Considering the frequency of adrenal deficiency, and having already discussed the symptoms and clinical signs, it would be useful to detail the various diagnostic tools at our disposal. We should be clear that we are talking here about moderate cases, and that Addison's disease, which is a major cortisol deficit, is not part of this discussion.
First, and most simply, cortisol can be measured in the blood. However we then depend upon a variable curve, known as the diurnal variations, which means levels follow the day/night cycle. Secretion of cortisol by the zona fasciculata of the adrenal cortex goes through a morning peak around sunrise, which is what wakes us (in conjunction with the fall of melatonin). This is followed by a slow decline over the day with a flattening of the curve towards bedtime, which is what helps us to fall asleep (with the help of the rise of melatonin).
We can see the difficulty of measuring cortisol in the blood, which is only taken at the beginning of the day. Such a blood test can only show an elevated peak, coming close to or exceeding the lab upper limit. Such a peak characterizes a pathologic stress and is usually followed by a subsequent collapse of the cortisol curve, reflected by severe fatigue mid-afternoon. Such an abnormal curve can lead to a small paradoxical rise at night, which will of course disturb restorative sleep.
It is for these reasons that the English favour salivary cortisol assays, with samples of cortisol taken throughout the day (upon rising-midday-around 5pm-bedtime) to obtain an insight into the cortisol curve. The reliability of salivary assays is disputed and only renowned laboratories with extensive experience in this field must be used. This test is often called the “Adrenal Stress Index” or ASI, which is of great interest for stress evaluation.
The cortisol curve is perfectly complementary to the testing of corresponding metabolites in a 24-hour urine collection. These are the various by-products of liver detoxification of cortisol. Their distribution is highly dependent on the genetic diversity of liver detoxification enzymes, the so-called genetic polymorphisms of the individual. Therefore their details don’t matter that much and we concentrate only on the result of the total metabolites grouped as 17-OH-steroids (or 17-hydroxy-steroids) in 24-hour urine, the markers of glucocorticoids.
This value truly reflects the glucocorticoid status of the patient as long as the collection of the 24-hour urine has been done correctly in line with the guidelines of the laboratory. It is, in fact, the integral curve of cortisol – this is the areas under the curve - and gives an overall idea of the secretion of cortisol throughout the 24-hour cycle. Only blood or salivary samples taken throughout the cycle results in a curve that allows us to better understand the cortisol fluctuations, but the 17-OH-steroids from urine can supply us with an overall view about a cortisol insufficiency which is the source of sadly misunderstood poor health.
For more information, you are invited to visit my website www.gmouton.com where you will find a detailed Power Point presentation (202 slides in English) in the section Conferences/Functional Hormonology/Adrenals. Very good reading!