11β-Hydroxysteroid dehydrogenase activity in acromegalic patients with normal or impaired carbohydrate metabolism

The 11β-hydroxysteroid dehydrogenase isoenzymes (11β-HSD) catalyse the interconversion of cortisol (F) and cortisone (E). Earlier studies demonstrated that growth hormone (GH) and insulin resistance may exert opposite effects on the conversion of E to F by 11β-HSD type 1. Therefore, in the present study we determined F and E concentrations in 562 plasma samples obtained from acromegalic patients during an active phase (76 patients) and after cure of the disease (68 patients). In addition, we examined whether type 2 diabetes mellitus or impaired glucose tolerance, which are frequently associated with active acromegaly could influence plasma F and E levels in these patients. We found that plasma F concentrations were similar in patients with active acromegaly and in those who were cured with pituitary surgery, irradiation and/or medical therapy (mean±S.E., 12.4±0.3 and 12.7±0.4μg/dl, respectively). However, plasma E levels were significantly higher in patients with active compared to those with cured acromegaly (2.8±0.1 and 2.2±0.1μg/dl, respectively; p<0.001), resulting in a lower F/E ratio in patients with active disease (4.6±0.1 vs. 5.9±0.2 in the cured group of patients; p<0.001). When the effect of altered carbohydrate homeostasis on plasma F and E was analysed, the results indicated significantly lower plasma E levels and higher F/E ratios in active acromegalic patients with type 2 diabetes mellitus or impaired glucose tolerance compared to those with normal carbohydrate metabolism (E, 2.5±0.1 and 3.0±0.1μg/dl, respectively; F/E, 5.1±0.2 and 4.4±0.1; p<0.001), whereas plasma F concentrations were similar in these two groups (12.1±0.4 and 12.6±0.3μg/dl, respectively). These findings indicate that disease activity exerts a significant impact on 11β-HSD in acromegalic patients, which is further modified with altered carbohydrate homeostasis, frequently present in patients with active disease.