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

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 micrograms/l) were clearly lower (p < 0.001) than those in normal subjects (170.2 +/- 4.7 micrograms/l). In Childhood Onset GHD (CO-GHD; no. = 40; age, mean +/- SE: 27.8 +/- 1.5 yr) IGF-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 micrograms/l, p < 0.0003). In both GHD and normal subjects IGF-I levels showed good, reproducibility (r = 0.92, p < 0.00001 and r = 0.62, p < 0.00001, respectively). In GHD, but not in normal subjects, IGF-I levels were positively associated to peak GH responses to GHRH + ARG (r = 0.57, p < 0.00001); on the other hand, the GH peak after ITT was not associated to IGF-I in GHD. In normal subjects, but not in GHD, IGF-I levels were negatively associated to age (r = -0.60, p < 0.00001). Considering individual IGF-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.

Impact of different cut-off limits of peak GH after GHRH-arginine stimulatory test, single IGF1 measurement, or their combination in identifying adult patients with GH deficiency

“…First of all, we defined normative values for IGF1 with 95% specificity in a large series of healthy subjects; this allowed a strict definition of diseased subjects with serum IGF1 below the normal value for age. The fact that 82% of patients with total hypopituitarism had serum IGF1 below the normal range for age clearly indicates that measurement of IGF1 in this context is a good indicator of GHD, in keeping with previous reports (10,(23)(24)(25)(26)(27); moreover, our findings overtake any specific cut-off point and extend the concept that IGF1 below strictly defined normative range for age identified most GHD patients when applied in the appropriate clinical context. However, several points, including local specific cut-offs, should be taken into consideration for IGF1 measurements, as recently outlined (28).…”

Adult GH deficiency - the value of IGF-I estimation

“…Total IGF-I has good intra-individual reproducibility and it is positively associated with the peak GH response to provocative tests (20). Based on these studies, we agree on the proposal that adult patients, with 3 or more pituitary deficits and low IGF-I, provocative tests are useless for the diagnosis of GHD.…”

Traumatic Brain Injury Causes Long-Term Reduction in Serum Growth Hormone and Persistent Astrocytosis in the Cortico-Hypothalamo-Pituitary Axis of Adult Male Rats

“…However, the reliability of serum IGF-1 as an indicator of GH deficiency is being debated (Aimaretti et al, 1998(Aimaretti et al, , 2003Granada et al, 2000). Specifically, the consensus guidelines for the diagnosis and treatment of adults with GH deficiency conclude that, ''a normal IGF-1 does not rule out GH deficiency'' (Ho, 2007).…”