Assessing Adrenals can be hit and miss, especially given that even more so than other labs, timing is everything. That’s why endocrinologists typically won’t look at anything less than a 24hr urine collection. If the total output is deemed to be high = Cushing’s and if it’s low = Addison’s. Sounds simple right? But to say only values outside of this reference range flag a problem might just be a case of throwing the baby out with the bathwater (or urine in this case!). Especially given it has been established that humans frequently fail at correct & complete 24hr urine collection! Alternatively we can use saliva or blood assays and capture the cortisol at any given time point, comparing that to expectations based on diurnal rhythm – but again, how are the reference ranges for these ascertained and is there such as thing as low normal. high normal results for cortisol, that actually warrant follow up investigation? I’m so glad you asked.
I see a number of patients who present with possible indications of flagging adrenals: from some distinguishing, but far from definitive features, in the clinical picture, to secondary lab markers. However, when they ‘limp’ over the line with their morning blood cortisol result I am often left talking to myself in an echo chamber about the need for more follow up.
But with the RCPA a.m. reference range of 200-650 nmol/L (Some seriously wide goalposts!) and some labs even going down to 150 with their minimum acceptable level for morning cortisol…are we right to still flag hypocortisolism (for any reason) as a differential in patients with low normal results?
Well Medscape yet again delivered Christmas 🤶 early last week with the largest study to date of blood cortisol, that has narrowed what’s ‘normal’ significantly…at least in terms of how low you can go before warranting further investigation. In this study they tested blood cortisol in the morning and afternoon, in over 1200 individuals presenting at an endocrinology clinic to determine in real world terms how low is too low (and associated with an increased likelihood of genuine adrenal insufficiency). They then gave this new ‘minimum cortisol’ a bit of test-run in 2 other large cohorts of patients to check it really did work as an effective cut off and wham bang…we now have a fully validated bare minimum… and guess what…it’s 275 nmol/L in the morning and 250 nmol/L in the afternoon!
Let’s be clear, their cut-off has what’s called a low ‘positive predictive value’ – which means most people (approx 2/3) with cortisol under this cut-off, upon further investigation (typically the ACTH stimulation test) will be found to be fine. BUT the point of this study was to ensure we don’t miss patients with adrenal problems just because they have ‘within range’ cortisol…and this new cut-off delivers on that.
This is big helpful news actually. Previously with patients who had am cortisol between 150- 275 we tended to find ourselves in ‘no man’s land’ – unable to provide enough of an argument about why adrenal insufficiency should still be on the differential list but unable to abandon that suspicion entirely. Thanks Medscape! Now if all the labs, RCPA and the referring physicians can just read this study and shift their goal posts…🙄
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