Effects of growth hormone replacement on cortisol metabolism in hypopituitary patients treated with cortisone acetate

Growth hormone (GH) replacement may inhibit 11 beta -hydroxysteroid dehydrogenase type 1 (11 beta HSD1) activity, resulting in diminished conversion of cortisone to cortisol. Moreover, GH replacement may lower bioavailability of hydrocortisone tablets. Therefore, substitution therapy with cortisone acetate could be disadvantageous during GH replacement. We conducted a randomized, placebo-controlled GH replacement( 1 to 2 U GH/day) study during 6 months, followed by a 6-month open extension study (2U GH/day). Twelve men and 12 women with GH deficiency, of whom 17 received cortisone acetate (25 to 37.5mg/day), participated. Eight patients were randomized to placebo initially. At baseline, after 6 and 12 months, urinary cortisol and cortisone metabolites were measured. No changes in urinary cortisol metabolites were observed after 6 months placebo (n= 8). After 6 months GH the urinary (tetrahydrocortisol + allotetrahydrocortisol)/tetrahydrocortison ratio ((THF + alloTHF)/THE ratio) was unaltered in cortisone acetate treated patients (n = 17) and in patients with intact adrenal function (n = 7), whereas after 12 months GH the ( TH F + alloTHF)/THE ratio decreased only in cortisone acetate treated patients(l dropout, n=9). Urinary THF and alloTHF were higher in cortisone acetate treated patients than in patients with intact adrenal function before GH and remained so after 12 months GH (p < 0.05 to p < 0.01). The sum of cortisol + cortisone metabolites did not change after GH in either group. The urinary free cortisol/free cortisone ratio, presumably reflecting renal 11 beta HSD2, activity. tended to decrease in cortisone acetate treated patients (p < 0.07 and p < 0.05 after 6 and 12 months GH, rrspectively). as well as in patients with intact adrenal function (p < 0.05 and a decrease in five/ six patients after 6 and 12 months GH, respectively). In conclusion. these results suggest that GH replacement decreases 11 beta HSD1 activity. which becomes manifest in patients receiving cortisone acetate substitution therapy. 11 beta HSD2 activity is unaltered or may even be increased. It is unlikely that the bioavailability of conventional doses of cortisone acetate is impaired after GH replacement.