Test ID: IGFB3
Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3), Serum
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Diagnosing growth disorders
Diagnosing adult growth hormone deficiency
Monitoring of recombinant human growth hormone treatment
As a possible adjunct to insulin-like growth factor 1 and growth hormone in the diagnosis and follow-up of acromegaly and gigantism
Method Name A short description of the method used to perform the test
Enzyme-Labeled Chemiluminescent Immunometric Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Insulin-Like Growth Factor Binding Protein 3, Serum
Somatomedin C binding protein
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 0.8 mL
Collection Instructions: Spin down promptly.
Additional Information: Indicate patient's age and sex.
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross OK |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Frozen | 14 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Insulin-like growth factor binding protein-3 (IGFBP-3) is a 264-amino acid peptide (MW 29 kD) produced by the liver. It is the most abundant of a group of IGFBPs that transport, and control bioavailability and half-life of insulin-like growth factors (IGF), in particular IGF-1, the major mediator of the anabolic- and growth-promoting effects of growth hormone (GH). Noncomplexed IGFBP-3 and IGF-1 have short half-lives (t1/2) of 30 to 90 minutes, and 10 minutes, respectively, while the IGFBP-3/IGF-1 complex is cleared with a much slower t1/2 of 12 hours. In addition to its IGF-binding function, IGFBP-3 also exhibits intrinsic growth-regulating effects that are not yet fully understood, but have evoked interest with regards to a possible role of IGFBP-3 as a prognostic tumor marker.
The secretion patterns of IGFBP-3 and IGF-1 mimic each other; their respective syntheses are primarily controlled by GH. Unlike GH secretion, which is pulsatile and demonstrates significant diurnal variation, IGFBP-3 and IGF-1 levels show only minor fluctuations. IGFBP-3 and IGF-1 serum levels therefore represent a stable and integrated measurement of GH production and tissue effect.
Low IGFBP-3 and IGF-1 levels are observed in GH deficiency or GH resistance. If acquired in childhood, these conditions result in short stature. Childhood GH deficiency can be an isolated abnormality or associated with deficiencies of other pituitary hormones. Some of the latter cases may be due to pituitary or hypothalamic tumors, or result from cranial radiation or intrathecal chemotherapy for childhood malignancies. Most GH resistance in childhood is mild to moderate, with causes ranging from poor nutrition to severe systemic illness (eg, renal failure). These individuals may have IGF-1 and IGFBP-3 levels within the reference range. Severe childhood GH resistance is rare and usually due to GH-receptor defects. Both GH deficiency and mild-to-moderate GH resistance can be treated with recombinant human GH (rhGH) injections. The prevalence and causes of adult GH resistance are uncertain, but adult GH deficiency is seen mainly in pituitary tumor patients. It is associated with decreased muscle bulk and increased cardiovascular morbidity and mortality, but replacement therapy remains controversial.
Elevated serum IGFBP-3 and IGF-1 levels indicate a sustained overproduction of GH, or excessive rhGH therapy. Endogenous GH excess is caused mostly by GH-secreting pituitary adenomas, resulting in gigantism, if acquired before epiphyseal closure, and in acromegaly thereafter. Both conditions are associated with generalized organomegaly, hypertension, diabetes, cardiomyopathy, osteoarthritis, compression neuropathies, a mild increase in cancer risk, and diminished longevity. It is plausible, but unproven, that long-term rhGH-overtreatment may result in similar adverse outcomes.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
1-7 days: < or =0.7 mcg/mL
8-14 days: 0.5-1.4 mcg/mL
15 days-11 months: unavailable
1 year: 0.7-3.6 mcg/mL
2 years: 0.8-3.9 mcg/mL
3 years: 0.9-4.3 mcg/mL
4 years: 1.0-4.7 mcg/mL
5 years: 1.1-5.2 mcg/mL
6 years: 1.3-5.6 mcg/mL
7 years: 1.4-6.1 mcg/mL
8 years: 1.6-6.5 mcg/mL
9 years: 1.8-7.1 mcg/mL
10 years: 2.1-7.7 mcg/mL
11 years: 2.4-8.4 mcg/mL
12 years: 2.7-8.9 mcg/mL
13 years: 3.1-9.5 mcg/mL
14 years: 3.3-10 mcg/mL
15 years: 3.5-10 mcg/mL
16 years: 3.4-9.5 mcg/mL
17 years: 3.2-8.7 mcg/mL
18 years: 3.1-7.9 mcg/mL
19 years: 2.9-7.3 mcg/mL
20 years: 2.9-7.2 mcg/mL
21-25 years: 3.4-7.8 mcg/mL
26-30 years: 3.5-7.6 mcg/mL
31-35 years: 3.5-7.0 mcg/mL
36-40 years: 3.4-6.7 mcg/mL
41-45 years: 3.3-6.6 mcg/mL
46-50 years: 3.3-6.7 mcg/mL
51-55 years: 3.4-6.8 mcg/mL
56-60 years: 3.4-6.9 mcg/mL
61-65 years: 3.2-6.6 mcg/mL
66-70 years: 3.0-6.2 mcg/mL
71-75 years: 2.8-5.7 mcg/mL
76-80 years: 2.5-5.1 mcg/mL
81-85 years: 2.2-4.5 mcg/mL
Tanner Stages:
Males
Stage I: 1.2-6.4 mcg/mL
Stage II: 2.8-6.9 mcg/mL
Stage III: 3.9-9.4 mcg/mL
Stage IV: 3.3-8.1 mcg/mL
Stage V: 2.7-9.1 mcg/mL
Females
Stage I: 1.4-5.2 mcg/mL
Stage II: 2.3-6.3 mcg/mL
Stage III: 3.1-8.9 mcg/mL
Stage IV: 3.7-8.7 mcg/mL
Stage V: 2.6-8.6 mcg/mL
Note: Puberty onset, ie, the transition from Tanner stage I (prepubertal) to Tanner stage II (early pubertal), occurs for girls at a median age of 10.5 (+/-2) years and for boys at a median age of 11.5 (+/-2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African-American girls. By contrast, for boys there is no definite proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage V (young adult) should be reached by age 18.
Interpretation Provides information to assist in interpretation of the test results
For all applications, insulin-like growth factor 1 (IGF-1) measurement has generally been shown to have superior diagnostic sensitivity and specificity compared with insulin-like growth factor binding protein 3 (IGFBP-3). IGFBP-3 testing should, therefore, usually be combined with IGF-1 testing. The combination of IGF-1 and IGFBP-3 measurements appears superior to determining either analyte alone in the diagnosis of growth hormone (GH) deficiency and resistance, and in the monitoring of recombinant human GH therapy. By contrast, in the diagnosis and follow-up of acromegaly and gigantism, IGFBP-3 measurement adds little if anything to IGF-1 testing.
IGF-1 and IGFBP-3 levels below the 2.5th percentile for age are consistent with GH deficiency or severe resistance, but patients with incomplete GH deficiency or mild-to-moderate GH resistance may have levels within the reference range. In GH deficiency, GH levels are also low and show suboptimal responses in stimulation tests (eg, exercise, clonidine, arginine, ghrelin, growth hormone-releasing hormone, insulin-induced hypoglycemia), while in severe GH resistance, GH levels are substantially elevated. However, dynamic GH testing is not always necessary for diagnosis. If it is undertaken, it should be performed and interpreted in endocrine testing centers under the supervision of an endocrinologist.
The aim of both pediatric and adult GH replacement therapy is to achieve IGF-1 and IGFBP-3 levels within the reference range, ideally within the middle to upper third. Higher levels are rarely associated with any further therapeutic gains, but could potentially lead to long-term problems of GH excess.
Elevated IGF-1 and IGFBP-3 levels support the diagnosis of acromegaly or gigantism in individuals with appropriate symptoms or signs. In successfully treated patients, both levels should be within the normal range, ideally within the lower third. In both diagnosis and follow-up, IGF-1 levels correlate better with clinical disease activity than IGFBP-3 levels.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) reference ranges are highly age-dependent and results must always be interpreted within the context of the patient's age.
Discrepant IGFBP-3 and IGF-1 results can sometimes occur due to liver and kidney disease; however, this is uncommon and such results should alert laboratories and physicians to the possible occurrence of a preanalytical or analytical error.
At this time, IGFBP-3 cannot be reliably used as a prognostic marker in breast, colon, prostate, or lung cancer.
IGFBP-3 assays exhibit significant variability among platforms and manufacturers. Direct comparison of results obtained by different assays is problematic. Re-baselining of patients is preferred if assays are changed.
Heterophilic antibodies in human serum can react with the immunoglobulins included in the assay components causing interference with in vitro immunoassays. Specimens from patients with autoimmune diseases or from individuals routinely exposed to animals or animal serum products can demonstrate this type of interference, potentially causing an anomalous result. The assay reagents have been formulated to minimize the risk of such interference; however, potential interactions between rare sera and test components can occur. For diagnostic purposes, the results obtained from this assay should always be used in combination with the clinical examination, patient medical history, and other findings.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Boscato LM, Stuart MC: Heterophilic antibodies: a problem for all immunoassays. Clin Chem 1988;34:27-33
2. Wetterau L, Cohen P: Role of insulin-like growth factor monitoring in optimizing growth hormone therapy. J Ped Endocrinol Metab 2000;13:1371-1376
3. Granada ML, Murillo J, Lucas A, et al: Diagnostic efficiency of serum IGF-1, IGF-binding protein-3 (IGFBP-3), IGF/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population. Eur J Endocrinol 2000;142:243-253
4. Parama C, Fluiters E, de la Fuente J, et al: Monitoring of treatment success in patients with acromegaly: the value of serum insulin-like growth factor binding protein-3 and serum leptin measurements in comparison to plasma insulin-like growth factor 1 determination. Metabolism 2001;50:1117-1121
5. Monzavi R, Cohen P: IGFs and IGFBPs: role in health and disease. Best Pract Res Clin Endocrinol Metab 2002;16:433-447
6. Boquete HR, Sobrado PGV, Fideleff HL, et al: Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-1 and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J Endocrinol Metab 2003;88:4702-4708
Method Description Describes how the test is performed and provides a method-specific reference
The Immulite 2000 IGFBP-3 is a solid-phase, enzyme-linked chemiluminescent immunoassay based on murine monoclonal antibodies. The patient sample and alkaline phosphatase-conjugated anti-insulin-like growth factor binding protein 3 (IGFBP-3) antibodies are simultaneously incubated with an antibody-coated bead. During this time, IGFBP-3 in the sample forms an antibody sandwich complex that binds to the streptavidin on the bead. Unbound enzyme conjugate is then removed by washing, after which substrate is added. The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light. The photon output is directly proportional to the concentration of IGFBP-3 in the sample.(Package insert: Immulite 2000 IGFBP-3 PIL2KGB-11, Siemens Medical Solutions Diagnostics, Los Angeles, CA, 2008-7-29)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday 5 a.m.-12 a.m., Saturday 6 a.m. – 6p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83520
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| IGFB3 | IGFBP-3, S | 2483-6 |
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