Arrow BackHealth Report — July 21, 2025
The use of the Diadia Health interpretive results received are intended for informational purposes only, and are not a substitute for medical advice. This includes all instances, in which the interpretive results are generated by using Artificial Intelligence. You should consult your primary care physician or other qualified healthcare provider for medical advice, diagnosis or treatment.

HPA Axis Dysregulation with Adrenal Hypoandrogenism

Your stress-response system (HPA axis) appears chronically over-activated and depleted, with low adrenal and gonadal androgens despite a normal single morning cortisol.

Your pattern points to a stress system that has been driven hard for decades and is now stuck in a high-alert but under-resourced state. Even though your single morning cortisol looks normal, your low DHEA sulfate, low pregnenolone, and low free and bioavailable testosterone show that your adrenal and gonadal hormone output is not keeping up with demand, while your symptoms of severe anxiety, depression, fatigue, and sleep disruption reflect how this plays out in your brain and body.

  • Genetic stress-response sensitization: Variants in CRHR1, FKBP5, and COMT have each been associated in human studies with altered HPA axis stress reactivity and higher vulnerability to stress-related anxiety or depression. In your case, this helps explain why you have felt “wired for anxiety” since childhood and why relatively ordinary stressors seem to hit you harder and longer than they might for someone without this inherited sensitivity. This genetic backdrop makes your stress system more reactive and slower to shut off, amplifying the impact of every other driver below.

  • Chronic hypervigilant cognitive patterns: Persistent anxiety, catastrophic worry, and constant scanning for threats are linked to sustained activation of limbic and hypothalamic circuits that drive ongoing HPA axis activation even without obvious external crises. Your long history of generalized anxiety, extreme startle response, and relentless “what if” thinking means your brain is repeatedly sending danger signals, so your stress system rarely gets a true off-switch. Over time, this entrenches a high-alert baseline that feels like exhaustion layered on top of anxiety.

  • Adrenal steroid precursor depletion: In chronic HPA overactivation, adrenal steroidogenesis can shift toward maintaining cortisol output at the expense of DHEA, pregnenolone, and downstream androgens, so you can see low DHEA sulfate and low testosterone even when a single morning cortisol appears normal. Your labs showing low DHEA sulfate, low pregnenolone, and low free and bioavailable testosterone fit this pattern of adrenal hypoandrogenism. Low DHEA sulfate and low testosterone in women have been associated with reduced stress resilience, lower energy, and higher rates of depressive symptoms, consistent with adrenal hypoandrogenism contributing to your fatigue and mood disturbance.

  • Sleep fragmentation and apnea stress load: Obstructive sleep apnea and severely fragmented sleep cause repeated nocturnal surges of sympathetic activity and cortisol, which promote chronic HPA axis dysregulation and can worsen daytime fatigue, mood symptoms, and cardiometabolic risk. Your severe sleep apnea, absence of slow-wave sleep, and shallow, broken sleep mean your stress system is being “pinged” over and over each night, instead of entering the deep restorative states needed to recalibrate cortisol and androgens. This nightly assault makes it much harder for your HPA axis and brain circuits to recover, even if daytime stress is low.

  • Relative mineralocorticoid insufficiency: Aldosterone is the main mineralocorticoid hormone regulating renal sodium and chloride reabsorption, so impaired aldosterone production or action, as in primary adrenal insufficiency or hypoaldosteronism, can lead to hyponatremia and low chloride levels. Your sodium and chloride being below both optimal and lab ranges suggest that your salt and fluid balance may be relatively under-supported, which can manifest as fatigue, low resilience to standing or heat, and a sense of being “drained,” and it fits with a broader picture of adrenal strain, even though you do not show full-blown adrenal failure.

Taken together, these drivers show how inherited stress sensitivity, lifelong hypervigilant thinking, adrenal androgen depletion, sleep-apnea–driven night-time stress surges, and possible mineralocorticoid under-support can interact to maintain HPA axis dysregulation, which in turn contributes to treatment-resistant depression, anxiety, and fatigue despite multiple medications. Conventional approaches often focus on neurotransmitters, single cortisol readings, or adding more psychotropic drugs, missing this multi-layered stress-system biology. Addressing these specific drivers in an integrated way—supporting more stable HPA signaling, restoring deeper sleep, improving adrenal hormone balance, and easing the cognitive hypervigilance—offers a more complete path to reducing your symptom burden and improving day-to-day function.

Your HPA axis dysregulation with adrenal hypoandrogenism is a high-level issue because it governs how your brain, pituitary, and adrenals coordinate the entire stress response, influencing cortisol, adrenal androgens, mineral balance, and autonomic tone. When this axis is chronically upregulated—as your genetics, lifelong anxiety, startle response, and sleep apnea suggest—it can drive or worsen many of your other causes, including mitochondrial dysfunction, insulin resistance, and low-T3 thyroid physiology. Elevated stress signaling suppresses thyroid hormone conversion in peripheral tissues, helps push your metabolism toward insulin resistance, and directly increases oxidative stress that batters your mitochondria. In turn, mitochondrial fatigue and low cellular energy feed back into your HPA axis by making everyday tasks feel like threats, which your brain interprets as a need for even more stress activation. Your nutrient deficiencies—especially low iron, protein, and magnesium—further weaken adrenal resilience and hormone synthesis, while methylation bottlenecks can alter glucocorticoid receptor sensitivity and HPA feedback loops. This bidirectional web explains why your anxiety and hypervigilance are so resistant to medication alone and why improving HPA balance can ease downstream issues in mood, sleep, thyroid, and metabolic function. Addressing this high-level hub will likely give you the broadest symptomatic relief, especially for your most disruptive experiences of being wired yet exhausted, unable to rest, and pushed into depressive crashes by chronic stress.
  • Your 'Extreme startle response and hypervigilance' are classic signs of a stress system that is running on overdrive. When your HPA axis is chronically activated, your brain’s threat-detection circuits stay sensitized, so even minor stimuli can trigger a strong alarm response. Over time, this constant scanning for danger becomes self-reinforcing, as poor sleep and repeated stress keep the system stimulated. This pattern is much more consistent with physiological stress-system dysregulation than with simple situational anxiety.
  • Your 'Treatment-resistant generalized anxiety disorder with severe hypervigilance and excessive worry' indicates that your stress circuitry has likely been reshaped by long-term overactivation. Persistent worry sends continuous signals through limbic brain regions to the hypothalamus, which in turn drives cortisol and adrenal output. When this loop has been active since childhood, as in your case, it often leads to a reset of your stress baseline at a much higher level than normal. This entrenched pattern strongly supports HPA axis dysregulation as an upstream driver.
  • Your 'Chronic fatigue from constant alertness; requires stimulant (Ritalin) for basic functioning' reflects the energy cost of being stuck in a high-alert state. When cortisol and adrenaline signaling are persistently elevated or erratic, your body spends energy as if it were continually facing a threat. Eventually, the adrenal system can no longer sustain this output smoothly, producing alternating periods of hyperarousal and exhaustion. This tired-and-wired state is very characteristic of advanced HPA-axis dysregulation.
  • Your 'Debilitating, persistent fatigue and low energy requiring stimulant support' aligns with the later stages of HPA dysregulation, where adrenal precursors and androgens are depleted. Cortisol may still show normal spot values, but the overall rhythm and downstream steroid balance become inefficient, leaving you feeling drained even while anxious. Low DHEA and testosterone further reduce your ability to tolerate stress and maintain muscle and brain energy. This helps explain why you feel profoundly exhausted yet need stimulants just to perform basic tasks.
  • Your 'Chronic sleep disruption with no slow-wave sleep and severe sleep apnea despite CPAP' both drives and reflects HPA-axis dysregulation. Normally cortisol falls at night to allow deep sleep, but when the HPA axis is dysregulated, nighttime cortisol can remain elevated or erratic, fragmenting sleep and preventing slow-wave stages. In turn, repeated arousals and apnea events act as stressors that push cortisol and adrenaline higher. This vicious cycle between poor sleep and stress hormones reinforces your HPA imbalance.
  • Your 'Persistent excessive worry across multiple life domains' keeps your HPA axis continually engaged, even in the absence of immediate threats. Every episode of catastrophic or future-oriented thinking triggers stress signals that release cortisol and catecholamines. Over years, this reshapes brain regions that regulate the HPA axis, making it harder for your system to calm down. This long-standing cognitive pattern is both a result of and a contributor to HPA dysregulation.

POTENTIAL DOWNSTREAM EFFECTS

Tissue-Level Hypothyroidism from Impaired T4-to-T3 Conversion, Insulin Resistance and Dysglycemia, Mitochondrial Dysfunction with Oxidative Stress, Multiple Nutrient and Protein Deficiencies (Iron, Magnesium, Protein), Methylation Dysfunction with Elevated Homocysteine

POTENTIAL CAUSED BY

Multiple Nutrient and Protein Deficiencies (Iron, Magnesium, Protein), Methylation Dysfunction with Elevated Homocysteine, Mitochondrial Dysfunction with Oxidative Stress

Recommended Action Steps

For HPA Axis Dysregulation with Adrenal Hypoandrogenism

Order an 8 AM serum cortisol with plasma ACTH to evaluate for primary or secondary adrenal insufficiency in the setting of your fatigue and hyponatremia . This will clarify whether a true cortisol deficiency is contributing to your HPA axis dysregulation and guide whether adrenal hormone replacement is needed.

Order morning serum aldosterone, plasma renin activity, and a basic metabolic panel to evaluate for hypoaldosteronism in the context of your low sodium and low chloride . This will help determine whether relative mineralocorticoid insufficiency is driving your electrolyte pattern, low blood volume symptoms, and adrenal strain.

Start oral DHEA 5-10 mg each morning with food to support your low DHEA sulfate and adrenal hypoandrogenism contributing to fatigue and low mood . Low-dose DHEA replacement can gently raise adrenal androgens toward a more physiologic range, which may improve energy, resilience, and overall stress tolerance.

Start transdermal testosterone 300 micrograms to 1 mg once daily for your documented low total and free testosterone with persistent fatigue and low libido despite other treatments . Physiologic-dose female testosterone replacement can restore androgen signaling in brain and muscle, which may enhance sexual desire, energy, and sense of well-being while remaining within a female reference range.

Start oral pregnenolone 10-25 mg each morning to support your low pregnenolone and downstream adrenal steroidogenesis in the context of HPA axis dysregulation and adrenal hypoandrogenism . Pregnenolone replacement can increase the steroid precursor pool that feeds into both cortisol and androgen production, potentially improving stress tolerance, mood stability, and overall adrenal resilience.

Detailed Insights

Supporting Biomarkers
Genetic Evidence
Conflicting Biomarkers

dhea sulfate

Low Levels

•

183 µg/dL

STRONG EVIDENCE

Your DHEA sulfate is below optimal while still within the reference range, indicating reduced adrenal androgen output from the zona reticularis. DHEA-S is produced mainly by the adrenals and acts as a long-lived marker of adrenal resilience, so a low value suggests chronic adrenal strain or underproduction. This pattern supports the idea that your adrenal glands are no longer keeping up with long-term stress demands even if cortisol snapshots look normal.

pregnenolone

Low Levels

•

71 ng/dL

STRONG EVIDENCE

Your pregnenolone level is below optimal, suggesting that the initial steroid precursor made from cholesterol in adrenal and gonadal cells is under-produced. Because pregnenolone feeds into both cortisol and androgen pathways, low levels constrain the entire steroidogenic cascade. This under-fueling of steroid synthesis fits with a picture of HPA axis burnout and hypoandrogenism.

sodium

Low Levels

•

132 mmol/L

MODERATE EVIDENCE

Your sodium is below both optimal and lab ranges, reflecting mild hyponatremia and possible impaired free water handling. Adrenal hypofunction and chronic HPA stress can reduce aldosterone and cortisol effects on the kidney, leading to renal sodium wasting and dilutional hyponatremia. This electrolyte pattern is mechanistically consistent with stress-related adrenal imbalance.

chloride

Low Levels

•

96 mmol/L

MODERATE EVIDENCE

Your chloride is also below both optimal and lab ranges, paralleling the low sodium and suggesting a broader low-extracellular-electrolyte state. Aldosterone deficiency and chronic adrenal stress can increase urinary loss of both sodium and chloride, especially when protein and solute intake are low. This reinforces the view that your adrenal and stress systems are affecting mineral balance.

testosterone bioavailable

Low Levels

•

2.4 ng/dL

MODERATE EVIDENCE

Your bioavailable testosterone is below optimal, indicating that the fraction of testosterone available to tissues is reduced. In women, adrenal DHEA contributes substantially to downstream androgen levels, so low DHEA and pregnenolone can manifest as low bioavailable testosterone. This supports the idea that adrenal hypoandrogenism is part of your HPA-axis dysregulation.

testosterone free

Low Levels

•

1.2 pg/mL

MODERATE EVIDENCE

Your free testosterone is below optimal, confirming that the unbound, biologically active androgen pool is low. Free testosterone is what directly activates androgen receptors in brain and muscle, so a reduced level impacts energy, mood, and resilience. This low free fraction, alongside low precursors, points to stress-related underproduction of androgens.