Plasma ACTH and cortisol profiles in Addisonian patients receiving conventional substitution therapy

Plasma ACTH and cortisol profiles were studied over 24 h in five Addisonian patients maintained in good health by conventional gluco- and mineralocorticoid treatment. Patients received their usual treatment (15--30 mg cortisol daily) in divided doses at 08.00 and 16.00 hours. Plasma cortisol concentrations differed from those of control subjects in being higher from 08.00 hours-noon and 17.00-18.00 hours and were unmeasurable (less than 20 nmol/l) during the period of active cortisol secretion (03.00-08.00 hours) observed in normal subjects. Peak plasma ACTH levels (618- greater than 1600 ng/l) occurred at 08.00-09.00 hours in the Addisonian patients and were much greater than those seen in control subjects (60-220 ng/l). Despite this, plasma ACTH fell promptly within 3 h of the morning dose to less than 100 ng/l and levels were indistinguishable from those seen in normal subjects over the period 12.00-02.00 hours. These results show that there are substantial differences between treated Addisonian and control subjects in respect of plasma cortisol and ACTH concentrations. The findings may lead to a better understanding of ACTH-cortisol relationships in disease states, including congenital adrenal hyperplasia where control of excessive ACTH secretion is clinically desirable.