Generality
Addison's disease is a clinical condition caused by primitive adrenocortical hormone deficiency; also known as corticosteroids, these hormones are produced by two small endocrine glands allocated in the fat that overhangs the kidneys and therefore called adrenals.
In their outermost portion, called cortical, these glands produce and secrete three types of hormones: androgens, glucocorticoids and mineralocorticoids.
The very important biological action of these hormones (which is missing in patients suffering from Addison's disease) can be summarized as follows:
- glucocorticoids, such as cortisol, participate in the control of glycaemia (increasing it), suppress the immune response and support the body in conditions of stress; deficiency leads to tiredness, easy fatigue, weakness, hypoglycemia, anorexia (loss of appetite), nausea, vomiting, abdominal pain and weight loss;
- the mineralocorticoids, like aldosterone, regulate the plasma concentration of sodium and potassium, favoring the reabsorption of the former and the excretion of the latter (they therefore have a hypertensive role). Aldosterone deficiency causes loss of water and salts, causing dehydration, hypotension and craving for salty foods;
The small amount of androgens produced at the adrenal level is especially important in women, as it supports sexual desire, hair growth, sebaceous secretion and a sense of general well-being.
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To learn more: Symptoms of Addison's Disease
The chronic lack of cortisol and aldosterone is responsible for the classic symptoms attributable to the untreated Addison's disease; in most cases, clinical manifestations gradually arise, characterized by weight loss, lack of appetite, muscle weakness and chronic fatigue; they can also be associated with nausea, vomiting, diarrhea, orthostatic hypotension (dizziness and blurring of sight when passing from a sitting or lying position to an erect one), irritability and depression, headache, sweating, hypoglycemia, a sharp propensity for salty foods and, in women, menstrual irregularities, amenorrhoea and loss of pubic and axillary hair.
The symptoms of Addison's disease are very varied in type and intensity, and include: fatigue, weakness, muscle pain, weight loss, depression, anorexia, dark skin (appears tanned), low blood pressure, nausea, vomiting, diarrhea, desire of salty food.
Another characteristic sign of Addison's disease (absent in secondary forms) consists of the so-called melanodermia: a hyperpigmentation of the skin (especially noticeable at the level of skin folds, such as knuckles, scars and elbows, knees) and mucous membranes such as lips and mammary areoles . This manifestation is due to the increased secretion of ACTH by the pituitary gland in an (ineffective) attempt to stimulate the production of cortisol by the adrenal gland, which however is not able to.
Since many of these symptoms arise and worsen in a tendentially slow and nuanced manner, they often end up being ignored, at least until a particularly stressful event, such as an illness or an accident, causes a drastic deterioration of the situation. The consequent "Addisonian crisis" (acute adrenal insufficiency) is accompanied by much more severe symptoms, such as weakness, apathy, confusion, severe hypotension up to hypovolemic shock (collapse of pressure and loss of consciousness), nausea, vomiting, abdominal pain and temperature.
Acute adrenal insufficiency (hypo-adrenal crisis) can occur before or after the diagnosis of Addison's disease, for example when the patient is exposed to strong physical stress (infections, trauma, surgery, severe dehydration due to excessive heat, vomiting and diarrhea) or when self-suspending cortisone-based replacement therapy.
In the absence of treatment, an Addisonian crisis can be fatal, just as the disease itself was lethal until the 1940s of the last century. Today, instead, after an adequate diagnosis, hormone replacement therapy guarantees the patient with Addison's disease a life expectancy equal to that of normal people. Often, however, the real problem is noticing his presence, which should be suspected whenever you are faced with persistent fatigue and easy exhaustion. It must be said, however, that these symptoms are highly non-specific and that Addison's disease is a rather rare disease, characterized by an incidence of 1/10 cases per 100, 000 people, with a preference for adults between 30 and 50 years.
Among the risk factors, besides the familiarity for the pathology, we recall the presence - in the same subject - of other autoimmune diseases, such as Hashimoto's thyroiditis, Graves' disease, pernicious anemia, type I diabetes mellitus, l hypoparathyroidism and primary gonadal insufficiency.
Causes
The clinical condition described above is caused by a hormonal deficiency that can recognize various causes of origin:
an altered development of the adrenal glands (ADRENALIC DISGNENESIS);
damage to or destruction of adrenocortical cells (SURRENALIC DESTRUCTION);
an ALTERATA STEROIDOGENESI (anomalies in the process of synthesis of adrenal cortical hormones starting from cholesterol).
Addison's disease is caused by damage to the adrenal cells, which fail to produce adequate amounts of cortisol and altestosterone. In secondary adrenal insufficiency, however, the symptoms are caused by the insufficient pituitary secretion of ACTH, a hormone that stimulates the adrenal gland to produce cortisol; in these cases, aldosterone levels remain normal.
The causes of Addison's disease include all those diseases that undermine the adrenal function causing hormonal deficiency; this is the case, for example, of autoimmune forms (around 80% of cases) and infectious forms (tuberculosis), typical of the past and of developing countries. Other causes of primary adrenal insufficiency include carcinomas or adrenal metastases, amyloidosis, haemochromatosis, adrenal haemorrhage, surgical removal of the adrenal glands or insufficient development due to congenital diseases.
In the forms of secondary renal failure, the adrenal glands do not fully perform their endocrine action due to poor responsiveness to a pituitary hormone, ACTH, which directs and stimulates activity. The lack of ACTH - which may also be due to a poor pituitary function - determines above all cortisol deficiency, while aldosterone levels generally remain normal. For the homeostatic balances that regulate our body, the same condition can occur when a person on cortisone therapy abruptly suspends treatment, or, again, after the surgical removal of secreting ACTH tumors.
