Recombinant Insulin-Like Growth Factor (IGF)-I Treatment in Short Children with Low IGF-I Levels: First-Year Results from a Randomized Clinical Trial

Abstract Background Children with non-acquired (na) growth hormone deficiency (GHD) diagnosed over decades in one center may provide perspective insight. Methods naGHD is divided into idiopathic GHD (IGHD), GHD of known cause (cGHD) and GHD neurosecretory dysfunction (NSD); time periods: <1988 (I); 1988–1997 (II); 1998–2007 (III); 2008–2015 (IV). Descriptive analyses were performed at diagnosis and during first year GH treatment. Results Patients (periods, N): I, 87; II, 141; III, 356; IV, 51. In cGHD (all), age, maximum GH, insulin-like growth factor-I (IGF-I), and insulin-like growth factor-binding protein-3 (IGFBP-3) (5.1 years, 3.6 μg/L, −5.3 standard deviation score [SDS], −3.7 SDS) were lower than in IGHD (all) (6.8 years 5.8 μg/L, −2.5 SDS, −1.0 SDS), but not height (−3.1 vs. −3.2 SDS). Characteristics of NSD were similar to that of IGHD. Patients with IGHD – not cGHD – diagnosed during 2008–2015 (IV) were the youngest with most severe GHD (maxGH, IGF-I, IGFBP-3), and first year height velocity (HV) and ∆ IGF-I (10.5 cm/year, 4.0 SDS) but not ∆ height SDS were the highest on recombinant human growth hormone (rhGH) (27 μg/kg/day). Conclusions Although during 1988–2007 patient characteristics were similar, the recently (>2008) stipulated more stringent diagnostic criteria – HV before testing, sex steroid priming, lower GH cut-off – have restricted diagnoses to more severe cases as they were observed before the rhGH era.

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Long-Term Treatment with Recombinant Insulin-Like Growth Factor (IGF)-I in Children with Severe IGF-I Deficiency due to Growth Hormone Insensitivity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-1610 ◽

2007 ◽

Vol 92 (3) ◽

pp. 902-910 ◽

Cited By ~ 143

Author(s):

Steven D. Chernausek ◽

Philippe F. Backeljauw ◽

James Frane ◽

Joyce Kuntze ◽

Louis E. Underwood ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Term Treatment ◽

Insulin Like Growth Factor ◽

Recombinant Insulin ◽

Long Term Treatment ◽

Igf I ◽

Growth Hormone Insensitivity

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Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency

Acta Endocrinologica ◽

10.1530/eje.0.1310027 ◽

1994 ◽

Vol 131 (1) ◽

pp. 27-32 ◽

Cited By ~ 33

Author(s):

Yukihiro Hasegawa ◽

Tomonobu Hasegawa ◽

Taiji Aso ◽

Shinobu Kotoh ◽

Osamu Nose ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Hormone Deficiency ◽

Insulin Like Growth Factor ◽

Normal Children ◽

Gh Treatment ◽

Factor Binding ◽

Short Children ◽

Igf I ◽

Igfbp 3

Hasegawa Y, Hasegawa T, Aso T, Kotoh S, Nose 0, Ohyama Y, Araki K, Tanaka T, Saisyo S, Yokoya S, Nishi Y, Miyamoto S, Sasaki N, Kurimoto F, Stene M, Tsuchiya Y, Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency. Eur J Endocrinol 1994;131:27–32. ISSN 0804–4643 We have shown previously that serum insulin-like growth factor binding protein-3 (IGFBP-3) levels have good predictive value for complete, but not partial, growth hormone deficiency (GHD). In this study, we compare IGFBP-3 levels in short children previously divided into groups on the basis of their post-stimulation GH levels. Complete GHD (N = 59) included those children with peak poststimulation GH < 5 μg/l. The partial GHD group (N = 49) had post-stimulation GH peaks of > 5 μg/l but < 10 μg/l. The normal children with short stature (N = 103) had post-stimulation GH peaks > 10 μg/l. Partial GHD and normal children with short stature also were divided into either low IGF-I or normal IGF-I subgroups. The clinical sensitivity of IGFBP-3 for complete GHD was 92%, whereas its sensitivity for partial GHD was 39%. For partial GHD, among those with low IGF-I (N = 19) 68% were also low for IGFBP-3, while 80% of those with normal IGF-I (N = 30) were also normal for IGFBP-3. The clinical specificity of IGFBP-3 for normal children with short stature was 69%. For these groups, among those with low IGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those with normal IGF-I (N = 81) also were normal for IGFBP-3. In addition, we tested whether IGFBP-3 can predict the response to GH treatment in prepubertal children by comparing pretreatment IGFBP-3 with the height gain achieved by 1 year of GH treatment. The incremental growth velocity during treatment correlated significantly with the pretreatment IGFBP-3 sd score (N = 46 r = –0.80, p < 0.005). The baseline IGFBP-3 sd score for all subjects correlated (N = 171, r = 0.51 p < 0.0001) with height. These data suggest that IGFBP-3 may reflect GH secretion status in most children being evaluated for GHD and that a low pretreatment IGFBP-3 sd score predicts improved growth during the first year of GH treatment. Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Umezono, Kiyose, Tokyo 204, Japan

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Different forms of insulin-like growth factor-binding protein-3 detected in serum and seminal plasma by immunofluorometric assay with monoclonal antibodies

Clinical Chemistry ◽

10.1093/clinchem/40.4.531 ◽

1994 ◽

Vol 40 (4) ◽

pp. 531-536 ◽

Cited By ~ 18

Author(s):

H Koistinen ◽

M Seppälä ◽

R Koistinen

Keyword(s):

Monoclonal Antibodies ◽

Growth Factor ◽

Seminal Plasma ◽

Binding Protein ◽

Normal Serum ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Recombinant Insulin ◽

Igf I ◽

Igfbp 3

Abstract Monoclonal antibodies against recombinant insulin-like growth factor-binding protein-3 (IGFBP-3) were produced to study the various forms of IGFBP-3 and to develop a specific immunofluorometric assay. We tested seven antibodies that showed no cross-reactions with the other five human IGFBPs. By immunoblotting, the main bands in normal serum were seen at > 90, 45, 41, 29, and 25 kDa. In pregnancy serum, the 29-kDa was stronger, and the double band at 41-45 kDa was weaker or totally absent. We characterized two immunofluorometric assays. IGF-I had no effect on either assay. Added IGF-II lowered the amount of recombinant IGFBP-3 measured by the 5C11/7F8 assay, but not by the 1B6/5C11 assay. In normal serum and follicular fluid, IGFBP-3 measurements were lower by the 5C11/7F8 assay, but in most pregnancy sera and amniotic fluids the assays gave similar results. The 5C11/7F8 assay also detected IGFBP-3 in seminal plasma, whereas the 1B6/5C11 assay did not. We conclude that the results of IGFBP-3 measurement depend on the antibodies used, and that different antibodies are suitable for the IGFBP-3 measurement in different body fluids.

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