Fig. 4.

Joint hydrocortisone (cyan part) and endogenous ACTH (red part) and cortisol (blue part) model structure. K_{in, ACTH} = Base*K_{out, ACTH}; K_tr=(N_tr + 1)/MTT. ACTH: Adrenocorticotropic hormone, ALB: Albumin, Base: ACTH baseline concentration, B_max: Maximum binding capacity of CBG, CBG: Corticosteroid binding globulin, CL: Clearance, Cortisol_b: Bound cortisol, Cortisol_u: Unbound cortisol, DEX: Dexamethasone, EC₅₀: ACTH concentration yielding half-maximum cortisol production, E_max: Maximum cortisol production rate constant, F: Bioavailability, γE: Hill factor for cortisol production, γI: Hill factor for ACTH suppression, K_a: Absorption rate constant, K_{in, ACTH}: ACTH baseline secretion rate constant, K_d: Dissociation constant cortisol-CBG, K_{out, ACTH}: ACTH elimination rate constant, K_tr: Transit rate constant, IC₅₀: Unbound cortisol concentration yielding half-maximum ACTH suppression, I_DEX: Dexamethasone-driven ACTH suppression, I_max: Maximum ACTH suppression by unbound cortisol, MTT: Mean transit time of oral hydrocortisone, N_tr: Number of transit compartments for oral hydrocortisone absorption, NS: Nonspecific binding cortisol-albumin, Pt1: Peak time morning surge, Pt2: Peak time midday surge, Q: Intercompartmental flow, SA1: Amplitude morning surge, SA2: Amplitude midday surge, SW1: Width morning surge, SW2: Width midday surge, Tn: nth transit compartment, V_c: Central volume of distribution, V_p: Peripheral volume of distribution