Residual Corticosteroid Production in Autoimmune Addison Disease

Abstract

Context Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison’s disease (AAD) produce corticosteroids even years after diagnosis. Objective Determine frequencies and clinical features of residual corticosteroid production in patients with AAD. Design Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid production was defined as quantifiable serum cortisol and 11-deoxycortisol, and residual mineralocorticoid production as quantifiable serum aldosterone and corticosterone after >18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test. Results Fifty-eight of 192 patients (30.2%) had residual glucocorticoid production, more common in men (n=33, p<0.002) and in shorter disease duration (median 6 [0-44] vs. 13 [0-53] years, p<0.001). Residual mineralocorticoid production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs. 13 [0-53] years, p<0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs. 0.100 [0.028-0.300] mg, p<0.005), and higher plasma renin concentration (median 179 [22-915] vs. 47.5 [0.6-658.0] mU/L, p<0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r=0.989, p<0.001) and plasma ACTH (r=-0.487, p<0.001). Conclusion In established AAD, one-third of the patients still produce glucocorticoids even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.