Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement

Abstract

A consensus exists that severe growth hormone deficiency (GHD) in adults is defined by a peak GH response to insulin-induced hypoglycemia (insulin tolerance test, ITT) of less than 3 microg/l based on a cohort of subjects with a mean age of 45 years. By considering one of the following two criteria for the diagnosis of probable permanent GHD, i.e. the severity of GHD (suggested by the presence of multiple pituitary hormone deficiencies (MPHD)) or the magnetic resonance (MR) imaging identification of structural hypothalamic-pituitary abnormalities, 26 patients (17 males, 9 females, mean age 20.8 +/- 2.3 years, range 17-25 years) were selected for re-evaluation of the GH response to ITT and their IGF-I concentration. Eight subjects had isolated GHD (IGHD) and 18 had MPHD. Normative data for peak GH were obtained after ITT in 39 healthy subjects (mean age 21.2 +/- 4.4 years, range 15.1-30.0 years) and the reference range for IGF-I was calculated using normative data from 117 healthy individuals. Mean peak GH response to ITT was significantly lower in the 26 patients (1.8+/-2.0 microg/l, range 0.1-6.1 microg/l) compared with the 39 controls (18.5 +/- 15.5 microg/l, range 6.1-84.0 microg/l; P < 0.0001). One subject with septo-optic dysplasia had a peak GH response of 6.1 microg/l that overlapped the lowest peak GH response obtained in normal subjects. There was an overlap for IGF-I SDS between subjects with IGHD and MPHD, as well as with normal controls. The diagnostic accuracy of a peak GH response of 6.1 microg/l showed a 96% sensitivity with 100% specificity. The maximum diagnostic accuracy with IGF-I SDS was obtained with a cut-off of -1.7 SDS (sensitivity 77%, specificity 100%) while an IGF-I < or = - 2.0 SDS showed a sensitivity of 62%. Our data show that the cut-off value of the peak GH response to ITT of less than 3 microg/l or 5 microg/l and of IGF-I of less than -2.0 SDS are too restrictive for the diagnosis of permanent GH deficiency in the transition period. We suggest that permanent GHD could be investigated more accurately by means of an integrated analysis of clinical history, the presence of MPHD, IGF-I concentration and the MR imaging findings of structural hypothalamic-pituitary abnormalities.