ABSTRACT: BACKGROUND: The diagnostic criteria for growth hormone (GH) deficiency (GHD) in adolescents and young adults are not yet clearly established.We evaluated the factors influencing the GH peak and plasma insulin-like growth factor (IGF) I in order to determine the cut-off limits for the diagnosis of GHD during the transition period. METHODS: 21 patients treated for GHD due to pituitary stalk interruption syndrome at 5.7 +/- 4.1 years were reevaluated at 16.0 +/- 1.8 years, 0.6 +/- 0.6 years after the end of GH treatment. Group 1 had isolated GHD (n = 9) and group 2 had multiple pituitary deficiencies (n = 12), including deficiencies of thyroid stimulating (n = 12), adrenocorticotropin (n = 8) and gonadotropin (n = 9) hormones. RESULTS: At diagnosis, group 1 had a greater pituitary height (2.8 +/- 1.2 vs 1.6 +/- 1.1 mm, P = 0.03) and GH peak (3.8 +/- 1.9 vs 1.6 +/- 1.5 ng/ml, P < 0.02) than did group 2.At last evaluation, group 1 had greater GH peak (3.9 +/- 1.9 vs 0.2 +/- 0.4 ng/ml, P = 0.0001) and plasma IGF I (211 +/- 88 vs 78 +/- 69 ng/ml, P < 0.002) than did group 2. No group 1 and 9 group 2 patients had an undetectable GH peak, while the 3 others had GH peak below 1 ng/ml.The GH peak decreased between diagnosis and last evaluation only in group 2 (P < 0.008). CONCLUSION: The GH peak response to pharmacological stimulation and the plasma IGF I concentration in young adults with GHD of childhood onset depend on the presence of additional pituitary deficiencies, reflecting a more severe defect of the hypothalamic-pituitary axis. The sex steroids cannot increase the IGF I if the GH secretion is zero.