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), corti sol, or dehydroepiandrosterone sulfate (DHEAS) before and during a corticot ropin releasing hormone (hCRH) test in patients with moderately active syst emic 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 du ring 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 predni solone (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, base line and stimulated DHEAS was low in relation to cortisol or ASD (i.e., shi ft from DHEAS to cortisol or ASD). In patients with SLE, baseline and stimu lated serum levels of adrenal hormones were lower in relation to IL-6 or TN F compared to HS or HS+P (p < 0.001). In contrast, in SLE patients, the bas eline and stimulated pituitary hormone adrenocorticotropin was normal in re lation to these cytokines. Conclusion. We found marked adrenal insufficiency and a shift in steroidoge nesis to cortisol in patients with SLE, but a completely normal pituitary f unction (in absolute values and in relation to IL-6 or TNF). This may depen d in part on prior longterm glucocorticoid therapy and changes of steroidog enesis due to cytokines. The situation in patients with SLE was not mimicke d by high dose short term prednisolone in healthy subjects. Further longitu dinal studies in untreated patients are needed to investigate the endocrine -immune interplay and its consequences during the course of SLE.