Original Editors - Elizabeth Bohnert from Bellarmine University's Pathophysiology of Complex Patient Problems project.
- 1 Addison's Disease
- 2 Clinically Relevant Anatomy
- 3 Prevalence
- 4 Characteristics/Clinical Presentation
- 5 Associated Co-Morbidities
- 6 Medications
- 7 Diagnostic Tests/Lab Tests/Lab Values
- 8 Causes
- 9 Adrenal Crisis
- 10 Physical Therapy Management
- 11 Differential Diagnosis
- 12 Resources
- 13 References
Addison’s disease is another name for primary chronic adrenal insufficiency. It is a condition where the adrenal cortex (the outer layer of the adrenal gland that produces mineralocorticoids, glucocorticoids, and androgens) is progressively destroyed, resulting in decreased secretions of hormones. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are the hormones that are affected by Addision's disease causing a global metabolic disorders and fluid imbalance.In the developed world, Addison's disease is most commonly caused by autoimmune disease however worldwide, tuberculosis is the most common cause.
Adrenal insufficiency may also be caused by long-term administration of corticosteroids or disorders of the hypothalamus or pituitary gland, but this is not Addison's disease.
Clinically Relevant Anatomy
The adrenal (suprarenal) glands are endocrine glands that are located superior to the kidneys. The adrenal glands have two layers the adrenal cortex (the outer layer) that is responsible for producing steroid hormones and the inner layer the medulla which is responsible for secreting the hormones that control our stress response, commonly referred to as our fight or flight response
The Adrenal Cortex
The adrenal cortex is the outer layer of the gland and is divided into three zones:
- Zona glomerulosa is where mineralocoticoids are produced. They help to control blood pressure and electrolyte balance ie aldosterone
- Zona Fasciculata this is where the glucocorticoids are produced. They help to regulate the metabolism and control the body’s response to stress i.e. cortisol and cortisone such as cortisol
- Zona Reticularis this is where androgens are converted into functional sex hormones (tortora)
Total loss of the steroid hormones secreted by the outer layer results in death due to dehydration and electrolyte imbalance. Unless corrected by hormone replacdement therapy death will usually occur within weeks, sometimes within a few days.
The Adrenal Medulla
The inner zone of the adrenal glands are responsible for producing catecholamine. These are hormones such as epinephrine (adrenaline) and norepinephrine (noradrenaline) and small amounts of dopamine whose function is to initiate a rapid response to stressful situations.
Addison’s disease occurs in about 1 in 100,000 Americans. About 8,400 people are currently diagnosed with Addison's disease in the UK. Even though it is seen throughout the lifespan in both genders, it most commonly occurs in middle-aged white females.
Addison’s disease will develop insidiously, with the signs of the disease not developing “until at least 90% of both glands is destroyed and the levels of circulating glucocorticoids and mineralocorticoids are significantly decreased.” Some of the clinical signs and symptoms of Addison’s disease include:
- Darkened pigmentation of the skin (especially of the mouth and scars), due to increased secretion of melanin-secreting hormone (MSH) corresponding with increased secretion of ACTH, which is released to try to stimulate the work of the adrenal glands
- Slowly developing weakness and fatigue
- Hypotension due to increased sodium excretion from decreased aldosterone secretion
- Severe abdominal, low back, or leg pain
- Gastrointestinal disturbances - such as nausea, vomiting, anorexia, weight loss, and diarrhoea
- Hypoglycemia due to decreased glucocorticoids causing decreased gluconeogenesis
- Decreased stress tolerance (infections, trauma, surgery, etc.)
- Salt craving
- Hypovolaemic shock,
- Low-grade fever
- a sudden crisis precipitated by intercurrent infection or stress.
Addison's disease should also be considered in a person with persistent, non-specific symptoms, such as:
- gastrointestinal symptoms
- cravings for salt
- musculoskeletal symptoms
- postural dizziness due to hypotension.
The possibility of Addison's disease should also be considered in people with:
- hypothyroidism whose symptoms worsen when thyroxine is started
- type 1 diabetes mellitus with recurrent unexplained hypoglycaemic episodes
- other autoimmune diseases
- or low sodium and high potassium levels on blood biochemistry.
Addison's disease can occur alone, or it can occur along with other autoimmune disorders, leading to polyendocrine syndrome.
- Type I Diabetes Mellitus
- Pernicious Anemia
- Vitiligo (a loss of pigment on areas of the skin)
- Chronic Active Hepatitis
Osteoporosis is more common among people with Addison's disease compared to healthy individuals because of the medical management with long-term steroid replacement therapy. Steroids have several effects on bones including increasing osteoclastic activity, decreasing osteoblastic formation, and decreasing the absorption of calcium in the intestines.
Bone Mineral Density T-Scores
|Normal||-1.0 or above|
|Osteopenia||-1.0 to -2.5|
|Osteoporosis||-2.5 or less|
|Severe Osteoporosis||-2.5 or less with 1 or more fragility fractures|
- Hydrocortisone is usually used for glucocorticoid replacement, but longer-acting glucocorticoids, such as prednisolone and dexamethasone, are sometimes used to avoid the peaks and troughs which may occur with hydrocortisone.
- Fludrocortisone is usually used for mineralocorticoid replacement.
- Dehydroepiandrosterone (unlicensed) may be prescribed by some specialists for androgen replacement.
Diagnostic Tests/Lab Tests/Lab Values
- Adrenocorticotropic Hormone (ACTH) Stimulation Test: This is the most common test performed in diagnosing Addison's disease. Blood cortisol and/or urine cortisol levels are measured following being administered with a synthetic form of ACTH. Normally cortisol levels will increase following the administration of the synthetic ACTH. However, patients with Addison's disease experience little or no increase in cortisol levels following the test. Diagnostically significant levels are elevated ACTH levels (≥ 50 pg/mL) with low cortisol levels (< 5 μg/dL [< 138 nmol/L]).
- Corticotropin-Releasing Hormone (CRH) Stimulation Test: This test is performed when there are abnormal results from the ACTH test. In this test, blood cortisol levels are measured 30, 60, 90, and 120 minutes following an intravenous injection of synthetic CRH. Patients with Addison’s disease will have increased levels of ACTH but no cortisol.
- X-ray or ultrasound of the abdomen may be performed following laboratory tests to determine if calcium deposits exist in the adrenal glands.
Test Results That Suggest Addison's Disease
|Serum Na||< 135 mEq/L|
|Serum K||> 5 mEq/L|
|Ratio of Serum Na:K||<30:1|
|Plasma Glucose, fasting||< 50 mg/dL|
|Plasma HCO3||< 15-20 mEq/L|
|BUN||> 20 mg/dL|
Evidence of calcification in adrenal areas
[Chart courtesy of Merck.com. Available at http://merck.com/mmpe/sec12/ch153/ch153b.html]
There are a number of causes for Addison’s disease, the most common causes are autoimmune adrenalitis, infectious adrenalitis from disease such as tuberculosis, the acquired immune deficiency syndrome (AIDS), syphilis or adrenal metastases such as lung, stomach, breast or colon cancer. About 70% of cases in the US and UK are due to idiopathic atrophy of the adrenal cortex, probably caused by autoimmune processes
Adrenal Crisis is rare but should not be overlooked. When in crisis, the patient with Addison's disease the adrenal glands gradually stop producing enough cortisol to supply the body. Cortisol is involved with many body systems and this condition can result in threat to life.
Signs of Adrenal Crisis include:
- Nausea and vomiting,
- Abdominal pain,
- Anorexia and chills.
If left untreated, symptoms of shock, fever and convulsions may follow. An adrenal crisis is a medical emergency.
Physical Therapy Management
There is very little information and research pertaining to the physical therapy management of patients with Addison's disease. Jakobi et al found that women with Addison's disease had a similar maximum voluntary force of the quadriceps muscle compared to the control group of healthy individuals, however, they had "altered contractile properties and decreased endurance compared with controls." Obviously, more research needs to be performed to determine the proper interventions that physical therapists should utilize to treat patient's with Addison's disease and also determine any limitations to treating these patients.
Therapist are equipped in helping people to overcome some of their symptoms prior to diagnosis to allow them to return to all levels of activities, such as:
- Slowly developing weakness and fatigue
- Severe abdominal, low back, or leg pain
- Musculoskeletal symptoms
- Ingestion of Heavy Metals: Excessive ingestion of heavy metals (such as arsenic poisoning) may lead to hyperpigmentation that is also seen with Addison's disease.
- Hemochromatosis: This is the most common form of iron overload. One of the common signs of this disorder is abnormal pigmentation of the skin, appearing grey or bronze.
- Peutz-Jeghers syndrome: This inherited disorder is also characterised by melanin spots in the oral mucosa, the lips, and the digits. However, along with this disease, patients develop polyps in the gastrointestinal system leading to abdominal cramping and blood in the stool, which are not all found in Addison's disease.
- Hypothyroidism: This refers to a deficiency of the thyroid hormone leading to a generalized decrease in metabolism. One of the most common signs of this disorder is the feeling of fatigue and sluggishness. However, it is common that people with this disorder experience weight gain, while patients with Addison's disease will lose weight due to the vomiting and anorexia.
- Hypopituitarism: This results from decreased hormone production by the anterior pituitary gland. Since ACTH is a primary hormone of the anterior pituitary, it is not released, thus decreasing the stimulation of the adrenals to release cortisol. Since there is a similar decrease in cortisol, this disorder has many of the common symptoms of Addison's disease, such as hypoglycemia, anorexia, nausea, and lethargy.
- Goodman CC, Fuller KS. Pathology: Implications for the Physical Therapist. St. Louis: Elsevier; 2009.
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- Compston J. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018;61(1), 7–16. https://doi.org/10.1007/s12020-018-1588-2 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997116/ (Accessed 13 July 2020)
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- Jakobi J, Killinger D, Wolfe B, Mahon J, Rice C. Quadriceps muscle function and fatigue in women with Addison's disease. Muscle Nerve. August 2001;24(8):1040-1049.
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- MayoClinic. Hypothyroidism. Available at: http://www.mayoclinic.com/health/hypothyroidism/DS00353/DSECTION=symptoms