Why does ACTH cause hyperpigmentation

Addison's disease

Synonym: primary adrenal insufficiency, "bronze disease"
English: Addison's disease

1 definition

The Addison's disease is a rare but potentially life-threatening disease with a complete loss of function of the adrenal cortex.

Addison's disease is a disease of the adrenal cortex (Primary adrenal insufficiency) to differentiate from secondary adrenal insufficiency.

2 etiology

In Addison's disease, the entire adrenal cortex is destroyed. Depending on the speed of the destructive process, failure-related symptoms can occur acutely or chronically. Acute deficiency symptoms (Addison's crisis) are life-threatening and require emergency medical treatment in the hospital.

The main causes of the underfunction of the adrenal cortex are:

Iatrogenically, Addison's disease can be caused by a bilateral adrenalectomy.

3 pathophysiology

The loss of function of the adrenal cortex results in a cortisol deficiency and, in contrast to the secondary disorders of the adrenal function, there is also a deficiency in mineral corticoids (aldosterone) and androgens (in women). ACTH secretion is significantly increased in primary Addison's disease.

The following metabolic changes occur due to the aldosterone deficiency:

The cortisol deficiency manifests itself as hypoglycaemia.

4 symptoms

The symptoms of the disease can initially be unspecific. In the full screen, it includes various organ systems:

4.1 skin

A typical Addison symptom is hyperpigmentation of the skin. It is caused by the release of α-MSH during the cleavage of ACTH from the precursor POMC. Particularly noticeable is the pigmentation of hand lines, fresh scars and lip edges as well as the skin of the genital region.

4.2 Gastrointestinal tract

4.3 Cardiovascular system

4.4 CNS

4.5 Other symptoms

Patients often complain of a general feeling of weakness. The combination of hypoglycemia and hypotension can cause the patient to suddenly become unconscious. Concomitant anemia is often found in the blood count. The retention values ​​can also increase.

In women, androgen deficiency triggers menstrual disorders, decreased libido, and loss of armpit and pubic hair.

Annotation: In summary, a symptom complex consisting of weakness, weight loss, hyperpigmentation and hypotension is most frequently indicative of the suspected diagnosis of Addison's disease.

4.6 Addison crisis

An Addison's crisis is the acutely life-threatening form of Addison's disease, which is caused by a very rapid loss of function of the adrenal gland (e.g. infarction), acute progression of a chronic loss of function or stressful situations (trauma, infectious disease) with existing latent Addison's disease.

The Addison's crisis manifests itself symptomatically in addition to the above symptoms as:

The restricted blood pressure regulation can lead to a severe and in any case life-threatening state of shock.

5 diagnostics

The further diagnostics that follow the medical history and physical examination serve primarily to differentiate Addison's disease from secondary adrenal insufficiency:

  • In the ACTH stimulation test, no increased cortisol secretion could be triggered in Addison's disease
  • The determination of a high ACTH level suggests primary Addison's disease
  • Low morning cortisol levels by morning determination

The best differential diagnosis, however, allows the different clinical symptoms of the two forms of insufficiency. If there are signs of Addison's crisis, glucocorticoids and mineral corticoids should be administered as a life-saving measure before further diagnostic steps are carried out.

5.1 Detection of autoantibodies

Autoantibodies against the adrenal cortex are associated with the occurrence of autoimmune adrenalitis. These autoantibodies can be detected using indirect immunofluorescence.

5.1.1 Material

1 ml of serum or plasma is required for the examination.

5.1.2 Reference range

With an initial dilution of 1:10, there should be no evidence of autoantibodies in the indirect immunofluorescence. If the serum is positive, the cytoplasm of the steroid hormone-producing cells in the cortex shows a granular to smooth fluorescence.

5.1.3 Interpretation

At the onset of autoimmune adrenalitis, the prevalence of autoantibodies is over 80%. With increasing atrophy of the adrenal glands, autoantibodies can be detected less and less. The determination of the adrenal autoantibodies enables the differential diagnostic differentiation from other causes of Addison's disease. However, positive antibody detection can also be present in diseases from the group of autoimmune polyendocrinopathies.

6 therapy

Therapy for Addison's disease consists of lifelong substitution of glucocorticoids and mineral corticoids. The affected patient must be instructed about the nature of his illness and any necessary therapy adjustments. If possible, he should carry an Addison passport with him in case of an emergency with a note of his illness.

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

In the event of an Addison's crisis, high doses of up to 200 mg hydrocortisone per day should be administered intravenously immediately. The treatment takes place in the hospital.

Mineral corticoid substitution takes place in the morning with the cortisol derivative fludrocortisone (about 0.1 mg / d), which has the same mineral corticoid effect as aldosterone. The aim of substitution is the normalization of electrolytes, renin and adequate blood pressure regulation with orthostasis (see Schellong test).

7 web links

8 sources

  • Lehnert, H: Rational diagnostics and therapy in endocrinology, diabetology and metabolism. 3rd edition, 2010. Thieme Verlag. DOI: 10.1055 / b-0034-13740
  • Laborlexikon.de, accessed on April 6, 2021
  • Stöcker W: Lexicon of medical laboratory diagnostics. Springer, Berlin, Heidelberg. 2019