ACU-).It appears that stimulated and spontaneous GH secretion is normal in children with active systemic JCA, but the response to endogenous and exogenous GH with regard to IGF-I and IGFBP-3 production is impaired, indicating a degree of GH insensitivity in such children. Copyright 1999 Harcourt Publishers Ltd
    Type: JOURNAL ARTICLE
     
  15. MANSSON B, SAXNE T: Development of skeletal abnormalities in children with juvenile chronic arthritis treated with growth hormone. Arthritis And Rheumatism 1998, 41:82-82.
    Organism:LUND UNIV,DEPT RHEUMATOL/LUND//SWEDEN/

  16. TOUATI G, PRIEUR AM, RUIZ JC, NOEL M, CZERNICHOW P: Beneficial effects of one-year growth hormone administration to children with juvenile chronic arthritis on chronic steroid therapy. I. Effects on growth velocity and body composition. J Clin Endocrinol Metab 1998, 83:403-409.
    Organism:Hopital Robert Debre, Paris, France.
    Abstract:     Severe growth retardation and profoundly altered body composition are observed in children with systemic forms of juvenile chronic arthritis receiving glucocorticoids. The purpose of this study was to assess the effects of recombinant human GH (rhGH) on growth velocity (GV) and body composition studied by dual-energy X-ray absorptiometry, during a 1-yr treatment course, together with potential adverse effects on glucose tolerance. Fourteen patients were treated with rhGH (1.4 U/kg per week) for 1 yr and were then studied for a 2nd yr off GH. Baseline GH secretion, GH binding protein (BP), insulin-like growth factor-I (IGF-I), and IGFBP3 levels were at the lower limit of normal. The rhGH treatment increased IGF-I and IGFBP3 plasma levels to above-normal values. All patients showed an increase in GV, and mean GV increased from 1.9-5.4 cm/yr (P < 0.001). Compared with the value on day 0, lean body mass increased by 12.2% (P < 0.01), and the fat mass excess fell by 19.5% (P < 0.01). Decreased glucose tolerance (as determined by oral glucose tolerance test) and increased glycosylated hemoglobin levels were observed during treatment. This effect may be attributed to insulin resistance, as reflected by induced hyperinsulinemia. Eleven children were monitored for 1 yr after the cessation of GH therapy. GV fell to pretreatment values, whereas height in SD score at the end of the 2nd yr was lower (P < 0.01) than before treatment. Weight and fat mass again increased markedly. Although long-term controlled studies are needed to assess the risks and benefits of GH therapy in this setting, our results suggest that rhGH may partially counteract the adverse effects of glucocorticoids on growth and metabolism in patients with chronic inflammatory disease
    Type: JOURNAL ARTICLE

  17. DE BENEDETTI F, ALONZI T, MORETTA A, LAZZARO D, COSTA P, POLI V, MARTINI A, CILIBERTO G, FATTORI E: Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J.Clin.Invest. 1997, 99:643-650.
    Organism:Clinica Pediatrica, Universita degli Studi di Pavia, IRCCS Policlinico San Matteo, ItalyPMID- 9045866
    Abstract:     Stunted growth is a major complication of chronic inflammation and recurrent infections in children. Systemic juvenile rheumatoid arthritis is a chronic inflammatory disorder characterized by markedly elevated circulating levels of IL-6 and stunted growth. In this study we found that NSE/hIL-6 transgenic mouse lines expressing high levels of circulating IL-6 since early after birth presented a reduced growth rate that led to mice 50-70% the size of nontransgenic littermates. Administration of a monoclonal antibody to the murine IL-6 receptor partially reverted the growth defect. In NSE/hIL-6 transgenic mice, circulating IGF-I levels were significantly lower than those of nontransgenic littermates; on the contrary, the distribution of growth hormone pituitary cells, as well as circulating growth hormone levels, were normal. Treatment of nontransgenic mice of the same strain with IL- 6 resulted in a significant decrease in IGF-I levels. Moreover, in patients with systemic juvenile rheumatoid arthritis, circulating IL-6 levels were negatively correlated with IGF-I levels. Our findings suggest that IL-6- mediated decrease in IGF-I production represents a major mechanism by which chronic inflammation affects growth

  18. NEECK G, MICHELS H: Endocrine aspects of paediatric rheumatic diseases. Baillieres.Clin.Rheumatol. 1996, 10:349-363.
    Organism:Department of Rheumatology and Physical Medicine, University of Giessen, Bad Nauheim, Germany.
    Abstract:     Compared to the now numerous studies on the endocrinology of rheumatic diseases in adults, only a small number of studies has been published on children with rheumatic diseases. Prolactin has been most extensively investigated, showing interesting parallels with the findings in adults with rheumatological diseases. Thus, analogous to adult RA most forms of JRA or JCA (with the exception of ANA-positive JRA with uveitis) appear to show, if anything, low to normal levels of prolactin. Since the prolactin levels in adult RA depend on the inflammatory activity, and the physiological prolactin secretion decreases in chronic stress (especially sleep disorders), these results are most likely to be explained as reactive non-specific mechanisms in the stress of the disease. However, specific mechanisms are also being discussed to explain the low prolactin levels in adult RA. The results of prolactin measurements in juvenile SLE, juvenile ankylosing spondylitis and ANA-positive JRA with a raised incidence of uveitis, contrast with this. These conditions sometimes show significantly higher prolactin levels compared to healthy controls. A correlation of the increase of prolactin concentration with the inflammatory activity has been described for juvenile ankylosing spondylitis. These results correlate well with those of adult forms such as diseases of the seronegative spondyloarthropathies type, SLE and iridocyclitis. Raised prolactin concentrations are also found in these diseases. The inflammation promoting and immunostimulatory effects of prolactin found especially in animal experiments are confirmed clinically in these diseases by reports of successful treatments with the prolactin inhibitor, bromocriptine. The results available up to now for human growth hormone in JRA and JCA tend to be comparable with the results for prolactin in these form of paediatric rheumatological diseases. Besides normal values above, all lowered concentrations are measured for this hormone. Apart from other non-specific factors, its diminished secretion is mainly determined by the inflammatory activity of the disease. Low levels of growth hormone are likely to be a significant factor in the growth retardation in children with inflammatory rheumatological diseases. Up to now, the small number of investigations on gonadotrophins and the sex hormones in juvenile SLE and various forms of JRA published have not as yet yielded unequivocal results. The endocrine aspects of paediatric rheumatological diseases are thus still incompletely elucidated. However, there are many promising avenues for further fruitful research in this field

  19. HOPP RJ, DEGAN J, CORLEY K, LINDSLEY CB, CASSIDY JT: Evaluation of growth hormone secretion in children with juvenile rheumatoid arthritis and short stature. Nebr.Med.J. 1995, 80:52-57.
    Abstract:     95249031 Department of Pediatrics, Creighton University School of Medicine, Omaha, Nebraska, USA (UNITED STATES) 0091-6730 ENGLISH 9508 INDEX MEDICUS Children with juvenile rheumatoid arthritis (JRA) often exhibit delayed skeletal development. Previous evaluations of growth hormone (hGH) levels in these children have used single-value blood determinations. We sought to extend information on possible hGH deficiency in children with short stature and JRA by measuring 24-hour hGH pulsatile secretion. Five children with JRA were identified as having a height less than the 3rd percentile, and one child with a height at the 25th percentile. Three of these had abnormally low 24-hour serum hGH secretion. Two underwent a 24-month trial of human recombinant hGH; both exhibited only marginally accelerated growth. These results suggest that children with JRA and persistent short stature may have low hGH secretion without an adequate physiologic response to exogenous hGH administration 0 (Recombinant Proteins);9002-72-6 (Somatotropin)

  20. LINDSLEY CB: Juvenile rheumatoid arthritis and spondyloarthropathies. Curr.Opin.Rheumatol. 1995, 7:425-429.
    Organism:Department of Pediatrics, University of Kansas Medical Center, Kansas City 66160-7330, USA.
    Abstract:     Further insight into the etiology and pathogenesis of juvenile rheumatoid arthritis (JRA) is presented in recent immunogenetic studies, particularly the allele associations of the pauciarticular pattern of disease. Evidence suggests that bacterial heat-shock proteins may be significant in the chronic inflammatory response in children with arthritis. Data on the role of complement activation and cytokines and their receptors also are presented. Coagulopathy in JRA may have more than one etiologic factor, including a viral agent, as may the disease itself. In the treatment of growth abnormalities in JRA, the neuroendocrine system, recombinant growth hormone, intravenous iron therapy, and nutritional supplementation are all areas of recent investigation. In outcome studies, ocular involvement and the presence of circulating IgM rheumatoid factor appear to be risk factors for disability. However, disease of less than 2 years' duration and absence of radiographic lesions likely predict good response to methotrexate therapy

  21. DAVIES UM, ROONEY M, PREECE MA, ANSELL BM, WOO P: Treatment of growth retardation in juvenile chronic arthritis with recombinant human growth hormone. J.Rheumatol. 1994, 21:153-158.
    Abstract:     94202067 MRC Clinical Research Centre, Northwick Park Hospital, Harrow, UK (CANADA) 0315-162X ENGLISH 9407 INDEX MEDICUS OBJECTIVE. To evaluate the effect of recombinant human growth hormone (rhGH) on the linear growth of children with persistently active juvenile chronic arthritis (JCA), most of whom were receiving steroid therapy. All of them were severely growth retarded, but had adequate GH secretion. METHODS. After monitoring height velocity for one year, children were treated for the following year with either 12 IU/m2 or 24 IU/m2 of rhGH. During this period disease activity, drug treatment, dietary intake and bone maturation as well as linear growth were documented. RESULTS. There was a significant increase in height velocity in almost all children during the treatment period. Children with mild to moderate disease activity grew at a better rate than those with very active disease. Children with polyarticular disease responded better than those with systemic JCA. Those children receiving high dose rhGH grew significantly more than those on the low dose regimen. Bone maturation did not exceed chronological age. CONCLUSION. We conclude the rhGH significantly increases the height velocity during one year of treatment. However, its effect on ultimate adult height remains unknown. Thus extensive longterm studies are required to evaluate the risk benefit ratio of this costly treatment 0 (Hormones);0 (Recombinant Proteins);9002-72-6 (Somatotropin)

  22. RYDHOLM U, HAGGLUND G: A case of pseudotumor from overgrowth of the fibula. Effect of growth hormone treatment of juvenile arthritis. Acta Orthop.Scand. 1994, 65:217-218.
    Organism:Lund University Department of Orthopedics, Sweden.

  23. WOO PM: Growth retardation and osteoporosis in juvenile chronic arthritis. Clin.Exp.Rheumatol. 1994, 12 Suppl 10:S87-90.
    Organism:Section of Molecular Rheumatology, Clinical Research Centre, Harrow, U.K.
    Abstract:     Disturbance of growth and bone metabolism is a serious problem in juvenile chronic arthritis. The major factors appear to be chronic disease activity and steroid therapy. Retardation of linear growth is due to disturbance of the neuroendocrine axis, where there is no obvious growth hormone deficiency, but marked reduction of the serum concentration of its mediator, insulin growth factor 1 (IGF-1). Its reduced serum concentration may be multifactorial. In addition, there is also evidence of target insensitivity to IGF-1. The role of the inflammatory cytokines in these endocrine disturbances is likely to be very important, and is the subject of current research

  24. ALLEN RC, JIMENEZ M, COWELL CT: Insulin-like growth factor and growth hormone secretion in juvenile chronic arthritis. Ann.Rheum.Dis. 1991, 50:602-606.
    Organism:Department of Rheumatology, Children's Hospital, Camperdown, Sydney, Australia.
    Abstract:     Insulin-like growth factor (IGF-1) concentrations were determined in a series of 23 children with juvenile chronic arthritis in conjunction with anthropometric assessment. When standardised z scores were used significant decreases in height and weight were shown in comparison with the normal age/sex matched means. Severe growth disturbance was seen, particularly in those with prolonged disease duration, which was independent of corticosteroid treatment, indicating disease activity itself is a major factor in the growth retardation. Eight children had low IGF-1 z scores--that is, less than -2.00 from age/sex matched mean. Low IGF-1 z scores were associated with low weight z scores but not with low height z scores. Overnight growth hormone secretory profiles were determined in 10 patients, including seven with low IGF-1, and showed generally normal secretion in all but one patient, who subsequently attained normal concentrations coincident with catch up growth. Increased pulse frequency of overnight secretion was commonly seen. Low IGF-1 concentrations probably result from varying factors, particularly nutritional, but do not reflect marked endocrinological abnormalities in most patients

  25. SVANTESSON H: Treatment of growth failure with human growth hormone in patients with juvenile chronic arthritis. A pilot study. Clin.Exp.Rheumatol. 1991, 9 Suppl 6:47-50.
    Abstract:     91284445 Department of Rheumatology, University Hospital of Lund, Sweden (ITALY) 0392-856X ENGLISH 9110 INDEX MEDICUS Six children with JCA and one with SLE, aged 11.7 to 17.1 years, have been treated with human growth hormone (hGH) for six months to three years because of growth retardation. Their height SDS score ranged from -2.4 to - 6.4. All have been treated with corticosteroids for 8.4 years on average. The doses of prednisolone were low at the start of the hGH therapy (mean 1.25 mg/day or 2.75 mg/alternate day). Daily doses of hGH ranged from 0.07 to 0.2 IU/kg body weight and day. The growth rate increased during the first year in all but one patient. The mean pretreatment growth rate was 2.8 cm (range 0.3 to 5.7) and had risen to 6.7 cm/year (range 2.8 to 12.4) after one year of treatment. Four patients entered puberty during the first year of treatment. No adverse side effects were observed. Further studies on greater number of patients and follow-up into adult life are needed in order to establish the efficacy of hGH therapy 9002-72-6 (Somatotropin)

  26. VORONOVICH NN, ZAICHIK AM, IUR'EV VV: [Status of the glucocorticoid function of the adrenal glands in patients with juvenile rheumatoid arthritis] Sostoianie gliukokortikoidnoi funktsii nadpochechnikov u bol'nykh iuvenil'nym revmatoidnym artritom. Revmatologiia.Mosk. 1991, 9-11.
    Abstract:     The authors studied the glucocorticoid function of the adrenals in 117 patients with juvenile rheumatoid arthritis (JRA) and in 37 children of the control group. Relation between the level of cortisol in the blood plasma and sex, age form and duration of the disease, indices of the clinical, laboratory and immunological activity, the nature of roentgenological changes in the joints and therapy was analysed. A decrease in the glucocorticoid function of the adrenal cortex correlated with the severity of the clinical forms and duration of the disease, being especially manifest in children of younger age. Hormonal therapy also causes significant and prolonged inhibition of the glucocorticoid function. The total contribution of the analysed sings of the disease being most significant for JRA from the clinical point of view did not influence much changes in cortisol concentration in the blood of the patients

  27. AITMAN TJ, PALMER RG, LOFTUS JK, ANSELL BM, ROYSTON JP, TEALE JD, CLAYTON RN: Serum IGF-I levels and growth failure in juvenile chronic arthritis. Clin.Exp.Rheumatol. 1989, 7:557-561.
    Abstract:     90075551 Clinical Research Centre, Harrow, Middlesex, U.K (ITALY) 0392-856X ENGLISH 9003 INDEX MEDICUS The association between growth failure and serum IGF-I levels has been assessed in 32 children with Juvenile Chronic Arthritis (JCA) aged 5-16 years. A spectrum from normal growth to severe growth failure was included in the study population. Height Standard Deviation Score (SDS) ranged from - 5.79 to +1.41 (median -1.22) and Height Velocity from 0.72-8.85 cm/yr (median 3.81 cm/yr). Known risk factors for growth failure (disease activity, steroid treatment, vertebral collapse) were confirmed. Additionally, height SDS was significantly correlated with serum IGF-I levels (rs = 0.49; p = 0.008); height velocity was significantly, although less strongly correlated with IGF-I levels (rs = 0.41; p = 0.027). There was no correlation between IGF-I levels and either of two indices of nutritional status, or between IGF-I levels and current steroid dose. The correlation of serum IGF-I with parameters of growth failure may be due to either insufficient secretion of growth hormone (GH) or defective GH action. In view of the recently increased availability of GH for treatment of short stature, it is important to distinguish between these two mechanisms 0 (Glucocorticoids);0 (Somatomedins);67763-96-6 (Insulin-Like Growth Factor I)

  28. KOROLENKO OA, ALIAKIN LN: [Anesthesiologic tactics in the case of children with rheumatoid arthritis receiving hormonal therapy] Anesteziologicheskaia taktika u detei s revmatoidnym artritom, poluchavshikh gormonal'nuiu terapiiu. Anesteziol.Reanimatol. 1989, 58-60.
    Abstract:     The efficacy of two types of perioperative corticosteroid therapy has been compared in 191 children with rheumatoid arthritis aged 4 to 15 years, who were preoperatively treated with steroid hormones. The data have been obtained that small doses of steroid hormones used for the prevention of acute adrenocortical insufficiency and differential approach to their application eliminate side effects of glucocorticoids and ensure more favourable conditions for surgery

  29. KALADZE NN, POKATILOVA VE: [Various complications of hormone therapy of children with rheumatoid arthritis]. Pediatriia 1981, 61-62.
    Abstract:     Type: JOURNAL ARTICLE