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Addison’s Disease – Causes And Symptoms

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Addison’s Disease – Causes And Symptoms

Addison’s disease is a condition characterized by adrenocortical insufficiency due to the destruction or dysfunction of the entire cortex of adrenal glands, affecting both mineralcorticoid and glucocorticoid synthesis and function. Usually, Addison’s disease onset occurs when 90% or more of both adrenal glands are destroyed or dysfunctional.

In 1855, Thomas Addison first described the main symptoms of adrenocortical insufficiency: asthenia, adynamia hyperpigmantation, arterial hypotension and digestive symptoms. The occurrence of Addison’s disease is rare, the reported prevalence being 40-60 cases per 1 million population. The disease affects both sexes and occurs mostly in adults, aged between 30 and 50 years.

Addison’s Disease Causes

In most cases Addison’s disease is an idiopathic autoimmune adrenocortical insufficiency due to lymphocytic infiltration of the adrenal cortex, autoimmune atrophy or fibrosis. Addison’s disease as a result of autoimmune atrophy and tuberculosis represent almost 90% of all cases of adrenocortical insufficiency.

In the support of autoimmune process lie antibodies against adrenal tissue, of which the main autoantigen is represented by steroidogenic enzyme 21-hydroxylase (21OH), but antibodies against this enzyme are not directly involved in adrenal tissue distruction.

Addison's Disease

Addison’s Disease

It was observed that patients with Addison’s disease may have a hereditary predisposition and this disease may be associated with other autoimmune diseases such as celiac disease, type 1 diabetes mellitus, Hashimoto thyroiditis, Graves disease, vitiligo, premature ovarian failure, myasthenia gravis, primary biliary cirrhosis and others.

Addison’s Disease Symptoms

The onset of  Addison’s disease symptoms is usually nonspecific and insidious. Symptoms that form the classic picture of Addison’s disease are represented by fatigue-adynamia, hyperpigmentation of the skin and mucous membrane, low blood pressure and digestive syndrome.

Fatigue is both physical and mental. It has a vesperal character (gets worse in the evening), then with evolution of the disease becomes permanent. Adynamia is characterized by muscle weakness and myalgias due to trophic and metabolic disorders caused by decreased secretion of cortisol, the main glucocorticoid hormone secreted by the adrenal gland. In advanced stages of illness, fatigue and adynamia are extremely intense and for this reason patients experience extreme difficulty in performing the smallest movements (speech, gestures are slow and difficult).

Skin hyperpigmentation

Skin hyperpigmentation

Skin and mucous membrane hyperpigmentation usually appears with months or years before the onset of other symptoms and appears due to the fact that the excess of adrenocorticotrophic hormone (ACTH) has a stimulant effect on the melanocytes to produce melanin. Hyperpigmentation is usually generalized, but is more prominent on elbows, knees, extensor surfaces, knuckles and skin region that are constantly exposed to the sun. Palmar creases, nail beds, mucous membranes of the oral cavity (especially the dentogingival margins and buccal areas), and the vaginal and perianal mucosa may be similarly affected. Skin and mucous membrane hyperpigmentation is always present in cases of Addison’s disease with long evolution and may be absent in cases with short evolution.

Low blood pressure is characterized by a systolic blood pressure below 80 mmHg and a diastolic blood pressure below 50 mmHg. Hypotension is accentuated in standing, when faintness may occur. Low blood pressure may be accompanied by a rapid pulse, with low amplitude and occasionally arrhythmias may occur.

Digestive syndrome occurs in approximately 90% of patients with Addison’s disease. It is characterized by loss of appetite, weight loss, nausea, vomiting, diarrhea and abdominal pain. Patients present “salt craving”, they instinctively raise their dietary salt intake, and salt restriction can cause disease decompensation. In most cases, patients with Addison’s disease have gastric  hypoacidity, but sometimes, peptic ulcer may occur.

Skin Changes

Skin Changes

Other symptoms that may occur in Addison’s disease are represented by:

  • Neurological disorders: muscle atrophy, mixed sensory deficits, rarely  may occur flaccid or spastic paralysis and paraplegia;
  • Psychiatric disorders: asthenia, fatigue, latency in reactions, difficult or abolished initiative, depression and anxiety. Intellectual activity is diminished.
  • Olfactory, auditory, visual and gustative perceptions are heightened.
  • In male patients impotence and decreased libido may occur, especially in those with compromised or borderline testicular function.
  • Female patients may present amenorrhea or menstrual cycle disorders, but fertility is preserved. In female patients with Addison’s disease pregnancy is contraindicated. Absence of axillary and pubic hair and decreased body hair may also appear as a result of the loss of the adrenal androgens, which represent the major source of androgen hormones in females.