Navigating the HPA Axis Paradox: Advanced Clinical Strategies for Functional Medicine Practitioners
by Dr. Dan Kalish
Is "adrenal fatigue" an outdated oversimplification? As functional medicine clinicians, we understand that chronic stress-related conditions —from debilitating fatigue and weight dysregulation to stubborn cognitive decline—are never about the adrenal glands failing in isolation. They are symptoms of a complex systemic failure in our ability to cope with all that comes at us. Three big issues push the HPA axis to exhaustion, in this order, emotional stress and spiritual disconnection, insulin resistance/lack of muscle mass AND chronic inflammation typically coming from GI or liver detox issues. It’s that simple.
The reality that emotional, dietary/exercise and inflammatory stress related problems make us sick, also lets you know how to make people well. Emotional connection, a rich spiritual life, eating to keep your insulin in check and exercising a lot, combined with the classic one two punch from the naturopathic/functional medicine playbook of GI and toxin treatments are what fundamentally get people well.
For practitioners focused on longevity and root-cause resolution, mastering the HPA axis protocols is a cornerstone of effective care. Being able to test the stress response and reset it is profound. In addition to learning the most impactful protocols using DHEA, pregnenolone, licorice root, phos serine and many other nutrients, you also need to address exercise, diet, emotional stress and GI and toxin related issues in every person you work with. This comprehensive, body system approach is what leads to consistent patient results.
The HPA Axis: Orchestrator of Systemic Health
The HPA axis is the central system that manages our stress, all of our stress. Emotional stress, dietary stress through insulin issues, even GI and toxin mediated stress all impact the adrenals. The HPA Axis meticulously regulates cortisol and DHEA production, sending messages from the brain to the adrenal glands to make more cortisol. When overtaxed this system’s feedlap loops fail and when this communication system breaks down, the resulting dysregulation impacts every cell in the body:
- Metabolic Function: Disrupted cortisol rhythm alters glucose regulation, increasing visceral fat accumulation and insulin resistance.
- Immune Modulation: Chronic hyper- or hypo-cortisol states suppress or over-activate the immune system, contributing to chronic inflammation and autoimmunity.
- Thyroid and Sex Hormone Health: Constant stress depletes thyroid and sex hormone levels.
Identifying these patterns requires moving beyond basic standard lab measurements to utilize dynamic HPA axis testing.
Beyond Basic Panels: Lab-Guided Programs
Effective systems-based functional medicine relies on precise, integrated lab interpretation. Single-point labs are insufficient; instead we need dynamic assessments of the processes in play, like the 24 hour pattern of cortisol production that provides the data we need for targeted interventions.
We gain crucial insights from Salivary Cortisol Panels, which reveal the essential day and night patterns: identifying flattened curves, the inappropriate late-evening peak (the "second wind"), or low morning output. This directly guides the timing of stress adaptation strategies and dosages for DHEA, pregnenolone, phos serine and licorice, which when used properly can reset HPA function.
For unparalleled granularity, DUTCH, Hormone Zoomer and HUMAP each provide detail on total cortisol production, clearance rates, and critical metabolite ratios. This level of analysis helps practitioners pinpoint phase-specific detoxification issues or production blocks essential for reestablishing a normal stress response.
Crucially, this data must be correlated with integrated markers—thyroid function, sex hormones, organic acid profiles, and inflammatory markers (like hs-CRP). Most especially one needs to address This advanced practitioner lab interpretation ensures you're addressing the root burden on the adrenals (e.g., gut dysbiosis, chronic infection, or metabolic stress), rather than simply managing the symptomatic what.
By the way, several generations of practitioners have already worked all this out. These treatment protocols are challenging to learn on your own, however, with a mentor/guide there by your side, case after case, you can learn to do this quickly.
The Next Level of Clinical Mastery
The functional medicine field is evolving rapidly. More and more people are becoming aware of terms like “metabolic health” and “functional labs”. The audience is out there for us now and they don’t need convincing, they just need results and programs that are actionable.
These topics— including the role of emotional well-being and our spiritual lives along with insulin handling and the microbiome– are all coming together into mainstream awareness now. We, as practitioners, just need to be able to handle the technical aspects of the job and take up the mantle as this generation's healers, facing down this generation's problems. We, most importantly, need to be healthy ourselves. Our first task in every Kalish Institute course is for each practitioner to test themselves. We take “physician heal thyself” very seriously.
If your goal is to get healthy and fit yourself, to transition from symptomatic relief to longevity medicine, then advanced training in these interconnected systems is the logical next step in your professional development.
Our intensive—Hormones & Immune Function—will explore these principles in depth. It’s part of the Kalish Longevity Certification, a program designed to give practitioners the lab-based strategies and communication tools to build personalized longevity protocols for their patients.
