It’s human nature to reach for simplistic explanations for complex concepts. While this practice can be helpful when communicating with patients, it can also play a detrimental role in perpetuating outdated ideas or terminology. As functional medicine practitioners blazing the trail in evidence-based medicine, it is critical to dispel outdated concepts as new research is made available. Two of the most common misinterpretations are the concepts of “adrenal fatigue” and “pregnenolone steal.”
“Adrenal Fatigue”
The term “adrenal fatigue” has existed for decades as a way to simplify the complexity of the physiologic changes that happen with chronic stress. While this term has helped to dismiss the idea that only extreme issues such as Addison’s or Cushing’s disease are clinically relevant, this term is simply not based in science. The adrenal glands don’t burn out due to overuse and exhaustion, instead it is now understood that cortisol output can be down-regulated due to chronic stress. This process is directed by feedback loops between the hypothalamus, which releases CRH to stimulate the anterior pituitary, and the pituitary gland, which releases ACTH to influence adrenal cortisol output. It is now understood that this feedback loop may become maladaptive as a result of constant demand/stress, where the adrenal gland becomes less sensitive to ACTH. This maladaptive process, or HPA axis dysfunction, best describes the reason that cortisol output decreases under chronic stress.
Pregnenolone Steal
The “pregnenolone steal” is a commonly found explanation for the depletion of DHEA and other hormones due to chronic stress. This theory comes from the idea that all steroid hormones are derived from a common precursor, pregnenolone, and the increasing demand for cortisol diminishes the amount of pregnenolone available to produce other hormones. In his research-based book, “The Role of Stress and the HPA Axis in Chronic Disease Management,” Thomas Guilliams dispels this notion and explains why it is incorrect; it simply boils down to physiology. When looking at a hormone cascade it’s important to remember that this conversion process is happening at a cellular level. With graphic representations that simplify the process, one mistakenly imagines one large pool from which all of our body’s hormones are formed. If you think about it, this would be extremely inefficient. Instead, the transformation of cholesterol to pregnenolone happens at the cellular level in the mitochondria of tissues where the hormone is needed. For example, cortisol production starting from pregnenolone occurs in the mitochondria of the zona fasiculata, whereas DHEA production occurs within the mitochondria of the zona reticularis. Additionally, there is no documented mechanism by which these two different zones and/or mitochondria are able to communicate with each other and therefore cannot “steal” from one another. In fact, cell culture studies have demonstrated a down regulation of DHEA production in the presence of ACTH during inflammatory stress. As research continues in this area, it is important to remember just how dynamic of a process all biological systems are with complex relationships, signaling factors, and exogenous influences.
The human body does not exist in linear formats as seen in text books, and therefore requires continued research to increase the understanding of how these mechanisms play out within the individual. Again, as functional medicine practitioners, it’s important to challenge outdated ideas and terminology when they arise, as this will continue to drive medicine forward in an informed, evidence based way.
Keep an eye out for Adrenal Mythbusters Part 2: DHEA/Cortisol ratio, DHEA supplementation and cortisol, and dried urine and the CAR (cortisol awakening response).
