This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Allen, D. B. Articles by Attie, K. M. Search for Related Content PubMed PubMed Citation Articles by Allen, D. B. Articles by Attie, K. M.

Treatment of Glucocorticoid-Induced Growth Suppression with Growth Hormone

Department of Pediatrics, University of Wisconsin School of Medicine (D.B.A.), Madison, Wisconsin 53792; and Genentech, Inc. (J.R.J., T.J.B., K.M.A.), South San Francisco, California 94080

Address all correspondence and requests for reprints to: David B. Allen, M.D., Department of Pediatrics, H4/448 CSC, 600 Highland Avenue, Madison, Wisconsin 53792. E-mail: dballen{at}facstaff.wisc.edu

	Abstract

Top Abstract Introduction Study Population Materials and Methods Results Discussion References

 
Growth failure is common during long term treatment with glucocorticoids (GC) due to blunting of GH release, insulin-like growth factor I (IGF-I) bioactivity, and collagen synthesis. These effects could theoretically be reversed with GH therapy. The National Cooperative Growth Study database (n = 22,005) was searched for children meeting the following criteria: 1) pharmacological treatment with GC and GH for more than 12 months, 2) known type and dose of GC, and 3) height measurements for more than 12 months. A total of 83 patients were identified. Monitoring of glucose, insulin, IGF-I, IGF-binding protein-3, type 1 procollagen, osteocalcin, and glycosylated hemoglobin levels was performed in a subset of patients. Stimulated endogenous GH levels were less than 10 µg/L in 51% of patients and less than 7 µg/L in 37% of patients. The mean GC dose, expressed as prednisone equivalents, was 0.5 ± 0.6 mg/kg·day. Baseline evaluation revealed extreme short stature (mean height SD score = -3.7 ± 1.2), delayed skeletal maturation (mean delay, 3.1 yr), and slowed growth rates (mean, 3.0 ± 2.5 cm/yr). After 12 months of GH therapy (mean dose, 0.29 mg/kg·weeks), mean growth rate increased to 6.3 ± 2.6 cm/yr, and height SD score improved by 0.21 ± 0.4 (P < 0.01). During the second year of GH therapy (n = 44), the mean growth rate was 6.3 ± 2.0 cm/yr. Prednisone equivalent dose and growth response to GH therapy were negatively correlated (r = -0.264; P < 0.05). Plasma concentrations of IGF-I, IGF-binding protein-3, procollagen, osteocalcin, and glycosylated hemoglobin increased with GH therapy, whereas glucose and insulin levels did not change.

The following conclusions were reached. The growth-suppressing effects of GC are counterbalanced by GH therapy; the mean response is a doubling of baseline growth rate. Responsiveness to GH is negatively correlated with GC dose. Glycosylated hemoglobin levels increased slightly, but glucose and insulin levels were not altered by GH therapy.

	Introduction

Top Abstract Introduction Study Population Materials and Methods Results Discussion References

 
GROWTH retardation is commonly experienced by children who receive long term treatment with glucocorticoids (GC). Doses commonly used for physiological replacement of prednisone (3–5 mg/m²·day; 0.075–0.125 mg/kg·day) or hydrocortisone (12–15 mg/m²·day; 0.3–0.375 mg/kg·day) can be sufficient for this effect. The pathogenesis of this growth suppression is complex, involving several steps in the cascade of events leading to linear growth (Fig. 1) (1). GC interfere with nitrogen and mineral retention and inhibit endogenous GH secretion (through augmentation of somatostatin tone), collagen synthesis, cartilage sulfation, chondrocyte mitosis, GH receptor binding, and insulin-like growth factor I (IGF-I) activity. Given that the degree of growth failure experienced by many GC-treated children is extreme, there is a great deal of interest in the potential reversal of GC-induced growth failure with GH therapy. This study of patients enrolled in the National Cooperative Growth Study (NCGS) examines the effects of GH therapy on GC-dependent children who have experienced growth failure.

View larger version (30K): [in this window] [in a new window]   Figure 1. Mechanisms of growth suppression by GC (derived from both in vivo and in vitro studies).

	Study Population

Top Abstract Introduction Study Population Materials and Methods Results Discussion References

	Materials and Methods

Top Abstract Introduction Study Population Materials and Methods Results Discussion References

 
Patients were grouped according to underlying diagnosis into one of four categories: 1) posttransplant (n = 45; including renal, heart, liver, and bone marrow transplant recipients), 2) inflammatory disease (n = 18; including juvenile rheumatoid arthritis, inflammatory bowel disease, Crohn’s disease, dermatomyositis, systemic lupus erythematosis, glomerulonephritis, nephrotic syndrome, and polyarteritis nodosa), 3) asthma (n = 16), and 4) other (n = 4; including patients with either Blackfan-Diamond syndrome or sarcoidosis). Grouping by diagnostic category (as opposed to GC dose) was motivated by the expectation that patients with the same diagnosis would share other etiological factors affecting growth. The effect of the GC dose was evaluated through correlation and regression analysis. Baseline growth rates were determined based upon a mean observation period of 9 months (range, 3–17 months).

A subset of patients (n = 25, including patients from all diagnostic categories), treated by NCGS investigators particularly interested in biochemical monitoring of the effects of combined GH and GC therapy, underwent testing immediately before and after 12 months of GH therapy to determine carbohydrate tolerance [fasting and 2 h postglucose load insulin and glucose levels, and glycosylated hemoglobin (GlyHb) measurement] and IGF-I, IGF-binding protein-3 (IGFBP-3), osteocalcin, and type 1 procollagen levels (all assays performed at Corning Nichols Institute, San Juan Capistrano, CA).

Statistical analysis

Descriptive statistics were generated for the entire cohort, and by diagnostic category for the following factors: gender, pubertal stage, change in pubertal status, age at initiation of GH therapy, baseline height SD score, bone age deficit, body mass index (BMI), maximum stimulated GH level, baseline growth rate, 12-month height SD score, 12-month growth rate, 12-month weighted average GC (prednisone equivalent) dose, and 12-month weighted average GH dose. Continuous factors are presented as the mean ± SD, and categorical factors are presented as percentages. Differences in mean values between diagnostic groups were tested with ANOVA, and differences in proportions were tested with ² tests.

The response to GH therapy was evaluated using the mean 12-month growth rate and the mean 12-month height SD score, relative to mean baseline values. Changes from baseline values were tested using paired t tests or signed rank tests as appropriate. The relationship of (log) GC dose to 12-month growth rate was assessed by Pearson correlation and multiple regression analysis. The relationship of (log) GC dose to change in (log) BMI was assessed by Pearson correlation. Predictors in the multiple regression analysis included baseline predicted height SD score, (log) GC dose, (log) GH dose, baseline growth rate, gender, diagnostic category, and change in pubertal status.

A result was considered statistically significant if P < 0.05. All statistical analyses were performed using the SAS software, version 6.11 (SAS Institute, Cary, NC).

	Results

Top Abstract Introduction Study Population Materials and Methods Results Discussion References

 
Baseline characteristics

Baseline characteristics, by diagnosis, are presented in Table 1. Two thirds of the children were male, and the mean age was 13 yr. Skeletal maturation was markedly delayed (mean delay, 3.1 yr), and the degree of short stature was extreme (mean height SD score, -3.7). The posttransplant patients, most of whom experienced prior growth retardation due to chronic renal disease (39 of 45 had renal transplants), appeared to be severely affected (mean height SD score, -3.8) as were patients in the "other" group (mean height SD score, -4.5). Pretreatment growth rates were markedly slowed (mean, 3.0 cm/yr), with children with asthma comprising the slowest growing group. The mean baseline BMI was 21.3 kg/m², corresponding to approximately the 75th percentile for 13-yr-old females and males. Patients with inflammatory disease tended to have lower BMI than posttransplant or asthma patients (although not statistically significant).

Information regarding provocative testing of GH secretion was available for 76 of the 83 children. Maximum stimulated GH levels were less than 7 µg/L in 37% and less than 10 µg/L in 51% of patients. Posttransplant patients, in general, had higher stimulated GH levels. Children with inflammatory disease were more likely to have provocative testing results compatible with the diagnosis of deficient GH secretion.

Response to GH therapy

Recombinant GH was administered in six or seven injections per week to the vast majority of children, with doses averaging 0.29 mg/kg·week (similar to the overall NCGS database). There was little difference in GH dose between subgroups. The effects of 12 months of GH therapy on growth rate and height SD scores are depicted in Fig. 2, A and B, respectively. The mean first year growth rates were significantly increased from baseline, with the mean 12-month growth rate approximately double the mean pretreatment growth rate in the overall cohort (P < 0.001) and in each subgroup. The mean growth rate increment was greatest in the asthma group, followed by the posttransplant and inflammatory disease groups. However, the response to GH therapy between underlying diagnoses did not vary sufficiently to reach statistical significance. A few children experienced slower growth rates, compared to pretreatment growth rate, during the first year of GH therapy, perhaps due to exacerbations of disease activity or the need for a higher GC dose.

View larger version (52K): [in this window] [in a new window]   Figure 2. A, Effect of GH and GC therapy on growth rate (mean ± SD) after 1 and 2 yr of treatment. Results are grouped by the therapeutic indication for GC therapy. B, Effect of GH and GC therapy on height SD score (mean ± SD) after 1 and 2 yr of treatment. Results are grouped by the therapeutic indication for GC therapy.

A previous study of a small number of GC-dependent patients has indicated an inverse relationship between response to GH and prednisone dose (3). This observation was also shown in NCGS GC-dependent children, in whom the 12-month growth rate was weakly inversely related to the logarithm of the GC dose (r = -0.264; P = 0.02; Fig. 3). This relationship was further confirmed by multiple regression analysis (n = 42) that adjusted for baseline Bayley-Pinneau predicted height SD score, prior growth rate, gender, diagnostic category, and change in pubertal status (factors found to predict 12-month growth rate in these patients). The logarithm of the GC dose was significantly inversely related to the 12-month growth rate (P = 0.001) after adjusting for these confounding factors. However, a threshold dose of GC, above which the growth rate response to GH therapy might predictably decline, could not be clearly discerned.

View larger version (16K): [in this window] [in a new window]   Figure 3. Relationship of GC dose to growth rate after 1 yr of treatment for patients receiving both GH and GC therapy. The circles are observed values, the solid line is the predicted values based on simple regression, and the dotted lines are the 95% confidence limits for the predicted values.

Combined treatment with GH and GC over a 12-month period resulted in an overall mean reduction in BMI of 0.5 kg/m² (P = 0.01). Subgroup analysis revealed greatest reduction in BMI in patients with asthma as well as the "other" group (-1.0 kg/m²), followed by posttransplant (-0.5 kg/m²) and inflammatory disease (-0.2 kg/m²) patients. These changes in small numbers of patients were not statistically significant. Changes in BMI were positively, but weakly, correlated with the logarithm of the GC dose (r = 0.288; P = 0.01) and showed no correlation with the GH dose.

Laboratory and adverse events

The effects of GH therapy on carbohydrate metabolism and other biochemical growth markers are shown in Table 2. Mean levels of GlyHb showed a slight increase (6.0% to 6.5%) that was statistically significant. However, only one patient (asthma) had a GlyHb level (8.4%) that fell outside the normal range for this assay (4–8%), and this patient had no signs or symptoms of diabetes mellitus. Fasting and stimulated plasma levels of glucose and insulin did not change significantly in those studied. However, one patient, with a family history of type II diabetes, developed polydypsia and hyperglycemia within 1 day of starting GH therapy and received short term insulin therapy. Statistically significant increases in IGF-I, IGFBP-3, osteocalcin, and type 1 procollagen occurred.

	Discussion

Top Abstract Introduction Study Population Materials and Methods Results Discussion References

Recognition of GC-mediated antagonism of GH secretion and action has renewed interest in the potential reversal of GC-induced growth failure by GH therapy. In 1952, Selye demonstrated in rats that addition of crude bovine GH reversed the growth inhibition caused by GC treatment (18). More recent animal studies have substantiated a dose-dependent compensation of growth-depressing effects of methylprednisolone by GH (19). IGF-I is also able to counterbalance GC-mediated growth retardation, although not as completely as GH, suggesting that the effects of GH in this setting cannot be mimicked by IGF-I (20).

Early treatment efforts in slowly growing children with rheumatic diseases, asthma, and inflammatory bowel disease using relatively low dose, three times weekly, pituitary-derived GH revealed either insignificant growth rate increments or acceleration in growth rate coincident with fluctuations in disease activity and GC dosage (21, 22). More recent preliminary investigations of daily, conventional dose (0.3 mg/kg·weeks) recombinant human GH therapy, in which GC dosages remained relatively constant, have shown a return to normal growth rates in children treated over a 12- to 24-month period (23). Markers of collagen synthesis were also increased by GH treatment (23). In these studies, persistence of disease activity and higher GC dosage (e.g. prednisone dose >0.35 mg/kg·day) (2) appeared to interfere with GH responsiveness. Several studies have also reported a salutary effect of GH therapy on the growth of children after renal transplantation. In these studies, most patients were treated with relatively low doses of GC (5–10 or 0.1–0.2 mg/kg·day prednisone) and had stable allograft function (24, 25).

This report describes the NCGS experience with 12-month GH treatment of 83 poorly growing, GC-dependent children (the largest cohort reported to date). The results suggest that the growth-suppressing effects of GCs can be counterbalanced by daily administration of GH at doses comparable to those frequently prescribed for treatment of GH deficiency (0.3 mg/kg·week). After 1 yr of GH therapy, the response was a doubling of the mean growth rate compared with the mean baseline growth rate and attainment of normal growth rates for age. Significant increases in levels of IGF-I, IGFBP-3, osteocalcin, and type 1 procollagen were also observed. Although it is difficult, if not impossible, to completely distinguish the relative effects of fluctuations in underlying chronic disease, GC dosage, and GH administration on growth in these children, the stability of GC dosage throughout the GH treatment administered to the vast majority of patients supports the presence of an independent salutory effect of GH.

Both dosage and type of GC can be correlated with the degree of growth suppression. Progressive impairment in statural growth as prednisone dosage exceeds 4–6 mg/m² (26), and the increased growth-retarding effect of prednisone in comparison with that of hydrocortisone is due to its longer half-life and corresponding reduced daily fluctuation in GC levels (27). In this study, responsiveness to GH was inversely related to GC dose, but did not depend on the type of GC-dependent disease. With regard to the effects of GH on other catabolic effects of GC (28), although small improvements in estimated body composition were observed, detailed studies of metabolic effects of GH in children receiving long term GC therapy have not yet been performed.

Short term risks of combined GH/GC therapy appear to be low. Elevated fasting and stimulated insulin levels have been previously observed during combined GH and GC treatment; however, these changes frequently predate institution of GH therapy, correlate with prednisone dosage, and are not affected by the addition of GH (29). Among our study population of GH-treated GC-dependent children, although some increase in GlyHb levels occurred, detectable elevations in blood glucose concentrations were rare, and with the exception of one patient who developed acute hyperglycemia, no persistent perturbations in carbohydrate metabolism were noted. Transient GH-induced exacerbations of chronic disease activity are also very unusual, but the number of patient-years available for study of this question remains small.

Other potential adverse effects of combined GH and GC therapy in children with GC-dependent disorders include stimulation of autoimmune disease activity, increased oncogenic risk in the setting of immune suppression, and, in transplant recipients, graft rejection or loss. With regard to renal allograft survival, the immunostimulatory effects of GH raise the theoretical possibility that GH therapy might reduce the effect of immunosuppression (30). Most investigators report no difference between GH-treated and control renal allograft patients with regard to changes in glomerular filtration rate, effective plasma flow, other measures of renal function, and rates of allograft rejection (31, 32, 33). However, increased serum creatinine concentrations and decreased creatinine clearance rates have been reported in a few GH-treated transplant patients (as seen in this study), and preliminary analysis of one randomized prospective study suggests that GH might slightly increase allograft rejection rates (34). Although the two episodes of transplant rejection that were considered to possibly relate to GH therapy did not appear to exceed the expected number of such occurrences, prospective study of a larger cohort of renal transplant patients is needed to address this important question. One possible advantage of GH therapy could be to allow daily, rather than alternate day, GC therapy; although alternate day dosing of GC is often prescribed to improve growth, it may reduce the intended immunosuppressive effect.

The influence of GH on the metabolism of drugs remains under investigation. Limited published data indicate that GH treatment may increase cytochrome P-450 (CP450) antipyrine clearance in man (35). These data suggest that GH administration may alter the clearance of compounds known to be metabolized by CP450 enzymes in the liver and other tissues (e.g. corticosteroids, sex steroids, anticonvulsants, and cyclosporin). Until further studies are conducted, careful monitoring is advisable when GH is administered in combination with GC, cyclosporin, or other drugs known to be metabolized by CP450 enzymes.

In summary, in a cohort of 83 poorly growing, GC-dependent children, the results suggest that the growth-suppressing effects of GCs can be variably overcome by GH. The short term risks of combined GH and GC treatment appear low; potential long term effects require further surveillance and study. Treatment of GC-dependent children with GH remains experimental; children considered for such treatment should be enrolled in studies that facilitate careful monitoring and data analysis.

	Acknowledgments

 
The authors acknowledge the following physicians who provided laboratory samples and information to the study: Gaya Aranoff, Barry Rich, Richard Levy, Kevin Corley, Robert Schwartz, and Thomas Aceto.

Received February 20, 1998.

Revised May 1, 1998.

Accepted May 6, 1998.

	References

Top Abstract Introduction Study Population Materials and Methods Results Discussion References

 

1. Allen DB. 1996 Growth suppression by glucocorticoid therapy. In: Rosenfield RL, ed. Growth and growth disorders. Philadelphia: Saunders; 699–718.
2. August GP, Lippe BM, Blethen SL, et al. 1990 Growth hormone treatment in the United States: demographic and diagnostic features of 2331 children. J Pediatr. 116:899–903.[CrossRef][Medline]
3. Rivkees SA, Danon M, Herrin J. 1994 Prednisone dose limitation of growth hormone treatment of steroid-induced growth failure. J Pediatr. 125:322–325.[CrossRef][Medline]
4. Beaufrer B, Horber FF, Schwenk WF. 1995 Glucocorticoids increase leucine oxidation and impair leucine balance in humans. Am J Physiol. 257:712–721.
5. Locascio V, Bonucci E, Imbimbo B. 1990 Bone loss in response to long term glucocorticoid therapy. Bone Miner. 8:39–51.[CrossRef][Medline]
6. Saville PD, Kharmosh O. 1967 Osteoporosis of rheumatoid arthritis: influence of age, sex, and corticosteroids. Arthritis Rheum. 10:423–430.[Medline]
7. Robinson ICAF, Gabrielsson B, Klaus B, Mauras N, Holmberg C, Mehls O. 1995 Glucocorticoids and growth problems. Acta Paediatr. 411:81–86.
8. Prockop DJ, Kivirikko KI, Tuderman L, Guzman NA. 1979 The biosynthesis of collagen and its disorders I. N Engl J Med. 301:13–23.[Medline]
9. Ristelli J. 1977 Effect of prednisolone on the activities of intracellular enzymes of collagen biosynthesis in rat liver and skin. Biochem Pharmacol. 26:1295–1298.[CrossRef]
10. Hyams JS, Moore RE, Leichtner AM, Carey DE, Goldberg BD. 1988 Relationship of type I procollagen to corticosteroid therapy in children with inflammatory bowel disease. J Pediatr. 112:893–898.[CrossRef][Medline]
11. Guistina A, Wehrenberg WB. 1992 The role of glucocorticoids in the regulation of growth hormone secretion: mechanisms and clinical significance. Trends Endocrinol Metab. 3:306–311.[Medline]
12. Nakagawa K, Ishizuka T, Obara T, Matsubara M, Akikawa K. 1987 Dichotomic action of glucocorticoids on growth hormone secretion. Acta Endocrinol. 116:165–171.
13. Wehrenberg WB, Janowski BA, Piering AW, Culler PF, Jones KL. 1990 Glucocorticoids: potent inhibitors and stimulators of growth hormone secretion. Endocrinology. 126:3200–3203.[Abstract]
14. Takahashi H, Bando H, Zhang C, Yamasaki R, Saito S. 1992 Mechanism of impaired growth hormone secretion in patients with Cushing’s disease. Acta Endocrinol (Copenh). 127:13–17.[Medline]
15. Miell JP, Corder R, Pralong FP, Gallard RC. 1991 Effects of dexamethasone on GHRH, arginine, and dopaminergic stimulated GH secretion and total plasma IGF-I concentrations in normal male volunteers. J Clin Endocrinol Metab. 72:675–681.[Abstract]
16. King APJ, Carter-Su C. 1995 Dexamethasone-induced antagonism of growth hormone (GH) action by down-regulation of GH binding in 3T3–F442A fibroblasts. Endocrinology. 136:4796–4803.[Abstract]
17. Unterman TG, Phillips LS. 1985 Glucocorticoid effects on somatomedins and somatomedin inhibitors. J Clin Endocrinol Metab. 61:618–626.[Abstract]
18. Selye H. 1952 Prevention of cortisone overdosage effects with the somatotropic hormone (STH). Am J Physiol. 171:381–384.[Free Full Text]
19. Kovacs G, Fine RN, Worgall S. 1991 Growth hormone prevents steroid-induced growth depression in health and uremia. Kidney Int. 40:1032–1040.[Medline]
20. Tomas FM, Knowles SE, Owens PC. 1992 Insulin like growth factor I (IGF-I) variants are anabolic in dexamethasone treated rats. Biochemistry. 282:91–97.
21. Morris HG, Jorgensen JR, Elrick H, Goldsmith RE, Subryan VL. 1968 Metabolic effects of human growth hormone in corticosteroid-treated children. J Clin Invest. 47:436–451.
22. McCaffery TD, Nasr K, Lawrence AM, Kirsner JB. 1974 Effect of administered human growth hormone on growth retardation in inflammatory bowel disease. Dig Dis. 19:411–416.[CrossRef]
23. Allen DB, Goldberg BD. 1992 Stimulation of collagen synthesis and linear growth by growth hormone in glucocorticoid-treated children. Pediatrics. 89:416–421.[Abstract/Free Full Text]
24. VanDop C, Jabs KL, Donohoue PA, Bock GH, Fivush BA, Harmon WE. 1992 Accelerated growth rates in children treated with growth hormone after renal transplantation. J Pediatr. 120:244–250.[CrossRef][Medline]
25. Hokken-Koelega ACS, VanZaal MAE, deRidder MAJ, et al. 1994 Growth after renal transplantation in prepubertal children impact of various treatment modalities. Pediatr Res. 35:367–371.[Medline]
26. Falliers CJ, Tan LS, Szentivanyi J, Jorgensen JR, Bukantz SC. 1963 Childhood asthma and steroid therapy as influences on growth. Am J Dis Child. 105:127–137.
27. Hyams JS, Carey DE. 1988 Corticosteroids and growth. J Pediatr. 113:249–254.[CrossRef][Medline]
28. Horber FF, Haymond MW. 1990 Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest. 86:265–272.
29. VanDop C, Donohoue PW, Jabs KL, Bock GH, Fivush BA, Harmon WE. 1991 Glucose tolerance in children with renal allografts and effect of growth hormone treatment. J Pediatr. 118:708–714.[CrossRef][Medline]
30. Manredi R, Tumietto F, Azzaroli L. 1994 Growth hormone (GH) and the immune system impaired phagocytic function in children with idiopathic GH deficiency is corrected by treatment with biosynthetic GH. J Pediatr Endocrinol. 7:245–251.[Medline]
31. Tonshoff B, Haffner D, Mehls O. 1993 Efficacy and safety of growth hormone treatment in short children with renal allografts. Kidney Int. 44:199–207.[Medline]
32. Hokken-Koelega ACS, Stijnen T, deJong RCJW, et al. 1996 A placebo-controlled, double-blind trial of growth hormone treatment in prepubertal children after renal transplant. Kidney Int. 49(Suppl 53):S128–S134.
33. Mentser M, Breen TJ, Sulliven EK, Fine RN. 1997 Growth hormone treatment of renal transplant recipients: the National Cooperative Growth Study experience–a report of the National Cooperative Growth Study and the North American Pediatric Renal Transplant Cooperative Study. J Pediatr 131:S20–S24.
34. Broyer M, Guest G, Crosnier H, Berard E. 1994 Recombinant growth hormone in children after renal transplantation. Lancet. 343:539–540.
35. Chueng NW, Liddle C, Coverdale S, Lou JC, Boyages SC. 1996 Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man. J Clin Endocrinol Metab. 81:1999–2001.[Abstract]

This article has been cited by other articles:

				J N Hoes, J W G Jacobs, M Boers, D Boumpas, F Buttgereit, N Caeyers, E H Choy, M Cutolo, J A P Da Silva, G Esselens, et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases Ann Rheum Dis, December 1, 2007; 66(12): 1560 - 1567. [Abstract] [Full Text] [PDF]

				S. Bechtold, P. Ripperger, R. D. Pozza, W. Bonfig, R. Hafner, H. Michels, and H. P. Schwarz Growth Hormone Increases Final Height in Patients with Juvenile Idiopathic Arthritis: Data from a Randomized Controlled Study J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3013 - 3018. [Abstract] [Full Text] [PDF]

				K. Lin-Su, M. G. Vogiatzi, I. Marshall, M. D. Harbison, M. C. Macapagal, B. Betensky, S. Tansil, and M. I. New Treatment with Growth Hormone and Luteinizing Hormone Releasing Hormone Analog Improves Final Adult Height in Children with Congenital Adrenal Hyperplasia J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3318 - 3325. [Abstract] [Full Text] [PDF]

				T. Mushtaq, P. Bijman, S. F. Ahmed, and C. Farquharson Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures Endocrinology, May 1, 2004; 145(5): 2478 - 2486. [Abstract] [Full Text] [PDF]

				R. P. A. Rooman, G. Kuijpers, R. Gresnigt, R. Bloemen, J. G. Koster, and S. C. van Buul-Offers Dexamethasone Differentially Inhibits Thyroxine- or Growth Hormone-Induced Body and Organ Growth of Snell Dwarf Mice Endocrinology, June 1, 2003; 144(6): 2553 - 2558. [Abstract] [Full Text] [PDF]

				S. Bechtold, P. Ripperger, D. Muhlbayer, H. Truckenbrodt, R. Hafner, O. Butenandt, and H. P. Schwarz GH Therapy in Juvenile Chronic Arthritis: Results of a Two-Year Controlled Study on Growth and Bone J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5737 - 5744. [Abstract] [Full Text] [PDF]

				S. F. Kemp Introduction Pediatrics, October 1, 1999; 104(4): 999 - 999. [Full Text]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Allen, D. B. Articles by Attie, K. M. Search for Related Content PubMed PubMed Citation Articles by Allen, D. B. Articles by Attie, K. M.