Adrenal Cortical Hypofunction
Addison’s Disease, Adrenal gland dysfunction is typically related to a maladaption to stress, as first reported by Hans Selye in the general adaptation theory (GAS).
The General Adaptation Syndrome (GAS)
In order to develop a general theory for the physiological response of humans and animals to stress, Hans Selye, former director of Experimental Medicine and Surgery at the University of Montreal, performed an integrated analysis of the effects of stress on adrenal gland function. He called his model of stress adaptation the General Adaptation Syndrome or GAS. The GAS was thought by Selye to outline how the organism adapts physiologically to stressors in its attempt to restore homeostasis.
The GAS has proven useful for many years by providing a model of how stress-induced illness arises and by giving clinicians some insight into how to manage stress related conditions in their patients. According to Selye, there are three stages of stress response: alarm phase (acute stress); resistance phase (chronic stress); and exhaustion phase (burnout).
Stress includes not only psychological stress but also any insult to the body that may tax the adrenal gland function, including chronic infections, allergies, exposure to chemical toxins, use of stimulants (such as caffeine and nicotine), poor nutrition, physical trauma, and poor sleep habits, Other contributing factors include exogenous steroid use, chronic hypoglycemia, and pharmaceutical and non-pharmaceutical drug use. For instance, many people develop adrenal exhaustion after a physical trauma, such as a car accident, after an acute exposure to toxins in the workplace, or after an extended course of corticosteroid treatment.
Alarm Phase (Acute Stress)
The alarm phase of the GAS occurs when a stress is first encountered and an alarm is sounded in the body. This alarm, sometimes called the fight or flight response, is associated with an activation of the sympathetic nervous system.
Hormonally, we see an increase in the release of cortisol from the adrenal cortex and epinephrine from the adrenal medulla. This response is a normal defense mechanism that engages when an organism is threatened, and serves a critical function by stimulating the organism to respond to the threat at hand. Once this phase is over, the body goes through a 24 to 48 hour period of recovery, during which one desires primarily to rest.
However, this response can be considered maladaptive when the hormonal release is not appropriate for the situation (e.g., in states of hyper-vigilance, chronic anxiety syndromes, post-traumatic stress disorder). Animal studies of prolonged alarm reactions associate this stage with weight loss, gastric ulcers, and immunosuppression.
Resistance Phase (Chronic Stress)
Due to the challenges of modern life, for many people the perceived stressors are not short term but chronic. In this second phase of the GAS, the organism is still reacting to a perceived stress or stresses, but some of the outwardly observable signs of stress are different. Levels of cortisol and epinephrine are still elevated. This chronic elevation results in weight gain, although the person may appear to have returned to normal functioning. However, immunity and inflammatory responses are still suppressed, and thus there is an increased susceptibility to opportunistic infections, neoplasia, arthritis, allergies, and autoimmune conditions. In addition, chronically elevated adrenal hormone levels may lead to depression, hyperlipidemia, atherosclerosis, hypertension, hyperinsulinemia, insulin resistance, diabetes, osteoporosis, and other degenerative diseases.
Exhaustion Phase (Burnout)
No matter how vital the person, chronic stress can eventually lead to the exhaustion phase, characterized by a deficient production of glucocorticoids and an episodic increase in epinephrine. This phase is associated with deficient glucocorticoid and mineralocorticoid production, sometimes combined with episodic pulses of excess epinephrine. This is commonly known as adrenal exhaustion.
Adrenal exhaustion is associated with decreased resistance to stress, premature aging, and, if left uncorrected, even death. Conditions that are common in people in this phase of the GAS include allergies, chronic fatigue syndrome, fibromyalgia, hypoglycemia, multiple chemical sensitivities, irritable bowel syndrome, hypotension, insomnia, hypothyroid, lack of motivation,
Addison’s disease is a failure of the adrenal cortex. It affects approximately four people in 100,000 and occurs in all age groups and among both sexes equally. Addison’s disease can be triggered by acute external stressors, such as infection, trauma, toxic chemical exposure, corticosteroid withdrawal, or extreme psychological stress.3 It is considered to be autoimmune in nature, and can affect other glands, including the thyroid and pituitary.
Symptoms
Symptoms include hyperpigmentation (mouth, areolae, perineum), weight loss, asthenia, depression, and postural hypotension causing vertigo. Extreme adrenal crisis can lead to vascular collapse with hypotension and azotemia.
Tests
Conventional tests to detect Addison’s include serum cortisol, 24-hour free cortisol, and the ACTH stimulation test. Standard electrolytes may be imbalanced with an elevation of serum potassium and depression of serum sodium.
Adrenal Insufficiency Syndrome
Adrenal insufficiency is common in Western culture due to the high amount of psychological stress, environmental toxins, and poor nutrition, all of which deplete adrenal reserves. Other lifestyle factors in adrenal insufficiency development include inadequate amount of sleep, eating infrequently, and lack of exercise. Adrenal insufficiency can be thought of as an acute or chronic impairment of adrenal function, as opposed to the failure of the gland, as seen in Addison’s disease. Therefore, it may be more difficult to diagnose adrenal insufficiency than Addison’s disease. Symptoms are an important consideration, as first identified by Dr John Tintera in 1956.
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Symptoms and Signs of Adrenal Insufficiency
Symptom Percentage of Patients
Excessive Fatigue 94%
Nervousness/Irritability 86%
PMS 85%
Salt Craving 84%
Depression 79%
Sweet Craving 75%
Allergies 73%
Headache 68%
Alcohol Intolerance 66%
Weakness 65%
Neck/Shoulder Pain 65%
Confusion 61%
Poor Memory 59%
Palpitations 57%
Poor Digestion 51%
Backache 48%
Lightheadedness 47%
Constipation or diarrhea 45%
Fainting 42%
Insomnia 40%
Dermatitis 39%
Signs
Postural Hypotension 93%
Dry Skin 91%
Scanty Perspiration 91%
Low basal body temp 85%
Sparse body hair 83%
Underweight 78%
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Tests
Lab testing may be helpful to diagnose adrenal insufficiency.
Salivary Cortisol: Salivary cortisol is likely the best single test, as saliva hormones indicate the amount of hormone inside cells and the testing is simple, non-invasive and easy to do. The best way to use saliva testing is to measure cortisol levels at least 4 times per day (waking, noon, afternoon, evening), which increases the chances of detecting a failure of adrenal reserve. Testing at various times in the day can also be correlated with perceived energy levels throughout the circadian rhythm cycle. DHEA-S and testosterone levels can also be measured with saliva testing, and if low are also considered to be indicators of adrenal exhaustion, whereas high levels may indicate adrenal resistance phase.
Urinary Cortisol: A 24-hour urinary cortisol test can be used to monitor the output and metabolism of the corticosteroids, aldosterone, and the sex hormones. Hypoadrenia is suspected for those in the bottom one-third of the “normal” range. Because the urine is collected in one container, this test gives a 24-hour average, and therefore the highs and lows may cancel each other out in many patients. However, if metabolites of these hormones are included, ratios of these hormones to their metabolites can give a fairly accurate picture of an individual’s adrenal hormone metabolism.
This is especially useful for diagnosing syndromes, such as Apparent Mineralocorticoid Excess (AME), in which cortisol is not metabolized effectively to cortisone (typically due to an altered expression of 11-b-hydroxy steroid dehydrogenase), leading to hypertension.
Urine 24- hour cortisol measurements can also be useful when performing an ACTH challenge test. In the challenge test adrenal reserve can be functionally measured by comparing 24-hour urinary cortisol before and after stimulation of the adrenal cortex with ACTH.5
Blood Tests: Blood tests can also be used to measure circulating hormone levels related to adrenal function. However, because of a wide variation in what is considered to be normal levels, many symptomatic patients may not show irregularities, since in most cases of adrenal fatigue, the cause is a functional lack of adrenal reserve, as opposed to outright Addison’s disease.
Nevertheless, on routine blood screening we may see the following in adrenal insufficiency:
- Serum Na low normal
- Serum K high normal
- BUN high normal or elevated
- Eosinophils high
- Cortisol low/normal
