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The Acid-Labile Subunit of Human Ternary Insulin-Like Growth Factor Binding Protein Complex in Serum: Hepatosplanchnic Release, Diurnal Variation, Circulating Concentrations in Healthy Subjects, and Diagnostic Use in Patients with Growth Hormone Deficiency

Department of Growth and Reproduction (A.J., E.M.-L., S.A.P., J.M., N.E.S.), National University Hospital, 2100 Copenhagen; Department of Clinical Physiology and Nuclear Medicine (S.M., J.H.), and Department of Endocrinology (M.H.R.), Hvidovre Hospital, 2740 Hvidovre; Department of Biostatistics (T.S.), Panum Institute, 2200 Copenhage N; Department of Pediatrics (K.W.K.), Glostrup County Hospital, 2600 Glostrup; Diagnostics Systems Laboratories, Inc. (J.M.), Webster, Texas 77598; and Centre of Preventive Medicine (S.R.), Glostrup County Hospital, University of Copenhagen, 2600 Glostrup, Denmark

Address all correspondence and requests for reprints to: Anders Juul, M.D., Ph.D., Department of Growth and Reproduction, Rigshospitalet Section 5064, 9 Blegdamsvej, DK-2100 Copenhagen Ø, Denmark. E-mail: ajuul{at}post4.tele.dk

Circulating insulin-like growth factor-I (IGF-I) is predominantly bound in the trimeric complex comprised of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). Circulating concentrations of IGF-I, IGFBP-3 and ALS are believed to reflect the GH secretory status, but the clinical use of ALS determination is not known. We therefore, determined the: 1) hepatosplanchnic release of ALS by liver vein catheterization (n = 30); 2) 24-h diurnal variation of ALS (n = 8); 3) normal age-related ranges of circulating ALS (n = 1158); 4) diagnostic value of ALS in 108 patients with childhood-onset GH deficiency (GHD). We found: 1) no significant arteriovenous gradient over the liver of ALS, IGF-I, and IGFBP-3; 2) the diurnal variation of ALS was 12% (mean coefficient of variation percent); 3) ALS levels increased throughout childhood with maximal levels in puberty, with a subsequent decrease with age in adults; and 4) ALS levels were below -2 SD in 57 of 79 GHD patients (sensitivity 72%) and above 2 SD in 22 of 29 patients with normal GH response (specificity 76%), which was similar, compared with the diagnostic utility of IGF-I and IGFBP-3. Finally, our findings indicate that hepatic ALS production is not measurable by this approach or, alternatively, that the liver is not the primary source of circulating ALS, IGF-I, or IGFBP-3 in humans. In conclusion, we have provided extensive normal data for a novel ALS assay and found that circulating ALS levels exhibit minor diurnal variation. We suggest that ALS determination may be used in future classification of adults suspected of GHD.

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