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 ofALS, 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.

Pulmonary function in adolescents with childhood asthma.

The aim of this study was to determine the pulmonary function in former and present asthmatics. We examined 77 persons aged 12-24 years, classified into four groups: 1) healthy subjects (controls) (n = 19), 2) former asthmatics (n = 19), 3) present mild asthmatics (n = 20), and 4) present severe asthmatics (n = 19). Although exhibiting no respiratory symptoms, former asthmatics had reduced airflow values measured by FEV1 (median (range) 89.7 (83-99) vs 101.4 (91-110)) and MEF25 (76.5 (68-94) vs 103.0 (97-124)), as compared with controls. Furthermore, former asthmatics had significantly increased PEF variability, as compared with controls, whereas no significant differences were found in static lung parameters, i.e. total lung capacity and residual volume, as compared with controls. In conclusion, former asthmatics, although now exhibiting no respiratory symptoms, were found to have obstructive airflow limitation, increased bronchial responsiveness, and normal lung volumes.