Insulin-like Growth Factor-binding Protein 3 (IGFBP-3)

CPT: 83520
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Test Details

Use

The insulin-like growth factor (IGF) system plays a critical role in the growth and differentiation of normal and malignant cells. The components of the IGF system include growth hormone (GH), IGF-I and II, type I and II receptors, IGF binding proteins and proteases. IGF binding proteins were first identified for their high affinity interactions with IGF-I and IGF-II.2

IGFBP-3 is the most abundant IGFBP species in circulation and binds 75% to 90% of circulating IGF-I in a ternary complex consisting of IGFBP-3, IGF-I and acid-labile subunit (ALS). IGFBP-3 modulates the activity of IGF-1 and to increase their half lives. It has been postulated that IGFBP-3 is regulated by GH and originates in the liver as low levels were observed in patients with impaired hepatic function.3

IGFBP-3 has historically been used in the investigation of growth hormone deficiency, acromegaly, hypopituitarism and to monitor recombinant GH therapy.4,5 IGFBP-3 is known to modulate the actions of IGFs in circulation as and at the IGF-1 receptor.3 IGFBP-3 has also been shown to exhibit distinct biological effects independent of the IGF/IGF-1 receptor axis.6,7 Recent studies have impaired interaction of IGFBP-3 with a variety of proteins or signaling cascades critical to cell cycle control and apoptosis; however, the actual mechanism of IGFBP-3 action is unclear.6

Limitations

Several factors influence IGFBP-3 levels, including age, sexual development, nutrition, and hepatic and renal function. IGFBP-3 increases during early childhood and puberty and then decreases slightly in adult life. Levels of this binding protein decrease during fasting and chronic malnutrition. IGFBP-3 levels are decreased in hepatic failure and diabetes mellitus, but are increased in chronic renal failure.

Methodology

Immunochemiluminometric assay (ICMA)

Reference Interval

See table.1

Insulin-like Growth Factor-binding Protein-3 (IGFBP-3)

Age

Male (μg/L)

Female (μg/L)

0 to 11 m

1113−3180

1053−3271

1 y

1289−3634

1221−3721

2 y

1465−4074

1388−4151

3 y

1637−4492

1553−4557

4 y

1801−4878

1713−4933

5 y

1942−5193

1854−5242

6 y

2039−5384

1945−5403

7 y

2096−5466

2019−5515

8 y

2153−5550

2096−5629

9 y

2221−5660

2180−5762

10 y

2300−5801

2270−5908

11 y

2385−5956

2360−6055

12 y

2463−6093

2444−6184

13 y

2528−6198

2517−6286

14 y

2580−6272

2580−6365

15 y

2614−6306

2636−6428

16 y

2638−6316

2682−6470

17 y

2657−6319

2718−6495

18 y

2678−6327

2749−6510

19 y

2700−6341

2779−6527

20 y

2723−6361

2809−6550

21 to 25 y

2753−6361

2855−6559

26 to 30 y

2683−6127

2752−6219

31 to 35 y

2610−5977

2573−5804

36 to 40 y

2571−5982

2504−5709

41 to 45 y

2515−6018

2409−5610

46 to 50 y

2374−5891

2343−5612

51 to 55 y

2251−5808

2306−5703

56 to 60 y

2133−5711

2238−5717

61 to 65 y

2027−5610

2161−5691

66 to 70 y

1926−5487

2059−5572

71 to 75 y

1779−5201

2005−5549

76 to 80 y

1673−5015

1950−5490

81 to 85 y

1632−5014

1925−5498

86 to 90 y

1665−5239

1961−5672

>90 y

Not established

Not established

Specimen Requirements

Specimen

Serum

Volume

1 mL

Minimum Volume

0.2 mL (Note: This volume does not allow for repeat testing.)

Container

Red-top tube or gel-barrier tube

Collection

If a red-top tube is used, transfer separated serum to a plastic container.

Storage Instructions

Refrigerate

Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

90 days

Freeze/thaw cycles

Stable x3

Clinical Information

Special Instructions

This test may exhibit interference when sample is collected from a person who is consuming a supplement with a high dose of biotin (also termed as vitamin B7 or B8, vitamin H, or coenzyme R). It is recommended to ask all patients who may be indicated for this test about biotin supplementation. Patients should be cautioned to stop biotin consumption at least 72 hours prior to the collection of a sample.

Footnotes

1. Friedrich N, Wolthers OD, Arafat AM, et al. Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-1 to IGFBP-3 ratio measured by new automated chemiluminescence assays. J Clin Endocrinol Metab. 2014 May; 99(5):1675-1686. 24483154
2. Ballard J, Baxter R, Binoux M, et al. On the nomenclature of the IGF binding proteins. Acta Endocrinol (Copenh). 1989 Nov; 121(5):751-752. 2555997
3. Holly JM, Perks CM. Insulin-like growth factor physiology: What we have learned from human studies. Endocrinol Metab Clin North Am. 2012 Jun; 41(2):249-263. 22682629
4. Blum WF, Ranke MB. Use of insulin-like growth factor binding protein 3 for the evaluation of growth disorders. Horm Res. 990; 33(Suppl 4):31-37. 1700965
5. Ranke MB, Schweizer R, Elmlinger MW, et al. Significance of basal IGF-I, IGFBP-3 and IGFBP-2. measurements in the diagnostics of short stature in children. Horm Res. 2000; 54(2):60-68. 11251368
6. Jogie-Brahim S, Feldman D, Oh Y. Unraveling insulin-like growth factor binding protein-3 actions in human disease. Endocr Rev. 2009 Aug; 30(5):417-437. 19477944
7. Mohan S, Baylink DJ. IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms. J Endocrinol. 2002 Oct; 175(1):19-31. 12379487

References

Baxter RC, Martin JL. Radioimmunoassay of growth hormone-dependent insulin-like growth factor binding protein in human plasma. J Clin Invest. 1986 Dec; 78(6):1504-1512. 2431001
Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR. A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: Its use for diagnosis of GH deficiency. J Clin Endocrinol Metab. 1990 May; 70(5):1292-1298. 1692331
Insulin-like Growth Factor Binding Protein-3 on the IDS iSYS, Device Code IS-4400, IFU Version 2011-11-29 V03. Fountain Hills, Ariz:Immunodiagnostic Systems Inc (IDS Inc).
Rosenfeld RG, Wilson DM, Lee PD, Hintz RL.. Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr. 1986 Sep; 109(3):428-433. 3746530

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140152 IGF-BP3 2483-6 140161 IGF-BP3 ug/L 2483-6

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