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Adrenal Fatigue and Its Progression


Many diseases progress through different stages normally as the body is unable to compensate for these changes.

Adrenal Fatigue Stage I is the Alarm Reaction. It is the flight or fight response. In this stage, the body is alarmed by stressors and mounts an aggressive anti stress response to reduce stress levels. Some doctors call this the early fatigue stage. Typically though, there is an increased ACTH from the pituitary gland that stimulates the adrenal glands into full gear to mount a retaliation response. The adrenal medulla is stimulated to secrete more epinephrin and the total cortisol output from the adrenal cortex is increased from the excitatory stimulus. There is a corresponding reduction in DHEA production. During this period, the body needs cortisol to overcome stress and production of cortisol is therefore increased.  After sometime, the adrenals will experience difficulties in meeting the body's ever increasing demand for cortisol.

Stage II is considered to be a resistance response phase.  It is due to prolonged periods of stress and the stress response.  With chronic or severe stress, the adrenals eventually are unable to keep up with the body's demand for cortisol.  As such, the cortisol output will start to decline from a high back to a normal level while the ACTH remains high, and with protracted ACTH and adrenal fatigue, less cortisol is produced due to the adrenal becoming exhausted.  While the morning, noon, or afternoon cortisol levels are often low, the nighttime cortisol level is usually normal.  A phenomenon called pregnenolone steal sets in.  Cortisol production becomes the predominant pathway of hormone production as the body favors the production of the cortisol hormone.  The other hormones such as pregnenolone, DHEA, testosterone, and estrogen are less favored and their production will decline.  As a result, total pregnenolone output is reduced but total cortisol output continues to be maintained at a normal level.  Careful analysis of the daily diurnal cycle of cortisol shows a dysfunctional pattern of abnormally low cortisol in the morning.  This is the time when cortisol is needed most.  Nighttime cortisol is usually still normal.

Stage III Exhaustion Phase.  Despite rising ACTH, the adrenals are no longer able to keep up with the increased demand for cortisol production.  This may happen over a few years.  Total cortisol output is therefore reduced and DHEA falls far below average.  The nighttime cortisol level is usually reduced as the hypothalamic pituitary-adrenal axis crashes and the body is unable to maintain homeostasis.  Severe sex hormonal imbalances in estrogen, progesterone, and the androgens are common and a precursor to adrenal failure.

Stage IV Adrenal Failure.  Eventually, the adrenals are totally exhausted.  Patients at this stage have high chance of cardiovascular collapse and death.