IS IGF BINDING PROTEIN-3 ASSESSMENT HELPFUL FOR THE DIAGNOSIS OF GH DEFICIENCY

OBJECTIVE The measurement of serum immunoreactive IGFBP-3 levels has b een proposed as a screening test to identify children with growth horm one deficiency (GHD). We tested the sensitivity and specificity of the IGFBP-3 assessment in comparison with the measurement of IGF-I. DESIG N We assessed the IGFBP-3 and IGF-I circulating levels in normal subje cts and patients with GHD or idiopathic short stature (ISS). PATIENTS Eighty-two normal subjects, 16 GHD, and 10 children with ISS were stud ied. Controls were divided into three age groups: group A, 1-4 years ( n = 16); group B, 5-9 years (n = 35), and group C, 10-14 years (n = 31 ). MEASUREMENTS All subjects underwent standard anthropometry. In shor t patients, GH secretory status was assessed by clonidine and arginine stimulation tests. IGFBP-3 and IGF-I circulating levels were measured by radioimmunoassay. RESULTS IGFBP-3 and IGF-I levels were closely re lated (r = 0.51, P < 0.0001) and IGFBP-3 was less age dependent than I GF-I (r = 0.57, P < 0.02 vs r = 0.64, P = 0.0001). Sensitivity (true p ositive ratio) and specificity (true negative ratio) of IGFBP-3 measur ement were 50 and 92% respectively, whereas sensitivity and specificit y of IGF-I assessment were 75 and 90% respectively. Below the age of 5 years, sensitivity was 20% for IGFBP-3 and 40% for IGF-I; specificity was 94% for IGFBP-3 and 88% for IGF-I. CONCLUSIONS IGFBP-3 measuremen t had poor sensitivity in detecting growth hormone deficient patients, offering no diagnostic advantage over IGF-I, even in the first years of life, although, due to the high specificity, the finding of subnorm al levels of IGFBP-3 was strongly suggestive of growth hormone deficie ncy. The presence of low IGFBP-3 and IGF-I levels in a short child wit h normal on response to provocative tests should prompt further invest igations, such as the determination of spontaneous GH secretion or ass essment of the GH binding proteins together with an IGF-I and/or IGFBP -3 generation test, in order to identify neurosecretory dysfunction or GH receptor deficiency. Finally, we believe that there is no definiti ve test for diagnosing or excluding growth hormone deficiency and deta iled analysis of the results of endocrine tests, clinical findings and other laboratory and radiological information is necessary to maximiz e diagnostic accuracy.