EFFECTS OF LONG-TERM GROWTH-HORMONE THERAPY ON ADRENAL STEROIDOGENESIS IN TURNER-SYNDROME

It has been shown that growth hormone (GH) and insulin-like growth fac tor-1 (IGF1) enhance steroidogenesis responsiveness to ACTH in culture d adrenal cells. To investigate the GH effect on adrenal steroidogenes is in non-GH-deficient subjects, we studied 9 girls with Turner syndro me (chronological age 5.5-7.2 years; bone age 5-7 years). In all subje cts an ACTH test (Synacthen depot, 0.25 mg i.v. with blood samples at 0 and 60 min) was performed basally at 8-9 a.m. and 6 months after GH therapy (1 IU/kg/week). 17-Hydroxypregnenolone (17PGN), 17-hydroxyprog esterone (17OHP), dehydroepiandrosterone (DHA), its sulfate (DHA-S), a ndrostenedione and cortisol were evaluated by radioimmunoassay. Two gr oups of normal girls were selected as controls: group A age-matched th e patients at the start of the study, and group B age-matched the pati ents at the end of the study. The responsiveness of each hormone to AC TH was expressed as the difference between stimulated and basal values . A p value of < 0.01 was considered to indicate significance. There w ere no significant differences between pre- and posttreatment basal va lues of 17PGN, 17OHP, DHA, androstenedione and cortisol in the Turner syndrome patients, whereas a significant increase was observed for bas al DHA-S (1.57 +/- 0.31; 1.89 +/- 0.43 mu mol/l, p < 0.01). Comparison of increments before and after GH treatment showed a significant incr ease in responsiveness to ACTH after GH therapy DHA (p < 0.01). The in crease in 17PGN was evident (p < 0.02), but the established significan t p value was not reached. No differences for 17OHP, androstenedione a nd cortisol were found. The stimulated 17PGN/17OHP ratio was significa ntly higher (p < 0.01) after GH, whereas the 17OHP/androstenedione rat io was considerably lower, but the p value was < 0.02. No differences between pretreatment values with the control group androstenedione was found, whereas basal and stimulated posttreatment values of DHA and s timulated values of 17PGN were higher in patients after GH therapy tha n in control group B. No differences between the 2 control groups were found. In conclusion our study showed that adrenal steroid responsive ness to ACTH increases in Turner syndrome after long-term treatment wi th high GH doses. An increase in the number of ACTH adrenal receptors and/or a modulation of enzyme activities may be suggested. The positiv e or negative pharmacological implications of these data remain to be determined especially when taking into consideration the wide use of G H therapy in non-GH-deficient subjects.