Diagnostic markers of permanent idiopathic growth hormone deficiency

Idiopathic GH deficiency is a clinically and biologically heterogeneous condition. We have attempted to improve its diagnosis by analysing the status of 52 patients, aged 0.1 to 17.5 yr, with GH peak responses after 2 pharmacological stimulation tests of less than 10 micrograms/L. Group 1 (n = 24) had certain GH deficiency because of pituitary stalk interruption syndrome, familial form, and/or microphallus and hypoglycemia. Group 2 (n = 13) had transient GH deficiency. The diagnosis remained uncertain in group 3 (n = 15). The control group (n = 77) had prepubertal idiopathic short stature. Growth failure began before 5 yr of age in 88% of group 1, 18% of group 2, and 33% of group 3 patients. The mean GH peaks and the numbers of patients with GH peaks below 7 or 7-10 micrograms/L were similar in the three groups. Levels of plasma insulin-like growth factor-I (IGF-I) and its binding protein-3 (BP-3) were significantly lower in group 1 than in groups 2 and 3 (P < 0.001) or in children with idiopathic short stature (P < 0.01). When the results of these two parameters were combined, only one patient with certain GH deficiency had normal values, but only one severely undernourished young child with transient GH deficiency had values below the lower limit for children with idiopathic short stature. The diagnosis for group 3 remained uncertain, even after spontaneous pubertal development (n = 4), as the GH peak was 4.5-10.7 micrograms/L and plasma IGF-I was normal in three cases, and BP-3 was normal in four cases. We conclude that certain GH deficiency is distinguished from transient GH deficiency by age at onset and plasma IGF-I and BP-3 levels. Many patients diagnosed as GH deficient had normal for age plasma IGF-I and BP-3 levels, indicating transient GH deficiency in many of them.