Measurement of IGFBP-3 is used in the diagnosis and monitoring of developmental disorders such as acromegaly and gigantism, in the diagnosis of growth hormone deficiency in adults, and in the monitoring of recombinant human growth hormone therapy.
Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) is a 264 amino acid peptide produced by the liver. It is the most abundant protein from the IGFBP group that transports and controls the bioavailability and half-life of insulin-like growth factors (IGF), in particular IGF-1, the major mediator of growth and anabolic effects of growth hormone (GH).
The modes of synthesis and secretion of IGFBP-3 and IGF-1 resemble each other and are mainly controlled by growth hormone. In contrast to the growth hormone secretion, which fluctuates and has significant daily variation, IGFBP-3 and IGF-1 levels show only slight fluctuations. Thus, the measurement of serum IGFBP-3 and IGF-1 levels represents a consistent and comprehensive measurement of the production and effectiveness of growth hormone activity in tissues.
Low levels of IGFBP-3 and IGF-1 are observed in growth hormone deficiency or growth hormone resistance. If low levels occur during childhood, they result in low stature. Childhood growth hormone deficiency may be an isolated disorder or may be related to deficiencies of other pituitary hormones. Some of the latter cases may be due to pituitary or hypothalamic tumors or may be the result of radiation or chemotherapy for malignancies. Most cases of growth hormone resistance in childhood are mild to moderate, with causes ranging from malnutrition to severe systemic disease (eg kidney failure). These children may have IGF-1 and IGFBP-3 levels within normal limits. Severe growth hormone resistance in childhood is rare and is usually due to growth hormone receptor defects. Both growth hormone deficiency and mild to moderate growth hormone resistance can be treated by the administration of recombinant human growth hormone (rhGH). The frequency and causes of growth hormone resistance in adults are not known, but growth hormone deficiency in adults is mainly observed in patients with pituitary tumors. This condition is associated with reduced muscle mass and increased cardiovascular morbidity and mortality.
Elevated serum IGFBP-3 and IGF-1 levels are observed in prolonged growth hormone overproduction or in excess rhGH treatment. The excess of endogenous growth hormone is mainly caused by pituitary adenomas that secrete GH, leading to gigantism if they occur before the closure of the epiphysis and to acromegaly if they occur after the epiphysis is closed. Both conditions are associated with generalized organomegaly, hypertension, diabetes, cardiomyopathy, osteoarthritis, neuropathies, increased risk of cancers, and reduced longevity.
Measurement of IGF-1 has been shown to have greater diagnostic sensitivity and specificity than measurement of IGFBP-3. Therefore, measurement of IGFBP-3 should be combined with measurement of IGF-1. The combination of IGF-1 and IGFBP-3 measurements is better than the individual measurement of each factor in the diagnosis of growth hormone (GH) deficiency, and the monitoring of recombinant human GH therapy. In contrast, in the diagnosis and monitoring of acromegaly and gigantism, the measurement of IGFBP-3 adds little to the measurement of IGF-1.
Laboratory test results are the most important parameter for the diagnosis and monitoring of all pathological conditions. 70%-80% of diagnostic decisions are based on laboratory tests. The correct interpretation of laboratory results allows a doctor to distinguish "healthy" from "diseased".
Laboratory test results should not be interpreted from the numerical result of a single analysis. Test results should be interpreted in relation to each individual case and family history, clinical findings, and the results of other laboratory tests and information. Your personal physician should explain the importance of your test results.
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