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HPA Stress

Stress accumulates as we interact with our environment, whether it is more emotional or physical in origin.  Our bodies ability to effectively deal with particular stressors often determines whether or not we are successful when faced with a challenge, such as a stressful work environment, making sure the bills are paid, or dealing with three children crying simultaneously!  Our ability to deal with these challenges is primarily coordinated by the hypothalamus-pituitary-adrenal (HPA) axis through a complex interplay between the hormones cortisol, dehydroepiandrosterone sulfate (DHEA-S) and their receptors.  Chronic stress such as untreated anxiety, sleep deprivation, illness or toxin exposure may eventually overwhelm our body’s ability to deal with it, resulting in adrenal “burn out” and other problematic health issues. The precision testing using the HPA Stress Panel is needed for accurate assessment and subsequent protocol recommendations geared towards resolution and supporting the body’s ability to deal with stress more efficiently.

Definition

Stress accumulates as we interact with our environment, whether it is more emotional or physical in origin.  Our bodies ability to effectively deal with particular stressors often determines whether or not we are successful when faced with a challenge, such as a stressful work environment, making sure the bills are paid, or dealing with three children crying simultaneously!  Our ability to deal with these challenges is primarily coordinated by the hypothalamus-pituitary-adrenal (HPA) axis through a complex interplay between the hormones cortisol, dehydroepiandrosterone sulfate (DHEA-S) and their receptors.  Chronic stress such as untreated anxiety, sleep deprivation, illness or toxin exposure may eventually overwhelm our body’s ability to deal with it, resulting in adrenal “burn out” and other problematic health issues. The precision testing using the HPA Stress Panel is needed for accurate assessment and subsequent protocol recommendations geared towards resolution and supporting the body’s ability to deal with stress more efficiently.

Etiology

Chronic stress causes circulating cortisol levels to remain high for a longer than normal period of time, leading to adrenal fatigue.  Adrenal fatigue can be classified into stages of progression, eventually leading to adrenal exhaustion.  Phase 0 is characterized by a healthy adrenal response where cortisol levels are within range with desired rhythm and the person is in homeostasis.  Then a stressful life event occurs, causing an elevation in cortisol levels.  We enter Phase 1 and begin to see increased HPA tone.  Then other stressful events occur, and the frequency of acute fight or flight situations mount as your body constitutively expresses cortisol.  The high degree of stress and cortisol output eventually progresses HPA axis dysfunction (zig-zag patterns) to early adrenal fatigue, where cortisol is elevated in the AM with HPA blunting thereafter.  As adrenal gland fatigue evolves to Phase 2, we see lower AM cortisol with HPA blunting thereafter.  In Phase 3, or hypoadrenia, the adrenals are no longer producing sufficient amounts of cortisol or DHEA, and the individual is no longer able to deal with stress effectively.

Clinical Presentation

Chronic elevations (Phase 1 & 2) of free cortisol may contribute to decreased expression of growth factors (GHRH, GH, IGF-1, GnRH, LH, E2, T) and diminished immune function and neurogenesis.  Other effects are increased blood pressure, blood glucose and abdominal visceral adiposity and cognitive imbalances such as anxiety, depression, and insomnia.  A hypocortisolic (Phase 3) patient may present with recent weight loss, fatigue, may be retaining water, and may be irritable and/or depressed.  They may have lower blood sugar, blood pressure, potassium and insulin sensitivity with high lipids.  The clinical effects of excessive HPA axis Activation are osteopenia, sarcopenia, syndrome X, cognitive decline, immunological compromise, fractures, frailty, CVD, memory loss, and infectious complications. 

Testing

In a healthy individual, both cortisol and DHEA-S follow a circadian pattern throughout the day.  The six time points of cortisol and three measurements of DHEA-S allows closer examination of one’s circadian pattern, allowing the practitioner to determine adrenal rhythm and assessing adrenal function.  The 4am cortisol measurement is a unique time point allowing the practitioner to evaluate a full 24 hour circadian rhythm. Cross referencing cortisol output with DHEA-S output provides a global evaluation of HPA Axis tone. Salivary cortisol testing is the preferred method of testing over venipuncture for several reasons.  First, the anticipation of a blood draw itself can elicit stress and trigger an increase in cortisol.  Second, salivary cortisol is preferred over serum cortisol because salivary levels represent the free, unbound hormone without cortisol binding globulin (CBG).  Third, salivary collection is ideal for multiple sampling throughout the day and is the preferred method in clinical studies evaluating adrenal function. 

 Remediation

To properly restore adrenal function, identification and removal of emotional and physical stressors is key.  The treatment methodology varies between the different phases of adrenal fatigue.  Phase 0 may be maintained with dietary supplementation of multivitamin/multimineral complex, Omega EFAs, Vitamin D3, and probiotics.  Sufficient Phase 1 support may require the addition of phosphatidylserine, Vitamin B5, B6, C, and E.  Utilization of melatonin may be helpful if cortisol is elevated at night.  Implement and maintain lifestyle modifications throughout.  Phase 2 may require the introduction of an adrenal glandular and/or herbal adaptogens to further modulate the stress response.  Once Phase 3 is reached, hypocortisolism occurs, and hydrocortisone supplementation is typically prescribed.  Lifestyle modifications includes incorporating stress management techniques like exercise, deep breathing, yoga, prayer and/or meditation.  Refined sugars and processed foods should be avoided, and steps should be taken to reduce or eliminate caffeine and alcohol consumption.  Reduce food-derived toxins by incorporating organic, non-GMO produce, and identify and remove foods that are pro-allergenic and cross-reactive.

 References:

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  2. Murialdo G, Nobili F, Rollero A, Gianelli MV, Copello F, Rodriguez G, Polleri A: Hippocampal perfusion and pituitary-adrenal axis in Alzheimer's disease. Neuropsychobiology 2000;42:51-57.
  3. Perez-Neri I, Montes S, Ojeda-Lopez C, Ramirez-Bermudez J, Rios C: Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanism of action and relevance to psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1118-1130.
  4. Kamin HS, Kertes DA: Cortisol and DHEA in Development and Psychopathology. Horm Behav 2016.
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  6. Steptoe A, Cropley M, Griffith J, Kirschbaum C. Job strain and anger expression predict early morning elevation in salivary cortisol. Psychosom Med 2000;62:286-92.
  7. Endocrinology and Metabolism Clinics of North America. Elsevier Publishing, ed. Anne R. Cappola. June 2013, vol. 42, no. 2.
  8. Circadian rhythm abnormalities – Association with the course of inflammatory bowel disease
  9. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous system
  10. A Tilted Axis: Maladaptive Inflammation and HPA Axis Dysfunction Contribute to Consequences of TBI
  11. HPA axis responses to psychological challenge linking stress and disease: What do we know on sources of intra- and interindividual variability?
  12. Stress and the HPA Axis: Balancing Homeostasis and Fertility

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