Adrenal Hormones Explained: A Complete Guide to Cortisol, DHEA, and What Your Labs Really Mean

Adrenal hormones play a central role in energy, stress resilience, sleep, and hormone balance, yet they’re often misunderstood or oversimplified.

Symptoms like fatigue, anxiety, poor sleep, burnout, blood sugar swings, and that “tired but wired” feeling are frequently tied to adrenal dysfunction. But this goes far beyond the idea of “adrenal fatigue.” Your adrenal glands don’t simply stop working, rather, your brain, nervous system, and hormones adapt to chronic stress over time.

Adrenal hormones do not function in isolation, and cortisol is only one piece of the puzzle. Appropriately testing and interpreting these markers can be challenging, especially when standard blood testing appears “normal,” despite ongoing symptoms.

In this blog, we’ll break down cortisol, DHEA, and pregnenolone – exploring what they mean, how to test them accurately, and what these markers truly reveal about adrenal function.

What Are Adrenal Hormones and Why Do They Matter?

Your adrenal glands sit on top of your kidneys and produce hormones that regulate stress, blood sugar, inflammation, and hormone production. They’re controlled by the HPA axis, the communication loop between your brain (hypothalamus and pituitary gland) and adrenal glands. 

This system is constantly responding to inputs like stress, sleep, inflammation, and blood sugar shifts, which is why adrenal function is closely connected to many other systems in the body. 

Cortisol, the main stress hormone produced by the adrenals, plays a key role in immune signaling and inflammation. When stress becomes chronic, adrenal hormone production decreases, which can impact ovulation, progesterone production, and thyroid function. This is why adrenal labs should always be interpreted in a broader context.

Key adrenal-related hormones include:

• Cortisol: Drives energy, “survival mode” (aka sympathetic nervous system state), blood sugar stability, and circadian rhythm
• DHEA / DHEA-S: Precursor to testosterone and estrogen, supports recovery, mood, and bone density, and reflects longer-term adrenal output
• Pregnenolone: Considered the “mother hormone,” as the precursor to cortisol and all steroid-based reproductive hormones (DHEA-S, progesterone, estrogen, and testosterone)

We can think about adrenal health as a balance between output (cortisol) and reserves (pregnenolone and DHEA). Over time, chronic stress can shift this balance, driving higher cortisol output while depleting upstream and downstream hormone reserves. This ultimately alters overall adrenal hormone patterns and stress resilience.

Pregnenolone and the “Hormone Cascade”

Pregnenolone is often called the “mother hormone” because it sits at the top of the steroid hormone cascade. It is made from cholesterol and can be converted into cortisol, DHEA, progesterone, and sex hormones estrogen and testosterone.

Low pregnenolone may reflect chronic stress demand, nutrient deficiencies, mitochondrial limitations, or broader HPA-axis strain. It doesn’t mean your body has “run out” of adrenal reserves, but it can signal that the upstream system is under pressure. 

The “pregnenolone steal” theory suggests that chronic stress shifts pregnenolone toward cortisol production, leaving less available for hormones like DHEA and progesterone. While helpful conceptually, this is an oversimplification. Hormone production is far more complex than a simple one-way shift and depends on a variety of regulatory factors, including enzyme activity, signaling pathways, inflammation, and nutrient availability.

Pregnenolone is best assessed via blood testing and should always be interpreted alongside cortisol, DHEA-S, and reproductive hormones. While not always essential to test, it does provide upstream context for how the entire hormone cascade is functioning. Learn when to test and optimal ranges in this week’s podcast episode (linked here).

Cortisol Markers and Testing Explained

Cortisol is often demonized due to its role in stress signaling, but it is essential for energy, blood sugar regulation, inflammation control, and regulating circadian rhythms. The goal is not low cortisol, rather, it’s a healthy daily rhythm: higher in the morning, gradually declining throughout the day.

High cortisol levels may reflect acute stress, underlying inflammation, poor sleep, or blood sugar instability. Chronically low cortisol levels indicate deeper dysfunction, and result from long-term psychological stressors as well as biological stressors, such as gut dysbiosis, mold mycotoxin and heavy metal exposure, parasitic infections, nutritional deficiencies, and low energy availability. Low cortisol levels typically follow chronically elevated cortisol levels that go unaddressed, reflecting a chronic stress adaptation, under-fueling, or HPA axis downregulation.

Cortisol testing methods matter, and they’re not all created equal. Saliva testing is the gold standard for assessing daily (diurnal) cortisol patterns. Urinary cortisol, as seen in tests like the DUTCH test, reflects total output and how cortisol is metabolized or broken down. Blood cortisol is the most limited, as it provides only a single snapshot and doesn’t capture patterns or free (available) cortisol. 

That being said, blood testing remains incredibly valuable for assessing other hormone markers and is still an important part of a comprehensive, root-cause approach depending on what other factors we’re looking to investigate more deeply.

Cortisone adds another layer to the cortisol conversation. It is the inactive form of cortisol and reflects how cortisol is being converted and deactivated or cleared, mainly by the kidneys. While most commonly tested in urine, it can provide insight into cortisol metabolism.

DHEA vs DHEA-S: What These Levels Really Mean

DHEA and DHEA-S are closely related but serve slightly different roles in assessing adrenal function. DHEA is the more active form and tends to fluctuate throughout the day, reflecting more short-term changes in stress signaling. In contrast, DHEA-S is the sulfated storage form (with a sulfur group added onto it), which is much more stable and is most commonly measured in blood labs to reflect longer-term adrenal output and reserve.

Both high and low levels of DHEA and DHEA-S can be clinically meaningful. Low levels of either may suggest chronic stress, depletion, and reduced resilience, and can also impact downstream hormone production, including testosterone and estrogen. On the other hand, elevated levels may indicate an increased acute stress response or, in some cases, excess androgen patterns such as those seen in PCOS.

In some cases, although not common, a DUTCH test may reveal high levels of DHEA with lower DHEA-S. This can reflect more acute adrenal activation alongside lower long-term reserves due to underlying inflammation. It may also point toward impaired sulfation, the conversion of DHEA to DHEA-S, though this should always be interpreted within the broader context of other hormones and adrenal markers.

Ultimately, DHEA and DHEA-S are most informative when evaluated alongside cortisol patterns and symptoms, as they help provide a more complete picture of both short-term stress response and long-term adrenal resilience.

What Adrenal Hormone Patterns Are Telling You About Adrenal Function

Adrenal health isn’t defined by a single number – it’s defined by patterns. When we evaluate adrenal hormones in the context of one another, we gain a clearer picture of symptoms like fatigue, low stress resilience, sleep disruptions, and hormone imbalances.

Each marker tells part of the story. Pregnenolone reflects upstream hormone capacity. Cortisol and cortisone reveal stress output, daily rhythm, and metabolism (depending on how they’re tested). DHEA and DHEA-S provide insight into resilience and longer-term adrenal reserves.

Ultimately, adrenal hormone testing isn’t about identifying “adrenal fatigue,” it’s about understanding how your body is adapting to stress and where it needs support. The right testing strategy depends on your health history, symptoms, and the root causes we’re working to uncover. 

In our 1:1 program, we take a comprehensive root-cause approach, assessing adrenal function alongside thyroid function, hormones, metabolism, and more to connect the full picture. If you’re ready for personalized support and to get to the bottom of your stubborn symptoms, apply to work with us today.