Comparing Cortisol Testing in Saliva and Urine

By Krista Anderson-Ross, ND | November 26, 2024

For years at Doctor’s Data, we have appreciated the value of the salivary Diurnal Cortisol Profile and the Adrenal Function Profile, which elucidate the diurnal cortisol rhythm based on 4 spot saliva collections throughout a typical day. The rise in cortisol 30 minutes after awakening, when cortisol should be at its highest point in a 24-hour period, reflects the responsiveness of the HPA axis to the physiological stress of awakening from sleep. Some biometric trackers now include a “readiness” metric based on the sleep score of the night before. After a poor night’s sleep, AM cortisol levels may be attenuated, lowering the readiness score.  

When interpreting low AM30 results in saliva testing (Figure A), it’s important to note if this result followed a typical night’s sleep. Often AM cortisol results appear surprisingly low if the patient woke much earlier than usual. For example, if a patient wakes up unusually early after a poor night’s sleep and collects saliva 30 minutes later, we expect cortisol levels to be suppressed by melatonin because normally they would still be asleep. In these cases, we suggest postponing collection until after a typical night’s sleep. 


A. Saliva Spot Collection 

 

In patients for whom you want to do a deeper exploration of the stress of waking, for example in patients with poor sleep and irregular schedules or wake times, the Cortisol Awakening Response (CAR) profile offers valuable insight into HPA axis responsiveness. The CAR is an important gauge for how prepared the nervous system is for the stressors of the day. Measurement involves three vials for collections: upon waking, 30 min later and 60 min later; providing additional data indicating an unresponsive or hyperactive HPA Axis, a delayed CAR, or a stress response that fails to turn off or is slow to recover. Note that a CAR profile consisting of two additional tubes can be added to any saliva profile that includes an AM30 cortisol collection. Figure B represents a delayed cortisol awakening response. 

B. Cortisol Awakening Response (CAR)

 

Another tool for evaluating adrenal output is urine metabolite testing – available both in the HuMap(Figure C) and the urine Adrenal Corticoid Profile. In contrast to the point-in-time spot collections of saliva, urine represents pooled results over the hours since the last void, better reflecting cortisol load because highs and/or lows will be reflected in an averaged value. Because urine cortisol testing is more affected by metabolic influences than salivary cortisol testing is, urine and saliva results for the same patient do not always look similar. For example, in a patient with a low AM30 saliva cortisol level, urine testing may surprisingly reveal an elevated waking level suggestive of cortisol spikes during the sleep period which could be due to the stress of poor sleep, inflammation, pain, light at night, blood sugar imbalance, etc. Additionally, a general preference for the active hormone cortisol over the inactive storage form cortisone, can indicate an alteration of the enzyme 11B-HSD, which can be the result of hypothyroidism, insulin resistance and inflammation (influences outside of the HPA axis that affect systemic cortisol activity). Urine testing can also reflect the influence of foods, coffee, exercise and perceived stress on an individual over the course of a day - peaks that can be missed in saliva. 

C. Urine Pooled Collection Results 

 

When urine reveals imbalances, the ordering provider may consider reflexing to saliva to gain insight into tissue levels of cortisol versus the influence of metabolic health on excreted corticoids. Many providers alternate between saliva and urine testing to assess levels and guide treatment. If a provider starts with saliva testing, a follow-up in urine may reveal additional perspective, and vice versa.  

 
 

For more information on each test along with treatment considerations, the following handouts are available on the Doctor’s Data website:

 
 
 
 
 
 

Hormone, Metabolite (HuMap) and Neurotransmitter Testing in Urine and Saliva - FAQs

Presented by Krista Anderson Ross, ND

December 4, 2024 at 12 PM Pacific

Session is approximately 60 minutes with Q&A

When it comes to interpreting hormone, metabolite (HuMap) and neurotransmitter results, providers often have the same questions. In an attempt to increase best practices and testing outcomes, we offer a webinar to clarify some of the most commonly asked questions. Such as:

  • What is the clinical utility of the HuMapcortisol panel and how does it compare to salivary hormone testing?
  • Does urinary neurotransmitter testing measure brain levels?
  • When should a perimenopausal woman with irregular cycles test hormones?
  • Should patients discontinue their psychoactive medications for neurotransmitter testing?
  • For which patients should you order the cortisol awakening response (CAR) and how to interpret results?
 
 

Laboratory, Endocrine, & Neurotransmitter Symposium

February 28 - March 2, 2025 in Austin, TX or Online

Earn up to 18.0 AMA PRA Category 1 Credit(s)


The Laboratory, Endocrine and Neurotransmitter Symposium (LENS) combines curriculum driven by research and real-world clinical scenarios, taught by engaging and seasoned practitioners and educators. Attendees return year after year to LENS to dive deep into neuroendocrine topics, leaving the weekend with a full toolkit of clinical tips, protocols, and practical applications that can be implemented right away in their practice.

 

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Disclaimer: All information given about health conditions, treatment, products, and dosages are for educational purposes only and do not constitute medical advice.

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