Addison’s Disease: A Naturopathic Approach
Amanda Hegnauer, ND
The most appropriate way to start breaking down the definition of Addison’s disease is to first look at the pathophysiological aspect of the adrenal gland. The adrenal glands are walnut-sized endocrine glands that sit atop the kidneys. Each suprarenal gland is structurally and functionally 2 endocrine glands in 1: The inner adrenal medulla consists of nervous tissue and acts as part of the sympathetic nervous system. The outer adrenal cortex encapsulates the medullary region and is glandular tissue. Each of these regions produces its own set of hormones, but all adrenal hormones help us cope with extreme, or stressful, situations.
The adrenal cortex synthesizes well over 2 dozen steroid hormones, collectively called corticosteroids, which in turn are synthesized from cholesterol. The large, lipid-laden cortical cells are arranged in 3 distinct layers or zones. The superficial layer formed by cell clusters is called the zona glomerulosa. This zone mainly produces mineralocorticoids, the primary hormone being aldosterone, which helps control the balance of minerals and water in the blood. The middle zona fasciculata cells secrete glucocorticoids such as cortisol. These cells are arranged, more or less, in linear cords. The cells of the innermost zona reticularis, abutting the adrenal medulla, have a netlike arrangement. These cells produce small amounts of adrenal sex hormones, or gonadocorticoids, chiefly androgens such as testosterone. Consequently, there is a division of labor in corticosteroid production; the entire spectrum of corticosteroids is produced by all 3 cortical layers.
The adrenal medulla, made up of spherical chromaffin cells that crowd around blood-filled capillaries, are modified ganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, into the blood.1 When the body is activated into its fight-or-flight status by some short-term stressor, the sympathetic nervous system is mobilized. Blood sugar levels rise, blood vessels constrict, and the heart beats faster, raising blood pressure; blood is also diverted from temporarily nonessential organs to the brain, heart, and skeletal muscles. At the same time, the adrenal medulla signals for the release of catecholamines, which reinforce and prolong the fight-or-flight response.
Stress and the Adrenal Gland
Stressful stimuli, whether emotional or physical, cause the hypothalamus to activate the adrenal medulla via sympathetic nerve impulses, and the adrenal cortex via hormonal signals. The medulla mediates short-term responses to stress by secreting catecholamines. The cortex controls more prolonged responses by secreting its steroid hormones. As you will see, it’s a beautiful “dance” between the medulla and cortex to balance the stress response. If, in any way, the nerve impulses of the short-term stress response or the hormonal balance of the long-term stress response are out of step, the body has an immediate reaction.
Short-Term Stress Response by the Adrenal Medulla
In a short-term stress response, the hypothalamus sends nerve impulses to the spinal cord. Preganglionic sympathetic fibers innervate the adrenal medulla and release catecholamines, with the following effects:
1. Increased heart rate
2. Increased blood pressure
3. Hepatic conversion of glycogen to glucose, and release of glucose into the blood
4. Dilation of bronchioles
5. Changes in blood flow patterns, leading to increased alertness, decreased digestive system activity, and reduced urine output
6. Increased metabolic rate
Long-Term Stress Response by the Adrenal Cortex
In a long-term stress response, the hypothalamus releases corticotropin-releasing hormone (CRH) to the corticotrope cells of the anterior pituitary. In response, the anterior pituitary releases adrenocorticotropic hormone (ACTH), which heads directly through the blood to the adrenal cortex, stimulating the release of mineralocorticoids and glucocorticoids.1,2
• Mineralocorticoids (chiefly aldosterone)
o Retention of sodium and water by kidneys
o Increased blood volume and blood pressure
• Glucocorticoids (chiefly cortisol)
o Proteins and fats converted to glucose or broken down for energy
o Increased blood sugar
o Suppression of the inflammatory and immune responses
Types of Adrenal Insufficiency
Primary chronic adrenocortical insufficiency, ie, Addison’s disease, is an uncommon disorder resulting from progressive destruction of the adrenal cortex and, often, the adrenal medulla.2 Because the condition arises from problems within the adrenal gland, it is termed “primary adrenal insufficiency,” and because the damage is incurred by the body’s own immune system, it is termed an autoimmune disease. Adrenal insufficiency, or hypofunction, may be caused by either primary adrenal disease (primary hypoadrenalism) or decreased stimulation of the adrenals owing to a deficiency of ACTH (secondary hypoadrenalism). The patterns of adrenocortical insufficiency can be considered under the following headings:
1. Primary acute adrenocortical insufficiency (adrenal crisis)
2. Primary chronic adrenocortical insufficiency (Addison’s disease)
3. Secondary adrenocortical insufficiency (hypothalamus or pituitary disorder)
Primary acute adrenocortical insufficiency (adrenal crisis): This can occur due to a variety of causes, including loss of the cortex, idiopathic (autoimmune disease), infection, acute hemorrhagic necrosis, metabolic failure in hormone production, and other causes. In patients with chronic adrenocortical insufficiency, a crisis is precipitated by any form of stress that requires an immediate increase in steroid output from glands that are incapable of responding. This may occur due to a rapid withdrawal of exogenous corticosteroids on whom a patient has been maintained, or failure to increase the steroid doses in response to an acute stress.3 Crisis may also occur as a result of a massive adrenal hemorrhage, which destroys the adrenal cortex. This can occur in newborns, following a prolonged and difficult delivery, in some patients maintained on anticoagulant therapy, post-surgical patients who develop disseminated intravascular coagulation (DIC), or when a massive adrenal hemorrhage complicates a bacterial infection, a condition known as Waterhouse-Friderichsen syndrome.4
Secondary adrenocortical insufficiency: As our main topic of discussion is Addison’s disease, let’s first discuss secondary adrenocortical insufficiency. This can be defined as any disorder of the hypothalamus and pituitary, such as metastatic cancer, infection, or infarction that reduces the output of ACTH. This in turn leads to the syndrome of hypoadrenalism, which has many similarities to Addison’s disease. Conversely, prolonged administration of exogenous glucocorticoids suppresses the output of ACTH and, in turn, adrenal function. Microscopically speaking, with secondary disease, the hyperpigmentation characteristic of primary Addison’s disease is absent because melanotropic hormone levels are low. Secondary hypoadrenalism is also characterized by deficient cortisol and androgen output but normal or near-normal aldosterone synthesis. Therefore, there is no marked decrease in sodium or increase in potassium. Note that a large intake of water can dilute the serum, thereby lowering the serum sodium level. Also note that ACTH deficiency can occur alone, but in some instances is only 1 part of entire hypopituitarism picture.
Addison’s Disease
Primary chronic adrenocortical insufficiency (Addison’s disease): Let’s move onto the main show… As noted above, one definition of Addison’s disease is an uncommon disorder resulting from progressive destruction of the adrenal cortex. This being said, a few noted folks who have been diagnosed with Addison’s disease include US President John F. Kennedy, scientist Eugene Merle Shoemaker, and singer Helen Reddy. Some have suggested that Jane Austen was diagnosed with Addison’s; however, others have disputed this. In general, clinical manifestations of adrenocortical insufficiency generally do not appear until at least 90% of the adrenal cortex has been compromised. Although all races and both sexes may be affected, certain causes of Addison’s disease, such as autoimmune adrenalitis, are much more common in whites, particularly women.2 A large number of diseases may attack the adrenal cortex, but more than 90% of all cases are attributable to autoimmune adrenalitis, tuberculosis, or metastatic cancers.2
Autoimmune adrenalitis accounts for 60-70% of cases of Addison’s.2 It may occur as a sporadic or familial disorder. In about half of these cases, the adrenal gland is the sole target of an autoimmune reaction, but in the remainder of cases, another autoimmune disease, such as Hashimoto’s disease, pernicious anemia, type 1 diabetes mellitus, and idiopathic hypoparathyroidism, is also present. Without diving too deeply into the immune system, lets define “autoimmune disease.” In autoimmunity, our adaptive (or acquired) immune response begins to malfunction. With healthy immune function, our adaptive immune system learns to recognize specific pathogens and create antibodies to them so that the next time the pathogen enters the body, the immune system can fight it off quickly, often without any evidence of being afflicted. Adaptive immunity requires time and exposure to develop. While the acquired immune response is undoubtedly beneficial to us, sometimes the adaptive immunity cells become misdirected and begin targeting healthy cells and tissues in the body rather than pathogens.5
This misdirected immune response is both initiated and exacerbated by excessive inflammation in the body. In a state of chronic inflammation and disease, the body is unable to repair damaged tissue more quickly than the rate of tissue destruction caused by the “hijacked” immune system. Furthermore, when the targeted tissue is involved in essential day-to-day functioning of the body, the autoimmune disease can become a threat to life.
The term “polyglandular syndrome” has been used to designate the various combinations of organ involvement. Circulating anti-adrenal antibodies are present in about half of the cases of autoimmune adrenalitis,6 as well as other types of antibodies related to involvement of other organs or tissues. The frequency of autoimmune adrenalitis is increased in association with certain histocompatibility antigens, particularly HLA-B8 and DR-3,6 suggesting some genetic predisposition. Perhaps we should also consider 21-hydroxylase deficiency. Autoimmune destruction of the adrenal cortex has also been noted as a cause of an immune reaction against the enzyme 21-hydroxylase. An enzymatic deficiency of 21-hydroxylase results in a defective conversion of progesterone to 11-deoxycorticosterone; this accounts for approximately 90% of cases of congenital adrenal hyperplasia.6 This can be associated not only with the thyroid and pancreas, but also the ovaries. A study found that 20.2% of women with Addison’s disease also had premature ovarian failure (POF) and that steroidogenic antibodies were predictive markers of POF in patients with Addison’s disease.7 Studies aside, in my conversations with practicing endocrinologists, they too have seen the prevalent connection between Addison’s disease and POF. So, which comes first – Addison’s disease or POF? This, of course, is to be determined with each individual patient.
Signs and Symptoms of Addison’s disease
Addison’s disease begins insidiously and does not come to attention until at least 90% of the adrenal cortex of both glands is destroyed and the levels of both circulating glucocorticoids and mineralocorticoids are significantly decreased. The initial manifestations include progressive weakness and easy fatigability, which may be dismissed as nonspecific complaints. If caught early enough, progressive weakness and fatigability can be identified as adrenal fatigue, perhaps a precursor to adrenal insufficiency, yet a very different diagnosis. Further concerns include gastrointestinal disturbances, including anorexia, nausea, vomiting, diarrhea, and weight loss. Labs may suggest hypercalcemia, hypoglycemia, hyponatremia, and hyperkalemia. In patients with primary adrenal disease, an increased circulating level of the precursor hormone, ACTH, stimulates melanocytes, with resultant hyperpigmentation of the skin, particularly of sun-exposed areas and at pressure points such as the neck, elbows and knees. It is important to note that stressors may precipitate an acute adrenal crisis, which may manifest as intractable vomiting, abdominal pain, hypotension, coma, and vascular collapse.8 Death occurs rapidly unless corticosteroid therapy is begun immediately. This being said, it is extremely important that Addison’s disease patients carry information on them for the attention of emergency medical technicians. This may include a medical alert bracelet and card.
Diagnosis and Testing
An accurate history and physical examination of the patient plays a large role in the diagnosis of any autoimmune disease. These diseases are commonly diagnosed by abnormalities in a routine blood test. For example, in the case of erythrocyte sedimentation rate (ESR) and/or C-reactive protein, a blood test will reveal inflammation of the tissue. This inflammation would, in turn, indicate an underlying pathology. Depending on one’s symptoms and the suspected diagnosis, tests specific to each disease would be run. A nice starting place is the antinuclear antibody (ANA) test, which reveals antibodies in one’s bloodstream. In the diagnosis of Addison’s disease, it is imperative to evaluate cortisol levels. Multiple blood and/or saliva cortisol levels collected at different times of the day can be used to evaluate both cortisol concentrations and diurnal variation. Normally, the level of cortisol in the blood rises and falls in a “diurnal variation” pattern, peaking early in the morning then declining throughout the day, reaching its lowest level about midnight. A 24-hour urine cortisol sample will not show diurnal variation; rather, it will measure the total amount of unbound cortisol excreted in 24 hours.9 What we are looking for is that normal, diurnal cortisol pattern; therefore, a salivary panel is perhaps the most efficient method for showing this pattern.
Assuming an abnormal level of cortisol is detected, the next step in diagnosis might be a cosyntropin (ACTH) stimulation test. This test involves measuring the level of cortisol in the blood before and after an injection of synthetic ACTH (which signals the adrenal glands to produce cortisol). If the adrenal glands are damaged, the ACTH stimulation test shows a limited or nonexistent output of cortisol in response to synthetic ACTH.10
In many cases, the interpretation of the results can be complex. Levels of both ACTH and cortisol vary throughout the day. Like cortisol, ACTH will normally be at its highest level in the morning and lowest at night. It will stimulate cortisol production, which will follow the same daily pattern but will rise after ACTH does, and fall to its lowest level very late in the evening. Conditions that affect the production of ACTH and cortisol often disrupt this diurnal variation.
Results of ACTH and cortisol tests are often evaluated together. Table 1 indicates the common patterns of ACTH and cortisol seen with different diseases involving the adrenal and pituitary glands.
Table 1. Levels of Cortisol & ACTH in Different Disorders
| Disease | Cortisol | ACTH |
| Cushing’s disease (pituitary tumor producing ACTH) | High | High |
| Adrenal tumor | High | Low |
| “Ectopic” ACTH (ACTH made by a tumor outside the pituitary, usually in the lung) | High | High |
| Addison’s disease (underactive or damaged adrenal glands) | Low | High |
| Hypopituitarism | Low | Low |
In addition to testing ACTH and cortisol, the blood should be evaluated for calcium, sodium, potassium, and blood sugar. In a healthy person, cortisol levels increase in response to a fall in glucose levels. A CT scan of the abdomen will check the size of the adrenal glands and reveal other abnormalities, providing insight as to the cause of the adrenal insufficiency. An MRI of the pituitary gland can indicate secondary adrenal insufficiency.
Treatment
All treatment for Addison’s disease involves hormone replacement therapy to correct the levels of steroid hormones the body isn’t producing. Fludrocortisone may be prescribed to replace aldosterone. Hydrocortisone, prednisone, or cortisone acetate may be used to replace cortisol.11 If your patient is ill with vomiting and can’t retain oral medications, injections may be needed.
To treat androgen deficiency in women, dehydroepiandrosterone (DHEA) can be prescribed. Some studies suggest that this adrenal hormone may improve overall sense of well-being and increase libido. DHEA seems to balance the effects of cortisol by improving the body’s ability to cope with stress. It is also a very powerful precursor to all of the major sex hormones, including estrogen, progesterone, and testosterone. This is why it is termed the “mother hormone” or “youth hormone.” This is important to note, as fatigued or insufficient adrenals can result in sex hormone imbalances, leading to increased incidence of PMS, menstrual irregularities, infertility, migraines, and symptoms associated with menopause and andropause.
An ample amount of sodium is recommended, especially during heavy exercise, when the weather is hot, or if gastrointestinal upset is present, such as diarrhea. A suggested increase in the temporary dosage of a corticosteroid medication is recommended when facing a stressful situation, such as an operation, an infection, or a minor illness.
Identify Sources of Inflammation
Treatment is very tricky for each diagnosed autoimmune disease. An underlying theme to autoimmune disease is inflammation. Thus, treating inflammation alongside appropriate medical care is imperative. Just as traditional treatments are specific to the diagnosed disease, so is the treatment of inflammation. Is there something specific that is causing and/or exacerbating one’s inflammation, such as food sensitivities? These are typically IgG-mediated allergic reactions. Most commonly, this elicits a delayed-hypersensitivity reaction, which can be associated with arthritis, autoimmune disease, eczema, migraines, gastrointestinal complaints, and many other chronic symptoms. After repeated exposures to the offending food, the IgG-specific antibody levels increase. Over time, these antibodies can result in excessive food antigen-antibody complexes that can tax the immune system every time one ingests that specific food. Other possible sources of inflammation include chronically elevated cortisol (sometimes seen in early-stage Addison’s) and insulin, heavy metal and other toxic burden, specific foods high in inflammatory prostaglandins, and unnecessary body fat.12 In a person with an immune system that is already under a great deal of stress, the strain of an external affliction will only further burden the body.
Diet
Sugar consumption in all forms, including glucose, fructose, and sucrose, will impair the ability of white cells to destroy biological agents. This effect begins within a half-hour of consumption and lasts for 5 hours. After 2 hours, immune function is reduced by 50% – a rather alarming statistic.13Other foods to minimize are caffeine, which puts the adrenals into that sympathetic nervous system mode, junk foods, processed foods, or foods that are low in nutrients and high in calories. Also minimize food with preservatives and colorings, trans fats, fast foods, artificial sweeteners, refined grains, and foods from the nightshade family. The alkaloids found in common nightshade vegetables are powerful, with potential adverse effects on various tissues, including the membranes of the cells of the body. They bioaccumulate, meaning that they remain unprocessed by the body and simply accumulate in tissues.
So what can one eat? Lean proteins, including beans and legumes, fish, lean poultry and eggs, are recommended. Organic or cage-free versions are a smart choice, as this reduces pesticide exposure. Adequate protein in the diet is important to maintain balanced blood sugar levels, which helps keep appropriate cortisol levels in the blood stream. Grains, legumes, nuts, and seeds are a fantastic way to supplement the diet. And don’t forget that fruits and vegetables are rich in phytonutrients.
Additional Therapies
Other therapies to consider and which are sometimes overlooked include stress reduction, rest, and nutritional supplementation. Stress reduction is an essential part of all efforts to normalize cortisol, decrease inflammation, and initiate the healing process. Each individual should explore and find the stress reduction techniques that work best for him- or herself. Meditation, physical activities, yoga, or even attitude changes might be considered. Without stress reduction, all therapeutic and support measures will eventually fail. Rest is essential for our minds and bodies to recharge and prepare for the next day. A lack of sleep places greater demands on every part of one’s physiology. The quality of sleep is just as important as the quantity of sleep.
Nutrition is imperative in everyone and should be monitored specifically in a patient diagnosed with adrenal fatigue or Addison’s disease. B vitamins and vitamin C serve as fuel for the adrenal glands. They act as “miracle grow” for the adrenal gland. Fatty acids, specifically phosphatidylserine,14 are important to nurture the adrenals and quiet them down at night if overactive. Botanical medicine is a beautiful way to balance stress, but be sure it is not contraindicated with your patient’s pharmacologic prescriptions. Perhaps consider adaptogenic herbs such as Withania somnifera (ashwagandha), Rhodiola rosea, or Glycyrrhiza glabra (licorice root). Curcuma longa (turmeric) is a wonderful anti-inflammatory herb and is said to produce fewer side effects than commonly-used pain relievers. Other therapies to pursue are homeopathy, acupuncture, and hydrotherapy, all of which broaden your treatment bag.
Essentially, the diagnosis of Addison’s disease can be scary to the patient and should be taken very seriously. However, a person with this diagnosis can live a relatively healthy lifestyle. It is important for patients to know their bodies and their symptoms, and to adjust accordingly. As a brilliant patient once said, “Some days you need to live your life by 50%.” (Instead of pushing yourself to complete everything on your “To Do” list, only do half.) Consider how one’s immune system is affected and how the immune system affects each organ of the body. Now consider this: Is one’s autoimmune disease solely responsible for the inflammation that is intensifying one’s symptoms? Or, could one’s lifestyle, nutrition, and hormones be contributing to the inflammation and exacerbating the autoimmune disease? Working closely with an endocrinologist and/or rheumatologist, identifying all sources of inflammation, and working with all the natural modalities at our disposal, can helpto ensure an effective outcome for our patients with Addison’s disease.
Amanda Hegnauer, ND is a licensed primary care naturopathic doctor in the state of New Hampshire. She earned her doctorate from Southwest College of Naturopathic Medicine in Tempe, AZ, and is currently the executive coordinator for the New Hampshire Association of Naturopathic Doctors. She holds a particular interest in chronic fatigue, autoimmune diseases, endocrinology, and gastroenterology. She also enjoys a focus on women’s health, including treating the symptoms of menopause and utilizing bioidentical hormone replacement therapy. Diet, lifestyle, and a solid biochemical foundation is the driving force of her practice at Whole Health Concord in Concord, NH, and Cougar Sound Spirits Healing Center in Sutton, NH. Her other interests include clinical nutrition, including vitamin and mineral supplementation, homeopathy, and botanical medicine.
References
1. Marieb EN. Human Anatomy & Physiology, 5th ed. San Francisco, CA: Benjamin Cummings; 2001.
2. Kumar V, Collins T, Kotran RS. Robbins Pathologic Basis of Disease, 6th ed. Philadelphia, PA: Saunders; 1999.
3. Munver R, Volfson IA. Adrenal insufficiency: diagnosis and management. Curr Urol Rep. 2006;7(1):80–85.
4. White PC. Adrenocortical insufficiency. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics, 19th ed. Philadelphia, Pa: Saunders Elsevier; 2011:1924-1930.
5. Parham P. The Immune System. New York, NY: Garland Publishing; 2000.
6. Speiser PW, New MI, White PC. Molecular genetic analysis of nonclassic steroid 21-hydroxylase deficiency associated with HLA-B14,DR1. N Engl J Med. 1988;319(1):19-23.
7. Reato G, Morlin L, Chen S, et al. Premature ovarian failure in patients with autoimmune Addison’s disease: clinical, genetic, and immunological evaluation. J Clin Endocrinol Metab. 2011;96(8):E1255-E1261.
8. Chakera AJ, Vaidya B. Addison disease in adults: diagnosis and management. Am J Med. 2010;123(5):409-413.
9. Lab Tests Online. American Association of Clinical Chemistry. http://labtestsonline.org/understanding.html. Accessed December 15, 2013.
10. Clinical Center; National Institutes of Health. Adrenocorticotrophic hormone (ACTH) stimulation test. http://cc.nih.gov/ccc/patient_education/procdiag/acth.pdf. NIH Web site. Accessed December 15, 2013.
11. National Endocrine and Metabolic Diseases Information Service. Adrenal Insufficiency and Addison’s Disease. National Institute of Diabetes and Digestive Health and Kidney Disease Web site. http://endocrine.niddk.nih.gov/pubs/addison/addison.aspx. Accessed August 20, 2012.
12. Chafen JJ, Newberry SJ, Riedl MA, et al. Diagnosing and managing common food allergies: a systematic review. JAMA. 2010;303(18):1848-1856.
13. Sanchez A, Reeser JL, Lau HS, et al. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr. 1973;26(11):1180-1184.
14. Hellhammer J, Fries E, Buss C, et al. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress. 2004;7(2):119-126.
