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Free Insulin-Like Growth Factor I Serum Levels in 1430 Healthy Children and Adults, and Its Diagnostic Value in Patients Suspected of Growth Hormone Deficiency¹

Department of Growth and Reproduction, National University Hospital (A.J., K.H., J.M., N.E.S.), the Center of Preventive Medicine, Glostrup County Hospital, University of Copenhagen (S.R.), and the Department of Pediatrics, Glostrup Amtssygehus (K.W.K.), Copenhagen; the Department of Pediatrics, Hvidovre Hospital (S.A.P.), Hvidovre; the Research Department of Human Nutrition, Royal Veterinary and Agricultural University (K.F.M.), Frederiksberg; and the Department of Biostatistics, Panum Institute (T.S.), Copenhagen, Denmark

Address all correspondence and requests for reprints to: Anders Juul, M.D., Ph.D., Department of Growth and Reproduction, GR 5064, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.

Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3 determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist.

Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed, commercially available immunoradiometric assay (Diagnostic Systems Laboratories) to establish valid normative data for this analysis. We studied the diagnostic value of free IGF-I in relation to total IGF-I and IGFBP-3 determinations in adults who were suspected of GHD. A GH provocative test, using oral clonidine, was performed in 108 adult patients who had previously been treated with GH in childhood.

In healthy subjects, free IGF-I levels increased during childhood, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of free IGF-I was apparent. We found unmeasurable free IGF-I values in 34 of the prepubertal children (3.3%). All individuals over 8 yr of age had measurable free IGF-I levels that amounted to approximately 1% of the total IGF-I concentrations. Free IGF-I levels were below -2 SD in 56 of 79 GHD patients (sensitivity, 71%) and above -2 SD in 24 of 29 patients with a normal GH response (specificity, 83%). Multiple linear regression analysis demonstrated that free IGF-I was significantly dependent on peak GH levels, duration of the disease, and number of other pituitary axes affected.

We conclude that free IGF-I serum levels increase during childhood with a peak in puberty, whereafter free IGF-I levels return to prepubertal levels. Three percent of healthy prepubertal children had unmeasurable free IGF-I levels using this assay. We found that determination of the free IGF-I serum concentration may predict the outcome of a GH provocative test in adults suspected of GHD, but that a single determination of free IGF-I offered no significant advantage compared to determination of total IGF-I or IGFBP-3 serum levels.

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