Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism

Oral DHEA administration to patients with hypoadrenalism, in addition to glucocorticoid and mineralcorticoid replacement, may improve both well-being and hormonal/metabolic parameters. Twenty patients (13 men, 7 women, 26-76 yr, 11 with Addison's disease, 9 with central hypoadrenalism) were recruited in a placebo-controlled, randomized study. Hormone levels, carbohydrate and lipid parameters, bone metabolism, body composition and psychological parameters were evaluated at baseline and after treatment with DHEA 50 mg/day or placebo for 4 months. After 4 months of DHEA administration, serum DHEAS levels raised both in men (from 0.71\ub10.18 to 8.28\ub11.66 \u3bcmol/l, p<0.005) and in women (from 0.25\ub10.07 to 5.65\ub11.93 \u3bcmol/l, p<0.05). Only in hypoadrenal women an increase in testosterone (T; from 0.4\ub10.1 to 1.45\ub10.26 nmol/l, p<0.05) and androstenedione (A; from 0.86\ub10.34 to 2.05\ub10.29 nmol/l, p<0.05) levels was observed. In men no significant modifications in T and 17-hydroxyprogesterone (1 7-OHP) levels were found, whereas serum SHBG significantly decreased. As far as the metabolic parameters are concerned, only in patients with Addison's disease a significant decrease in total cholesterol and in low-density lipoproteins after 4 months of DHEA administration was found. No changes in glucose metabolism and insulin sensitivity were observed. In basal conditions, mean serum osteocalcin (OC) was normal and significantly decreased after DHEA treatment. A significant reduction in body fat mass percentage (BF% after DHEA administration was observed. As far as well-being is concerned, DHEA replacement did not cause any relevant variation of subjective health scales and sexuality in both sexes. Our study confirms that DHEA may be beneficial for female patients with hypoadrenalism, mainly in restoring androgen levels. Concerning the health status, more sensitive and specific instruments to measure the effects of DHEA treatment could be necessary

Tic21 is an essential translocon component for protein translocation across the chloroplast inner envelope membrane

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Effects of chronic administration of PPAR-\u3b3 ligand rosiglitazone in Cushing's disease

Objective: Rosiglitazone, a thiazolidinedione compound with peroxisome proliferator-activated receptor-\u3b3 (PPAR-\u3b3 -binding affinity, is able to suppress adrenocorticotropic hormone (ACTH) secretion in treated mice and in AtT20 pituitary tumor cells. These observations suggested that thiazolidinediones may be effective as therapy for Cushing's disease (CD). Patients and methods: Rosiglitazone (8 mg/day) was administered to 14 patients with active CD (13 women, one man, 18-68 years). Plasma ACTH, serum cortisol (F) and urinary free cortisol (UFC) levels were measured before and then monthly during rosiglitazone administration. Results: In six patients a reduction of ACTH and F levels and a normalization of UFC were observed 30-60 days after the beginning of rosiglitazone administration: there was a significant difference between basal and post-treatment values for UFC (1238\ub1211 vs 154\ub1 40 nmol/24 h, P < 0.03), but not for ACTH (15.9\ub13.7 vs 7.9\ub10.9 pmol/l) and F levels (531\ub173 vs 344\ub158 nmol/l). Two of six cases, followed up for 7 months, showed a mild clinical improvement. Eight patients were nonresponders after 30-60 days of rosiglitazone treatment: their ACTH, F and UFC levels did not differ before and during drug administration. Immunohistochemical analysis of pituitary tumors removed from two responder and two nonresponder patients showed a similar intense immunoreactivity for PPAR-\u3b3 in about 50% of cells. Conclusions: The administration of rosiglitazone seems able to normalize cortisol secretion in some patients with CD, at least for short periods. Whether the activation of PPAR-\u3b3 by rosiglitazone might be effective as chronic pharmacologic treatment of CD needs a more extensive investigation through a randomized and controlled study