Addison's disease

Generality

Addison's disease is a clinical condition caused by primary adrenocortical hormone deficiency; Also known as corticosteroids, these hormones are produced by two small endocrine glands located in the fat overlying the kidneys and therefore called the adrenal glands.

In their outermost portion, called cortical, these glands produce and secrete three types of hormones: androgens, glucocorticoids and mineralocorticoids.

The concentration of cortisol is normally regulated by the pituitary and the hypothalamus. The latter sends the CRH hormone to the pituitary gland and the gland responds by producing one of its hormones which is ACTH; this hormone stimulates the adrenal glands to produce cortisol; in turn, the cortisol concentration participates in the regulation of the ACTH concentration.

The very important biological action of these hormones (which is lacking in patients suffering from Addison's disease) can be summarized as follows:

glucocorticoids, such as cortisol, participate in the control of blood sugar (by increasing it), suppress the immune response and support the body under stressful conditions; the deficiency causes tiredness, easy fatigue, weakness, hypoglycemia, anorexia (loss of appetite), nausea, vomiting, abdominal pain and weight loss;
mineralocorticoids, such as aldosterone, regulate the plasma concentration of sodium and potassium, favoring the reabsorption of the former and the excretion of the latter (therefore they have a hypertensive role). Aldosterone deficiency causes loss of water and salts, causing dehydration, hypotension and a 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 development, sebaceous secretion and a sense of general well-being.

Symptoms

For further information: Symptoms of Addison's disease

Chronic cortisol and aldosterone deficiency is responsible for the classic symptoms attributable to untreated Addison's disease; in most cases, clinical manifestations arise gradually, characterized by weight loss, lack of appetite, muscle weakness and chronic worsening fatigue; they can also be associated with nausea, vomiting, diarrhea, orthostatic hypotension (dizziness and blurred vision when passing from a sitting or lying position to standing), irritability and depression, headache, sweating, hypoglycemia, a distinct propensity for salty foods and , in women, menstrual irregularities, amenorrhea and loss of pubic and axillary hair.

Symptoms of Addison's disease are very varied in type and intensity, and include: fatigue, weakness, muscle aches, weight loss, depression, anorexia, dark skin (looks tanned), low blood pressure, nausea, vomiting, diarrhea, desire of salty food.

Another characteristic sign of Addison's disease (absent in the secondary forms) is the so-called melanoderma: 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 in an attempt (ineffective) to stimulate the production of cortisol by the adrenal gland, which, however, is unable to.

Since many of these symptoms tend to arise and worsen in a slow and subtle way, they often end up being ignored, at least until a particularly stressful event, such as an illness or an accident, causes a drastic worsening of the situation. "Addisonian crisis" (acute adrenal insufficiency) is accompanied by much more severe symptoms, such as weakness, apathy, confusion, severe hypotension up to hypovolemic shock (drop in blood pressure and loss of consciousness), nausea, vomiting, abdominal pain and fever.

Acute adrenal insufficiency (hypoadrenal crisis) can occur before or after the diagnosis of Addison's disease, for example when the patient is exposed to severe physical stress (infections, trauma, surgery, severe dehydration due to excessive heat, vomiting and diarrhea) or when self-suspending steroid replacement therapy.

In the absence of treatment, an Addisonian crisis can be fatal, just as the disease itself was lethal until the 1940s. Today, however, 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 its 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 nonspecific 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 of age.

Among the risk factors, in addition to the familiarity for the disease, we remember the presence - in the same subject - of other autoimmune diseases, such as Hashimoto's thyroiditis, Graves' disease, pernicious anemia, type I diabetes mellitus, "hypoparathyroidism and" primary gonadal insufficiency.

Causes

The clinical condition described above is caused by a hormonal deficiency that can recognize different causes of origin:

impaired development of the adrenal glands (ADRENAL DYSGNENESIS);

damage / destruction of adrenal cortical cells (ADRENAL DESTRUCTION);

an ALTERED STEROIDOGENESIS (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 are unable to produce adequate amounts of cortisol and altestosterone. In the "secondary adrenal insufficiency, however, the symptoms are caused by" insufficient pituitary secretion of ACTH, a hormone that stimulates the adrenal gland to produce cortisol; in these cases the aldosterone levels remain normal.

The causes of origin of Addison's disease include all those diseases that undermine the functionality of the adrenal glands causing hormonal deficiency; this is the case, for example, of autoimmune forms (about 80% of cases) and infectious ones (tuberculosis), typical of the past and of developing countries.Other causes of primary adrenal insufficiency include adrenal carcinomas or metastases, amyloidosis, hemochromatosis, adrenal hemorrhages, surgical removal of the adrenal glands or their insufficient development due to congenital diseases.

In the forms of secondary renal insufficiency, the adrenal glands do not fully carry out their endocrine action due to the low responsiveness to a pituitary hormone, ACTH, which directs and stimulates its activity. ACTH deficiency - which may also be due to poor pituitary function - mainly determines cortisol deficiency, while aldosterone levels are generally maintained within the normal range. For the homeostatic balances that regulate our organism, the same condition can occur when a person in cortisone therapy abruptly suspends treatment, or, again, after the surgical removal of ACTH-secreting tumors.