1Dept Clin Biochemistry, King's College Hospital London SE5 9PJ; 2Regional Endocrine Unit, Southampton General Hospital, Southampton SO16 6YD.
Acute cortisol increase in man, whether from endogenous or exogenous sources, is associated with changes in cortisol:cortisone equilibrium. We have examined these during normal daily circadian rhythms and following treatment with hydrocortisone. Following local ethical committee approval, four adult volunteers (2 male) collected urine samples over 3 hour periods starting from midnight and over hourly periods between 0600 & 0900 to define the morning cortisol peak. They provided saliva samples at the same intervals (female data not available). After one day, they took hydrocortisone orally (25mg) at midnight and continued collection for a further day. Urine 11-OH-, 11-oxo- and total cortisol metabolites (FM, EM & CM) were analysed by high resolution gas chromatography and urine (U) and saliva (S) cortisol (F) and cortisone (E) were assayed using specific immunoassays. The x-fold increases from nadir to peak on Day 1 (males, females) were: CM: 4.2, 6.0, 4.7, 6.5; UF: 16.9, 11.4, 14.3, 17.1; UE: 6.6, 7.7, 6.2, 3.6; SF: 25.7, 12.2; SE: 18.5, 11.4; FM/EM: 1.5, 1.4, 1.1, 1.3; UF/UE: 6.5, 3.1, 3.9, 3.1; SF/SE: 1.6, 2.5. The x-fold increases from pre-treatment value at 2100-2400 (2400 for saliva) to post treatment peak on Day 2 were: CM: 4.7, 4.2, 8.6, 8.0; UF: 40.8, 43.9, 109, 95; UE: 16.3, 17.4, 29.2, 20.7; SF: 175, 104; SE: 31.6, 25.7; FM/EM: 1.7, 4.1, 2.3, 1.7; UF/UE: 2.5, 2.5, 3.8, 5.7; SF/SE: 12.2, 4.1. We conclude that salivary cortisol is the most sensitive marker of cortisol increase, assisted by a marked change post dose in SF/SE, perhaps as a result of overloading of 11HSD II in the parotid glands. SF thus offers an improved marker for hypercortisolaemia.