HPA Axis Dysfunction

Most of us have some familiarity with cortisol (the primary “stress hormone”). It is important to realize that its function is wide-ranging and intimately related to whether you are in a state of good health or not.

When cortisol production and breakdown are appropriate and normal, well – all is usually good. However, when we find ourselves in a situation where the cortisol levels or pattern are not normal (hyper-cortisolism, hypo-cortisolism, or some form of diurnal dysrhythmia), the HPA axis (Hypothalamus/Pituitary/Adrenal Axis) is not functioning normally and needs to be corrected.

With HPA dysfunction, maladaptive changes occur (i.e. adrenal fatigue) and a variety of illness and symptoms develop (i.e. hypoglycemia, chronic fatigue, osteoporosis, renal calculi, depression, chronic inflammation, poor learning, hypothyroidism, PMS, severe menopause, truncal obesity) to name a few.

Stress is a part of all of our lives. While we all know stress when we see it, it is amazing that biologists have not agreed on the definition of stress for more than 75 years! Stress can be emotional, physical, or as a result of metabolic dysfunction.

How much stress is “normal”? Is stress defined by the changes made in adapting to stress or the dysfunctions associated with the failure to adapt to the stress?

Although we primarily think of stress as “negative stress” – ie “distress”, positive events can also elicit similar physiologic responses! What is clear is that stress can have a major impact on our health and well being, as well as the progression in many cases to chronic disease.

Chronic HPA Axis Stress

4 General Categories Of Chronic Hpa Axis Stress

Working to identify the source of chronic stress is vital to treat and prevent disease progression. There are 4 general categories of chronic HPA Axis stress that need to be evaluated:

Sleep Disturbance

  • Sleep Deprivation
  • Sleep Apnea
  • Disturbed Sleep Patterns
  • Insomnia
  • Shift Work

Mental and Emotional

  • Anger, Worry, Grief, Fear
  • Job Stress
  • Financial Pressure
  • Traumatic Memories
  • Relationship Issues


  • Tissue Damage etc
  • Allergies (food, air, skin)
  • IBD, Celiac
  • Arthritis
  • Obesity, Central Adiposity
  • Toxic Burden

Glycemic Dysregulation

  • Meal Skipping
  • High Glycemic Impact Meals
  • Alcohol consumption
  • Calorie Depleting Diets
  • Hormonal Dysregulation

Identifying and addressing HPA Axis Dysfunction is critical to enhancing health and wellness. While each patient is surely unique, it is important to recognize the very existence of HPA axis dysfunction and to use appropriate assessment and therapeutic strategies to fit an individual patient’s needs.

Through the use of careful and thoughtful history and exam, as well as targeted laboratory tests, a therapeutic strategy will emerge based on your personal needs. Tools such as the ARK program, 4-point cortisol/DHEAS testing, and clinically relevant questionnaires are part of our tool chest.

Stress Response And Hpa Axis

Hans Selye (and his book “The Stress of Life”) provided a framework for researchers to try to understand the nuances of how stress interacts with human physiology. From his work, a 3 stage model emerged which is still the basis of much of the stress-related research to this day.

The human stress-response system has, as key components the hypothalamic-pituitary-adrenal (HPA) axis, and the sympathetic nervous system (SNS). Suffice it to say that there are complex interactions that occur, affecting such key hormones as cortisolthyroidLeptinInsulin, and from there many other body systems and other hormones.

The normally functioning HPA-axis has 3 attributes:

  1. circadian rhythm of activity in the system
  2. Various feedback loops
  3. Various stressors that can affect the HPA axis, and can override circadian & feedback controls

The ultimate goal, of course, is your health and wellbeing.

Common Conditions Related To The Stress/HPA Axis

By addressing the HPA axis, we very directly affect common conditions related to the stress/HPA axis:

  • Sleep Disorders
  • Hormone Disorders
  • Common GI Complaints

While variable, most patients following good glycemic control habits will usually see symptom changes within 5 to 7 days of starting corrective protocols. Adrenal function often takes 3 to 6 months or longer before there is a measurable improvement in adrenal function.

Dietary patterns that drive poor glycemic control

  • Skipping breakfast
  • Low-calorie dieting
  • Too long between meals
  • Eating high-glycemic-index foods
  • Junk food diets
  • Eating greater than a 2:1 ratio of carbohydrates to protein at any meal

Some causes of GI Inflammation:

  • Foods that inflame (Gluten/Gliadin, Soy, Casein/Lactoalbumin, corn)
  • Hidden pathogens (Helicobacter pylori, Cryptosporidium parvuum, Giardia lamblia, Entamoeba histolytica)

Physiological conditions resulting from sleep loss or disruption

  • Just six days of reduced sleep causes rise in bedtime cortisol and promotes insulin resistance.
  • TSH release, which occurs at bedtime, is reduced by as much as 30 percent.
  • GH release (Growth Hormone) is reduced and prolonged. Longer exposure to peripheral tissues increases insulin antagonism.