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

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 o...