Altered function of the hypothalamic stress axes in patients with moderately active systemic lupus erythematosus. II. Dissociation between androstenedione, cortisol, or dehydroepiandrosterone and interleukin 6 or tumor necrosis factor.
OBJECTIVE
To investigate adrenocorticotropin, androstenedione (ASD), cortisol, or dehydroepiandrosterone sulfate (DHEAS) before and during a corticotropin releasing hormone (hCRH) test in patients with moderately active systemic lupus erythematosus (SLE) undergoing low dose longterm glucocorticoid therapy, and to examine these hormones in relation to interleukin 6 (IL-6) or tumor necrosis factor (TNF).


METHODS
Serum levels of hormones and cytokines were measured before and during an hCRH test. The results of 12 patients with SLE were compared to 12 healthy subjects (HS) and 12 healthy subjects given prior short term prednisolone (HS+P).


RESULTS
Baseline and stimulated serum ASD, cortisol, and DHEAS were lower in patients with SLE vs. HS (p<0.005), but baseline and stimulated plasma adrenocorticotropin was normal in SLE. In SLE, but not in HS+P or HS, baseline and stimulated DHEAS was low in relation to cortisol or ASD (i.e., shift from DHEAS to cortisol or ASD). In patients with SLE, baseline and stimulated serum levels of adrenal hormones were lower in relation to IL-6 or TNF compared to HS or HS+P (p< 0.001). In contrast, in SLE patients, the baseline and stimulated pituitary hormone adrenocorticotropin was normal in relation to these cytokines.


CONCLUSIONS
We found marked adrenal insufficiency and a shift in steroidogenesis to cortisol in patients with SLE, but a completely normal pituitary function (in absolute values and in relation to IL-6 or TNF). This may depend in part on prior longterm glucocorticoid therapy and changes of steroidogenesis due to cytokines. The situation in patients with SLE was not mimicked by high dose short term prednisolone in healthy subjects. Further longitudinal studies in untreated patients are needed to investigate the endocrine-immune interplay and its consequences during the course of SLE.
Zietz
B
B
Department of Internal Medicine I, University Medical Center Regensburg, Germany.
Reber
T
T
Oertel
M
M
Glück
T
T
Schölmerich
J
J
Straub
R H
RH
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000735:Androstenedione / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D003687:Dehydroepiandrosterone / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D010913:Pituitary-Adrenal System / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone