Circulating IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 Molar Ratio Concentration and Height Outcome in Prepubertal Short Children on rhGH Treatment over Two Years of Therapy

Objective: To investigate the occurrence of abnormally elevated values of biomarkers of growth hormone (GH) action in short children on recombinant human GH (rhGH) therapy. Methods: Sixty-three prepubertal short children were examined: 31 with GH deficiency (GHD), 25 small for gestational age (SGA), and 9 with Turner syndrome (TS). The main outcomes were the following: standard deviation score (SDS) values of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio before, at the 1st and at the 2nd year on rhGH and Δheight (Ht)-SDS to evaluate GH treatment efficacy (adequate 1st-year ΔHt SDS: >0.4 SDS for GHD and >0.3 SDS for non-GHD). Results: Seventy-eight percent of GHD, 78% of SGA and 55% of TS children had adequate 1st-year ΔHt SDS. In GHD, 88% of IGF-I SDS and IGFBP-3 SDS that were ≤–2.0 SDS at baseline normalized on treatment. Abnormal IGF-I values >+2.0 SDS were observed in 52% of SGA and in 55% of TS patients on rhGH. Within each group, the IGF-I/IGFBP-3 molar ratio increased significantly from pretreatment and throughout therapy, remaining within normal range for most patients. ΔIGF-I/IGFBP-3 molar ratio SDS were significantly higher in children with an adequate response (p < 0.01). Conclusion: Non-GHD groups presented markedly elevated concentrations of GH biomarkers on rhGH and normal IGF-I/IGFBP-3 molar ratio in most patients. Since there is a lack of consensus regarding the molar ratio usefulness, we think that interventions towards a more physiological IGF-I serum profile should be implemented.

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Growth Hormone Therapy in Children with Kabuki Syndrome: 1-year Treatment Results

Hormone Research in Paediatrics ◽

10.1159/000479368 ◽

2017 ◽

Vol 88 (3-4) ◽

pp. 258-264 ◽

Cited By ~ 9

Author(s):

Dina A. Schott ◽

Willem J.M. Gerver ◽

Constance T.R.M. Stumpel

Keyword(s):

Growth Hormone ◽

Gh Deficiency ◽

Standard Deviation Score ◽

Height Velocity ◽

Kabuki Syndrome ◽

Body Proportions ◽

Leg Length ◽

Gh Treatment ◽

Igf I ◽

Rhgh Treatment

Background/Aims: Kabuki syndrome (KS) is a rare genetic malformation syndrome, resulting in characteristic features such as short stature. We investigate whether growth hormone (GH) treatment increases linear height and influences body proportions in KS children. Methods: In this prospective study, 18 genetically confirmed prepubertal KS children (9 females and 9 males) aged from 3.8 to 10.1 years (mean 6.8 ± 2.1 years) were treated with recombinant human GH (rhGH) for 1 year. Calculations for height, height velocity, BMI, sitting height, and subischial leg length were made. Bone age, insulin-like growth factor (IGF-I), and IGF binding protein 3 (IGFBP-3) were also measured. Results: This study showed an increase in height standard deviation score (SDS) for the whole group from –2.40 to –1.69 (p < 0.05) after 1 year of rhGH treatment. The change in height SDS within 1 year was >0.7 SDS for 10 subjects and >0.5 SDS for 3 subjects. The mean IGF-I SDS at the start of the study was –0.70 (±1.07), which increased after 12 months to 1.41 (±0.91) (p < 0.05). KS children who received rhGH at a younger age displayed significantly greater increases in height than those who started when they were older. The same was true for both gene mutation KMT2D versus KDM6A and for GH deficiency versus non-GH deficiency KS children (p < 0.05). Throughout the course of rhGH treatment, the subjects’ body proportions remained normal. Conclusions: All participants experienced catch-up growth during the year of rhGH treatment, but without an influence on body proportions.

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Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0297 ◽

2017 ◽

Vol 30 (2) ◽

Cited By ~ 3

Author(s):

Lucia Schena ◽

Cristina Meazza ◽

Sara Pagani ◽

Valeria Paganelli ◽

Elena Bozzola ◽

...

Keyword(s):

Growth Hormone ◽

Final Height ◽

Standard Deviation Score ◽

Bone Age ◽

Gh Treatment ◽

Short Children ◽

Igf I ◽

Height Gain ◽

The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

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Diagnostic efficiency of serum IGF-I, IGF-binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population

Acta Endocrinologica ◽

10.1530/eje.0.1420243 ◽

2000 ◽

pp. 243-253 ◽

Cited By ~ 33

Author(s):

ML Granada ◽

J Murillo ◽

A Lucas ◽

I Salinas ◽

MA Llopis ◽

...

Keyword(s):

Normative Data ◽

Gh Deficiency ◽

Reference Population ◽

Molar Ratio ◽

Diagnostic Efficiency ◽

Adult Gh Deficiency ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein ◽

Igfbp 3

OBJECTIVE: To analyse the diagnostic role of serum IGF-I, IGF-binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and urinary GH (uGH) excretion in adult GH deficiency (GHD). DESIGN: Twenty-seven adults (age range: 18-71 years) with severe GHD, defined by a peak GH response to an insulin tolerance test below 3microg/l in patients with at least one additional pituitary hypofunction. Reference values were established from a selected age- and body mass index-matched population (154 healthy adults grouped in four age groups). METHODS: IGF-I and IGFBP-3 were measured by RIA (Nichols) and results expressed as standard deviation (s.d.) scores from our reference population and assay normative data (s.d. score Nichols). uGH was measured by IRMA. RESULTS: Within the control group, IGF-I, IGFBP-3, IGF-I/IGFBP-3 ratio standardisation regarding our control population and IGF-I with respect to the assay normative data resulted in disappearance of age-related differences. However, IGFBP-3 s.d. score Nichols resulted in mean values between +1.4 and +2.5 s.d. score. Greatest diagnostic efficiency was for IGF-I standardised with respect to our controls (97.2%), followed by s.d. score IGFBP-3 (92.9%). s.d. score IGF/IGFBP-3 ratio and uGH showed poor diagnostic efficiency. Any combination of at least two abnormal parameters raised specificity to 100%. IGF-I standardised with respect to assay reference (s.d. score Nichols) showed similar diagnostic value (95.0%) whereas IGFBP-3 showed low sensitivity (33. 3%). Within the GHD patients, those with three or more additional deficiencies had lower s.d. score IGF-I than those with only two or one. CONCLUSION: We underline the importance of an appropriate reference population for correct interpretation of GH secretion markers. Considering our results, specificity obtained with two simultaneous abnormal parameters when referred to an adequate reference population may add valuable information to alternative GH stimulation tests to confirm adult GHD.

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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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Development of an RIA for salmon 41 kDa IGF-binding protein

Journal of Endocrinology ◽

10.1677/joe.0.1780275 ◽

2003 ◽

Vol 178 (2) ◽

pp. 275-283 ◽

Cited By ~ 31

Author(s):

M Shimizu ◽

A Hara ◽

WW Dickhoff

Keyword(s):

Coho Salmon ◽

Molar Ratio ◽

Gh Treatment ◽

Igf Binding Proteins ◽

Igf I ◽

Igf Binding ◽

Molecular Masses ◽

Size Type ◽

Igf Binding Protein ◽

Igfbp 3

Salmon plasma contains at least three IGF-binding proteins (IGFBPs) with molecular masses of 41, 28 and 22 kDa. The 41 kDa IGFBP is similar to mammalian IGFBP-3 in size, type of glycosylation and physiological responses. In this study, we developed an RIA for the 41 kDa IGFBP. The 41 kDa IGFBP purified from serum was used for antibody production and as an assay standard. Binding of three different preparations of tracer were examined: (125)I-41 kDa IGFBP, (125)I-41 kDa IGFBP cross-linked with IGF-I and 41 kDa IGFBP cross-linked with (125)I-IGF-I (41 kDa IGFBP/(125)I-IGF-I). Only binding of 41 kDa IGFBP/(125)I-IGF-I was not affected by added IGFs, and therefore it was chosen for the tracer in the RIA. Plasma 41 kDa IGFBP levels measured by RIA were increased by GH treatment (178.9+/-4.9 ng/ml) and decreased after fasting (95.0+/-7.0 ng/ml). The molarities of plasma 41 kDa IGFBP and total IGF-I were comparable, and they were positively correlated, suggesting that salmon 41 kDa IGFBP is a main carrier of circulating IGF-I in salmon, as is mammalian IGFBP-3 in mammals. During the parr-smolt transformation (smoltification) of coho salmon, plasma 41 kDa IGFBP levels showed a transient peak (182.5+/-10.3 ng/ml) in March and stayed relatively constant thereafter, whereas IGF-I showed peak levels in March and April. Differences in the molar ratio between 41 kDa IGFBP and IGF-I possibly influence availability of IGF-I in the circulation during smoltification.

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THE SHORT-TERM INCREASES OF IGF-I AND IGFBP-3 DURING GH TREATMENT PREDICT THE LONG-TERM GROWTH RESPONSE IN SHORT CHILDREN

Pediatric Research ◽

10.1203/00006450-199305001-00272 ◽

1993 ◽

Vol 33 ◽

pp. S48-S48

Author(s):

W F Blum ◽

S Rosberg ◽

M B Ranke ◽

K Albertsson-Wikland

Keyword(s):

Growth Response ◽

Short Term ◽

Gh Treatment ◽

Short Children ◽

Igf I ◽

Igfbp 3

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Can exaggerated response to a GH provocative test identify patients with partial GH insensitivity syndrome?

Acta Endocrinologica ◽

10.1530/eje.0.1460319 ◽

2002 ◽

pp. 319-323 ◽

Cited By ~ 9

Author(s):

Y Rakover ◽

A Silbergeld ◽

I Lavi ◽

R Masalha ◽

IB Shlomo

Keyword(s):

Short Stature ◽

Binding Protein ◽

Standard Deviation Score ◽

Bone Age ◽

The Other ◽

Provocative Test ◽

Igf I ◽

Parental Height ◽

The Difference ◽

Igfbp 3

OBJECTIVES: In the majority of children with short stature, the etiology is unknown. Mutations of the GH receptor (GHR) have been reported in a few children with apparent idiopathic short stature (ISS). These patients had low IGF-I, IGF-binding protein-3 (IGFBP-3) and GH-binding protein (GHBP), but a normal or exaggerated GH response to provocative stimuli, suggestive of partial GH insensitivity (GHI). We attempted to identify children with partial GHI syndrome, based on their response to GH provocative stimuli and other parameters of the GH-IGF-I axis. SUBJECTS AND METHODS: One hundred and sixty-four pre-pubertal children (97 boys, 67 girls) aged 7.2 (0.5-16.75) years were studied. All had short stature with height <3rd centile. The weight, bone age (BA) and body mass index (BMI) of the subjects, as well as the parents' heights and mid parental height (MPH) were assessed. Basal blood samples were taken for IGF-I, IGFBP-3 and GHBP. All subjects underwent a GH provocative test with either clonidine, arginine or insulin. The subjects were divided into three groups: (A) patients with peak GH concentration <18 mIU/l in two different provocative tests (GH deficiency - GHD, n=33); (B) patients with peak GH between 18.2 and 39.8 mIU/l (normal response, n=78); (C) patients with peak GH >40 mIU/l (exaggerated GH response, n=53). RESULTS: No significant differences were found in age, height (standard deviation score (SDS)), parental height (SDS) and the difference between chronological age and bone age (DeltaBA) between the groups. Patients with GHD were heavier (P=0.039) and had significantly higher BMI (SDS) (P=0.001) than the other groups. MPH (SDS) was lower in the group of exaggerated responders (P=0.04) compared with the other groups. No significant differences were found between the groups for the biochemical parameters when expressed nominally or in SDS, except for IGFBP-3 (SDS), which was lower in the GHD group (P=0.005). The GHBP levels were not lower in the group of exaggerated GH response to provocative stimuli. Height (SDS) correlated negatively with basal GH values in pooled data of all the subjects (r=-0.358, P<0.0001), in normal responders (r=-0.45, P<0.0001) and in the exaggerated responders (r=-0.341, P<0.0001), but not in the GHD group. CONCLUSION: Exaggerated GH response to provocative tests alone does not appear to be useful in identifying children with GHI.

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Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4

Journal of Endocrinology ◽

10.1677/joe.0.1360091 ◽

1993 ◽

Vol 136 (1) ◽

pp. 91-104 ◽

Cited By ~ 119

Author(s):

L. R. Donahue ◽

W. G. Beamer

Keyword(s):

Body Composition ◽

Growth Factor ◽

Gh Deficiency ◽

Body Water ◽

Insulin Like Growth Factor ◽

Gh Therapy ◽

Factor I ◽

Igf I ◽

Body Compartments ◽

Igfbp 3

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104

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Phenotype and Genetic Analysis of a Syndrome Caused by an Inactivating Mutation in the Growth Hormone-Releasing Hormone Receptor: Dwarfism of Sindh1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.11.5226 ◽

1998 ◽

Vol 83 (11) ◽

pp. 4065-4074

Author(s):

Hiralal G. Maheshwari ◽

Bernard L. Silverman ◽

Josée Dupuis ◽

Gerhard Baumann

Keyword(s):

Gh Deficiency ◽

Postnatal Growth ◽

N Gene ◽

Molecular Characteristics ◽

Clinical Genetic ◽

Gh Treatment ◽

Gh Secretion ◽

Absolute Requirement ◽

Igf I ◽

Igf Binding

We report, in detail, a new form of familial dwarfism, including its phenotypic features, hormonal profile, and molecular basis. Following a newspaper report of severe dwarfism in two villages in the province of Sindh, Pakistan, we organized an expedition to study its clinical, genetic, and molecular characteristics. We identified 18 dwarfs (15 male, 3 female), all members of a consanguineous kindred, ranging in age from newborn to 28 yr. Mean height was 7.2 sd below the norm, with mean adult heights of 130 cm for males and 113.5 cm for females. Body proportions and habitus were normal; but head circumference was 4.1 sd, and blood pressure approximately 3 sd below the norm. There was no dysmorphism, no microphallus, and no history of hypoglycemia. Serum GH did not respond to provocative stimuli (GHRH, l-dopa, or clonidine). Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were low (5.2 ± 2.0 ng/mL and 0.42 ± 0.13 μg/mL, respectively; mean ± sd) but rose normally with GH treatment. One affected, dwarfed couple had a son, demonstrating fertility in both sexes. Clinical and endocrinological evidence suggested isolated GH deficiency with a recessive inheritance pattern. The GH-N gene was found to be intact. Linkage analysis of microsatellite chromosomal markers near other candidate genes yielded a high LOD score (6.26) for the GHRH receptor (GHRH-R) locus. DNA sequencing revealed a nonsense mutation (Glu50→Stop) in the extracellular domain of the GHRH-R. This mutation predicts a severely truncated GHRH-R; it is identical to that recently reported in four patients from two other families. Inheritance is autosomal recessive (chromosome 7p) with a high degree of penetrance. Relatives heterozygous for the mutation had moderately decreased IGF-I levels and slightly blunted GH responses to GHRH and l-dopa, but they showed only minimal or no height deficit. This syndrome represents the human homologue of the little (lit/lit) mouse and closely resembles its phenotype. It demonstrates the absolute requirement of GHRH signaling for pituitary GH secretion and postnatal growth in humans, and its relatively minor (but discernible) biological importance in extrapituitary sites. The syndrome is distinct from other forms of GH deficiency with respect to microcephaly, asymptomatic hypotension, and absence of features such as facial dysplasia, significant truncal obesity, microphallus, or hypoglycemia. Its discovery raises the possibility of milder mutations in the GHRH-R gene as potential causes for partial GH insufficiency and idiopathic short stature.

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IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH

Acta Endocrinologica ◽

10.1530/eje.0.1440237 ◽

2001 ◽

pp. 237-243 ◽

Cited By ~ 13

Author(s):

X Zhou ◽

KY Loke ◽

CC Pillai ◽

HK How ◽

HK Yap ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Growth Retardation ◽

Bone Age ◽

Gh Treatment ◽

Igf Binding Proteins ◽

Steroid Dependent ◽

Igf I ◽

Igf Binding ◽

Pre Treatment ◽

Igfbp 3

OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.

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