Adrenal hypofunction – Addison’s disease

primary adrenal hypofunction, secondary adrenal hypofunction, Addison's disease

Addison's disease is a chronic condition that affects the adrenal cortices and results in a deficiency of important hormones. This causes sufferers to feel exhausted and their skin to turn brown. That is why it is also called "Hemochromatosis".

Overview: What is adrenal hypofunction?

The adrenal glands are small organs located above each of the two kidneys. They consist of the adrenal medulla on the inside and the adrenal cortex on the outside. The cells of the adrenal cortex have the task of producing vital hormones that are involved in numerous bodily functions. These include mineralocorticoids such as aldosterone, glucocorticoids (“stress hormones”) such as cortisol, and a precursor hormone of the male sex hormones, dehydroepiandrosterone (DHEA).

In adrenal hypofunction, the cells can no longer perform this function properly. This leads to a weakness in performance or function, a so-called insufficiency. Experts therefore refer to this failure of the adrenal cortex as adrenal insufficiency (NNR insufficiency).

This results in a hormone deficiency. This can cause numerous specific and non-specific complaints. Without therapy for adrenal hypofunction, the consequences are potentially life-threatening. Therefore, it is important to detect the disease early and to treat it adequately.

The disease is named after the English physician Thomas Addison. Therefore, it is also called Addison’s disease.

Adrenal hypofunction – frequency and age

Adrenal hypofunction is a rare disease that can be divided into two forms in terms of cause:

Primary adrenal hypofunction refers to Addison’s disease proper and involves the adrenal gland itself. It occurs in about 100 out of one million people. The annual rate of new cases is five per million population, and the incidence has been increasing in recent years. It results from autoimmune-mediated inflammation in more than 80 percent of cases in industrialized countries and most commonly affects individuals in younger to middle age. In principle, however, the disease can occur at any age. Overall, women fall ill more frequently than men.

Secondary adrenal hypofunction results from a Secondary adrenal hypofunction of the pituitary gland (hypophysis) or the superior part of the diencephalon (hypothalamus). Weakness of the anterior pituitary lobe occurs in 300 out of one million people. Since there are numerous possible causes, there is no age- or gender-specific group of people affected.

Adrenal hypofunction: causes and risk factors

As mentioned earlier, in Addison’s disease, the adrenal cortex can no longer produce certain hormones such as cortisol, aldosterone, and dehydroepiandrosterone (DHEA).

In an autoimmune disease, the immune system produces antibodies and inflammatory cells against the body’s own substances. In the case of Addison’s disease, this attack is directed against the cells of the adrenal cortex. As a result, it can no longer perform its task of producing hormones. In about 60 percent of patients with autoimmune adrenal insufficiency, other autoimmune diseases often directed against other endocrine glands develop in the course of the disease.

  • an infection by tuberculosis or with the cytomegalovirus (CMV)
  • surgical removal of the adrenal cortex
  • Hemochromatosis (hereditary iron storage disease)
  • Amyloidosis (deposits of proteins (protein substances) outside the cells)
  • Adrenoleukodystrophy (inborn error of metabolism)

The most common reason for secondary adrenal weakness is treatment with synthetic glucocorticoids (cortisone preparations), such as those commonly used to treat rheumatism, autoimmune diseases, allergies or asthma. As a result, pituitary-adrenal hypofunction and, subsequently, adrenal insufficiency may develop. It is important to note that the risk of adrenal insufficiency increases with the dose and duration of glucocorticoid therapy.

  • A benign tumor of the pituitary gland
  • A severe traumatic brain injury
  • Radiation or surgery to the pituitary gland or diencephalon area.
  • An inflammation of the pituitary gland (as a spontaneous autoimmune disease or as a result of immunotherapy against a cancer).

Symptoms: Adrenal hypofunction

As a result of the autoimmune disease, the tissue of the adrenal cortex gradually perishes. However, symptoms usually do not occur until around 85 percent of the cells have been destroyed.

Because the adrenal cortex produces several hormones that have different functions and roles in the body, a wide variety of symptoms can occur. These are often non-specific, so may be due to other diseases or disorders. The most common complaints include:

  • Fatigue
  • Weakness
  • Nausea and vomiting
  • Weight loss
  • Low blood pressure
  • Cardiac arrhythmias
  • Salt hunger
  • Potency disorders
  • Absence of menstruation
  • Breathing probelms
  • Confusion, depression
  • in children and adolescents growth disorders

Man sits on the sofa and holds hands in front of his face. A typical and noticeable symptom of Addison’s disease is a brown discoloration of the skin. This phenomenon is also called “bronze skin disease”. This also discolors areas of the skin that are not exposed to the sun, or those that do not normally tan. This affects even the palms, lips or mucous membrane. The reason is cortisol deficiency due to adrenal insufficiency. This causes the level of adrenocorticotropic hormone (ACTH) in the blood to be elevated. This messenger substance stimulates the pigment-forming cells (melanocytes), causing the skin to turn brown. In contrast, in secondary adrenal hypofunction, the brown coloration is absent.

Adrenal hypofunction: Diagnosis at the USZ

Adrenal hypofunction is a rare condition. Recognition, diagnosis and therapy require special clinical experience and expertise. Fatigue and exhaustion are very non-specific symptoms and therefore provide little clear evidence of Addison’s disease. Therefore, we will perform multiple blood tests for accurate diagnosis. Important clues for adrenal hypofunction provide

  • a low level of cortisol
  • further deficiency of other adrenal hormones (aldosterone, DHEAS)
  • a disturbed electrolyte balance (sodium deficiency, potassium excess)
  • an increased concentration of adrenocorticotropic hormone (ACTH)
  • Antibodies as an indication of autoimmune disease.
  • Lack of stimulability of the adrenal gland in a functional test

However, it often takes a long time before a clear diagnosis can be made. Often, several examinations are necessary for this purpose. To make matters worse, the disease is very rare and symptoms are often very non-specific. Therefore, we do not always have adrenal hypofunction “on the screen” right away.

Adrenal hypofunction: prevention, early detection, prognosis

As an autoimmune disease, Addison’s disease is partly hereditary. Thus, in this case, prevention is hardly possible. In case of frequent occurrence of other autoimmune diseases (e.g. type 1 diabetes, hypothyroidism, vitiligo), a targeted follow-up may be useful.

It is also important to keep a close eye on hormone levels when being treated with glucocorticoids (cortisone preparations).

Course and prognosis of adrenal hypofunction

The decisive factor for the course of the disease is how quickly the tissue of the adrenal cortex is destroyed and the organ fails. Without treatment, the disease continues to progress. As a result, the body becomes weaker and weaker. In some cases, affected individuals may even fall into a coma as a result. Triggers for these adrenal crises can be other diseases, accidents or surgeries that “unmask” a previously unknown hypofunction.

If, on the other hand, hormone replacement therapy is administered sufficiently and early on, those affected have a good life expectancy and quality of life. However, it is important that the required hormone doses are individually adjusted.

If, for example, the need for cortisol increases in situations of physical or mental stress, but the dose is not increased, this can also lead to a life-threatening Addisonian crisis. This risk also exists if the body cannot sufficiently absorb the hormone due to diarrhea or vomiting. In such cases, it is important that you, as the person concerned, are well trained and seek medical advice immediately if in doubt.

Because of possible complications, you should also always carry an emergency identification card and an emergency hydrocortisone kit.

Adrenal hypofunction: treatment with hormones

Once a diagnosis has been made, further therapeutic decisions are anchored in an interdisciplinary team, for example together with the Department of Neurosurgery in the case of diseases of the pituitary gland. Therapy with hormones depends on the cause of the disease. In the case of autoimmune adrenal insufficiency, the cause cannot usually be eliminated. In this case, the main goal of treatment is to relieve symptoms and improve quality of life through hormone replacement therapy. For this purpose, we prescribe different hormones:

  • Hydrocortisone: In the case of a deficiency of glucocorticoids, it is administered. They usually take it two to three times a day.
  • Fludrocortisone: If there is an undersupply of mineral corticosteroid, the deficiency is corrected by taking fludrocortisone daily.

Important to know: The destroyed tissue of the adrenal cortex cannot regenerate. Therefore, hormone replacement therapy must be given for life. However, recovery of the hormonal axis is possible in diseases of the pituitary gland or after glucocorticoid therapy.