Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults

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Abstract
IGF-I is the best marker of GH secretory status but it also depends on the nutritional status and peripheral hormones such as insulin, glucocorticoids, thyroid hormones and gonadal steroids. Though monitoring IGF-I levels is the best way for evaluating appropriate GH replacement, the usefulness of IGF-I assay in the diagnosis of adult GH deficiency (GHD) is still matter of debate. To clarify this point in a large population of GHD adults (no.=135, 61 women and 74 men; age, mean±SE: 43.8±1.4 yr, range 20–80 yr) we studied IGF-I levels, their reproducibility and association to peak GH response to GHRH+arginine (GHRH+ARG) test and insulin tolerance test (ITT). The results in GHD were compared with those in a large population of normal subjects (no.=336, 233 women and 103 men, aged 20–80 yr). Mean IGF-I levels in GHD (77.8±4.9 µg/l) were clearly lower (pIGF-I levels were lower than those in Adult Onset GHD (AO-GHD; no.=95, age, mean±SE: 50.7±1.4 yr) (56.6±9.7 vs 87.1 ±5.4 µg/l, pIGF-I levels showed good, reproducibility (r=0.92, pr=0.62, pIGF-I levels were positively associated to peak GH responses to GHRH+ARG (r=0.57, pIGF-I in GHD. In normal subjects, but not in GHD, IGF-I levels were negatively associated to age (r=−0.60, pIGF-I levels there was a clear overlap between GHD and normal subjects. However, this overlap was strongly dependent on age. In fact, in the third and fourth decade of life 83.6% of GHD had IGF-I levels below the 3rd centile of normal values; on the other hand, in the fifth-sixth decade and in ageing 47% and only 12% of GHD, respectively, had IGF-I levels low for age. In conclusion, our results demonstrate that IGF-I levels represent a reproducible marker of GH status and are reduced more in CO-GHD than in AO-GHD adults. An overlap exists between GHD and normal subjects, however this is small up to the 4th decade of life. Thus, though normal IGF-I levels do not rule out the existence of GHD, up to 40 yr low IGF-I levels strongly point to GHD if malnutrition and liver disease have been ruled out.