Persistence of Diurnal Rhythmicity in Plasma ACTH Concentrations in Cortisol-Deficient Patients1

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Abstract
The diurnal variation in plasma ACTH levels was studied in 6 addisonian patients under carefully controlled conditions of cortisol deficiency. Cortisol replacement therapy was gradually reduced until the total daily dose was 8.4 mg or less. Although there was no clinical evidence of adrenal insufficiency on this regimen, plasma and urinary 17-hydroxycorticosteroids (17-OHCS) were subnormal and plasma ACTH rose to high levels. In each patient, plasma ACTH levels were much higher at 6 AM than at 6 PM. In 4 patients, the suboptimal cortisol dosage was rearranged so that it was given only at night. Despite the fact that plasma 17-OHCS levels were higher at 6 AM than 6 PM, plasma ACTH concentrations were still higher at 6 AM in 3 of 4 patients In patients recovering from prolonged pituitary-adrenal suppression, during a phase in which their plasma 17-OHCS were subnormal and plasma ACTH supernormal, a similar diurnal rhythm in plasma ACTH was observed. It is concluded that a diurnal rhythm in ACTH secretion persists even in the presence of chronic cortisol deficiency.