Running Cortisol? Don’t miss this second test
Testing cortisol has been a clutch move in integrative medicine, but are we doing it correctly to give your patients the most insight into their symptoms? In this article, we’re going to highlight the diagnostic challenges of running cortisol alone and how to use this assessment in a way that catches adrenal insufficiency in your patient population.
Any hormone that has a diurnal release or a circadian pattern has inherent accuracy challenges when applied to real-world medicine. In many papers on burnout and cortisol, even the studies published have varying times of day at which cortisol was tested, or fail to mention the time of day in the paper at all. The circadian pattern of cortisol can be affected by the duration of sleep, shift work, and, perhaps most importantly, the patient’s baseline cortisol awakening response.
When enduring an acute stressor, the majority of patients will have cortisol levels rise to meet the demands on the body to manage the situation. With repeated stress, however, there are varying responses depending on the patient’s past experiences (ACES for example) and their ability to habituate to the current situation [1]. Most patients will habituate to repeated stressors, and their cortisol levels will appear more normal over time, even if the stressor itself remains unchanged. Some patients, however, have an exaggerated stress response and cortisol release after a repeated stressor. Cortisol levels in these two scenarios are apples to oranges, and hard to compare. Unless we’ve run multiple cortisol tests on our patient over time, and have tracked their stress response in the face of repeated acute stressors, it’s challenging to line up a cortisol “result” with their symptomology or experience of burnout.
Lab tests are useful when they are consistent and can be stacked up reliably against the patient experience. Cortisol testing for stress fails to meet most of the basic requirements of diagnostic lab tests, and for the purposes of understanding how stressed an individual is, a single cortisol value offers little to no more benefit than simply asking the patient.
However, testing cortisol still has a role in Naturopathic Medicine, specifically when we are curious about adrenal insufficiency.
Primary or secondary adrenal insufficiency may present at a naturopathic office, given the vague and often disconnected-seeming symptoms, or the waxing and waning of poor health status that may plague a patient early in their diagnostic process. Primary adrenal insufficiency (or Addison’s Disease) may begin with progressive loss of cortisol production under stressful states, but leave a patient capable of maintaining blood pressure and health status in low-stress states. Patients with secondary adrenal insufficiency from concussion, medication-induced (notably immune checkpoint inhibitors) or other systemic states may have their adrenal symptoms mixed in with other chronic disease symptoms, and can mask the diagnosis until a full adrenal crisis is present.
Adrenal crisis remains a well-documented and potentially life-threatening complication in patients with adrenal insufficiency[2]. Although we may not come across this clinical scenario in practice often, if you are presented with a patient who has vague, possibly adrenal-related symptoms, in addition to testing morning cortisol between 7-9 am, adding ACTH to support your diagnosis and expedite the assessment of a possible adrenal insufficiency is prudent.
In primary adrenal insufficiency, such as Addison’s, the defect in cortisol production is at the level of the adrenal gland. Cortisol will be low or low normal, and ACTH is often significantly elevated, sometimes 2× or more above the upper limit in primary adrenal insufficiency. Elevated ACTH may be able to help differentiate a low-normal cortisol level from a low level in patients who straddle the reference range, and if found, elevated ACTH can help expedite the assessment of your patient when you refer them to endocrinology.
In secondary adrenal insufficiency, ACTH will be low or abnormally low alongside low cortisol. In a healthy HPA axis, ACTH should rise when cortisol levels are low or low normal, and an inappropriately low ACTH points toward a hypofunctioning pituitary or tertiary adrenal insufficiency higher up the hormonal chain. A low-normal ACTH and low cortisol on their own won’t be diagnostic, but will give a significant clue into the need for ACTH stimulation testing and/or pan-pituitary function testing to determine the cause of the imbalance.
It’s not uncommon for practitioners to test cortisol for “stress symptoms” and miss the opportunity to test morning ACTH alongside it. It’s also common to connect a low-normal cortisol to symptoms of burnout or stress, when a more thorough investigation of hormonal stress reserve is warranted.
If choosing to test cortisol in your patient, pair it with an ACTH test and be cautious when connecting stress symptoms to cortisol levels. Adrenal insufficiency is an important rule-out in patients with low physical resiliency under stress, and NDs are uniquely poised to uncover the cause of poor health status in patients by offering comprehensive hormonal testing, including ACTH.