Addison Disease

Introduction

Primary adrenal insufficiency, or Addison's disease, is a chronic, rare condition which occurs when the adrenal glands fail to produce any or a high enough level of

• Mineralocorticoids, e.g. aldosterone
• Glucocorticoids, e.g. cortisol
• Adrenal androgens, e.g. dehydroepiandrosterone (DHEA)

Adrenal insufficiency most often involves the destruction of all regions of the adrenal cortex.

• In developed countries, autoimmune dysfunction is responsible for most cases (80-90%), whereas tuberculosis predominates as the cause in developing countries.
• It is more common in women than men, and onset tends to be between the ages of 30-50 years of age.

Medications may also cause primary adrenal insufficiency by

• Inhibit cortisol synthesis (e.g. ketoconazole)
• Accelerate cortisol metabolism (e.g. phenytoin, rifampin, phenobarbital)

Secondary insufficiency is characterized by reduced glucocorticoid production secondary to ACTH levels.

Symptoms

The symptoms of adrenal insufficiency are non-specific.

• Appetite loss, unintentional weight loss
• Discolouration of the skin
• Dehydration
• Increased thirst and need to urinate frequently
• Salt, soy sauce or liquorice cravings
• Oligomenorrhoea (irregular or infrequent periods in women)
• No energy or motivation (fatigue, lethargy), low mood
• Sore/painful, weak muscles and joints.

Further symptoms can occur gradually over months or years.

• Chronic exhaustion leading to depression
• Diarrhoea
• Nausea and vomiting
• Postural hypotension, which can lead to dizziness and fainting
• Reduced libido, especially in women

Chronic Management

Once diagnosis of primary adrenal insufficiency is confirmed,

• Glucocorticoid replacement therapy with hydrocortisone is recommended in all patients.
• Hydrocortisone is considered as the first-line drug because
• It is the closest imitation of what the body produces.
• It is absorbed into the body quicker than other corticosteroids.
• It can be easily measured in the bloodstream, making monitoring of dosage easier.
• For hydrocortisone or cortisone, the majority of the dose (67%) is given in the morning and the remainder (33%) is given 6 to 8 hours later to duplicate the normal circadian rhythm of cortisol production.
• Once daily dexamethasone or prednisolone can also be used but are less common.
• Monitoring parameters should include body weight, postural blood pressures, subjective energy levels, and signs of frank glucocorticoid excess.
• Mineralocorticoid replacement with fludrocortisone is recommended in all patients with confirmed aldosterone deficiency.
• Titrate dose individually based on blood pressure, serum sodium and potassium concentration, and plasma renin activity.
• Some patients may not require fludrocortisone once stabilised on hydrocortisone.
• The dose of fludrocortisone may need to be increased when the patient is exposed to high temperatures and/or humidity - this is to compensate for the increased salt loss from sweating.
• Consider trial of dehydroepiandrosterone (DHEA) in women with primary adrenal insufficiency who have low libido, depressive symptoms, and/or low energy levels despite receiving optimized glucocorticoid and mineralocorticoid replacement therapies.

Increased doses of glucocorticoids are required in patients experiencing medical or surgical stress to prevent adrenal crisis.

• Sick-day rules: Double or triple the glucocorticoid replacement dose.
• Life-threatening symptoms such as severe dehydration, hypotension, hypovolaemic shock, altered consciousness, seizures, stroke or cardiac arrest may develop; if left untreated, adrenal crisis may lead to death or permanent disability.

External Links

• Adrenal Insufficiency
  
• Cleveland Clinic - Addison's Disease