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Adrenal Disease
Updated: 5/24/2004
The adrenals are two crescent-shaped glands that sit on top of each kidney. The adrenal glands secrete hormones directly into the bloodstream. They are divided anatomically and functionally into two main parts: the medulla (middle) and the cortex (rind) (Clayman 1989). Additionally, each division of an adrenal gland consists of internal layers that produce different hormones.
The inner part, or adrenal medulla, manufactures epinephrine and norepinephrine, also known as commonly known as adrenaline and noradrenaline. These hormones are the "fight or flight" hormones that are released in potentially life-or-death situations. Their release increases one's heart rate , and blood pressure , and diverts more blood to the brain, heart, and skeletal muscles. This is important when discussing stress.
The adrenal cortex surrounds the adrenal medulla and responds to a different type of stress. This is where the steroid hormones are made. These include cortisone, hydrocortisone, testosterone, estrogen, 17-hydroxy-ketosteroids, DHEA, pregnenolone, aldosterone, androstenedione, progesterone, and some other intermediate hormones. Many of these hormones are also made elsewhere in the body, but aldosterone, cortisone, and hydrocortisone are made only in the adrenal glands.
The hormone aldosterone, together with the kidneys, regulates the balance of sodium and potassium in the body. This regulation is critical to many areas o f physiological function, including the ability to react to stress, maintain fluid balance, and regulate blood pressure.
Two disorders often associated with impaired function of the adrenal glands are Addison's disease and Cushing's syndrome.
Addison's Disease: Adrenal Insufficiency
Addison's disease is a profound chronic adrenal failure caused by damage or disease of the adrenal gland, resulting in a deficiency of cortisol. This disease is sometimes called chronic adrenal insufficiency or hypocortisolism. The most important job of cortisol is to help the body respond to stress. Among its other vital tasks, cortisol is partly responsible for:
- Maintaining blood pressure and cardiovascular function
- Balancing the effects of insulin in breaking down sugar for energy
- Slowing the immune system's inflammatory response
- Regulating the metabolism of proteins, carbohydrates, and fats
Addison's disease is characterized by muscle weakness, reduced blood sugar, nausea, loss of appetite, weight loss, and low blood pressure, which can impact the act of standing, causing dizziness or fainting. Skin changes also are common in Addison's disease, with areas of hyperpigmentation or dark tanning that are mostly visible on scars, skin folds, toes, lips, mucous membranes, and pressure points, such as the elbows, knees, and knuckles.
Cushing's Syndrome: Overproduction of Cortisol
The overproduction of cortisol by the adrenal glands leads to Cushing's syndrome (Clayman 1989). Cushing's syndrome also results when glucocorticoid drug hormones (such as hydrocortisone, prednisone, methylprednisolone, or dexamethasone) are taken in excess for a prolonged period of time. These steroid hormones are often used to treat inflammatory-related illnesses such as asthma, rheumatoid arthritis, systemic lupus erythematosus, and some allergies.
The overproduction of cortisol in the adrenal glands can happen in two ways. A pituitary tumor could be producing too much ACTH (adrenocorticotropic hormone, produced by the pituitary gland), stimulating the adrenals to grow and to produce too much cortisol, or a benign or malignant tumor outside the pituitary such as in the lung, thymus gland, pancreas, or other organs can produce too much ACTH. The pituitary form is classically called Cushing's disease.
Cushing's syndrome is characterized by central obesity; sparing of the arms and legs (thin extremities); a round, reddish moon face; buffalo hump; and a protuberant abdomen. Many people with Cushing's syndrome experience severe fatigue, weak muscles, ulcers, thin skin, high blood pressure, and high blood sugar. Irritability, anxiety, and depression are also very common. Women with Cushing's syndrome will usually have excess hair growth (hirsu i tism) on their face, necks, chests, abdomens, and thighs. Their menstrual periods may become irregular or stop. Men may have decreased fertility and desire for sex.
Adrenal Fatigue
Constant stress and poor nutrition can weaken the adrenal glands. When stress continues over prolonged periods of time, the adrenal glands can deplete the body's hormonal and energy reserves, and the glands may either shrink in size or hypertrophy (enlarge). The overproduction of adrenal hormones caused by prolonged stress can weaken the immune system and inhibit the production of white blood cells that protect the body against foreign invaders (in particular lymphocytes and lymph node function). Adrenal dysfunction can disrupt the body's blood sugar metabolism, causing weakness, fatigue, and a feeling of being run down. It can also interfere with normal sleep rhythms and produce a wakeful, unrelaxing sleep state, making a person feel worn out even after a full night's sleep.
If a person succumbs easily to allergies and infections, feels constantly drained and exhausted, and experiences low blood sugar and blood pressure, the culprit may be weak adrenals. Adrenal insufficiency is sometimes linked to chronic fatigue. In some fatigued patients, thyroid problems may overlap adrenal problems. In these cases, the status of the adrenal glands and the thyroid gland must be assessed. The appropriate treatment should be undertaken only after this determination is made. If adrenal fatigue is suspected, the patient should be evaluated by a physician with experience in recognizing and treating adrenal fatigue and issues of the relative Addisonian state. It is very important to make sure that full-blown Addison's disease is not the problem, since it must be treated vigorously (Ehlert et al. 2001; Tsigos et al. 2002). In most communities, a qualified internist or internal medicine subspecialist will begin the investigation.
Diagnosis
If disturbed adrenal function is suspected, the levels of hormones such as hydrocortisone, aldosterone, epinephrine, and ACTH may be measured in blood, plasma, and urine. There are also tests (by injection) to measure the effects of substances that normally modify the production of a specific hormone. One test is called the ACTH challenge test. When ACTH is injected, there should be an increase in adrenal hormone output. If this does not happen, adrenal fatigue is probable. These tests are also helpful in localizing the underlying cause of a particular disorder (e.g., to distinguish between Cushing's syndrome caused by an adrenal tumor from that caused by pituitary disease). Conversely, a very high potency corticosteroid (dexamethasone) can be used to assess the suppressability of cortisone production in Cushing's syndrome.
If disease of the adrenal glands is suspected, imaging studies (abdominal x-ray, MRI, CT scan, arteriography, radionuclide scanning, and IV scanning of the position of kidneys using an IV dye) may show the presence of adrenal calcification, a tumor, atrophy, or the overgrowth of a gland.
Factors that May be Overlooked in Diagnosis
Cortisone is produced mainly in a reversible reaction from cortisol; it is also secreted in small amounts from the adrenal cortex. The term hydrocortisone refers to both naturally produced cortisone and the pharmaceutical preparation used to treat various inflammatory disorders. Naturally produced hydrocortisone is a glucocorticoid, meaning that it helps to regulate normal blood glucose concentration by converting amino acids and fatty acids to glucose, when needed, in a process called gluconeogenesis.
Synthetic hydrocortisone drugs (corticosteroids) became available in the late 1940s and were heralded as a miraculous treatment for rheumatoid arthritis due to their suppression of the immune system. However, it did not take long to learn that there was a serious price to pay for chronic corticosteroid use. People taking synthetic hydrocortisone developed many symptoms and physical abnormalities such as the symptoms of Cushing's syndrome, resulting from the body's overexposure to corticosteroids.
As a result of these adverse reactions, an often irrational approach developed in the medical community to the question of relative adrenal function. A person who has total failure of the adrenal glands is said to have Addison's disease even though low steroid levels can also be caused by failure of the hypothalamus , thalamus, and pituitary areas of the brain. In this case, the adrenal glands still function. In the case of Cushing's syndrome, the disease may manifest due to physical abnormality or as the result of corticosteroid use.
When a physician evaluates a patient relying solely upon laboratory data, the patient is considered either normal or having Addison's disease or Cushing's syndrome. There may be no analysis of other contributing factors. This protocol is directed only at the function of the adrenal glands. However, just as in thyroid dysfunction (see the Thyroid Deficiency protocol), normal laboratory tests do not exclude what some physicians refer to as adrenal fatigue (or relative Cushing's or Addisonian states).
The association of impaired immune function and the administration of synthetic corticosteroids ha ve s blurred an important fact. Decreased levels of corticosteroids also impair immune function. What further complicates the matter is the fact that it is now thought that the continual overproduction of cortisol, not in the range that would produce Cushing's syndrome, contributes to immune suppression, atherosclerosis, brain cell injury, and accelerated aging.
Drug Treatments
Addison's Disease
Adrenal Cortical Extract
A few physicians recommend adrenal cortical extract (ACE), which contains all the corticosteroids in the proper proportions. ACE used to be widely available in this country, but at the present time it is not. Complementary physicians may have had experience with it. At times of increased stress, the addition of adrenal glandulars may be advisable but must be monitored carefully. Long-term use is not recommended and is likely hazardous. (The FDA removed all products containing adrenal cortex from market in 1997 due to concerns regarding contamination.)
Hydrocortisone
Cortisol is usually replaced orally with hydrocortisone tablets. The doses of this medication are adjusted to meet the needs of individual patients. During a critical stage, when blood pressure and blood sugar are dangerously low and potassium levels are high, therapy can involve the injection of hydrocortisone, saline, and dextrose.
Cushing's Syndrome
Treatment of Cushing's syndrome will depend upon the cause of the disorder. If the disorder is caused by long-term corticosteroid use, the drug must be slowly decreased and the patient weaned under medical supervision. If it is caused by a pituitary or adrenal tumor, surgery is necessary to remove it. In Cushing's syndrome caused by an ectopic ACTH-secreting tumor, the tumor is resected. For a year after cessation of high-dose corticosteroid therapy, even minor illnesses can cause a full-blown Addisonian collapse. If the tumor is malignant and has metastasized and resection is not possible, treatment may include a combination of chemotherapy, immunotherapy, and radiation therapy.
Drugs such as ketoconazole, aminoglutethimide, or metyrapone may also be given to suppress cortisol metabolism and secretion. The European drug KH3 (the active ingredient is procaine), which can block some of the cell-damaging effects of cortisol and help protect against cortisol toxicity, is beneficial for Cushing's disease. KH3 has been also known for its beneficial effects in aging and depressed people (Cohen et al. 1974; Hall et al. 1983). A suggestion would be to take 1-2 KH3 capsules in the morning on an empty stomach and 1-2 KH3 capsules in mid-afternoon, also on an empty stomach. |