Endocrine Abstracts

Whereas it was previously accepted that patients needed between 20 and 30mg of hydrocortisone daily, current estimates are much lower at approximately 10mg per day. The next question - which appears uncontroversial - is the choice of drug. This is universally accepted as being hydrocortisone. But is it? The adrenal glands secrete both cortisol and cortisone and there is now increasing evidence that 11betaHSD-1 can, in a tissue-specific manner, convert cortisone to cortisol. Thus the level of cortisone in the blood may be important to provide a substrate that allows differential levels of glucocorticoid in different tissues.

Cortisol is secreted in both a circadian and ultradian rhythm. The natural peak of cortisol occurs early - prior to awakening - and the best we can do at present in terms of hormone replacement, is to give a relatively large morning dose after awakening. We are unable to provide the peaks of cortisol that occur during every day hassles and exercise etc. A much greater weakness is our failure to follow the natural ultradian rhythmicity of cortisol secretion. Cortisol is secreted in a pulsatile fashion with peaks and troughs throughout the day. This has major effects on glucocorticoid responsive genes which can be differentially affected depending on the pattern of glucocorticoid exposure. Ignoring the troughs of cortisol that occur even during the morning in normal people (and which explain the great variance in basal levels seen in most studies) could lead to misleading conclusions on appropriate levels of hormone replacement. Indeed, many studies refer to arbitrary reference ranges or targets which tend to overemphasise the importance of avoiding low glucocorticoid concentrations - even though periods of low receptor occupancy may be very important.