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.
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.