Addison's disease is a condition associated with impaired adrenal cortex function. This situation can be very serious and sometimes even life-threatening and that is why we should know more about it. It is necessary to know some basic facts about adrenal glands, their anatomy and function.
Adrenal gland is a pair organ located - as the name suggests – above both kidneys. The adrenal glands are composed of cortex and medulla and they create a number of important hormones. In the cortex glucocorticoids and mineralocorticoids are produced. Glucocorticoids (most important hormone of this group is cortisol) have a great influence on the metabolism and immune system of the body, they allow us to survive stress situations. Mineralocorticoids, whose main representative is hormone called aldosterone, have effects on kidneys and blood vessels. They reduce losses of sodium into the urine, increase potassium loss and help to constrict blood vessels to elevate blood pressure. The cortex produces sex hormones.
The mechanism of production control of these hormones is also worth noting. Cortisol production is controlled by our brain; control centers are located in hypothalamus and pituitary gland. Their control over cortisol production is administered by hormones called CRH (Corticotropin-releasing hormone) and ACTH (Adrenocorticotropic hormone). Adrenal aldosterone production is controlled from both brain and kidneys.
The kidneys produce a hormone called renin which enters adrenal glands with blood flow and this hormone causes an increased production of aldosterone.
Addison's disease is therefore a disorder of the adrenal cortex which is connected with reduction or complete loss of cortical hormone production (cortisol and aldosterone).
Why does the malfunction occur? The most common cause is an autoimmune inflammation of adrenal tissue. Classic Addison's disease is therefore linked to the formation of antibodies against cells of the adrenal cortex and belongs to the group of autoimmune diseases. The direct cause of antibodies occurrence is not known and probably can be attributed to genetic predisposition combined with a viral infection that changes parameters of patient’s immune system.
The adrenal cortex, however, may be suddenly destroyed by some infections, typically by meningococcal infection. Severe forms of this infection cause hemorrhage of both adrenal glands which leads to impairment of their function. This is known as Waterhouse - Friderichsen syndrome.
It is also important to note that any damage done to hypothalamus or pituitary gland (tumor, infection, and trauma) may decrease production of ACTH hormone and thus will also undermine cortisol production with similar symptoms as by above mentioned autoimmune Addison's disease. This uncommon condition is sometimes referred to as a central form of Addison's disease. The difference is that the cortex is intact (it only lacks the control brain hormone) and that aldosterone production is less influenced.
Long-term deficiency of cortical hormones manifests as general fatigue, low blood pressure, weight loss, recurrent episodes of abdominal pain and abnormal thirst. Loss of aldosterone function leads to higher losses of sodium in urine and on the contrary to accumulation of potassium in the body. High levels of potassium leads to diarrhea and can cause lethal heart rhythm disorders.
When adrenal cortex is damaged and concentration of cortical hormones lowers, the brain centers recognize low concentration of cortisol in the body and tries to improve this state - starts to produce a lot of CRH and ACTH hormones. That also increases production of certain pigment substances. Because of this sick people often paradoxically look very healthy and tanned (even in winter) and dark spots (so called graphite spots) appear in their oral mucosa.
In central form of Addison's disease CRH and ACTH production is reduced and hyper pigmentation does not appear. In addition by central form aldosterone production is not so heavily impaired and thus the disease symptoms are less severe.
The above symptoms can guide the physician to a suspicion. In addition we find lower blood concentration of sodium and higher potassium blood concentration. It is essential to assess concentrations of ACTH and cortisol from the blood. Cortisol is always reduced in Addison's disease. ACTH will be reduced only in the central form of Addison's disease (i.e. damaged hypothalamus or pituitary gland).In autoimmune form of Addison disease caused by damage to the adrenal gland, we can serologically diagnose auto antibodies in patient's blood. By using imaging methods we can check the condition o adrenal gland a brain structures. Adrenal glands are examinable by abdominal ultrasound, both brain and adrenal glands can also be visualized by computed tomography or magnetic resonance imaging.
Treatment is administered by an endocrinologist. In acute cases it is necessary to supplement body fluids by infusions and treat any infectious complications. Overall it is then necessary to complement the missing hormones. In the absence of cortisol and aldosterone we use artificially produced glucocorticoids (cortisol replacement therapy) with a small dose of aldosterone replacement. The medication must be regular; dosage should be increased during stress situations (infections, physical trauma etc).