Presentation of primary adrenal insufficiency (Addison's disease) may be acute or insidious, with progressive substantial fatigue and generalised weakness associated with mucocutaneous hyperpigmentation, hypotension and/or postural hypotension, and salt craving.
Adrenocorticotrophic hormone stimulation test is the definitive test to confirm or exclude the diagnosis of early primary adrenal insufficiency.
All patients require mineralocorticoid and glucocorticoid replacement therapy for life.
Use of a medical alert (bracelet or card) warning about their condition, and education on when to increase glucocorticoid replacement doses appropriately during surgery and during any stressful or infectious conditions, is vital to prevent potentially life-threatening adrenal crises.
Treatment complications arise from over-replacement of mineralocorticoid and/or glucocorticoid.
Primary adrenal insufficiency (PAI) was first described by Thomas Addison and is commonly known as Addison's disease. PAI is a disorder that results from intrinsic diseases that affect the cortex of the adrenal glands, causing impairment in the synthesis and secretion of all steroids (glucocorticoids and/or mineralocorticoids) normally secreted by the three cortical layers. The main adrenal steroids that are deficient and also physiologically important include cortisol, aldosterone, and dehydroepiandrosterone (DHEA), as well as its sulfated conjugate, DHEA-S.
Cortisol deficiency in PAI reduces the feedback to the hypothalamic-pituitary axis and results in elevation of adrenocorticotrophic hormone (ACTH) level to enhance stimulation of the adrenal cortex. This is in contrast to central adrenal insufficiency, which occurs as a result of impaired ACTH secretion caused by pituitary (secondary) or hypothalamic (tertiary) diseases. In most patients with central adrenal insufficiency, secretion of mineralocorticoids (aldosterone) is maintained.
Adrenal deficiency in children is not specifically covered in this topic, but should result in referral to a paediatric endocrinology specialist. Also not covered here is congenital adrenal hyperplasia, which includes diseases associated with deficiencies in any of the enzymes involved in adrenal steroid synthesis. See our topic 'Congenital adrenal hyperplasia' for information on this condition.
History and exam
Key diagnostic factors
- presence of risk factors
- weight loss
- acute circulatory collapse with hypotension and tachycardia
- salt craving
Other diagnostic factors
- gastrointestinal symptoms (nausea, vomiting, abdominal pain)
- postural hypotension
- arthralgia and myalgia
- axillary and pubic hair loss in women
- female sex
- adrenocortical autoantibodies
- adrenal haemorrhage
- autoimmune diseases
- coeliac disease
- tuberculosis (TB)
- non-TB bacterial infection
- fungal infection
- drugs that inhibit cortisol production
- metastatic malignancy
1st investigations to order
- morning serum cortisol
- plasma adrenocorticotrophic hormone (ACTH)
- serum electrolytes
- urea and creatinine
Investigations to consider
- adrenocorticotrophic hormone (ACTH) stimulation test
- plasma renin activity
- serum aldosterone
- serum dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S)
- adrenal antibodies
- adrenal CT or MRI
- insulin hypoglycaemia test
- overnight single-dose metyrapone test
minor intercurrent stress
severe intercurrent stress
stable and/or after treatment of acute episode
- Adrenal suppression due to the use of glucocorticoid or other drugs with glucocorticoid activity (e.g., medroxyprogesterone acetate therapy)
- Central (secondary or tertiary) adrenal insufficiency (pituitary or hypothalamic lesions)
- Guidelines for the management and prevention of acute adrenal insufficiency
- Adrenal insufficiency - emergency management practice guideline
Primary adrenal insufficiency (Addison's disease): what is it?
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