Diagnostic reliability of a single IGF-I measurement in 237 adults with total anterior hypopituitarism and severe GH deficiency

OBJECTIVE Within an appropriate clinical context, GH deficiency (GHD) in adults must be demonstrated biochemically by a single provocative test. Insulin-induced hypoglycaemia (ITT) and GH-releasing hormone (GHRH) + arginine (ARG) are indicated as the tests of choice, provided that appropriate cut-off limits are defined. Although IGF-I is the best marker of GH secretory status, its measurement is not considered a reliable diagnostic tool. In fact, considerable overlap between GHD and normal subjects is present, at least when patients with suspected GHD are considered independently of the existence of other anterior pituitary defects. Considering the time and cost associated with provocative testing procedures, we aimed to re-evaluate the diagnostic power of IGF-I measurement. DESIGN To this goal, in a large population [n = 237, 139 men, 98 women, age range 20-80 years, body mass index (BMI) range 26.4 +/- 4.3 kg/m(2) ] of well-nourished adults with total anterior pituitary deficit including severe GHD (as shown by a GH peak below the 1st centile limit of normal response to GHRH + ARG tests and/or ITT) we evaluated the diagnostic value of a single total IGF-I measurement. IGF-I levels in hypopituitary patients were evaluated based on age-related normative values in a large population of normal subjects (423 ns, 144 men and 279 women, age range 20-80 years, BMI range 18.2-24.9 kg/m(2) ). RESULTS Mean IGF-I levels in GHD were lower than those in normal subjects in each decade, but not the oldest one (74.4 +/- 48.9 vs. 243.9 +/- 86.7 mug/l for 20-30 years; 81.8 +/- 46.5 vs. 217.2 +/- 56.9 mug/l for 31-40 years; 85.8 +/- 42.1 vs. 168.5 +/- 69.9 mug/l for 41-50 years; 82.3 +/- 39.3 vs. 164.3 +/- 60.3 mug/l for 51-60 years; 67.5 +/- 31.8 vs. 123.9 +/- 50.0 mug/l for 61-70 years; P < 0.0001; 54.3 +/- 33.6 vs. 91.6 +/- 53.5 mug/l for 71-80 years, P = ns). Individual IGF-I levels in GHD were below the age-related 3rd and 25th centile limits in 70.6% and 97.63% of patients below 40 years and in 34.9% and 77.8% of the remaining patients up to the 8th decade, respectively. CONCLUSIONS Total IGF-I levels are often normal even in patients with total anterior hypopituitarism but this does not rule out severe GHD that therefore ought to be verified by provocative testing of GH secretion. However, despite the low diagnostic sensitivity of this parameter, very low levels of total IGF-I can be considered definitive evidence of severe GHD in a remarkable percentage of total anterior hypopituitary patients who could therefore skip provocative testing of GH secretion.