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.
Juul
A
A
Department of Growth and Reproduction, National University Hospital, Copenhagen, Denmark. ajuul@post4.tele.dk
Møller
S
S
Mosfeldt-Laursen
E
E
Rasmussen
M H
MH
Scheike
T
T
Pedersen
S A
SA
Kastrup
K W
KW
Yu
H
H
Mistry
J
J
Rasmussen
S
S
Müller
J
J
Henriksen
J
J
Skakkebaek
N E
NE
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000097:blood* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000378:metabolism; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012016:Reference Values; D014781:Viscera / Q000378:metabolism*
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone