Common insulin-like growth factor 1 (IGF-1) gene polymorphisms are not associated with the growth hormone (GH)-dose in adults with GH-deficiency

Recent data suggest that the plasma concentration of insulin-like growth factor binding protein 3 (IGFBP-3) is useful as a screening test for growth hormone (GH) deficiency. In this study, we measured by radioimmunoassay the levels of IGFBP-3 in a group of 20 subjects (12 males) of 5 years and 7 months to 16 years of age undergoing standard GH testing following cranial irradiation. The patients had received 1800 to > 6000 cGy of radiation to the hypothalamic-pituitary region, a median of 2.7 years (range 2–7 years) prior to testing. The IGFBP-3 concentrations were discordant with the results of GH testing 60% (12/20) of the time. Although IGFBP-3 levels were below the mean for age in 14 of 15 GH-deficient (peak GH <10 μg/l) patients, only three of 15 GH-deficient patients had IGFBP-3 concentrations that fell below age-adjusted norms. In contrast, the IGFBP-3 levels were within the normal range in all five patients with normal GH responses. The low sensitivity (20%) of IGFBP-3 in predicting the subjects with abnormal responses was not improved by adjusting the values for bone age or stage of puberty. We conclude that a single plasma determination of IGFBP-3 is not a useful screening test for GH deficiency among patients previously treated with cranial irradiation.

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Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents

Acta Endocrinologica ◽

10.1530/eje.0.1340184 ◽

1996 ◽

Vol 134 (2) ◽

pp. 184-189 ◽

Cited By ~ 22

Author(s):

Yukihiro Hasegawa ◽

Tomonobu Hasegawa ◽

Makoto Takada ◽

Yutaka Tsuchiya

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Gh Deficiency ◽

Hormone Deficiency ◽

Insulin Like Growth Factor ◽

Igf Binding Proteins ◽

Factor I ◽

Igf I ◽

Igf Binding ◽

Growth Factor I

Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y. Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol 1996;134:184–9. ISSN 0804–4643. Serum levels of total insulin-like growth factor I (IGF-I) correlate with growth hormone (GH) secretory status and are a useful parameter in the diagnostic evaluation of GH deficiency. Serum total IGF-I levels represent the combined quantity of free or unbound IGF-I and IGF-I that is bound to specific IGF binding proteins. Free IGF-I (fIGF-I), which is postulated to be the bioactive fraction, accounts for only a small fraction of the total amount. We have recently developed a new immunoradiometric assay (IRMA) for plasma fIGF-I and have investigated fIGF-I in relation to GH status. The simple, non-extraction assay procedure involves the capture of unbound IGF-I by anti-IGF-I antibody coated to polystyrene beads and detection by a radiolabelled anti-IGF-I antibody directed to a separate epitope. Preliminary studies demonstrated that the f IGF-I IRMA does not measure IGF-I that is complexed to IGF-binding proteins and that the equilibrium between the free and bound fractions is not disturbed during the assay. Free IGF-I levels were compared to total IGF-I levels measured in the same IRMA after acid–ethanol extraction of the samples. Normal levels of fIGF-I from infancy through adulthood were found to have a close correlation with total IGF-I levels, with the lowest levels occurring in infancy and peak levels during puberty. Patients with complete GH deficiency had low levels of both fIGF-I and total IGF-I, with 94% and 100% of the levels below the 5th percentile for age, respectively. On the other hand, approximately 90% of patients with normal IGF binding protein-3 levels among partial GH deficiency and normal short children had free and total IGF-I levels above the 5th percentile for age. These data indicate that the clinical utility of plasma fIGF-I measurements is similar to measurements of total IGF-I in the evaluation of childhood GH deficiency. Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Urnezono Kiyose, Tokyo 204, Japan

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