Addison Disease (Primary Adrenal Cortex Insufficiency)

Definition and Meaning of Addison Disease

Addison disease is the term for primary adrenocortical insufficiency. This means that functions of the outer portion of the adrenal gland known as the cortex is impaired. The impairment is not a consequence of any other disease and is therefore referred to as primary adrenocortical insufficiency. The adrenal cortex is mainly responsible for the production and secretion of two types of hormones – mineralocorticoids and glucocorticoids. Small amounts of male hormones (androgens) are also produced in the adrenal cortex. Addison disease means that the production of these hormones are impaired. The effects and symptoms of Addison disease is therefore due to lower than normal levels of mineralcorticoids and glucocorticoids as well as androgens to some extent.

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Incidence of Adrenal Gland Insufficiency

Overall Addison disease is rare. It occurs in about 4 to 6 out of 100,000 people. Addison disease due to unknown causes is slightly more common among females but overall there is no significant gender difference. Although it can also occur in children, Addison disease is more common among adults particularly in the 30 to 50 year age group.

Location of Gland Problem

The adrenal gland sits at the top of the kidney. There are two adrenal glands – one on either side. The gland has a central portion known as the medulla and an outer layer known as the cortex. The problem in Addison disease lies in the cortex of the adrenal gland. This portion of the adrenal gland produces three types of hormones :

  • Glucocorticoids like cortisol
  • Mineralcorticoids like aldosterone
  • Androgens (male sex hormones) like testosterone

Picture of the adrenal glands from Wikimedia Commons

Low Mineralocorticoids and Glucocorticoids

In Addison disease the adrenal cortex is destroyed or dysfunctional where it cannot produce sufficient amounts of the adrenocortical hormones. The main effects are seen with a deficiency of mineralocorticoids and glucocorticoids. Adrenal gland insufficiency is a chronic disorder and develops over a period of time. The symptoms associated with mineralocorticoid and glucocorticoid deficiency therefore develop slowly. In order for Addison disease to occur, both adrenal glands have to be affected where at least 90% of adrenocortical function is impaired.

Mineralocorticoid Deficiency

The mineralocorticoids like aldosterone regulate the electrolyte levels in the body. It facilitates the retention of sodium and excretion of potassium through the urine, sweat, saliva and even within the gut. When deficient, it leads to problems with blood pressure (hypotension), severe dehydration and acidosis (increased blood acidity).

Glucocorticoid Deficiency

The glucocorticoids like cortisol has a wide range of effects in the body including regulating the metabolism of foods, immune function and stress response. This is seen as a difficulty in controlling the blood glucose levels within a normal range (mainly hypoglycemia), weight loss, weakness and depression. The body’s response to tissue injury is also impaired.

Androgen Deficiency

Androgens (male sex hormones) are produced in small quantities by the adrenal cortex in both men and women. Loss of adrenal androgen does not have significant consequences in males since most of the androgens are produced by the testes. However, in women it can affect the distribution of body hair and sexual function to some degree.

Picture of the adrenal gland layers from Wikimedia Commons

Symptoms of Low Adrenocortical Hormones

The symptoms of Addison disease are due to a deficiency of mineralocorticoids and glucocorticoids, and to a less extent due to low androgen levels. The intensity of symptoms depends on the severity of the condition. Very severe symptoms may arise at times of stress when an adrenal crisis occurs.

  • Weakness
  • Fatigue
  • Low blood pressure (hypotension)
  • Low blood glucose (hypoglycemia)
  • Hyperpigmentation (darkening) of the skin and mucous membranes like inside the mouth.
  • Hypopigmentation (loss of skin pigmentation) in small patches usualy in hyperpigmented areas.
  • Loss of body hair in women, particularly the armpit and pubic hair.
  • Sexual dysfunction in women.
  • Muscle aches
  • Joint pains
  • Nausea
  • Vomiting
  • Diarrhea (sometimes)
  • Decreased appetite
  • Weight loss
  • Irritability
  • Depression
  • Dizziness
  • Fainting spells (sometimes)

Types of Adrenal Cortex Insufficiency

Adrenocorticotropin hormone (ACTH) secreted by the pituitary gland stimulates the adrenal cortex to release hormones. Adrenal cortex insufficiency can be broadly divided into primary and secondary depending on whether the problem is related to ACTH or not.

Primary

In primary adrenocortical insufficiency, the cortex of the adrenal gland is damaged, destroyed or dysfunctional for various reasons. Deficiency of adrenocortical hormones are due to the problem with the adrenal cortex despite normal and sometimes even elevated ACTH levels. Addison disease is the primary type.

Secondary

In secondary adrenocortical insufficiency, the cortex of the adrenal gland is normal but ACTH levels are lower than normal. Therefore the adrenal cortex is underactive. The problem lies in the pituitary gland and not the adrenal gland.

Adrenal Crisis vs Addison Disease

Addison disease is one type of primary adrenal cortex insufficiency. It is a chronic condition that develops gradually. Another primary type is an adrenal crisis. It is an acute condition where there is a sudden and severe deficiency of the adrenocortical hormones. Adrenal crisis tends to arise in Addison disease patients when there is a sudden cessation of corticosteroid therapy or there is an increased demand for adrenocortical hormones.

Causes and Risk Factors of Addison Disease

The exact cause of Addison disease is not always known. In the majority of cases it appears to be an autoimmune mechanism that results in adrenal gland gland. The other cases of Addison disease may be due to infections and tumors of the adrenal gland or bleeding within the gland that leads to functional impairment.

Idiopathic Autoimmune Addison Disease

This accounts for about 70% of Addison disease cases. Idiopathic means that the cause is unknown. Autoimmune means that the immune system is targeting the healthy tissue in the body. This leads to tissue damage and even destruction over time. The adrenal gland often shrinks in size (atrophy). A person who has an existing autoimmune disease is at a greater risk of this type of Addison disease.

Adrenal Gland Diseases

In these cases, the adrenal gland is diseased and therefore underfunctioning. It may be seen with :

  • Adrenal gland tumors, benign or malignant, although sometimes there can be an increase in gland function.
  • Infections of the adrenal gland such as tuberculosis (TB) and HIV infection.
  • Adrenal hemorrhage where there is bleeding within the gland.
  • Certain drugs like anticoagulants.

Addison Disease Tests and Diagnosis

There are various tests that should be conducted when diagnosing Addison disease. Some of these tests confirm low hormone levels while other tests differentiate between primary and secondary adrenocortical insufficiency. Blood tests are usually sufficient to confirm the diagnosis. In addition, imaging studies may be conducted to identify any lesions within the adrenal gland or pituitary gland. Various other investigation are utilized to monitor the symptoms and complications of Addison disease.

Laboratory tests that should be conducted include serum cortisol, adrenocorticotropin hormone (ACTH) levels and sodium and potassium levels to confirm low mineralocorticoids. An ACTH stimulation test involves injecting synthetic ACTH into the body and then testing the cortisol levels. If the adrenal gland does not respond to the ACTH by producing more cortisol, then the gland itself is damaged or dysfunctional as is the case in Addison disease.

Treatment of Addison Disease

Addison disease is a chronic disease and the aim of treatment is to restore the levels of the deficient hormones. This is achieved with steroid hormone replacement therapy which may be administered orally or through injections.

  • Aldosterone (mineralocorticoid) deficiency is restored with fludrocortisone.
  • Cortisol (glucocorticoid) deficiency is restored with prednisone or hydrocortisone.
  • Androgen (male sex hormone) deficiency is restored with dehydroepiandrosterone.

Ideally an adrenal crisis should be prevented by administering steroids prior to a major stress to the body such as surgery. This can be achieved through an IV (intravenous) infusion of hydrocortisone.

References :

www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001416/

www.mayoclinic.com/health/addisons-disease/DS00361

emedicine.medscape.com/article/116467-overview

www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/adrenal_disorders/addisons_disease.html

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