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Salivary Cortisol vs Urinary Cortisol: Test Profile Considerations for your Patients

Salivary Cortisol vs Urinary Cortisol: Test Profile Considerations for your Patients 

(Information provided by Doctor’s Data Clinical team)


Salivary Cortisol Testing 

Saliva provides a direct measurement of bioavailable cortisol and has become the gold standard for diurnal assessment of the HPA axis. Due to the ease of collection and precisely timed data points (AM 30, noon, evening, night) a representation of the diurnal pattern can be established. Saliva also offers a unique way to measure a provoked stress response via the Cortisol Awakening Response (CAR), a well-researched measure of HPA axis reactivity reflected in the rise in cortisol that occurs after waking. This data may then be extrapolated to give a practitioner the best idea of what a patient's stress response may look like throughout their day - useful for assessing the acute stress response as well as daily cortisol rhythms. 

The cortisol awakening response can only be tested in saliva. The CAR is a predictable release of cortisol measured at the time of awakening, at the peak in cortisol output approximately 30 minutes after waking, and a third collection 60 minutes after waking. The CAR is perhaps the most reported measure of cortisol in clinical research, used as a biomarker for stress related HPA Axis abnormalities. It can indicate whether the HPA axis is responding (reacting) appropriately to the physiologic stress of going from a sleeping to waking state manifesting in a spike of cortisol, the highest point in the diurnal rhythm for the day, or if a blunted or delayed CAR is observed due to chronic stress exposure interfering with HPA axis signaling. 

In most cases, salivary cortisol is the preferred way to test HPA Axis activity, although it may miss the influence of daily stressors.


Benefits of salivary cortisol testing: 

  • Allows for measurement of the diurnal pattern of cortisol over the course of the day 
  • Allows for the addition of the cortisol awakening response (CAR) 
  • Considered to be the gold standard for assessing HPA Axis function 
  • Uniformly low salivary levels of cortisol may indicate follow-up testing is needed to evaluate pathology like Addison’s Disease. 


Urinary Corticoid Testing: 

Urine provides an indirect measurement of cortisol. Urine testing provides additional information on cortisone and the corticoid metabolites. Saliva testing is the gold standard, but urine can provide some insight that salivary testing cannot. 

Urine measurements represent a pooled average of the urine that has collected in the bladder since the last void, while salivary cortisol represents a single point in time. It takes about 90 minutes for cortisol to be excreted in the urine after it is secreted from the adrenal cortex, so all urinary cortisol levels are shifted by 90 minutes.   

Urine corticoid testing likely provides better insight into how a patient’s metabolic state is influencing corticoid metabolism. For example, measuring the cortisol and cortisone metabolites THE and THF provide information on how inflammation and thyroid health are affecting metabolism. 

The first urine sample collected is the waking sample. If there are any elevations in the patient’s cortisol secretion during sleep, it will be reflected in the waking sample. It is essentially an overnight average of secreted cortisol.  

Another benefit of urinary testing is assessing cortisol (the active form) and cortisone (the storage form).  In a healthy individual, urinary cortisone should be secreted at higher amounts than cortisol. If your patient is favouring cortisol, they are likely inflamed (common etiologies are blood sugar dysregulation, insulin resistance, and obesity) or experiencing thyroid dysfunction. 

Additionally, urine testing may better reflect the influence of foods, exercise, and perceived stress on an individual over the day. These peaks may be missed in saliva, as saliva testing is measuring points in time.  

Benefits to urinary corticoid testing: 

  • Can measure the diurnal pattern of free cortisol and free cortisone.
  • Because saliva is testing points in time, it is possible that it will miss the influence of fleeting cortisol spikes associated with stressful stimuli.
  • Urine may catch these due to the pooling of urine in the bladder over hours.
  • May reflect the influence of exercise, coffee consumption, hypoglycemic episodes, etc. contributing to cortisol peaks not caught in saliva. 
  • May be more reflective of the inflammatory role cortisol can play outside the HPA axis, which is associated with certain syndromes such as metabolic syndrome, insulin resistance, obesity, and thyroid and liver function.  
  • When imbalances are found in urine, it is a consideration to reflex to salivary cortisol testing to determine how the HPA Axis is functioning vs the influence of metabolic health on excreted corticoids.