A comparison between low-dose (1 mu g), standard-dose (250 mu g) ACTH stimulation tests and insulin tolerance test in the evaluation of hypothalamo-pituitary-adrenal axis in primary fibromyalgia syndrome

Objective: Primary fibromyalgia syndrome (PFS) is a nonarticular rheumatolo gical syndrome characterized by disturbances in the hypothalamo-pituitary-a drenal (HPA) axis. The site of the defect in the HPA axis is a matter of de bate. Our aim was to evaluate the HPA axis by the insulin-tolerance test (I TT), standard dose (250 mug) ACTH test (SDT) and low dose (1 mug) ACTH test (LDT) in patients with PFS. Design and Patients: Sixteen patients (13 female, three male) with PFS were included in the study. Sixteen healthy subjects (12 female, four male) ser ved as matched controls. ACTH stimulation tests were carried out by using 1 mug and 250 mug intravenous (i.v.) ACTH as a bolus injection after an over night fast, and blood samples were drawn at 0, 30 and 60 min. The ITT was p erformed by using i.v. soluble insulin, and serum glucose and cortisol leve ls were measured before and after 30, 60, 90 and 120 min. The 1 mug and 250 mug ACTH stimulation tests and the ITT were performed consecutively. Results Peak cortisol responses to both the low dose test (LDT) and standar d dose test (SDT) (589 +/- 100 nmol/l; 777 +/- 119 nmol/l, respectively) we re lower in the PFS group than in the control group (1001 +/- 370 nmol/l; 1 205 +/- 386 nmol/l, respectively) (P < 0.0001). Peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group were lower than in the control gro up (1219 +/- 412 nmol/l) (P < 0.0001). Six of the 16 patients with PFS had peak cortisol responses to LDT lower than the lowest peak cortisol response of 555 nmol/l obtained in healthy subjects after LDT. There was a signific ant difference between the peak cortisol responses to LDT (589 +/- 100 nmol /l) and peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group (P < 0.0001). Peak cortisol responses to SDT (777 +/- 119 nmol/l) were sim ilar to peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group . Conclusion: We conclude that the perturbation of the HPA axis in PFS is cha racterized by underactivation of the HPA axis. Some patients with PFS may h ave subnormal adrenocortical function. LDT is more sensitive than SDT or IT T in the investigation of the HPA axis to determine the subnormal adrenocor tical function in patients with PFS.