Systemic amyloidosis with AA-type amyloid deposition is the major complication of FMF, leading to end stage renal disease. There is no clear data on the prevalence of adrenal involvement in patients with FMF amyloidosis. The aim of this study is to determine the adrenal axis function in patients FMF with amyloidosis. Twenty patients with FMF with amyloidosis (F/M: 10/10, mean age; 38 +/- A 11 SD years), twenty without amyloidosis (F/M: 14/6, mean age 32 +/- A 10 years), and healthy controls (F/M: 12/8, mean age: 30 +/- A 7.6 SD years) were recruited. A dose of 250 mg tetracosactide (Synacthen) was then administered intravenously and further blood samples collected 30 and 60 min later. Blood samples were separated and collected at 4A degrees C, and serum cortisol levels were measured. A normal cortisol response to Synacthen was defined as a post-stimulation peak cortisol value of > 18 mg/d either at 30 or 60 min. sample. The mean disease duration was 8.8 +/- A 6 SD years, (range, 2-21) in FMF patients without amyloidosis compared to 16 +/- A 9.5 years (range, 0-30) in FMF with amyloidosis (P = 0.001). The cortisol concentrations increased significantly at 30 and 60 min compared to baseline after injection of synacthen in all groups. There were no statistically significant differences found among three groups, for basal, 30 and 60 min for cortisol levels (P = 0.154). FMF patients with amyloidosis do not exhibit overt adrenal insufficiency even though their basal cortisol levels were mildly lower.