Addison’s disease – Definition – Description – Causes – Treatment
Addison’s disease Definition
Addison’s disease is a disorder involving disrupted functioning of the part of the adrenal gland called the cortex. This results in decreased production of two important chemicals (hormones) normally released by the adrenal cortex: cortisol and aldosterone.
Addison’s disease Description
The adrenals are two glands, each perched on the upper part of the two kidneys. The outer part of the gland is known as the cortex; the inner part is known as the medulla. Each of these parts of the adrenal gland is responsible for producing different types of hormones. Cortisol is a very potent hormone produced by the adrenal cortex. It is involved in regulating the functioning of nearly every type of organ and tissue throughout the body, and is considered to be one o the few hormones absolutely necessary for life. Cortisol is involved in: the very complex processing and utilization of many nutrients, including sugars (carbohydrates), fats, and proteins the normal functioning of the circulatory system and the heart the functioning of muscles normal kidney function production of blood cells the normal processes involved in maintaining the skeletal system proper functioning of the brain and nerves the normal responses of the immune system Aldosterone, also produced by the adrenal cortex, plays a central role in maintaining the appropriate proportions of water and salts in the body. When this balance is upset, the volume of blood circulating throughout the body will fall dangerously low, accompanied by a drop in blood pressure. Addison’s disease is also called primary adrenocortical insufficiency. In other words, some process interferes directly with the ability of the adrenal cortex to produce its hormones. Levels of both cortisol and aldosterone drop, and numerous functions throughout the body are disrupted. Addison’s disease occurs in about four in every 100,000 people. It strikes both men and women of all ages.
Addison’s disease Causes
Causes of adrenal insufficiency can be grouped by the way they cause the adrenals to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to the gland being damaged).
Adrenal dysgenesis
All causes in this category are genetic, and generally very rare. These include mutations to the SF1 transcription factor, congenital adrenal hypoplasia (AHC) due to DAX-1 gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). DAX-1 mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes.
Impaired steroidogenesis
To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith-Lemli-Opitz syndrome and abetalipoproteinemia.
Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations.[2] Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole), while others accelerate the normal breakdown of hormones by the liver (e.g. rifampicin, phenytoin).
Adrenal destruction
Autoimmune adrenalitis can be a cause of Addison's disease. Autoimmune destruction of the adrenal cortex (often due to antibodies against the enzyme 21-Hydroxylase) is a common cause of Addison's in teenagers and adults. This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2).
Adrenal destruction is also a feature of adrenoleukodystrophy (ALD), and when the adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g. in Waterhouse-Friderichsen syndrome or antiphospholipid syndrome), particular infections (tuberculosis, histoplasmosis, coccidioidomycosis), deposition of abnormal protein in amyloidosis.
Other Causes to Addison’s disease
Less common causes of Addison’s disease are
* chronic infection, mainly fungal infections
* cancer cells spreading from other parts of the body to the adrenal glands
* amyloidosis, a disease that causes abnormal protein buildup in, and damage to, various organs
* surgical removal of the adrenal glands
* AIDS-associated infections
* bleeding into the adrenal glands
* genetic defects including abnormal adrenal gland development, an inability of the adrenal gland to respond to ACTH, or a defect in adrenal hormone production.
How is adrenal insufficiency diagnosed?
In its early stages, adrenal insufficiency can be difficult to diagnose. A review of a patient’s medical history and symptoms may lead a doctor to suspect Addison’s disease.
A diagnosis of adrenal insufficiency is confirmed through laboratory tests. The aim of these tests is first to determine whether levels of cortisol are insufficient and then to establish the cause. Radiologic exams of the adrenal and pituitary glands also are useful in helping to establish the cause.
Addison’s disease Treatment
Maintenance treatment
Treatment for Addison's disease involves replacing the missing cortisol, usually in the form of hydrocortisone tablets, in a dosing regimen that mimics the physiological concentrations of cortisol. Alternatively one quarter as much prednisolone may be used for equal glucocorticoid effect as hydrocortisone. Treatment must usually be continued for life. In addition, many patients require fludrocortisone as replacement for the missing aldosterone. Caution must be exercised when the person with Addison's disease becomes unwell, has surgery or becomes pregnant. Medication may need to be increased during times of stress, infection, or injury.
Resources
http://en.wikipedia.org/wiki/Addison%27s_disease
