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Patient Information

What are the adrenal glands?

The adrenal glands sit atop the kidneys on both side of the body. They consist of an inner core named the medulla which is surrounded by a cortex made of 3 separate layers. The main role of the adrenal glands is hormone production and each layer of the organ is responsible for a different hormone.

Adrenaline, 'the fight or flight' stress hormone, is produced in the medulla core. The cortex is responsible for essential steroid hormones cortisol and aldosterone which are produced in  different layers. Cortisol helps the body to fight inflammation and control blood sugar levels while aldosterone contributes to blood pressure regulation. The cortex is also responsible for the production of sex hormones in another of its layers, known as adrenal androgens. 

What is adrenal insufficiency?

 Adrenal insufficiency is when the adrenal glands are incapable of producing sufficient amounts of essential steroid hormones, cortisol and aldosterone. 

What are the symptoms of adrenal insufficiency?

Symptoms of adrenal insufficiency normally develop gradually over time and include;

  • Severe fatigue and weakness
  • Loss of weight
  • Skin hyperpigmentation
  • Feeling faint
  • Low blood pressure

Other less common symptoms include;

  • Nausea
  • Vomiting 
  • Salt craving
  • Painful muscles and joints

What are the causes of adrenal insufficiency?

Adrenal insufficiency can have several causes. The most common is Addison's disease, named for its discoverer Thomas Addison. Addison's disease is an auto-immune disease, meaning the body's own immune system attacks the adrenal glands. Another causes of adrenal insufficiency is tumours in the pituitary gland, which controls the adrenal production of steroid hormones. More information on these causes of the disease can be found on the Society of Endocrinology's Patient Information page. 

Our research focuses on another cause of adrenal insufficiency, inherited genetic mutations. The pituitary gland controls hormone production in the adrenals through signaling in a negative feedback loop. This works though the action of a hormone called ACTH (adrenocorticotropic hormone). ACTH travels from the pituitary gland to the adrenals and induces cortisol production, this coristol then tells the pituitary gland to stop producing ACTH. However, when the adrenals glands are incapable of producing cortisol, this feedback loop breaks down. The overproduction of ACTH consequently leads to hyperpigmentation of the skin, an early indicator of the disease. 

There are multiple proteins which, when incorrectly coded by DNA, can cause the breakdown of this loop. MC2R encodes the receptor in the adrenal cells that interact with ACTH. If the receptor is faulty, the message from the pituitary gland can not enter the adrenals cells and therefore no cortisol is produced. Another gene, MRAP, is involved in the transport of the MC2R receptor to the cell membrane. Therefore if this protein is non-functional, it also results in no cortisol production.

Another example is the STAR protein, in this case ACTH instructs the adrenal cells to produce cortisol but production breaks down within the cell. Cortisol is produced from cholesterol and STAR is tasked with the transport of cholesterol to the mitochondria, where cortisol is produced. If this protein is dysfunctional then cortisol synthesis itself can not continue.

These proteins are all produced from cell machinery reading their DNA sequence blueprint, the gene. When a gene is altered (mutated) this can result in either the protein being built incorrectly or not being built at all and therefore the function of the protein is not carried out. Our group has discovered several mutations in genes that can cause adrenal insufficiency that you can read about here

For more information please follow the link below to the Society of Endocrinology's Patient Information website.



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