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Addison’s Disease Causes

What Leads to Adrenal Insufficiency?

Adrenal insufficiency—when your adrenal glands don’t produce enough of the hormone cortisol—can be caused by a primary adrenal gland disorder (this is called Addison’s disease or primary adrenal insufficiency).

Alternatively, adrenal insufficiency can be caused by a deficiency of the adrenocorticotropin hormone (ACTH). ACTH stimulates the adrenal glands to produce cortisol, so if there’s too little ACTH, you may have low levels of cortisol (this is called secondary adrenal insufficiency).
Much more rare—but still a possible cause of adrenal insufficiency—is an injury to the hypothalamus, a gland in the brain that produces releasing and inhibiting hormones (hormones that tell the other endocrine glands to start and stop production). A hypothalamic injury can lead to a corticotrophin-releasing hormone (CRH) deficiency. CRH is what tells the pituitary gland to produce ACTH, which then stimulates cortisol production in the adrenal glands. A CRH deficiency can lead to an ACTH deficiency—and then to adrenal insufficiency.
Primary Adrenal Insufficiency: Addison’s Disease
The outer layer of the adrenal glands is called the adrenal cortex. If the cortex is damaged, it may not be able to produce enough cortisol.
A common cause of primary adrenal insufficiency is an autoimmune disease that causes the immune system to attack healthy tissues. In the case of Addison’s disease, the immune system turns against the adrenal gland(s). There are some very rare syndromes (several diseases that occur together) that can cause autoimmune adrenal insufficiency. 
Autoimmune Polyendocrine Syndrome
Autoimmune polyendocrine syndrome (APS) is a rare cause of Addison’s disease. Sometimes referred to as multiple endocrine deficiency syndrome, APS is further categorized as type 1 or type 2.
APS type 1. Symptoms start during childhood. Almost any organ can be affected by autoimmune damage. Fortunately it is extremely rare—only several hundred cases have been reported worldwide. Conditions associated with APS type 1 include:
  • Addison’s disease
  • Diminished parathyroid function
  • Delayed or slow sexual development
  • Vitamin B12 malabsorption / deficiency (pernicious anemia)
  • Candidiasis (chronic yeast infection)
  • Hepatitis
APS Type 2. Symptoms primarily develop in adults aged 18 to 30. Conditions associated with APS type 2 include:
  • Addison’s disease
  • Underactive or overactive thyroid function
  • Delayed or slow sexual development
  • Diabetes
  • White skin patches (vitiligo)
  • Celiac disease
When people with APS type 2 are affected by Addison’s disease and thyroid disease, this condition is sometimes called Schmidt’s syndrome.
Other causes of primary adrenal insufficiency include:
  • Amyloidosis—protein build up in organs (very rare)
  • Bleeding into the adrenal glands
  • Cancer that spreads to the adrenal glands
  • Infections (bacterial, fungal, tuberculosis) of the adrenal glands
  • Surgical removal of the adrenal glands
Secondary Adrenal Insufficiency: ACTH Deficiency
Secondary adrenal insufficiency is caused by a lack of the adrenocorticotropin hormone (ACTH). ACTH is made in the pituitary gland. It’s your brain’s signal to the adrenal glands, telling them to make cortisol. 
By far the most common cause of this type of adrenal insufficiency is chronic steroid use. When steroids (which have the same action as cortisol) are taken to treat other medical conditions, the brain stops sending the ACTH signal to the adrenals to make the body’s own cortisol. Once steroids are stopped, it can take a long time for the brain to resume sending this signal, which causes adrenal insufficiency. 
The following conditions can also affect ACTH production and therefore hinder cortisol secretion:
  • Loss of blood flow (circulation) to the pituitary gland
  • Pituitary tumor, or other brain tumor that puts pressure on the pituitary
  • Radiation treatment of pituitary tumor
  • Surgical removal of the pituitary gland or hypothalamus
  • Severe head injury
  • Severe infection
Addison’s Disease: When It Becomes a Crisis
The symptoms of Addison’s disease may slowly develop and progress. Sometimes a stressful event or illness causes symptoms to suddenly develop or worsen. Adrenal crisis—or Addisonian crisis—is a condition that merits urgent medical attention because these symptoms can be fatal.
The symptoms of an Addisonian crisis include:
  • Dehydration and/or severe vomiting and diarrhea
  • Stabbing pain in the abdomen, low back, or legs
  • Low blood pressure (shock)
  • Low blood sugar
  • Loss of consciousness
Life-saving treatment with steroids can only be given if the emergency medical team knows that you have adrenal insufficiency; the symptoms of Addisonian crisis can affect your thinking and even cause loss of consciousness, so it’s essential that all patients with adrenal insufficiency wear a medical alert bracelet or necklace that clearly states their diagnosis.


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