IGF-1 and IGFBP 3 in Growth Hormone Deficiency Role of Insulin Like Growth Factor-1 (IGF-1) and IGF Binding Protein 3 in the Diagnosis of Growth Hormone Deficiency: Changing Paradigm

Abstract

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. Serum IGF-I levels are monitored during GH replacement treatment in subjects with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GHrelated side-effects. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 hours and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. We hereby review the various literatures at disposal justifying the use of IGF-1 and IGBP3 for diagnosis of growth hormone deficiency.Data Source: We searched PUBMED and MEDLINE database for relevant articles including key words. References of each article were further reviewed for final synthesis of the manuscript.

GH Provocative Test in Diagnosis of GH deficiency in Childhood, Can We Trust on Them?

“…Although in all papers reviewed, as shown in table 3, the only of the GH stimulation tests that has obtained 100% specificity and 100% sensitivity, it has been the Glucagon test in the study of Eren et al [9], on the contrary, on the study of Kota et al [10], the specificity was 85% and sensitivity was 73%, so it could better be considered that ITT should be one of the preferred GH stimulation tests (gold standard test) [4,11], because it has been the test that has obtained higher percentages of sensitivity and specificity: Borges et al [12] (sensitivity 100% and specificity 96,98%), Guzzetti et al [13] (sensitivity 94,4% and specificity 89,6%), Rhee et al [14] (sensitivity 93,6% and specificity 78,4%), Guo et al [15] (sensitivity 48% and specificity 76% -the lowest percentages of all papers compared), Eren et al (sensitivity 91% and specificity 65%); Maghnie et al [16] (sensitivity 96% and specificity 100%), Shalet et al [4] (sensitivity 100% and specificity 97%) and Tillman et al [17] (sensitivity 73% and specificity 85%). On the other hand, the other stimulation tests of the GH (L-dopa, Arginine HCl, Clonidine and GHRH) could hardly be considered as the gold standard test (in fact, it is not described in the last papers the sensitivity and the specificity about the Propanolol test), because they are not the most used for the detection of growth hormone defects, in addition to the percentages of sensitivity and specificity differ considerably from some studies to others [17][18][19][20][21][22][23].…”

The Growth Hormone Deficiency Short Stature Is the Predominant Type Among Young School Girls in Gaza, Palestine.

“…Age independence of IGFBP-3 makes it a useful marker of GH-IGF axis during infancy. The best diagnostic accuracy (sensitivity of 97% and specificity of 95%) is however achieved by combining IGF-1 and IGFBP-3 assays, which are now replacing GH-based investigations for evaluation and monitoring of disorders of the GH-IGF axis [30,31].This usefulness was disputed, in a study in Bangkok, Thailand, suggesting that the measurement of IGF-1 and IGFBP-3 cannot be used in diagnosing GHD [32]. The age range in the previous study was 0.9 to 19.9 years where huge fluctuations in IGF-1 and IGFBP-3 are expected.…”