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Addison's disease



Addison’s disease is a primary adrenal insufficiency disorder. It is an autoimmune condition, which means that the immune system attacks the body and in this case targets the adrenal cortex. Therefore the adrenal glands stop producing enough cortisol, aldosterone and dehydroepiandrosterone. For the adrenal gland to not function appropriately and produce insufficient amounts of hormone, 90% of the cortex needs to be damaged or destroyed. Addison’s disease can become life threatening if left untreated.

The Adrenal Glands

The adrenal cortex is made up of three layers, zona glomerulosa, zona fasciculata and zona reticularis. The zona glomerulosa is the outermost layer of the cortex and is the main site for production of aldosterone. Aldosterone helps regulate blood pressure by increasing absorption of sodium and excretion of potassium in the kidneys at the distal convoluted tubule and collecting duct.Adrenal Glands

Zona fasciculata is in the middle of zona glomerulosa, and zona reticularis. It produces glucocorticoids, such as cortisol. Cortisol levels peak in the morning and reach its lowest level at midnight. It helps break down fats and protein, and regulates blood glucose levels, it also has a role in suppressing the immune system and can increase due to high stress levels.

Zona reticularis is the innermost layer of the adrenal cortex. It produces androgens such as dehydroepiandrosterone (DHEA) and a precursor of testosterone, androstenedione. Androgens stimulate the development of male characteristics. Androgens are present in both male and females.Adrenal Hormones


All the three zones of the adrenal cortex are destroyed progressively, zona glomerulosa is affected first. This condition is a dysfunction of the autoimmune system and production of autoantibodies against adrenal cortex. The adrenal cortex is attacked directly by antibodies. The other causes may include metastatic deposits, tuberculosis and fungal infections. Risk factors such as being female will increase the chance of an autoimmune condition, the patients infected with HIV are also at risk of this disease.

Signs and Symptoms

Symptoms, which could indicate Addison’s disease, are as follows:Adrenal Gland

  • Fatigue is a symptom all patients with Addison’s disease complain about
  • Anorexia (loss of appetite)
  • Hyperpigmentation of the mucosa especially sun-exposed regions of the body may indicate the disease
  • Salt craving is specific to the disease and patients will have reduced aldosterone production and therefore be hyponatraemic
  • Weight loss is common in all patients
  • Nausea and vomiting
  • Hypotension
  • Muscle pain
  • Joint pain


  • Initial investigations if the patient presents with such symptoms is to check for electrolyte imbalance. Hyponatraemia (low sodium levels) and hyperkalaemia (raised potassium) can be found on initial blood tests. Sometimes, in advanced disease there can be hypercalcaemia (raised calcium). It is important to check to urea levels in patients with Addison’s disease. Full blood count is very useful to check for anaemia and eosinophilia.
  • Cortisol levels are to be checked in the morning at 8 am or 9 am, there would be deficiency.
  • The ACTH stimulation test is useful, as it would try to stimulate the production of the low adrenal levels and if the levels remain low this helps with diagnosis.
  • Adrenal antibodies can be looked for however these are not specific to the disease.
  • Plasma renin activity can be checked and would be raised in this case. Check for plasma DHEA and aldosterone, they will be suppressed.
  • On imaging, adrenal CT scan or MRI could be helpful showing atrophy of the adrenals.


Stabilising the patient is key to begin with and therefore corticosteroids need to be given to patients even if the diagnosis is not yet confirmed. Dexamethasone or hydrocortisone for one to three days. 0.9% Sodium Chloride intravenous fluid can be administered to help with hypotension and dehydration. Glucose can be carefully administered if the patient is hypoglycaemic.

The low adrenal hormone levels need to be addressed to manage the condition. Oral mineralocorticoid and glucocorticoid replacement therapy are commenced lifelong.


Patients need to be annually checked to ensure their glucocorticoid and mineralocorticoid levels are within suitable ranges as high levels can lead to hypertension and oedema. Secondary Cushing’s syndrome can occur in patients with over replacement of the hormones. Dosages need to be changed in this case. Long-term usage of replacement can lead to osteopenia or osteoporosis. Patients diagnosed with Addison’s disease need to carry a medical alert with them to warn others about their condition in the case of them experiencing a medical emergency.

Addisonian Crisis
An Addisonian crisis occurs either as a result of undiagnosed Addison’s disease or for those patients where there is a presence of acute stressors like underlying infection, trauma or severe illness. This requires emergency medical treatment with the replacement of fluid and corticosteroids as it can be life threatening. 1L of 0.9% sodium chloride is administered quickly and then further fluids are to be given over 24 hours of at least 2L to 4L. The underlying cause needs to be investigated and treated as well. Patients with an Addisonian crisis will experience symptoms of sudden pain in their legs, abdomen and back and severe diarrhoea, vomiting. They will have severely low blood pressure, hypoglycaemia, hyponatraemia, hyperkalaemia, confusion, fever, convulsions, and can loose consciousness. It is very important to not delay treatment.
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Show references


  • Murray Longmore, Ian Wilkinson, Andrew Baldwin, Elizabeth Wallin: Oxford Handbook of Clinical Medicine, 9th Edition. 
  • Robert Volpe: Autoimmune Diseases of the Endocrine System. CRC press.
  • Richard A. Helms, David J. Quan: Textbook of Therapeutics: Drug and Disease Management. 8th Edition. Lippincott Williams & Wilkins.
  • Nessar Ahmed, Maureen Dawson, Chris Smith, Ed Wood: Biology of Disease. 
  • William A. Petit, William A. Jr Petit, Christine A. Adamec: The Encyclopedia of Endocrine Diseases and Disorders. Facts on file library of health and living.
  • Ian R. Mackay, Noel R Rose: The Autoimmune Diseases. 5th Edition.

Author, Review and Layout:

  • Shahab Shahid
  • Uruj Zehra
  • Catarina Chaves


  • Adrenal glands - ventral view - Irina Münstermann
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