Improvement of treatment of primary adrenal insufficiency by administration of cortisone acetate in three daily doses

In the present study, we compared the effects of 3 daily administrations of cortisone acetate vs a classical regimen with 2 daily administrations, in patients with primary adrenal insufficiency (PAI). We enrolled 34 patients with PAI treated with 2 daily doses of cortisone acetate (2/3 of the total daily dose early in the morning, 1/3 in the afternoon) who were subdivided into two groups: group A (no.=18; 4 males, 14 females; age: median 55 yr, range 24-88) continued with the standard 2 daily administrations, group B (no.=16; 8 males, 8 females; age: median 44 yr, range 27-70) switched to 3 daily administrations (3/6 of the daily dose early in the morning, 2/6 after lunch, 1/6 after dinner), but without any change of the total daily dose. After 6 months of therapy, basal and 90-min post-cortisone acetate ACTH levels in group B (219 pg/ml, range 19.9-1197, and 84 pg/ml, range 14.4-480, respectively) were significantly lower than those observed at the beginning of the study (482 pg/ml, range 58-1900 and 215 pg/ml, range 52-1832, respectively; p=0.001 and p=0.027, respectively). No statistically significant differences were observed in group A. Similarly, 24-h urinary cortisol (UFC) excretion increased significantly after 6 months of a 3-dose therapy in group B (from 74.6 μg/24 h, range 24-148, to 98.8 μg/24 h, range 48-214; p=0.006), but not in group A (p=ns). Moreover, UFC excretion after 6 months of a 3-dose therapy was significantly higher than after 6 months of a 2-dose therapy (98.8 μg/24 h, range 48-214 vs 49.8 μg/24 h, range 11-183, p=0.032). No significant variations of basal and 90-min post-cortisone levels of cortisol were observed in either group. Our study demonstrates that the subdivision of the total daily dose of cortisone acetate in 3 administrations increases total UFC excretion and reduces plasma ACTH levels, thus improving the substitutive therapy.