Addison's disease, also known as primary adrenal insufficiency and hypocortisolism, is a long-term endocrine disorder in which the adrenal glands do not produce enough steroid hormones. Symptoms generally come on slowly and may include abdominal pain, weakness, and weight loss. Darkening of the skin in certain areas may also occur.Under certain circumstances, an adrenal crisis may occur with low blood pressure, vomiting, lower back pain, and loss of consciousness. An adrenal crisis can be triggered by stress, such as from an injury, surgery, or infection.
Addison's disease arises from problems with the adrenal gland such that not enough of the steroid hormone cortisol and possibly aldosterone are produced, most often due to damage by the body's own immune system in the developed world and tuberculosis in the developing world. Other causes include certain medications, sepsis, and bleeding into both adrenal glands. Secondary adrenal insufficiency is caused by not enough adrenocorticotropic hormone (ACTH) (produced by the pituitary gland) or corticotropin-releasing hormone (CRH) (produced by the hypothalamus). Despite this distinction, adrenal crises can happen in all forms of adrenal insufficiency. Addison's disease is generally diagnosed by blood tests, urine tests, and medical imaging.
Treatment involves replacing the absent hormones. This involves taking a corticosteroid such as hydrocortisone and fludrocortisone. These medications are usually taken by mouth. Lifelong, continuous steroid replacement therapy is required, with regular follow-up treatment and monitoring for other health problems. A high-salt diet may also be useful in some people. If symptoms worsen, an injection of corticosteroid is recommended and people should carry a dose with them. Often, large amounts of intravenous fluids with the sugar dextrose are also required. Without treatment, an adrenal crisis can result in death.
Addison's disease affects about 0.9 to 1.4 per 10,000 people in the developed world. It occurs most frequently in middle-aged females. Secondary adrenal insufficiency is more common. Long-term outcomes with treatment are typically good. It is named after Thomas Addison, a graduate of the University of Edinburgh Medical School, who first described the condition in 1855.The adjective "addisonian" is used to describe features of the condition, as well as people with Addison's disease.
Signs and symptoms
Hyperpigmentation as seen in a woman with Addison's disease
Darkening of the gums due to increased pigment as seen in Addison's disease
The symptoms of Addison's disease generally develop gradually. Symptoms may include fatigue, muscle weakness, weight loss, nausea, vomiting, loss of appetite, lightheadedness upon standing, irritability, depression, and diarrhea. Some people have cravings for salty foods due to the loss of sodium through their urine.Hyperpigmentation of the skin may be seen, particularly when the person lives in a sunny area, as well as darkening of the palmar crease, sites of friction, recent scars, the vermilion border of the lips, and genital skin. These skin changes are not encountered in secondary and tertiary hypoadrenalism.
Low blood pressure with or without orthostatic hypotension (blood pressure that decreases with standing)
Darkening (hyperpigmentation) of the skin, including areas not exposed to the sun. Characteristic sites of darkening are skin creases (e.g., of the hands), nipple, and the inside of the cheek (buccal mucosa); also, old scars may darken. This occurs because melanocyte-stimulating hormone (MSH) and ACTH share the same precursor molecule, pro-opiomelanocortin (POMC). After production in the anterior pituitary gland, POMC gets cleaved into gamma-MSH, ACTH, and beta-lipotropin. The subunit ACTH undergoes further cleavage to produce alpha-MSH, the most important MSH for skin pigmentation. In secondary and tertiary forms of adrenal insufficiency, skin darkening does not occur, as ACTH is not overproduced.
Addison's disease is associated with the development of other autoimmune diseases, such as type I diabetes, thyroid disease (Hashimoto's thyroiditis), celiac disease, or vitiligo. Addison's disease may be the only manifestation of undiagnosed celiac disease. Both diseases share the same genetic risk factors (HLA-DQ2 and HLA-DQ8 haplotypes).
The presence of Addison's in addition to mucocutaneous candidiasis, hypoparathyroidism, or both, is called autoimmune polyendocrine syndrome type 1.The presence of Addison's in addition to autoimmune thyroid disease, type 1 diabetes, or both, is called autoimmune polyendocrine syndrome type 2.
An "adrenal crisis" or "Addisonian crisis" is a constellation of symptoms that indicates severe adrenal insufficiency. This may be the result of either previously undiagnosed Addison's disease, a disease process suddenly affecting adrenal function (such as adrenal hemorrhage), or an intercurrent problem (e.g., infection, trauma) in someone known to have Addison's disease. It is a medical emergency and potentially life-threatening situation requiring immediate emergency treatment.
Characteristic symptoms are:
Sudden penetrating pain in the legs, lower back, or abdomen
Severe vomiting and diarrhea, resulting in dehydration
Low blood pressure
Syncope (loss of consciousness and ability to stand)
Hypoglycemia (reduced level of blood glucose)
Confusion, psychosis, slurred speech
Hyponatremia (low sodium level in the blood)
Hyperkalemia (elevated potassium level in the blood)
Hypercalcemia (elevated calcium level in the blood)
Journal of Autoimmune Disorders