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OAT Axis Imbalance
By: Michael Lam, MD, MPH

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Adrenal Fatigue

The adrenal glands are the main stress control system of the body. Adrenal Fatigue is a decrease in the adrenal glands' ability to carry out this normal function. It is commonly caused by chronic stress from any source (including emotional, physical, mental, or environmental) that exceeds the body's capacity to adjust appropriately to the demands placed on it. Adrenal Fatigue has a broad spectrum of non-specific yet often debilitating symptoms. The onset of this disease is often slow and insidious.

Stressors that can lead to Adrenal Fatigue include anger, chronic illness, depression, surgery, high sugar intake, over exercise, sleep deprivation, just to mention a few. One of the most commonly overlooked causes of Adrenal Fatigue is chronic or severe infection. Such infection can occur sub-clinically with no obvious signs at all. Parasitic and bacterial infections including Giardia and H. pylori are often the main culprits. Not to be missed is a tooth that has had root canal work done but still contains germs that secrete toxins chronically.

Signs and symptoms of Adrenal Fatigue include tendency to gain weight, especially around the waist, and inability to lose it; high frequency of the flu and other respiratory diseases where symptoms tend to last longer than usual; a tendency to tremble when under pressure; reduced sex drive; lightheadedness when rising from a supine position; brain fog; lack of energy in the afternoon; reliance on coffee to get the day started; craving for salty and fatty food; chronic pain of unknown origin; and feeling better during a vacation. None of the signs or symptoms by themselves can definitively diagnose Adrenal Fatigue. When taken as a group, these signs and symptoms do form a specific Adrenal Fatigue syndrome or picture that of a person under stress.

Adrenal Fatigue Progression:

Stage 1: Alarm Reaction (Flight or Fight Response). At this stage, the body is alarmed by the stressors and mounts an aggressive anti-stress response to reduce stress levels. There are generally no outward symptoms of decompensation, as the anti-stress response mediated by an increased cortisol output from the adrenals is well within the body's output capacity. The person conducts a normal life but does notice that coffee helps to get the day going, even though an ever increasing amount may be needed.

Stage 2: Resistance Response. With chronic or severe stress, the adrenals eventually are unable to keep up with the body's demand for cortisol. Normal daily functions can be carried out, but the sense of fatigue is pronounced at the end of each day as the body needs more rest than usual to recover. Despite a full night's rest, the body does not feel refreshed in the morning. Anxiety starts to set in, and the person becomes easily irritable. Insomnia becomes more common, as it takes longer to fall asleep. There is also frequent awakening as well. Infections can become more recurrent. PMS and menstrual irregularities surface, and symptoms suggestive of hypothyroidism (such as sensations of feeling cold and a sluggish metabolism) become prevalent.

Stage 3: Exhaustion. As adrenal function weakens further, the body's need for adrenal hormones remains unabated if stress is not reduced. The adrenals are having tremendous difficulty and may no longer be able to keep up with the ever increasing demand for cortisol production. Cortisol output may plateau and start to decline. This progression usually happens gradually over a long period of time, perhaps years.

Because the variety of symptoms presented at this stage can be convoluted and overwhelming, it is helpful, from a clinical recognition perspective only, to further delineate this stage into four broad overlapping phases. The boundaries of each phase are decidedly indistinct. They do not represent an absolute sequential gradation process and should not be viewed as such. Most if not all suffering from adrenal exhaustion usually present signs and symptoms in various degrees of each phase concurrently. That is the norm. The more advanced the exhaustion, however, the more late phase manifestation is presented.

  • Phase A - Chronic Single System Dysfunction. In this phase, mild symptoms characteristic of first and second stage Adrenal Fatigue continue to worsen and become persistent or chronic. The slightly elevated blood pressure now becomes low throughout the day, mild musculoskeletal pain turns into chronic fibromyalgia around the clock, frequent recurrent infections are the norm as compared to intermittent infections, occasional mental feeling of "blues" become mild depression, sleep pattern becomes more disrupted as insomnia becomes chronic, fatigue that usually occur during the end of occasional stressful days become an everyday event, just to mention a few of the symptoms. There is moderate reduction in carrying out normal daily activities. Not all organs are dysfunctional to the same degree and at the same time. The organ system that is constitutionally weakest is the first one to decompensate, while other organ systems appear to be intact. For example, one may have severe insomnia, but otherwise doing alright, relatively speaking. Sufferers continue to be active physically in self-guided programs or under the care of health professionals. Numerous doctors are normally consulted by this stage; nevertheless, the condition does not usually get better over time, but in fact gets worse.

  • Phase B - Multiple Endocrine Axis Dysfunction. The endocrine system in our body is linked hormonally in a series of axis for optimal function. The Ovarian-Adrenal-Thyroid (OAT) axis in women and Adrenal-Thyroid (AT) axis in men are particularly important. When these axes become imbalanced, the adverse feedback loop creates a vicious cycle of cascading decompensations, involving multiple organ systems at the same time. Typical presentations in females involve symptoms of under-active thyroid, imbalanced ovarian hormones and low adrenal function. Ovarian-adrenal-thyroid axis imbalance and ovarian-thyroid axis imbalance are two examples where key axes are involved in females. In males, the adrenal-thyroid axis may be compromised.

    The sufferer's physical and emotional state continues to deteriorate and they enter into a state of confusion. They are unable to logically dissect the myriad of systematic manifestations of multiple hormonal axis imbalances. Almost all conventional and many naturally oriented physicians alike are at a lost in understanding this phase of the condition. Patients are often abandoned to self-navigate through these turbulent waters. Not knowing what to do and who to turn to, sufferers continue to self-navigate, often using inappropriate nutrients that are not conducive to healing and subjecting the body to continued trial and error. This often worsens the condition over time.

  • Phase C - Disequilibrium State. As the body continues its downward path of impaired functions, it gathers steam. Gradually, the body becomes severely compromised in trying to maintain the fine controls of homeostasis. Normal equilibrium is therefore lost. The body will try its hardest to maintain equilibrium through activation of various compensatory responses within the autonomous nervous system but its crude response and damaged receptor sites along with impaired metabolic and detoxification pathways give rise to paradoxical and exaggerated responses. The body's internal thermostat is "broken". Common symptoms include heart palpitation, dizziness, orthostatic hypotension, anxiety, adrenaline rush, temperature intolerance and strong heart beat.

    These crude and exaggerated responses will further undermine the existing weak adrenal function. Clinical manifestation of this include swings in blood sugar level, fragile blood pressure state, reactive hyper-adrenergic responses including heart palpitations, night sweats, and a state of hyper-anxiety followed by depression. Sufferers are usually frustrated and feel abandoned by their physicians. The body is literally "falling apart" internally. Sufferers at this stage are often incapacitated and frequently called the "living dead". It is imperative that healthcare at this point be totally put under a qualified specialist physician as this level of dysfunction is well beyond the expertise of even the most astute of naturally oriented health care providers.

  • Phase D - Near Failure. All hormones in the body are interrelated to one another in some form. Many important hormones are dependent on other hormones to work. For example, estrogen is needed for progesterone to work. As the cortisol hormone falls below the minimum required for normal daily function and output fails, the body may down-regulate the amount needed in order to preserve what is on hand for only the most essential of bodily functions. This down-regulation further reduces cortisol output, exaggerating a downward vicious cascade cycle. Paradoxical reactions become extreme as the body becomes unable to tolerate any form of nutritional support and in fact gets worse due to a wide variety of reasons amidst a state of low-clearance of toxic metabolites, which accumulate internally.

As this happens to one organ system, the rest of the body also down-regulates and reacts unfavorably. Digestion slows to conserve energy, clearance of metabolites slows to conserve energy, and basal metabolic rate drops to conserve energy. Weight loss is extremely difficult. At this phase, the adrenals have lost most of their ability to serve as the body's stress control center. It becomes hypersensitive and reacts negatively to any attempts to jump start it for reasons not well understood. The adrenals continue to exhibit frequent crashes through physiological mechanisms that defy conventional scientific logic. Current concepts point to the likelihood of pump failure, low-clearance state, positive feedback loops, receptor site dysfunction, and electron driven retoxifications as possible etiology for the wide variety of extreme paradoxical reactions commonly seen in this phase. Basic nutrients critical to proper adrenal function, such as Vitamin C, become severely depleted. Administration of Vitamin C, cortisol, DHEA, and pregnenolone, all of which are normally required and welcomed by the adrenals, cease to bring about any improvement in symptoms but may instead become ineffective and possibly toxic. The more the adrenals are exhausted, the less the adrenals can tolerate medication or nutrients, even in small doses. Nothing appears to work in this phase. Any attempted administration of nutrients by mouth or by intravenous injection in fact may make the condition worse. The brutal downward decompensatory cycle is well entrenched. Sufferers become desperate and try to overcome their physical and mental exhaustion on their own to no avail. Depression sets in and suicidal tendencies surface.

This is not a state to be in for self-navigating. Expert professional guidance is absolutely needed. Unfortunately, qualified physicians in this area are extremely rare.

Stage 4: Failure. Eventually, the adrenals are totally exhausted. Patients at this stage have a high chance of cardiovascular collapse and death. When Adrenal Fatigue has advanced to this stage, the line between it and Addison's disease, also called adrenal insufficiency, can get blurry. Symptoms at this stage include sudden penetrating pain in the lower back, abdomen or legs, severe vomiting and diarrhea, dehydration, low blood pressure and loss of consciousness. Addisonian crisis is rare, as in most cases; the symptoms are severe enough that patients are quick to seek medical treatment before a crisis occurs. However, in about 25 percent of patients, the symptoms first appear during an Addisonian crisis. Left untreated, an Addisonian crisis can be fatal. While the etiology of the conditions may be different, the ultimate clinical presentations can be quite similar in both Addisonian crisis and Stage 4 Adrenal Fatigue as they represent a continuum of decompensation in adrenal functions.

As the body progresses through to the more advanced stages of Adrenal Fatigue, the overall array of symptoms generally become more pronounced and convoluted. Fatigue can become unbearable as the body's ability to deal with normal stresses of life weakens with each stage. In severe cases of Adrenal Fatigue, the body can often exhibit multiple unusual and paradoxical reactions that one does not normally expect. This is especially prevalent in Stage 3. This is reflective of deepening adrenal exhaustion, with disequilibrium, loss of homeostasis, multiple endocrine axis imbalance, pump failure, receptor site sensitivity or retoxification reaction of the body. Symptoms can include:

  • A sense of fatigue or malaise instead of a sense of calm when taking steroids.
  • A sudden onset of anxiety attacks and impending doom at rest.
  • Sudden onset of heart palpitations despite normal cardiac function.
  • Sudden onset of fluctuating blood pressure.
  • Being constipated instead of having loose bowel when taking high doses of Vitamin C or magnesium.
  • A sense of getting wired up and feeling anxious after taking Vitamin C, adrenal glandulars or herbs.
  • Feeling more toxic instead of feeling better when going through a detoxification program like juice fasting.
  • Feeling a sense of well-being after taking selected nutrients, only to be followed by a "crash".

Although sub-clinical adrenal dysfunction and its various stages were recognized as distinct clinical syndromes since the turn of the 20th-century, most conventional physicians are unfamiliar with this condition because it is difficult to diagnose correctly by traditional blood tests. Adrenal hormones may be low in the case of Adrenal Fatigue, but are still within the "normal" range and not low enough to warrant the diagnosis of Addison's disease by regular blood tests. Conventional physicians are not taught the significance of sub-clinical Adrenal Fatigue. They are misguided by the results of blood tests, which unfortunately, are not sensitive enough to detect sub-clinical Adrenal Fatigue. As a result, patients tested for adrenal functions are told they are "normal" but in reality, their adrenal glands are performing sub-optimally, with clear signs and symptoms coming from the body that are crying out for help and attention.

Adrenals and OAT Axis Imbalance

The adrenal glands are usually the first in the order of endocrine functions to breakdown when stress has overwhelmed the body's normal compensatory response. Unfortunately, this is seldom recognized as a pathological state. Acceptable social compensatory actions such as coffee intake often mask the underlying problem as the adrenals are put in over-drive to cover up the early signs and symptoms of Adrenal Fatigue. The next endocrine gland to be affected is the insulin-producing portion of the pancreas. The body's blood sugar becomes imbalanced and this dysfunction is temporarily fixed by the intake of soda drinks, energy potions and donuts. After the pancreas comes the thyroid. Sluggishness, feeling cold and weight gain are the predominant symptoms that bring patients to their physicians, usually for the first time. This is often when hypothyroidism is first diagnosed. Thyroid replacement medication is routinely prescribed. However, over 70 percent of those patients taking thyroid medications still are symptomatic over time. Along with hypothyroid are symptoms of estrogen dominance, a state reflective of ovarian system dysfunction. Presenting symptoms include PMS, endometriosis, lumpy breasts, and irregular menstrual cycle. Hormone replacement medication may work short term, but unless the adrenals are first attended to, the patient's response is often blunted and ultimately fails. Finally, the parathyroid glands, the pineal gland, the autonomic nervous system, and the hypothalamus become affected. By this time, the OAT axis is severely imbalanced.

Adrenal Fatigue is often the last to be detected and only considered seriously, when the patient is already severely decompensated, with concurrent severe ovarian and thyroid involvement. Even when detected, there is inadequate attention paid to the frequent concurrent ovarian and thyroid imbalance in what is now a full-blown state of Ovarian-Adrenal-Thyroid (OAT) axis imbalance.

The key to this imbalance lies in the adrenal glands, for it is there that cortisol is modulated. In Adrenal Fatigue, internal cortisol imbalance often creates a condition of multiple organ resistance, including the thyroid and ovaries. Adrenal Fatigue is an important common and often overlooked cause of secondary clinical or sub-clinical hypothyroidism. Classically, the patient presents himself to the doctor's office complaining of fatigue, dry skin, weight gain, low body temperature, and insomnia. Thyroid laboratory test results show either normal or high TSH, normal or low T3 and free T3, normal or low T4 and free T4. The patient is normally prescribed a variety of thyroid replacement medications. Temporary improvement may be experienced by the patient but the improvement ultimately fails as recovery response is blunted and the symptoms continue to persist. Excessive thyroid medicine may be prescribed to normalize what may appear to be sub-optimal blood levels. The body is put on overdrive as the basal metabolic rate is raised. This can unmask pre-existing adrenal weakness; exacerbate existing Adrenal Fatigue and trigger adrenal exhaustion and adrenal crisis. Anti-depressants are often prescribed as a solution to control symptoms as the physicians run out of options to help the sufferer. This seldom works but will instead often make the OAT imbalance worse off.

It is important to recognize that optimum adrenal function plays a key role in this imbalance. When the adrenals are weak, cortisol induced, organ resistance applies to nearly all other hormone regulated organs including the ovaries, the thyroid, and the pancreas. Few hormones are allowed to work at their optimal levels in the presence of Adrenal Fatigue. A multitude of hormones including insulin, progesterone, estrogen and testosterone become affected. The normal negative feedback loop can be blunted and binding carrier hormones in the blood can be disrupted. The ability of each hormone to regulate and fine-tune its target organ to achieve homeostasis is therefore often compromised. Blood pressure can become erratic, blood sugar levels may experience wide swings, bipolar and anxiety states come at will, reactive adrenaline rush becomes uncontrollable, brain fog becomes prevalent, metabolic function slows down and menstrual flow becomes irregular.

Due to their lack of clinical training on Adrenal Fatigue, clinicians often find themselves treating symptoms of weak thyroid and ovarian systems while ignoring adrenal dysfunction. Let us take a look at how this can lead to devastating effect. In early stages of Adrenal Fatigue, cortisol output is high as the body attempts to neutralize stress by producing more of it. However, when too much cortisol is produced, it will have multiple undesirable effects. For example, cortisol blocks the progesterone receptors, making them less responsive to progesterone. Progesterone normally produced by the adrenals comes to a halt in favor of cortisol production.

Insufficient progesterone production leads to an imbalance between estrogen and progesterone. With reduced progesterone to offset estrogen, the body may experience estrogen dominance. It is no coincidence that we see a proliferation of conditions associated with excessive estrogen such as PMS, fibroids, and pre-menopausal syndrome when women reach their mid thirties and early forties.

Many chronically ill patients have both low adrenal and thyroid functions. In such cases, it is important to begin the recovery process by supporting the adrenal glands before raising the thyroid hormone. Otherwise, increased circulation of the thyroid hormone may further strain the already weak adrenal glands, leading to adrenal crashes and further decompensation. Recovery plans focusing on single organ dysfunction without considering the axis imbalance often fail and may in fact make the condition worse off.

Attempts to rebalance ovarian and thyroid hormones without careful attention to adrenal hormones often fail. Conversely, an approach focusing on adrenals first often leads to spectacular results as the ovarian hormones and the thyroid hormones will often rebalance themselves as the adrenal glands recover.


The thyroid gland acts like the body's barometer. Its main function is to help cells convert oxygen and calories into energy. It regulates heart rate, blood pressure, body temperature, metabolism, and growth.

More than 10 million Americans have been diagnosed with thyroid disease and another 13 million people are estimated to have undiagnosed thyroid problems. About 10 percent of the adult population is afflicted with this frequently overlooked disease of epidemic proportion. A dysfunctional thyroid can affect almost every aspect of health. It is one of the most under-diagnosed hormonal imbalances of aging, together with estrogen dominance, and Adrenal Fatigue. It is estimated by age 50, one out of every twelve women will have some degree of hypothyroidism. By age 60, it is one out of six. In fact, among the elderly, hypothyroidism is sometimes misdiagnosed as dementia.

The thyroid gland, under TSH signal, secretes two essential thyroid hormones: triiodothyronine (T3) and thyroxine (T4), which is responsible for regulating cell metabolism in every cell in your body. A healthy person secretes all of the circulating T4 (about 90 to 100 mcg daily) and about 20 percent of the circulating T3. The T4 made by the thyroid gland circulates throughout the body and is converted into approximately equal amounts of T3 and reverse T3 ( rT3). Most of the biological activity of thyroid hormones is due to T3. It has a higher affinity for thyroid receptors and is approximately four times more potent than T4. rT3 acts as a braking system to T3. Not only is it inactive (having only 1 percent of T3 activity), it binds to T3 receptors and block the action of T3. T4 should therefore be considered a pro-hormone and precursor to T3 and rT3. Normal physiological production ratio of T4 to T3 is 3.3:1. A properly functioning thyroid gland requires a perfect balance of T4, T3, and rT3. The T3/rT3 ratio is therefore one of the most useful markers for true tissue hypothyroidism and a crucial marker of diminished cellular function.

There are a variety of factors that can contribute to the development of thyroid problems: such as exposure to external radiation, over-consumption of soy products, taking drugs such as lithium that have anti-thyroid effects, over-consumption of uncooked "goitrogenic" foods, such as broccoli, turnips, radish, cauliflower and brussels sprouts, adrenal insufficiency or fatigue (commonly caused by chronic stress), mercury intoxication (amalgams are 50 percent mercury), auto-immune diseases and infection.

As one of the master regulators of body metabolism, symptoms of low thyroid function generate a global response. Symptoms include:

  • Fatigue and low energy, with need for daytime naps due to defect at cellular energy conversion and difficulty in converting from T4 to T3.

  • Skin that becomes dry, scaly, rough, and cold due to increase demand on metabolism ( e.g. cold weather) with little thyroid reserve.

  • Excessive unexplained hair loss due to slowing down of cell turnover and tissue/hair production.

  • Sensitivity to cold in a room when others are warm due to sluggish conversion of nutrients and oxygen to heat.

  • Brain fog, depression due to inadequate levels of thyroid in brain.

  • Constipation that is resistant to magnesium supplementation.

  • Unexplained weight gain due to reduced metabolism that enlarges fat cells which sequester T4, causing depletion and further sluggishness.

  • High cholesterol resistant to cholesterol lowering drugs.

  • Low libido, PMS, miscarriage, and infertility due to disruption of testosterone, estrogen, and progesterone.

  • Abdominal cramping and IBS due to reduced muscular activity of bowl wall due to thyroid depletion.

Hypothyroidism can be primary or secondary. Primary hypothyroidism can easily be cured with administration of thyroid replacement therapy. If hypothyroid symptoms such as low body temperature, fatigue, dry skin and weight gain persist despite thyroid replacement therapy regardless of laboratory values, one must look elsewhere for the cause of low thyroid function.

Secondary hypothyroidism is low thyroid function caused by malfunction of another organ system. One of the most frequently overlooked causes is Adrenal Fatigue. Adrenal Fatigue is perhaps the most common cause of secondary low thyroid function, both clinically and sub-clinically. Low adrenal function often leads to low thyroid function, classically evidenced by high thyroid binding globulin (TBG), low free T4, low free T3, high TSH, and low body temperature. Few physicians are trained to detect this connection. Fortunately, secondary hypothyroidism can be reversed when the underlying root problem (such as Adrenal Fatigue) is resolved.

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