Fig. 5

Optimised metyrapone treatment and subcutaneously continuous hydrocortisone replacement. Plasma 24-hour cortisol and corticotrophin (ACTH) profiles of one individual participating in study stage 1. The subject received the optimal metyrapone (Fig. 4, participant C) along with hydrocortisone substitution therapy, subcutaneously (SC), in a continuous manner via Animas® Vibe™ Insulin Pump. The pattern of continuous SC hydrocortisone administration is presented in Table 3; between 08:00 pm–02:00 am the flow rate of hydrocortisone substitution is 0.1 mg/h, followed by an increase to 2 mg/h between 02:00–08:00 am, to drop to 1 mg/h between 08:00 am–12:00 pm, followed by a further decline to 0.4 mg/h between 12:00–08:00 pm. (Total daily dose adds up to 19.8 mg/day.) The black arrows indicate the time points of shifting from one flow rate to the next. Due to technical problems, blood samples of the first 5 hours of the study could not be analysed. This mode of hydrocortisone replacement tries to mimic the normal circadian profile (daily cortisol levels rise in the early morning hours reaching their peak around 08:00 am, near 500 nmol/L before starting to fall throughout the rest of the day to reach their trough around 02:00 am of the next day, near 50 nmol/L) but without the physiologically underlying ultradian rhythm. ACTH fluctuations within normal values confirm the physiological state of the hypothalamic-pituitary-adrenal axis.