Growth hormone therapy with three dosage regimens in children with idiopathic short stature

Rekers-Mombarg, L.T.M.; Massa, Guy; Wit, J. M.; Matranga, Anna M.C.; Buckler, John; Butenandt, O; Chaussain, J. L.; Frisch, H; Leiberman, Esther; Yturriaga, R.

doi:10.1016/s0022-3476(98)70020-4

Cited by 34 publications

(28 citation statements)

References 26 publications

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“…GH dose effects on height velocity, height sd score (SDS), and final height have been reported for patients in this study (6,12,13), as have safety data (13,14). Studies of pubertal timing and growth (15), immunological function (16), and quality of life (17) have been reported for subsets of these patients.…”

Section: Main Outcome Measuresmentioning

confidence: 69%

Effect of Growth Hormone Dose on Bone Maturation and Puberty in Children with Idiopathic Short Stature

Crowe¹,

Rekers-Mombarg²,

Robling³

et al. 2006

The Journal of Clinical Endocrinology & Metabolism

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Context: GH at 0.22 mg/kg⅐wk has been shown to have no effect on pubertal onset or pace, whereas GH at 0.5 mg/kg⅐wk has been shown to advance pubertal onset and bone maturation.Objectives: Our objectives were to determine whether 0.37 mg/kg⅐wk GH advanced pubertal onset, pace, or bone maturation relative to 0.24 mg/kg⅐wk GH; whether 0.37 mg/kg⅐wk GH led to pubertal onset at an inappropriately early age; and whether age at start of GH therapy influenced pubertal onset. Design:We conducted a randomized, open-label study to final height. Patients:We studied children with idiopathic short stature.Intervention: Patients were treated with 0.24 mg/kg⅐wk, 0.24 increasing to 0.37 mg/kg⅐wk, or 0.37 mg/kg⅐wk. Main Outcome Measures:We assessed age at pubertal onset and rates of bone maturation, Tanner stage development, and increase in testicular volume (boys only).Results: For the primary comparison between the 0.24 and 0.37 mg/kg⅐wk dose groups, median ages of pubertal onset (in years) were similar (13.7 vs. 13.5 for boys and 11.7 vs. 11.4 for girls) and were greater than those for the general population for each sex. Age at start of GH therapy did not appear to influence pubertal onset for either sex. Rates of pubertal pace and bone maturation were not significantly different between the 0.24 and 0.37 mg/kg⅐wk dose groups for either sex.Conclusion: GH at 0.37 mg/kg⅐wk does not appear to accelerate pubertal onset, pace, or bone maturation compared with GH at 0.24 mg/kg⅐wk in patients with idiopathic short stature. From a clinical standpoint, our results suggest that the approved dose range of up to 0.37 mg/kg⅐wk GH does not lead to pubertal onset at an inappropriately early age. between GH activity and pubertal timing. Before GH treatment became available, marked delays in pubertal onset were observed in children with isolated GH deficiency (1). Additionally, pubertal delays of 3-7 yr are observed in children with GH insensitivity (2).Randomized controlled studies of recombinant human GH (somatropin) treatment of patients with idiopathic short stature (ISS) have yielded differing results regarding the influence of GH on pubertal onset, pubertal pace, and bone maturation. Although Leschek et al. (3) demonstrated no effect on pubertal onset or pace in boys who began low-dose (0.22 mg/kg⅐wk) GH at a mean age of 12 yr, Kamp et al. (4) demonstrated acceleration of pubertal onset and bone maturation by approximately 1 yr in boys and girls who began high-dose (0.5 mg/kg⅐wk) GH at a mean age of 8 yr. These results suggest that the influence of GH on pubertal timing and bone maturation may be dose-dependent. Thus, based on the current literature, decisions regarding GH dosing are limited by uncertainty as to which doses between 0.22 and 0.5 mg/kg⅐wk might accelerate puberty and bone maturation in patients with ISS.We tested the influence of GH dose on pubertal onset, pubertal pace, and bone maturation during a randomized, open-label study to final height in patients with ISS (mean age, 9.8 yr) randomized to one of three GH dose...

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Section: Main Outcome Measuresmentioning

confidence: 69%

Effect of Growth Hormone Dose on Bone Maturation and Puberty in Children with Idiopathic Short Stature

Crowe¹,

Rekers-Mombarg²,

Robling³

et al. 2006

The Journal of Clinical Endocrinology & Metabolism

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“…Due to the inclusion criteria in the ISS studies [37], all except 1 of these children were older than 4 years. Therefore the GHD children were divided into three age groups and the ISS children into two groups, to allow for proper comparisons.…”

Section: Resultsmentioning

confidence: 99%

Plasma Levels of Insulin-Like Growth Factor (IGF)-I, IGF-II and IGF-Binding Protein-3 in the Evaluation of Childhood Growth Hormone Deficiency

et al. 1998

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Background: Traditionally, measurement of plasma IGF-I and more recently of IGFBP-3 are used to distinguish GHD from idiopathic short stature in slowly growing children, using a single blood sample. In earlier studies it was claimed that IGFBP-3 was superior to IGF-I, but more recently doubts around this claim have arisen. The role of serum IGF-II has never been studied extensively. On theoretical grounds, it can also be hypothesized that molar ratios of these peptides might be of additional value. Design: Retrospective, multicentre, cohort study. Patients: 96 children evaluated for short stature. Methods: Serum IGF-I, IGF-II, IGFBP-3 and various molar ratios were, after correction for age and sex using SD scores, compared to the maximum serum GH peak after two standard provocation tests using four different methods (t-test, χ², likelihood ratios and ROC curves). In addition, the correlations between these parameters and the short-term (1 year) and long-term (3 years) response to GH therapy were calculated. Results: IGF-I performed better than IGFBP-3, but the best results were achieved by the molar ratio IGF-I:IGF-II. However, IGFBP-3 correlated better with the short-term response to GH therapy than IGF-I or the ratios, and none of the parameters investigated was found to be related to the response of long-term GH therapy.

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“…Hereby, a GH peak of 10–20 mU/l is usually labeled ‘partial’ GHD. However, taking into account the poor reproducibility, it is very unlikely that a maximum GH peak between 10 and 20 mU/l provides reliable information with regard to partial impairment of stimulated GH secretion [1, 2, 3, 4, 5, 6, 13, 14, 15, 16, 17, 27]. Rather is it likely that children with a maximum GH peak of 10–20 mU/l are for the most part a selected subgroup of children with normal GH secretion, but who had two low peaks just by chance.…”

Section: Discussionmentioning

confidence: 99%

“…Our final height analysis suggests that GH-treated children tend to reach their genetic growth potential irrespective of maximum GH peak, although there is much interindividual variation in responsiveness. Even in ISS good responders to GH treatment seem to exist [9, 13], and the as yet poorly recognizable children with partial GHD may also have a good responsiveness. On the other hand, a large proportion of untreated ISS children seem to reach their genetic growth potential without GH treatment [9, 30].…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that patients with ‘severe GHD’ show an excellent growth response to GH replacement therapy [7, 8]. It has also been reported that the same treatment, even at a higher dose, has a reduced effect on the short-term and hardly any effect on the long-term growth in children with ISS and nonimpaired GH secretion [9, 10, 11, 12, 13, 14]. Logically, one would expect an intermediate response in children with partial impairment.…”

Section: Introductionmentioning

confidence: 99%

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Growth Response to Recombinant Human Growth Hormone (GH) in Children with Idiopathic Growth Retardation by Level of Maximum GH Peak during GH Stimulation Tests

Broeck¹,

Arends

Hokken-Koelega

2000

Horm Res Paediatr

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Due to their lack of reproducibility, it is unlikely that GH stimulation tests can provide reliable diagnostic information to distinguish partial isolated GH deficiency (GHD) from idiopathic short stature (ISS). We hypothesized that the classical distinction between these groups, essentially based on stimulatory GH peaks, is artificial and that, as a consequence, the average response to GH treatment will not be different between them. The hypothesized lack of prognostic validity of stimulatory GH peaks was studied in 435 prepubertal children with nonorganic growth retardation. Children were categorized as ‘severe GHD’, ‘partial GHD’ or ‘ISS’, if the maximum rise in their serum GH during two GH stimulation tests was 0– 10 mU/l, 10–20 mU/l, or >20 mU/l, respectively. Children with ‘partial GHD’ had short-term (1- and 2-year) and long-term (till final adult height) growth responses similar to those of children with ISS, significantly lower than the response seen in children with ‘severe GHD’. In children with stimulatory GH peaks >10 mU/l, including those currently considered partially GH deficient, the maximum GH peak was not a significant determinant of growth response in the short or the long term. In conclusion, ‘partial GHD’ is ill defined and cannot be distinguished from ISS based on the currently applied auxological or GH stimulation test criteria alone. More research is required for better identification of (all) children who will respond to GH treatment, whether or not GH deficient.

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Growth hormone therapy with three dosage regimens in children with idiopathic short stature

Cited by 34 publications

References 26 publications

Effect of Growth Hormone Dose on Bone Maturation and Puberty in Children with Idiopathic Short Stature

Effect of Growth Hormone Dose on Bone Maturation and Puberty in Children with Idiopathic Short Stature

Plasma Levels of Insulin-Like Growth Factor (IGF)-I, IGF-II and IGF-Binding Protein-3 in the Evaluation of Childhood Growth Hormone Deficiency

Growth Response to Recombinant Human Growth Hormone (GH) in Children with Idiopathic Growth Retardation by Level of Maximum GH Peak during GH Stimulation Tests

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