Addison's disease

Synonym: primary adrenal insufficiency
German: Morbus Addison

1 Definition

Addison's disease is a rare, but potentially lethal disease with a complete loss of function oft the adrenal glands.

Addison's disease as a disease of the adrenal cortex (primary adrenal insufficiency) is to be differentiated from secondary adrenal insufficiencies.

2 Etiology

In Addison's disease, the entire adrenal cortex is destroyed. According to the speed of the destroying process, the deficiency symptoms can be acute or chronically and gradually increasing. Acute deficiency symptoms (Addisonian crisis), as a potentially lethal condition, require medical emergency treatment at a hospital.

Causes of the adrenal cortex hypofunction especially are:

• Organ-specific autoimmune disease with antibody production against adrenal cortex tissue (occasionally also in the course of an pluriglandular insufficiency. This leads to the production of autoimmune 21-hydroxylase-antibodies.
• Polyendocrine autoimmune diseases in form of the Schmidtsí syndrome
• Hemorrhagic infarction (sepsis, Waterhouse-Friedrichsen syndrome, arterial hypertension, hemorrhagic diathesis)
• Tuberculosis of the adrenal gland
• Hemochromatosis
• Adrenogenital syndrome
• metastases of a primary tumor
• Toxicity of medicinal drugs (eg. ketoconazol)
• Amyloidosis of the adrenal glands

A possible iatrogenic cause of Addison's disease is a bilateral adrenalectomy.

3 Symptoms

From the loss of function of the adrenal cortex results a cortisol deficiency, and, in contrast to the secondary functional adrenal disorder, a mineralcorticoid (aldosterone) deficiency adds to that. The ACTH secretion is enormously increased in primary Addison's disease.

The symptoms are caused by a hormonal deficiency and the excessive ACTH secretion.

• Aldosterone deficiency
  • Hypotension
  • Hyponatremia
  • Hyperkalemia
  • Acidosis
  • "Salt appetite"
• Cortisol deficiency
  • Sensation of weakness
  • Nausea and vomiting
  • Weight loss
  • Hypoglycemia
• Increased ACTH secretion
  • Hyperpigmentation of the skin, caused by the release of α-MSH due to the split-off of ACTH from the precursor POMC.

A 69-Year-Old Female with Tiredness and a Persistent Tan

An androgen deficiency in women can manifest by the loss of the axillary and pubic hair. In the blood cell count, you frequently can find a concomitant anemia. The retention values can increase, too.

• Comment: In summary, the most frequent symptom complex consists of weakness, weight loss, hyperpigmentation and hypotension and is pathbreaking for the suspected diagnosis Addison's disease.

3.1 Addison's crisis

An Addisonian crisis is the acutely life-threatening progressive form of Addison's disease, which can be caused by a rapid loss of function of the adrenal gland (eg. infarction), acute progression of a chronic loss of function, or else by stress situations (trauma, infectious disease) in the case of an existing latent Addison's disease.

Addisonian crisis symptomatically manifests, in addition to the symptoms named above, as:

• Vigilance disorder
• Dehydration
• Fever
• Hypoglycemia
• Pseudoperitonitis

Due to the limited blood pressure regulation, the patient can slide into a severe, in any case life-threatening, state of shock.

4 Diagnostics

The further diagnostics continuative to taking the clinical history and physical exam predominantly serves the differentiation between Addison's disease and a secondary adrenal insufficiency.

• In Addison's disease, the ACTH stimulation test does not trigger an increased cortisol secretion
• The demonstration of a high ACTH level speaks for primary Addison's disease
• Low morning cortisol levels in morning sample taking

The best differential diagnosis, however, bases on the different clinical symptom complexes of both forms of insufficiency. When signs of an Addisonian crisis emerge, you should administer glucocorticoid and mineral corticoids as a life-saving measure even before taking further diagnostic measures.

5 Therapy

The therapy of Addison's disease consists in the lifelong substitution of glucocorticoids and mineral corticoids. However, the patients concerned have to be instructed about the nature of their disease and potentially adaptations of therapy. As far as possible, they should carry an Addison pass with a statement of the disease for emergency situations.

The glucocorticoid substitution should be recreating the natural circadian rhythm (eg. 25mg of hydrocortisone in the morning, 10mg at noon). Increased physical stress requires a temporary increase in dosage.

In an Addisonian crisis, high doses of up to 200mg of hydrocortisone per day should be immediately administered via intravenous infusion. The treatment takes place at the hospital.

The mineral corticoid substitution consists in the morning administration of the cortisol derivative fludrocortisone, which has the same mineral corticoid effect as aldosterone. The goals of the substitution are the normalization of the electrolytes, of the renin, and a sufficient blood pressure regulation in orthostasis (see Schellong test).