Growth hormone (GH) isoforms following acute 22-kDa GH injection: is it useful to detect GH abuse?

The aim of the study was to investigate the influence of an acute administration of 22-kDa hGH (22-kDa GH) on 22-kDa GH and 20-kDa GH serum levels, biological activity of GH (Nb2-GH) and on 22-kDa/20-kDa GH ratio, in order to verify whether the assessment of the GH isoforms could be a potential tool for diagnosing GH abuse. Twenty-eight children (21 M, 7 F), age 10.4 +/- 0.8 y, affected by idiopathic isolated GH deficiency and 10 children (8 M, 2 F), age 9.2 +/- 2.3 y affected by constitutional growth delay, were evaluated. After an overnight fast, a basal blood sample was obtained between 8 a.m. and 9 a.m. and a dose of 22-kDa GH was then administered subcutaneously (0.1 U/Kg). Blood was drawn after 2, 4 and 6 h, for the evaluation of 22-kDa GH, Nb2-GH and 20-kDa GH serum levels. Similar results were obtained in patients and controls: a significant rise, although of variable amplitude, of 22-kDa GH and Nb2-GH was found (p < 0.001) and the maximum peak was detected after 4 h in the majority of subjects. No acute changes in 20-kDa GH serum levels were observed. The 22-kDa/20-kDa GH ratio increased progressively, due to the rising levels of 22-kDa GH. A positive correlation was seen between 22-kDa GH and Nb2-GH levels at baseline and at 2, 4 and 6 h (p < 0.014, r = 0.99). Since in normal subjects the ratio of endogenous 22-kDa GH and 20-kDa GH is constant, an altered ratio of 22-kDa/20-kDa GH is highly suggestive of GH abuse. The short period of time available for the evaluation however (within 3 h from GH injection), severely limits this investigational tool in athletes.