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11β-Hydroxysteroid dehydrogenase activity in acromegalic patients with normal or impaired carbohydrate metabolism
Authors:Agnes Mondok  Edit Glaz  Miklós Tóth  Gabriella Beko
Institution:a 2nd Department of Medicine, Semmelweis University, 46 Szentkirályi, Budapest, H-1088 Hungary
b Central Clinical Laboratory, Semmelweis University, Budapest, Hungary
c Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
Abstract: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 ± 0.4 μg/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 ± 0.1 μg/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 ± 0.1 μg/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 ± 0.3 μg/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.
Keywords:Acromegaly  11β-hydroxysteroid dehydrogenase  Cortisol  Cortisone  Type 2 diabetes
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