STRESS, NEUROTRANSMITTERS, AND HORMONES Adrenomedullary Response to Hypoglycemia in First-degree Relatives of Patients with Rheumatoid Arthritis J. Rovensky, a R. Imrich, b A. Penesova, b Z. Radikova, b A. Scipova, c M. Vlcek, b and M. Vigas b a National Institute of Rheumatic Diseases, Piestany, Slovakia b Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia c Outpatient Rheumatology Unit, St. Lucas Hospital, Galanta, Slovakia Our recent studies showed blunted adrenomedullary responses to insulin-induced hy- poglycemia in premenopausal females with rheumatoid arthritis (RA) and systemic scle- rosis, suggesting dysregulation of the adrenomedullary hormonal system (AMHS). Since no relationship has been found between degree of AMHS dysfunction and clinical or in- flammatory parameters in those patients, we hypothesize the presence of an inherited perturbation of the AMHS. To test this hypothesis, we evaluated adrenomedullary re- sponses to insulin-induced hypoglycemia (0.1 IU/kg) in premenopausal female subjects: 17 glucocorticoid-na¨ ıve RA patients, 15 healthy first-degree family members (FDR), and 18 age- and body mass index–matched healthy controls. Our results demonstrate that when compared to controls, RA patients had lower baseline epinephrine levels (P = 0.01) and lower area under response curve (AUC) levels of norepinephrine (P < 0.001) and epinephrine (P < 0.003). In contrast, FDR had lower (P = 0.001) AUC levels of nore- pinephrine compared to controls and higher (P = 0.033) AUC levels of epinephrine com- pared to RA patients. There were no significant differences in epinephrine response between FDR and controls. Although we found lower norepinephrine responses to hy- poglycemia in FDR of RA patients, adrenomedullary responses to hypoglycemia does not appear to be altered to the degree found in RA patients. Key words: epinephrine; rheumatoid arthritis; hypoglycemia Introduction A substantial body of evidence indicates that the autonomic nervous system, including the adrenomedullary hormonal system (AMHS), participates in modulation of immune func- tions. 1 Epinephrine secreted from the adrenal medulla binds to adrenergic receptors, which are expressed on various subtypes of periph- eral blood immune cells. The catecholamines Address for correspondence: Prof. Jozef Rovensky, MD, DSc, National Institute of Rheumatic Diseases, Nabr. I. Krasku 4, 921 23 Piestany, Slovakia. Voice: +421-33-7723508; fax: +421-33-7721192. rovensky.jozef@nurch.sk affect immune cell trafficking from systemic cir- culation to sites of inflammation. 2 At the local level, immune responses to both epinephrine and norepinephrine appear to have opposing effects: by suppressing T helper (Th) 1-type, and by enhancing Th2-type. 3 The predom- inance of Th1 responses appears to play a part in the pathogenesis of rheumatoid arthri- tis (RA). 4 Thus, inadequate catecholamine at the systemic and/or at the local level might be involved in the complex physiopathogenesis of RA. Our recent studies showed blunted adrenomedullary responses to insulin-induced hypoglycemia in premenopausal females Stress, Neurotransmitters, and Hormones: Ann. N.Y. Acad. Sci. 1148: 552–555 (2008). doi: 10.1196/annals.1410.070 C  2008 New York Academy of Sciences. 552