About the Adrenal Glands
The adrenal glands are two small structures that sit on top of the kidneys, deep in the back, behind the abdominal cavity and well beneath the back muscles. Although they are small, usually weighing each about a tenth of an ounce, they are powerful factories that produce many hormones that are critically important to your overall health and well-being.
The adrenal glands are divided into an outside layer called the cortex and an inner layer called the medulla. Cells in the adrenal cortex make steroid hormones derived from cholesterol, including glucocorticoids (cortisol), mineralocorticoids (aldosterone) and androgrens. The medulla makes catecholamines (adrenaline).
Each of these hormones has a specific function in the body. Various diseases can result from excess or deficiencies of the adrenal hormones described below.
Cortisol is a glucocorticoid which is necessary to sustain all cells and to respond to physical stress. A low cortisol level can lead to subtle but serious problems, and in severe cases of stress and emergency, to shock and even death.
Aldosterone is a mineralocorticoid which is necessary to maintain the balance of sodium and potassium in the body and helps to stabilize blood pressure.
Androgens are hormones that promote the growth of axillary (underarm) and pubic hair in both males and females. In the male after puberty, the adrenal production of androgens plays a very small role compared with the potent androgen testosterone, which is produced by the testes. In the female, androgens produced by the adrenal gland are the major source. An excess of androgens in females can cause an increase in facial and body hair, acne, thinning of scalp hair and in great excess, can cause deepening of the voice and muscle enlargement.
The hormones adrenaline and noradrenaline (collectively referred to as “catecholamines”) are the “fight or flight” hormones. They control the caliber of blood vessels in the skin, muscles and internal organs as well as regulate the strength and speed of the heartbeat. In stressful situations, their output is increased which leads to a rapid pulse, higher blood pressure, shakiness, sweating, pallor and/or blanching of the skin.
How do you know if you have an adrenal problem? Adrenal diseases, fortunately, are quite rare and many of the symptoms of adrenal diseases can also be seen in other medical diseases and even in healthy people. From the symptoms described in the “About the Adrenal Glands” section, it is likely that many of us might qualify for testing. Testing for adrenal diseases is quite complicated and often requires the help of an endocrinologist to determine the likelihood of over or under-function of the adrenal gland or a tumor of the adrenal gland.
How are diagnoses of adrenal disorders made? The hormones produced by the adrenal gland can be measured in the blood, urine and saliva. If certain abnormalities are found, it may be necessary to perform imaging of the adrenal gland with a CT scan, MRI or specialized nuclear scans. Further testing of the pituitary may be necessary when labs suggest a “secondary” cause for adrenal disease (see pituitary section). It is extremely important to consult with an expert in hormones (an endocrinologist) who can order and interpret the appropriate tests.
Low levels of the hormones of the adrenal gland may result from disease in the adrenal gland itself (“primary” adrenal insufficiency) or from failure of the pituitary gland to adequately stimulate the production of adrenal hormones (“secondary” adrenal insufficiency).
In both cases, insufficient cortisol is produced, leading to weakness, fatigue, vague abdominal pain, occasionally with nausea and vomiting, low blood pressure, dizziness and fainting. People with inadequate cortisol fail to respond well to physical stress such as injury, anesthesia, surgery or other medical illnesses and can develop “adrenal crisis” in these situations. Adrenal crisis is a severe state characterized by profound weakness, low blood pressure, dehydration, shock and, ultimately, death if untreated.
If the adrenal gland itself is diseased, there is also a failure to produce aldosterone. A low aldosterone level can lower the blood pressure further and result in loss of sodium and water with accumulation of excess potassium. In primary adrenal insufficiency, there may be excess pigmentation of the skin, particularly in areas of skin creases, in the gums and inner lining of the mouth. When the disorder is due to pituitary failure, aldosterone deficiency and increased pigmentation do not occur.
The most common cause of primary adrenal failure is due to an attack by the immune system on the cells of the adrenal cortex (autoimmune disease) which is seen more frequently in people with other autoimmune diseases, including chronic thyroiditis, type 1 diabetes, hypoparathyroidism, pernicious anemia, myasthenia gravis and systemic lupus erythematosis (SLE). Adrenal failure may also occur as a result of infections of the adrenal gland such as tuberculosis, mycobacterium avarium intracellulare (MAI); fungi such as histoplasmosis; viruses, including cytomegalovirus (CMV)). It occurs more commonly in patients with Human Immunodeficiency Virus (HIV), as a result of either the virus itself or the “opportunistic infections” listed above which can occur in this population.
Adrenal hyperplasia (Adrenal insufficiency)
All adrenal cortical hormones are produced by a series of biochemical steps. Each step requires an enzyme to make the process move forward to the next step. Adrenal hyperplasia refers to a number of genetic deficiency states in which one of these enzymes is either missing or significantly reduced. As a result, there is a reduction in the production of a specific enzyme and a “build-up” of the chemicals preceding the enzyme step. These chemicals are then “shunted” through other pathways, much like traffic detouring a roadblock. The products of these detour pathways are then produced in excess. Depending on which enzyme is decreased, a pattern is seen of an excess of certain adrenal hormones and a deficiency of others.
These disorders are genetic, with some appearing at birth and others diagnosed later in development, usually around puberty.
The most common of these genetic disorders is 21-hydroxylase deficiency, which may be present at birth with “ambiguous genitalia” in females due to an excess of adrenal androgens. In boys, the male genitalia are normal. In both genders, some variations of this disorder include a reduction in mineralocorticoids, resulting in decreased blood pressure, low body sodium and excess potassium. In older children, there can be an accelerated growth rate, but a shorter growing period, leading to short stature. In girls, signs of excess androgens, including acne, facial hair, deepening of the voice and increased muscle mass, are often present. If the disorder is not apparent during childhood, signs may present around the time of puberty, including absent or irregular menstrual periods and signs of androgen excess (increased hair growth, acne).
A more rare form of adrenal hyperplasia is caused by deficiency of the enzyme 11-hydroxylase, which leads to increased androgens and excessive mineralocorticoid activity, causing high blood pressure and a loss of potassium.
What if a tumor is found on my adrenal gland on a CT scan? Once an adrenal tumor is noted, tests of the blood and urine should be performed to determine if the tumor is overproducing any of the adrenal hormones. Specialized CT scans and MRI scans can yield clues about whether the tumor is benign or malignant. It is important to remember that fewer than 10% of adrenal tumors over-secrete hormones, and less than 1/1000 are cancerous. Once adrenal tumors are determined to be benign and non-hormone secreting, commonly called an “adrenal incidentaloma,” they can be continued to be monitored with routine imaging and lab tests.
Adrenal tumors can be divided into benign or malignant, functional (hormone-secreting) or non-functional (not hormone secreting). Malignant tumors comprise less than 0.1% of all adrenal tumors and may secrete cortisol, androgens, mineralocorticoids, more than one type of hormone or no hormones at all. Benign tumors secrete only one type of hormone, with cortisol being the most common, catecholamines less common, and aldosterone the least common.
Most adrenal tumors are non-functional (non-hormone secreting). In fact, as many as 8-10% of us have adrenal nodules, which are often incidentally found on imaging studies performed for other reasons or noted at autopsy. If an adrenal nodule is found, it is very important to confirm there is no evidence of a pheochromocytoma due to the serious, even fatal, consequences of not treating this rare type of tumor. Pheochromocytomas make up only 3% of all incidentally found tumors, while Cushing’s syndrome tumors (cortisol-producing) account for 7% and aldosterone-secreting tumors about 0.5%. The remainder of adrenal tumors are non-secretory. Small non-secretory tumors do not require treatment, whereas large tumors will be monitored closely with imaging or may require surgery to confirm they are not malignant.
Cushing’s syndrome An excess of cortisol characterizes Cushing’s syndrome, which may be caused by a specific kind of pituitary (brain) tumor that stimulates the adrenal glands to produce excess cortisol or by a tumor of the adrenal gland itself, which overproduces the hormone. More rarely, other non-pituitary tumors can overstimulate the adrenal glands to produce too much cortisol.
The symptoms of Cushing’s disease include lack of menstrual cycles in women, an increase in fat deposition in specific locations in the body (face, upper back, above the collar bones and in the abdomen), high blood pressure, easy bruising, weakening of the bones with osteoporosis and fractures, muscle weakness, thinning of the skin, acne, and dark purple stretch marks (striae). Most cases of Cushing’s syndrome result in an excess of cortisol alone, and are rarely combined with an excess of androgens or mineralocorticoids (see below).
Hyperaldosteronism is a condition where too much aldosterone is produced by the adrenal glands, which can lead to a high blood pressure and loss of potassium (hypokalemia). Most cases of hyperaldosteronism are caused by benign (non-cancerous) tumors of the adrenal gland, which overproduce aldosterone. If severe, muscle weakness and kidney problems may result. About one-third of cases of hyperaldosteronism are due to overfunction of the cells (hyperplasia) rather than a tumor.
Pheochromocytoma A pheochromocytoma is a tumor of the adrenal medulla, which overproduces adrenaline (epinephrine) and noradrenaline (norepinephrine), leading to a high blood pressure, which may be continuous or intermittent. There may be episodes of a fast heartbeat with palpitations, weight loss, sweats, blanching or flushing, headache and chest pain. Although fewer than 0.1% of all people with high blood pressure harbor this tumor, under certain circumstances, testing is important to evaluate for this disorder, due to the potential fatality from “crisis” consisting of severe hypertension and heart arrhythmia. Up to 25% of pheochromocytomas may be familial, occurring more frequently in people with rare hereditary disorders, including multiple endocrine neoplasia type 2 (MEN 2), Von Hippel Lindau disease and Neurofibromatosis. Genetic testing is available for these disorders and for family members of affected patients.
How should you proceed if you are diagnosed with an adrenal problem? Adrenal diseases are very treatable, but because the treatment may be complicated, supervision by an endocrinologist is crucial.
When adrenal surgery is necessary, your endocrinologist can direct you to a surgeon who specializes in surgery on this gland. Often, though not always, these operations can be performed laparascopically in select institutions.
How are adrenal disorders treated? Once a diagnosis is made, the correct treatment can be instituted. In cases where hormones are missing, pills are given which can replace insufficient hormones. If you have adrenal insufficiency, your endocrinologist will prescribe an oral steroid (usually hydrocortisone or prednisone) and usually a synthetic mineralocorticoid (i.e., Florinef) if you have primary adrenal insufficiency.
It is important to never skip your medicine and to wear an ID tag so that emergency personnel can give you the correct medication in an acute situation if you are unable to speak for yourself.
In acute stress, it is important to receive much higher doses of steroids than the usual daily maintenance dose, called “stress dose steroids.” Failure to receive stress doses can result in serious disease and death.
In cases of adrenal hyperplasia, treatment with cortisone or synthetic corticosteroids will restore normal hormone levels and reduce the output of excess abnormal hormones. This should be done under the direct supervision of an endocrinologist to avoid over-treatment and to ensure the correct balance is being maintained.
Hyperaldosteronism, if caused by a tumor, usually requires surgery. If no tumor is seen, hyperaldosteronism can be treated with a blood pressure medication (spironolactone).
Tumors of the adrenal gland or the pituitary gland should only be treated only by experienced surgeons. Your endocrinologist can refer you to an expert surgeon in your area.