Can Adults with severe Growth Hormone Deficiency (AsGHD) and a low IGF-I be distinguished from those with a normal IGF-I?

IGF-I is an important measure of disease activity in states of GH deficiency and excess. Therefore, it is interesting that a significant proportion of AsGHD have normal IGF-I levels. In an attempt to understand the factors determining IGF-I values in patients with severe AGHD we have compared age-, gender- and BMI-matched GHD patients (defined by the international consensus criteria, peak GH <3ng/mL) with low and normal IGF-I (Norms: n=5, 3 males, age 42 (31–54), BMI=32.8 (22.4–33.3)kg/m²; Los: n=5, 2 males, age 43 (38–53), BMI 36.5 (30.9–39.9)kg/m²). Mean GH was calculated from a 24h profile (20 minute sampling). GH was assessed using a sandwich-type immunoassay (intra- and inter-assay CV <7%, limit of detection 0.1ng/mL). IGF-I was measured by a immunoradiometric assay (sensitivity 4.4–5.2%, specificity of 5.7–7.4%, lower limit of detection 6 mcg/l). Statistical analysis was performed using GraphPad Prism software. There was no difference between the groups in peak GH during the diagnostic stimulation test (0.3 (<0.3–1.2) ng/mL v 0.3 (<0.3–0.8) ng/mL, P=0.84), age of onset (Norms and Los childhood/adult=3/2), prior irradiation status (Norms=3, Los=2) and current DEXA body composition (total fat 31106 (20322–45725)g v 35548 (29159–46072), P=0.22; %trunk fat 33.5 (30.4–46.9)% v 39.2 (28.9–42.2)%, P=1; lean mass 50183 (46656–66119)g v 55299 (45239–74339)g, P=0.84. However, Los had more other pituitary hormone deficiencies than Norms (P=0.03, 3 (1–3) vs. 1 (0–1)). Mean 24h GH tended to be lower in patients with low IGF-I levels (Norms: median 0.1, range <0.1–0.13ng/mL v Los: all <0.1ng/mL). In conclusion, other than IGF-I levels the only differences between the cohorts were a tendency for more pituitary hormone deficiencies and lower 24hr GH secretion in those with a low IGF-I. The significance of these observations requires further investigation.