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

A Juul; S Møller; E Mosfeldt-Laursen; M H Rasmussen; Thomas Harder Scheike; S A Pedersen; K W Kastrup; Hao Yu; J Mistry; S Rasmussen; J Müller; J Henriksen; N E Skakkebaek

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

A Juul, S Møller, E Mosfeldt-Laursen, M H Rasmussen, Thomas Harder Scheike, S A Pedersen, K W Kastrup, Hao Yu, J Mistry, S Rasmussen, J Müller, J Henriksen, N E Skakkebaek

76 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	83
Issue number	12
Pages (from-to)	4408-15
Number of pages	8
ISSN	0021-972X
Publication status	Published - 1998

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Juul, A., Møller, S., Mosfeldt-Laursen, E., Rasmussen, M. H., Scheike, T. H., Pedersen, S. A., Kastrup, K. W., Yu, H., Mistry, J., Rasmussen, S., Müller, J., Henriksen, J., & Skakkebaek, N. E. (1998). 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. Journal of Clinical Endocrinology and Metabolism, 83(12), 4408-15.

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. / Juul, A; Møller, S; Mosfeldt-Laursen, E et al.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 12, 1998, p. 4408-15.

Research output: Contribution to journal › Journal article › Research › peer-review

Juul, A, Møller, S, Mosfeldt-Laursen, E, Rasmussen, MH, Scheike, TH, Pedersen, SA, Kastrup, KW, Yu, H, Mistry, J, Rasmussen, S, Müller, J, Henriksen, J & Skakkebaek, NE 1998, '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', Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 12, pp. 4408-15.

Juul A, Møller S, Mosfeldt-Laursen E, Rasmussen MH, Scheike TH, Pedersen SA et al. 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. Journal of Clinical Endocrinology and Metabolism. 1998;83(12):4408-15.

Juul, A ; Møller, S ; Mosfeldt-Laursen, E et al. / 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. In: Journal of Clinical Endocrinology and Metabolism. 1998 ; Vol. 83, No. 12. pp. 4408-15.

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title = "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",

abstract = "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.",

author = "A Juul and S M{\o}ller and E Mosfeldt-Laursen and Rasmussen, {M H} and Scheike, {Thomas Harder} and Pedersen, {S A} and Kastrup, {K W} and Hao Yu and J Mistry and S Rasmussen and J M{\"u}ller and J Henriksen and Skakkebaek, {N E}",

year = "1998",

language = "English",

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T1 - The acid-labile subunit of human ternary insulin-like growth factor binding protein complex in serum

T2 - hepatosplanchnic release, diurnal variation, circulating concentrations in healthy subjects, and diagnostic use in patients with growth hormone deficiency

AU - Juul, A

AU - Møller, S

AU - Mosfeldt-Laursen, E

AU - Rasmussen, M H

AU - Scheike, Thomas Harder

AU - Pedersen, S A

AU - Kastrup, K W

AU - Yu, Hao

AU - Mistry, J

AU - Rasmussen, S

AU - Müller, J

AU - Henriksen, J

AU - Skakkebaek, N E

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

M3 - Journal article

SN - 0021-972X

VL - 83

SP - 4408

EP - 4415

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 12

ER -