Urinary 24-hour free cortisol excretion has been advocated for monitoring of replacement quality. However, after exogenous glucocorticoid administration, urinary cortisol excretion shows considerable interindividual variability. More importantly, following glucocorticoid absorption cortisol-binding globulin (CBG) will be rapidly saturated, resulting in transient but pronounced increases in renal cortisol excretion. Thus, one cannot refer to normal ranges for healthy subjects when judging urinary cortisol excretion during replacement therapy in AI. However, in cases of suspected under-replacement, e.g. due to non-compliance, urinary cortisol measurements may be helpful.
To measure a random serum cortisol without knowing the exact time of preceding glucocorticoid administration is not helpful in monitoring glucocorticoid replacement. Some authors have suggested regular measurements of serum cortisol day curves during replacement therapy aiming at serum cortisol concentrations within the normal range. However, due to their pharmacokinetic properties, none of the exogenous glucocorticoids currently used is suitable to mimic the diurnal cortisol pattern found in healthy subjects.
Thus, in the absence of objective parameters indicating replacement quality, the physician has to rely primarily on clinical judgment, carefully taking into account signs and symptoms potentially suggestive of glucocorticoid over- or under-replacement. Under-replacement bears the risk of incipient crisis and significant impairment of well-being. Conversely, chronic over-replacement may lead to substantial morbidity including impaired glucose tolerance, obesity and osteoporosis. With currently recommended doses of 15 to 25 mg hydrocortisone osteoporosis is not to be expected. Therefore, bone mineral density measurements are not required for regular monitoring in AI.