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A Functional Medicine Protocol for Hypo-Responsiveness Adrenal Dysregulation

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A Functional Medicine Protocol for Hypo-Responsiveness Adrenal Dysregulation

The cost of daily living, bills, traffic, work, school, kids, and trying to do too many things at once are typical daily stressors we all live with. If these daily stressors are ignored or left uncontrolled, the resulting stress impacts your health and well-being.

The body's stress response involves hormones released by the adrenal glands. Hypo responsiveness adrenal dysregulation refers to a condition where the adrenal glands are not functioning optimally. This can disrupt the body's stress response system, leading to fatigue, weakness, dizziness, and low blood pressure.

Hypo-responsiveness adrenal dysregulation can be caused by chronic stress, infections, autoimmune disorders, and other factors that affect the adrenal glands' function. Functional medicine approaches this condition by identifying and addressing the underlying causes to restore proper adrenal function and improve overall health.


What is The HPA Axis?

When you encounter a difficult or stressful situation, your body responds by releasing a series of hormones and triggering certain body functions, collectively called your body's stress response. A major part of the stress response is the hypothalamic-pituitary-adrenal axis or HPA axis. The HPA axis is a hormone communication network between the hypothalamus, the anterior pituitary gland, and the adrenal glands.

This HPA axis mechanism controls the body’s stress response by modulating hormones released from the adrenal glands. The primary hormone involved in the stress response is cortisol, often called the stress hormone. Other hormones, such as aldosterone, norepinephrine, and epinephrine, are also released from the adrenal glands during the stress response.

The release of these hormones causes your heart rate to speed up, your blood pressure to rise, your breathing to quicken, you start sweating, and your muscles to tense up. The stress response is a survival mechanism, also referred to as the “fight-or-flight” response. These changes increase your focus and make you stronger and faster so you can defeat or escape the threat (or stress).

The HPA axis helps the body adapt to and regulate stress. Occasional acute stress is normal. When you experience stress, your HPA axis is activated, and the body’s stress response ensues. Once the stress has passed, the HPA axis restores your body's biology to a normal, unstressed state. Sometimes dysfunction occurs in the HPA axis, impairing this response.

What is Hypo-Responsiveness Adrenal Dysregulation?

Hypo-responsiveness adrenal dysregulation occurs when the HPA axis fails to elicit the proper hormone response to stress. Your adrenal glands don’t produce enough cortisol or aldosterone. This is also called adrenal insufficiency. At the most extreme, this can lead to an adrenal crisis, a severe deficiency of cortisol that can be life-threatening.

There is primary adrenal insufficiency, also called Addison's disease, in which the issue arises in the adrenal glands and results in reduced adrenal hormone production. Secondary adrenal insufficiency is an issue with the pituitary gland not producing enough of the hormone that triggers the adrenal glands to release hormones. Tertiary adrenal insufficiency is an issue with the hypothalamus not releasing enough hormone to signal the pituitary to trigger the adrenal glands to release hormones. In all cases, the result is decreased production of adrenal hormones or hypo responsiveness adrenal dysregulation.

Signs of Hypo-Responsiveness Adrenal Dysregulation

Hypo responsiveness adrenal dysregulation often develops slowly over time, and symptoms are general, which means this condition can be missed or mistaken for another health condition.

Signs and symptoms of hypo responsiveness adrenal dysregulation include:

  • Chronic fatigue
  • Muscle weakness
  • Reduced appetite
  • Weight loss
  • Pain in the abdomen
  • Nausea or vomiting
  • Diarrhea
  • Joint Pain
  • Depression
  • Irritability
  • Sleep disturbances
  • Low blood glucose
  • Salt cravings
  • Low blood pressure
  • Orthostatic hypotension (blood pressure that drops when you go from lying down to standing up, which can result in feeling dizzy or fainting)
  • Menstrual irregularities, or amenorrhea
  • Decreased libido
  • Darkening of the skin (especially on skin folds, scars, knees, elbows, knuckles, lips, and mucous membranes)

What Causes Hypo-Responsiveness Adrenal Dysregulation

Corticosteroids: The most common cause for hypo responsiveness adrenal dysregulation occurs when people that have been taking corticosteroid medications for a long time abruptly stop taking them. Taking corticosteroids for a long time decreases the hormones naturally produced by the hypothalamus, which reduces the pituitary hormone signal to the adrenals, reducing natural cortisol release. Since you’re taking it in medication form, your adrenal glands don't need to produce as much. Abruptly discontinuing the medication doesn’t allow the adrenal glands to gradually and naturally ramp up their own cortisol production.

Primary adrenal insufficiency: (Addison’s disease) is most commonly caused by autoimmune disease. Autoimmune diseases are conditions where your body’s immune system attacks your own tissues. In the case of Addison’s disease, your immune system attacks your adrenal glands. Autoimmunity can also play a role in secondary adrenal insufficiency, in which case your immune system attacks your pituitary gland.

Genetic disorders: that influence how the adrenal glands or pituitary glands develop or function can play a role, as can cancer of these glands. Sometimes the pituitary or adrenal glands are surgically removed to treat other conditions, which would impact the entire HPA axis and result in reduced production of adrenal hormones.

Mediations: In addition to abruptly discontinuing corticosteroid medications, other medications such as antifungal drugs and a general anesthesia drug called etomidate can cause hypo responsiveness adrenal dysregulation.

Chronic stress: is a major factor involved in dysfunction in the HPA axis. It can be associated with an increase in cortisol release. However, repeated exposure to the same stressor can decrease cortisol release over time.

Inflammation: can cause dysfunction in the HPA axis resulting in hypo responsiveness adrenal dysregulation. Inflammation can reduce cortisol release and is also associated with increased susceptibility to autoimmune conditions.

Postpartum: During the postpartum period, the body undergoes many changes, including hormonal fluctuations. This period is associated with decreased hypothalamic hormone release that triggers this HPA axis cascade, resulting in reduced HPA axis activity.

Hypothyroidism: is also associated with decreased secretion of hypothalamic hormones, resulting in decreased HPA axis activity.

Functional Medicine Labs to Test for Root Cause of Hypo-Responsiveness Adrenal Dysregulation

When assessing hypo responsiveness adrenal dysregulation, comprehensive blood testing and physical examination would include markers and imaging to identify whether infection, inflammation, and cancer are factors that may be contributing to the cause of this condition. A thorough history would indicate whether medications are the main issue. The following are functional laboratory tests that can further help identify the root cause.

Hormone Testing

Measuring adrenal hormones is essential in identifying problems in the HPA axis, including hypo responsiveness adrenal dysfunction. The DUTCH Plus™ is a urine test that assesses sex and adrenal hormones and their metabolites, the daily cortisol rhythm, and the Cortisol Awakening Response, or CAR. If sleep disturbances are an issue, this test also offers an insomnia cortisol sample to test cortisol levels during the night.

Thyroid health can be measured with a comprehensive thyroid hormone panel.

Testing for aldosterone is typically performed with a blood test and is offered by BostonHeart Diagnostics.

Autoimmune Testing

A comprehensive autoimmune reactivity panel, such as the Cyrex Array 5, can help identify autoantibodies predictive for specific conditions. Assessing these antibodies can determine whether there is an autoimmune process in the body causing damage to tissues, glands, or organs. This panel can help identify Addison’s disease.

Comprehensive Stool Analysis

Increased intestinal permeability, often called leaky gut, is a common feature of autoimmune diseases. This can be assessed with a comprehensive stool test with a marker for intestinal permeability called zonulin. It will give you information about the functional health of the gut, which is essential for managing autoimmune conditions.

Micronutrient Testing

Chronic stress can cause the depletion of various micronutrients, including zinc, magnesium, calcium, and B vitamins. The SpectraCell's Micronutrient Test is a blood test measuring 31 vitamins, minerals, fatty acids, and amino acids that provides valuable information on overall nutrient status. This test also covers Vitamin D, which is essential to test as Vitamin D deficiency is prevalent in autoimmune conditions.

Vitamin D, offered by Ayumetrix, can be tested separately or may be included in a comprehensive blood workup.


Functional Medicine Treatment Protocol for Hypo-Responsiveness Adrenal Dysregulation

A functional medicine treatment protocol for addressing hypo responsiveness adrenal dysregulation takes a whole-person, patient-centered approach to improve health and promote well-being.

There is an emphasis on stress management since stress plays a significant role in HPA axis dysfunction. Mind-body therapies are valuable ways to minimize the effects of stress on the body by activating the body’s relaxation response.

Honoring the body’s sleep and wake cycles is important since cortisol is a hormone that follows a circadian pattern. This means the typical daily cortisol fluctuations follow a pattern synchronized with the daily 24-hour clock. As such, focusing on adequate quality sleep is extremely important for healing from adrenal dysregulation.

Therapeutic Diet and Nutrition Considerations for Hypo-Responsiveness Adrenal Dysregulation

Therapeutic diet and nutrition considerations for hypo responsiveness adrenal dysregulation include a focus on electrolytes, adequate protein and healthy fats, and foods high in micronutrients while avoiding processed sugar and caffeine. Goals with nutrition for this condition include maintaining electrolyte and blood sugar balance and improving the micronutrient status of the body.

Electrolyte balance is vital since adrenal insufficiency can be associated with low aldosterone, which regulates water and sodium (salt) levels in the body. Increasing the salt in your diet can help support electrolyte balance if you have this condition.

Blood sugar balance is essential since cortisol plays a role in regulating blood sugar levels. A Mediterranean diet can improve blood sugar control and support the regulation of the HPA axis. A Mediterranean eating style focuses on healthy fats such as olive oil, seasonal vegetables and fruits, herbs, legumes, and whole grains. High-fiber plant-based foods are the focus of a Mediterranean diet; however, seafood, poultry, dairy, eggs, and red wine are also enjoyed in moderation.

Supplements Protocol for Hypo-Responsiveness Adrenal Dysregulation

The following are supplements commonly used to manage this condition. However, it’s vital to individualize treatment based on lab results.

Cortisol Calm for Hypo Responsiveness Adrenal Dysregulation

Cortisol Calm is a supplement containing Vitamin D, L-theanine, and adaptogenic herbs. Adaptogenic herbs, such as ashwagandha and Rhodiola, have stress-relieving effects and help the body adapt to stress by regulating the HPA axis. Vitamin D deficiency is linked to an increased prevalence of autoimmune conditions and is vital for optimal health, making it a critical micronutrient to optimize. L-theanine is an amino acid found in green tea, and evidence indicates it may reduce stress in people exposed to stressful conditions.

Cortisol Calm Dose:The suggested use is to take one capsule in the morning and evening, with meals, or follow the advice of your health practitioner.

Duration: Until Symptoms Subside or Retesting Confirms Labs are Stabilizing

Multivitamin Multimineral Supplement

A multivitamin multi-mineral supplement offers a wide range of essential vitamins and minerals for optimum health. A supplement such as the Designs for Health DFH Complete Multi™ with Copper is a great way to support the body in healing from hypo responsiveness adrenal dysregulation. This multivitamin contains Vitamin C, B vitamins, magnesium, and zinc, which are important for regulating the body’s stress response. It also contains Vitamin D.

DFH Complete Multi™ with Copper Dose: Recommendations include taking two capsules of this supplement with lunch and dinner or following your health practitioner's guidance.

Duration: Until Symptoms Subside or Retesting Confirms Labs are Stabilizing

Omega-3 Fatty Acids for Hypo Responsiveness Adrenal Dysregulation

Omega-3 fatty acids are critical for overall health. They reduce inflammation and are shown to regulate the HPA axis, both of which are important factors in hypo responsiveness adrenal dysregulation. Omega-3 fatty acids are also beneficial for autoimmune conditions.

Omega-3 Dose: A typical prescription for Omega-3 fatty acid supplements for reducing inflammation includes 2.5 grams daily

for four months.

L-Glutamine for Hypo Responsiveness Adrenal Dysregulation

L-glutamine is an amino acid necessary for optimal gut health as it provides the fuel source for the cells lining the gut. Factors such as stress can increase inflammation and cause damage to the gut lining, increasing gut permeability (leaky gut), which is associated with autoimmunity and can lead to hypo responsiveness adrenal dysregulation. L-glutamine reduces intestinal permeability and gut inflammation, promoting healing of the gut lining.

L-Glutamine Dose: L-glutamine is commonly prescribed at 5 grams

Duration: 3 times per day, taken on an empty stomach for eight weeks.

Vitamin D for Hypo Responsiveness Adrenal Dysregulation

Vitamin D is vital for optimal health. This micronutrient reduces inflammation, regulates glucose metabolism, and modulates the immune response. Vitamin D deficiency is linked to an increased prevalence of autoimmune conditions. If lab testing reveals a vitamin D deficiency, this nutrient may be included in your supplement regimen.

Vitamin D Dose: A “loading dose” is often required to normalize blood levels of Vitamin D. The typical loading dose is 50,000 IU

Duration: 3 times per week for 1 month or once per week for 2 to 3 months.

*When optimal blood levels of Vitamin D are achieved, a maintenance dose of 800 to 2,000 IU of Vitamin D3 per day is typically needed to maintain these levels.

It’s important to consider all sources of supplemental nutrients. For example, in this protocol, the multivitamin contains 1,000 IU of vitamin D3, and Cortisol Calm includes 400 IU of vitamin D3. So after the loading dose restores optimal blood levels of vitamin D, these supplements may satisfy the daily vitamin D3 requirement, and an additional supplement may not be necessary. It’s essential to monitor blood levels of vitamin D with testing to determine whether these supplements provide a high enough dose to maintain normal blood levels of vitamin D.

When to Retest Labs for Hypo-Responsiveness Adrenal Dysregulation

When retesting labs to monitor the effectiveness of treatment in hypo responsiveness adrenal dysregulation, it is best to retest Vitamin D levels after 3 to 6 months of Vitamin D supplementation. This time frame is also appropriate for retesting adrenal hormones, micronutrients, comprehensive stool analysis, and autoimmune markers. Treatment should be adjusted and individualized based on results.



Hypo-responsiveness adrenal dysregulation is a condition in which the adrenal hormone response to stress is reduced. It often develops slowly over time, and symptoms are general. For this reason, it’s easy for providers to miss this condition or mistake the symptom picture for another health issue. This is why a thorough laboratory workup that includes functional tests is vital for this condition.

Functional lab testing helps determine the underlying root cause of what aspects of your biology aren’t functioning properly and explains why you aren't feeling your best. Your test results help your functional medicine practitioner develop a customized treatment plan supporting your journey to better health and well-being.

A functional medicine protocol for hypo-responsive adrenal dysregulation factors in all elements affecting your health status, such as stress levels, medications, sleep quality, and nutrient levels, and includes lifestyle changes, dietary recommendations, and supplements to support you on your path to wellness.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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