Reassessment of the optimal growth hormone cut-off level in insulin tolerance testing for growth hormone secretion in patients with childhood-onset growth hormone deficiency during transition to adulthood

Context: Retesting of patients with childhood-onset growth hormone deficiency (CO-GHD) is recommended after completion of growth hormone (GH) treatment. Aim: To identify patients who are at risk of persistent GHD, and to evaluate the most reliable cut-off level for GH secretion using the insulin tolerance test (ITT) in the transition from childhood to adulthood. Results: Ninety patients (22 female) with CO-GHD were retested using the ITT 1.1 ± 1.1 years after discontinuation of therapy. Fifty-eight of 77 patients (75%) initially diagnosed with idiopathic GHD showed normalization of GH secretion. Thirteen patients were diagnosed with multiple pituitary hormone deficiency (MPHD) and diagnosis was reconfirmed in all of them, except for one patient. IGF-I levels of patients with persistent GHD were significantly lower (112 ± 74 ng/ml [range 22-283] vs 245 ± 107 ng/ml [range 31-505], p<0.01). IGF-I levels correlated positively with GH peak during ITT (r = 0.54, p <0.01), but the wide range of IGF-I levels shows that IGF-I alone cannot replace retesting in many cases. The best sensitivity and specificity scores were obtained when a GH cut-off level below 5.0 ng/ml for patients in the transition phase was used. ROC analysis demonstrates that ITT is a reliable test for evaluation of GH secretion in the transition phase (ROC-AUC 0.97). Conclusions: Patients with CO-GHD should be retested after discontinuation of therapy to identify those who may profit from further replacement therapy. Patients with organic or genetic GHD or MPHD are likely to have persistent GHD, whereas 75% of our patients with idiopathic GHD showed normalization of growth hormone secretion. IGF-I levels alone are not reliable in the diagnosis of adult GHD in many cases. The best sensitivity and specificity scores were found when a GH cut-off level below 5.0 ng/ml was used in patients with GHD in the transition from childhood to adulthood.