797 Neuroendocrine Manifestations in Sjögren’s Syndrome Relation to the Neurobiology of Stress ELIZABETH O. JOHNSON a,c AND HARALAMPOS M. MOUTSOPOULOS b a Department of Anatomy, School of Medicine, University of Ioannina, Ioannina, Greece b Department of Pathophysiology, Medical School, National University of Athens, Athens, Greece ABSTRACT: Evidence suggests that autoimmune rheumatic diseases are associ- ated with neuroendocrine dysfunction. Sjögren’s syndrome (SS) is proposed as an ideal model to study perturbations in the neuroimmune axis, since patients tend to be medication free and studies are not confounded by the effects of chronic immunosuppressive therapy. The functional integrity of the adrenal, gonadal, and thyroid axes was assessed in SS. Pituitary function of the HPA axis was evaluated directly by determining the ACTH released during oCRH stimulation, while adrenal function was assessed indirectly by endogenous ACTH released during oCRH stimulation. Low basal activity of the HPA axis was associated with pituitary hyporesponsiveness to exogenous CRH, as well as hyporesponsiveness of the adrenal glands to endogenous ACTH. These find- ings are compatible with a central deficiency of the adrenal axis. An overall attenuated and delayed LH and FSH response to LHRH stimulation was also indicative of central dysfunction of the gonadal axis in SS. SS patients demon- strated elevated basal TSH levels and evidence of mild hypothyroidism. Basal prolactin concentrations were also elevated in SS, and both TSH and PRL showed relatively increased responses to TRH stimulation. The data suggest a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thy- roid. It is not clear if any one system plays a primary role in the expression of the disease. Rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones. Taken together, adrenal and gondadal steroid hormone deficiency, plus elevated PRL levels, probably greatly affect immune function in SS patients. INTRODUCTION Cellular and molecular biological techniques have demonstrated that immune and inflammatory processes bidirectionally communicate with the central nervous sys- tem (CNS). A body of evidence now suggests that disruptions of this communication may be associated with susceptibility to or severity of autoimmune/inflammatory disease. 1 One working hypothesis is that a relationship between autoimmunity and c Address for correspondence: Elizabeth O. Johnson, Ph.D., Assistant Professor of Anatomy, Department of Anatomy, School of Medicine, University of Ioannina, Ioan- nina 45 110, Greece. Voice: +30-651-97 584; fax: +30-651-67 860.