Adrenal Insufficiency and Addison’s Disease Symptoms and Causes


Adrenal insufficiency is characterized by insufficient production of adrenal gland hormones such as cortisol and aldosterone.  The adrenal glands  are small organs located above each kidney. The adrenal gland consists of an inner layer called the medulla and an outer layer (shell) called the cortex. Each layer produces several different hormones that control many body systems. Hormone production is regulated by interactions between the hypothalamus , pituitary gland ,  and adrenal glands. Signaling and  feedback system If any part of it is not working, it can cause significant disorders and discomfort in the body. Primary adrenal insufficiency, also called Addison’s disease, negatively affects both cortisol and aldosterone levels. Insufficient or damaged adrenal glands cause this disease. Pituitary dysfunction results in secondary adrenal insufficiency and typically only affects cortisol production.  

Cortisol is a glucocorticoid hormone produced by the adrenal gland shell. Cortisol affects the metabolism of carbohydrates, proteins and fats, and blood sugar levels, acts as an anti-inflammatory and helps the body react to stress. The mineralocorticoid aldosterone produced by the adrenal gland regulates the balance of salt and potassium in the blood. If these two hormones are not sufficient, the body becomes weak, dehydrated, unable to maintain blood pressure or respond to stress appropriately.

Addison’s disease is detected in patients of all ages and affects both men and women equally. Symptoms of insufficiency may not appear until about 80-90% of the adrenal gland is damaged.

About 70% of primary adrenal insufficiency is due to an autoimmune process. In about 30% of cases, damage to the adrenal gland is due to other causes, such as tuberculosis , bacterial , viral and  fungal infections , adrenal bleeding , and spread of cancer to the adrenal glands. Rarely, it may be due to a genetic abnormality in the adrenal glands.

Secondary adrenal insufficiency is due to a decrease in the production of the pituitary hormone ACTH (adrenocorticotropic hormone). ACTH is the messenger of the pituitary gland. The adrenal gland tells the shell to start producing cortisol. If there is ACTH deficiency due to a pituitary   tumor or another cause, cortisol production is not stimulated.  Secondary adrenal insufficiency may occur due to abrupt discontinuation of corticosteroid therapy ( such as prednisone given to relieve inflammation in  diseases such as rheumatoid arthritis ). These treatments suppress natural cortisol production. It may take several weeks or months for normal production to resume. In secondary adrenal insufficiency, aldosterone production is usually unaffected. 


Symptoms and Causes

Symptoms associated with adrenal insufficiency are often vague and nonspecific. It can occur gradually, first appearing in times of stress, then gradually increasing in severity over several months. The following findings can be detected:

  • Stomach ache
  • Reduction in body hair
  • Dehydration of the body in Addison’s disease
  • diarrhea or constipation
  • dizziness and fainting
  • Tiredness  
  • Hyperpigmentation in Addison’s disease – particularly dark patches of skin folds, in some cases black spots on the forehead and face, and/or color changes around the nipples, lips, and rectum, the last part of the intestines
  • Joint and muscle pains
  • low blood pressure
  • Low blood sugar ( hypoglycemia)
  • muscle weakness
  • Salt starvation in Addison’s disease
  • Vomiting
  • weight loss

Sometimes, however, causes and symptoms of adrenal insufficiency can appear suddenly. In about 25% of cases, adrenal insufficiency is diagnosed during an adrenal crisis (also called Addisonian crisis). Increased stress, trauma, surgery or severe infection period can cause this crisis. It can be fatal if left untreated. Possible causes and symptoms of an adrenal crisis include:

  • Kidney failure
  • Loss of consciousness
  • low blood pressure
  • Severe pain in the lower back, abdomen or legs
  • Severe vomiting and diarrhea leading to dehydration
  • Shock


Findings such as hyperpigmentation, weakness, low blood pressure and salt starvation, which seem to be aggravated especially during periods of stress, may cause the doctor to suspect adrenal gland insufficiency. Laboratory tests are used to determine whether adrenal insufficiency is present, to differentiate between primary and secondary deficiencies, and to try to identify the underlying cause of the disease. Tests are requested to evaluate the patient’s electrolyte balance, blood sugar level, and kidney functions. These tests are ordered during an adrenal crisis to determine the severity of imbalances and to monitor the effectiveness of treatment.

Laboratory Tests
Cortisol : Blood levels vary normally, peaking in the early morning hours. If the adrenal gland  either does not function normally or is not stimulated by ACTH, cortisol levels will remain consistently low. Cortisol levels are used in conjunction with ACTH and ACTH stimulation tests to help diagnose adrenal insufficiency.

ACTH : ACTH is a  pituitary  hormonethat stimulates the adrenal glands to produce cortisolIt is the initial test that is initially requested to assess whether the pituitary is secreting appropriate amounts of ACTH. In a patient with adrenal insufficiency, low ACTH levels indicate secondary adrenal insufficiency, while high levels indicate primary adrenal insufficiency (Addison’s disease). The ACTH test is often ordered together with the ACTH stimulation test.

ACTH stimulation test: This test concerns the measurement of cortisol level in the patient’s blood after injection of synthetic ACTH. If the adrenal glands are functional, cortisol levels will increase in response to ACTH stimulation. If they are damaged or dysfunctional, they will respond minimally to ACTH. This rapid screening test may be ordered along with the ACTH test initially. If the test result is not normal, then a 1-3 day prolonged ACTH stimulation test may be performed to help differentiate primary and secondary adrenal insufficiency.

Aldosterone : To help diagnose Addison’s disease, blood and urine aldosterone levels are measured to determine whether the adrenal gland is secreting aldosterone. Low levels are another indication that the patient may have primary adrenal insufficiency.

Electrolytes : Electrolytes (sodium, potassium, chloride, and carbon dioxide) are measured to help identify and assess the severity of an existing electrolyte imbalance and to monitor the effectiveness of treatment. Electrolytes can be affected by many diseases. In Addison’s disease, sodium, chloride, and carbon dioxide can often be low and potassium very high.

BUN and   Creatinine tests: These are tests to monitor kidney functions.

Blood sugar levels: It can be very low during an adrenal  crisis. This test may be ordered to help monitor the patient during a crisis.

Occasional tests
Insulin-induced hypoglycemia test: The doctor will occasionally order this test to help diagnose adrenal insufficiency. For the pituitary stress test, after the patient is injected with insulin, blood glucose and cortisol levels are measured at predetermined intervals. In healthy people, blood sugar levels drop while cortisol concentrations rise. In adrenal insufficiency, cortisol levels will remain at low levels, while blood sugar levels will first decrease and then gradually normalize.

Renin : Renin activity is elevated in primary adrenal insufficiency because aldosterone deficiency causes increased sodium losses from the kidneys. Thus, blood sodium levels decrease, the liquid component of blood decreases, blood volume and pressure decrease, and ultimately renin production from the kidneys is stimulated.

21-hydroxylase autoantibodies: 21-hydroxylase autoantibodies are sometimes ordered as part of the diagnostic process when autoimmune Addison’s disease is suspected Although not widely used at this time, it is considered a good marker of autoimmune Addison’s disease.

Examinations Other than Laboratory Tests Radiological examinations can be used to look for calcification
in the adrenal gland shell , which may be due to tuberculosis  infection .

CT (computed tomography) or MRI (magnetic resonance imaging) scans are sometimes used to investigate the size and shape of the adrenal glands and pituitary. Infections and cancers can enlarge the adrenal glands. In autoimmune diseases and secondary adrenal insufficiency, the adrenal glands are often normal or small.



Although treatments are available for primary adrenal insufficiency, complete recovery does not occur. If the discomfort is due to an infection, the patient may regain some of their adrenal gland function once the infection has passed. Even if the patients have widespread and permanent damage to the outer layer (shell) of the adrenal gland, they can lead a fairly normal healthy life by replacing the missing hormones and taking a few precautions.

In secondary adrenal insufficiency, if the cause is pituitary damage or disease, the patient very rarely responds to treatment. However, if the underlying cause can be eliminated, for example, if the deficiency is due to corticosteroid therapy, cortisol production may eventually resume. Secondary adrenal insufficiency requires hormone replacement therapy.


Sources of the article

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